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Li X, Chen Y, Qiao G, Ni J, Chen T, Wang Y, Wu C, Zhang Q, Ma T, Gao S, Zhang M, Shen Y, Wu J, Yu J, Que R, Zhang X, Sun K, Xiao W, Jiang T, Bai X, Liang T. 5-Year survival rate over 20 % in pancreatic ductal adenocarcinoma: A retrospective study from a Chinese high-volume center. Cancer Lett 2025; 619:217658. [PMID: 40118244 DOI: 10.1016/j.canlet.2025.217658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/18/2025] [Accepted: 03/19/2025] [Indexed: 03/23/2025]
Abstract
Standardized clinical management of pancreatic adenocarcinoma (PDAC) remains challenging and high-volume centers provide essential insights for establishing effective multimodal treatment approaches. This retrospective observational study evaluated the impact of standardized, multimodal clinical management on survival outcomes in patients with PDAC across all stages, based on NCCN guidelines resectability criteria, at a high-volume center. From 2019, 4143 patients were diagnosed with PDAC, with 3268 patients receiving further treatment, including surgical resection and/or systemic therapy. The median overall survival (OS) was 18.5 (95 %CI 17.5-19.4) months for the treated cohort and the 5-year survival rate reached 23.3 %. Patients who underwent surgical resection had significantly improved median OS compared to those who received non-surgical treatments (28.4 months vs. 13.0 months, P < 0.001), with corresponding 5-year survival rates of 31.6 % vs. 15.0 %. Moreover, the patients who received NAT followed by surgical resection had improved survival outcomes compared to those who underwent upfront surgical resection in both resectable (median OS: 37.5 months vs. 28.9 months, P < 0.01) and borderline resectable group (median OS: 31.8 months vs. 18.4 months, P < 0.001). This study demonstrated a 5-year survival rate exceeding 20 % for PDAC across all stages at our center. The application of evidence-based treatment strategies through the multidisciplinary team, accompanying with standardized and comprehensive therapeutic managements, high patient adherence, have been considered as critical determinants in enhancing therapeutic efficacy and improving long-term prognosis for patients with PDAC.
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Affiliation(s)
- Xiang Li
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Yiwen Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Guoliang Qiao
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Ni
- Information Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tao Chen
- Department of Radiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yangyang Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Chengyi Wu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Qi Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Tao Ma
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Shunliang Gao
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Min Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Yan Shen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Jian Wu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Jun Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Risheng Que
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Xiaochen Zhang
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ke Sun
- Department of Pathology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenbo Xiao
- Department of Radiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tian'an Jiang
- Department of Ultrasound, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Cancer Center, Zhejiang University, Hangzhou, China.
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2
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Brada LJH, Schouten TJ, Daamen LA, Seelen LWF, Walma MS, van Dam R, de Hingh IH, Liem MSL, de Meijer VE, Patijn GA, Festen S, Stommel MWJ, Bosscha K, Besselink MG, van Santvoort HC, Molenaar IQ. Evaluation of Short and Long-term Outcomes After Resection in Patients With Locally Advanced Versus (Borderline) Resectable Pancreatic Cancer. Ann Surg 2025; 281:1026-1031. [PMID: 38557955 DOI: 10.1097/sla.0000000000006289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
OBJECTIVE To evaluate short and long-term outcomes after pancreatectomy in patients with locally advanced pancreatic cancer (LAPC) compared with patients with (borderline) resectable pancreatic cancer [(B)RPC]. BACKGROUND Selected patients diagnosed with LAPC are increasingly undergoing resection after induction chemotherapy. To evaluate the benefit of this treatment approach, it is helpful to compare outcomes in resected patients with primary LAPC to outcomes in resected patients with primary (B)RPC. METHODS Two prospectively maintained nationwide databases were used for this study. Patients with (B)RPC undergoing upfront tumor resection and patients with resected LAPC after induction therapy were included. Outcomes were postoperative pancreas-specific complications, 90-day mortality, pathologic outcomes, disease-free interval, and overall survival. RESULTS Overall, 879 patients were included; 103 with LAPC (12%) and 776 with (B)RPC (88%). Patients with LAPC had a lower World Health Organization performance score and ageadjusted Charlson Comorbidity Index. Postoperative pancreas-specific complications were comparable between groups, except delayed gastric emptying grade C, which occurred more often in patients with LAPC (9% vs 3%, P = 0.03). Ninety-day mortality was comparable. About half of the patients in both groups [54% in LAPC vs 48% in (B)RPC, P = 0.21] had a radical resection (R0). Disease-free interval was 13 months in both groups ( P = 0.12) and overall survival from the date of diagnosis was 24 months in patients with LAPC and 19 months in patients with (B)RPC ( P = 0.34). CONCLUSIONS In our nationwide prospective databases, pancreas-specific complications, mortality, and survival in patients with LAPC after pancreatectomy are comparable with those undergoing resection for (B)RPC. These outcomes suggest that postoperative morbidity and mortality after tumor resection in carefully selected patients with LAPC are acceptable.
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Affiliation(s)
- Lilly J H Brada
- Department of Surgery, UMC Utrecht Cancer Center and St Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Utrecht, The Netherlands
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
| | - Thijs J Schouten
- Department of Surgery, UMC Utrecht Cancer Center and St Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Utrecht, The Netherlands
| | - Lois A Daamen
- Department of Surgery, UMC Utrecht Cancer Center and St Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Utrecht, The Netherlands
| | - Leonard W F Seelen
- Department of Surgery, UMC Utrecht Cancer Center and St Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Utrecht, The Netherlands
| | - Marieke S Walma
- Department of Surgery, UMC Utrecht Cancer Center and St Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Utrecht, The Netherlands
| | - Ronald van Dam
- Department of Surgery, Maastricht UMC+, Maastricht, The Netherlands
- Department of General and Viseral Surgery, University Hospital Aachen, Aachen, Germany
| | - Ignace H de Hingh
- Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Aachen, Maastricht, The Netherlands
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Mike S L Liem
- Department of Surgery, Medical Spectrum Twente, Enschede, The Netherlands
| | - Vincent E de Meijer
- Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Gijs A Patijn
- Department of Surgery, Isala, Zwolle, The Netherlands
| | | | - Martijn W J Stommel
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Koop Bosscha
- Department of Surgery, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
| | - Hjalmar C van Santvoort
- Department of Surgery, UMC Utrecht Cancer Center and St Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Utrecht, The Netherlands
| | - Izaak Quintus Molenaar
- Department of Surgery, UMC Utrecht Cancer Center and St Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Utrecht, The Netherlands
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3
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Tang Y, Huang C, Chen D, Gong Y, Chen L, Chen W, You L, Miao Z, Zhang H. Discovery of homocamptothecin derivative TOP-0618 as a radiosensitive agent for the treatment of pancreatic cancer. BMC Cancer 2025; 25:936. [PMID: 40414856 DOI: 10.1186/s12885-025-14347-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Accepted: 05/16/2025] [Indexed: 05/27/2025] Open
Abstract
BACKGROUND Pancreatic cancer is one of the most lethal malignancies characterized by a complex tumor microenvironment (TME) and highly heterogeneous nature, making it resistant to radiotherapy. This study aims to evaluate the radiosensitizing effect of homocamptothecin derivative TOP-0618 on pancreatic cancer. METHODS Clonogenic assays and cell viability assays were used to evaluate the radiosensitizing effects of TOP-0618 on pancreatic cancer cells. Cell cycle and apoptosis were detected using flow cytometry. A pancreatic bi-flank xenograft tumor model was used to evaluate the radiosensitivity of TOP-0618. H&E staining analyses and TUNEL staining were used to examine necrosis and apoptosis of pancreatic xenograft tumors. RESULTS Cytotoxicity assays revealed that IC50 values of TOP-0618 against PANC-1 and MIAPaCa-2 cells were 1.442 µmol/L and 1.198 µmol /L, respectively. Additionally, clonogenic assays revealed that TOP-0618 exerted radiosensitizing effects on both pancreatic cells, and the sensitizer enhancement ratio (SER) of TOP-0618 was 1.14 for the PANC-1 cell line and 1.65 for the MIAPaCa-2 cell line. The preliminary study revealed that TOP-0618 improved radiosensitivity by enhancing G2/M phase arrest and increasing the apoptosis of pancreatic cells. Subsequently, in a pancreatic bi-flank xenograft tumor model, TOP-0618 combined with irradiation significantly inhibited tumor growth, and increased necrosis and apoptosis in pancreatic xenograft tumors. CONCLUSIONS Our work demonstrates the radiosensitizing effect of homocamptothecin derivative TOP-0618 on pancreatic cancer both in vivo and vitro, and lays a foundation for clinical transformation.
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Affiliation(s)
- Yin Tang
- Department of Radiation Oncology, Changhai Hospital affiliated to Naval Medical University, Shanghai, 200433, China
- Department of Gastroenterology, The 83 rd Group Army Hospital, 83 rd Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453000, China
| | - Chengyi Huang
- Department of Radiation Oncology, Changhai Hospital affiliated to Naval Medical University, Shanghai, 200433, China
| | - Di Chen
- Department of Radiation Oncology, Changhai Hospital affiliated to Naval Medical University, Shanghai, 200433, China
| | - Yangyang Gong
- Department of Radiation Oncology, Changhai Hospital affiliated to Naval Medical University, Shanghai, 200433, China
| | - Liang Chen
- Department of Radiation Oncology, Changhai Hospital affiliated to Naval Medical University, Shanghai, 200433, China
| | - Wenjuan Chen
- Department of Radiation Oncology, Changhai Hospital affiliated to Naval Medical University, Shanghai, 200433, China
| | - Liang You
- School of Pharmacy, Naval Medical University, Shanghai, 200433, China
| | - Zhenyuan Miao
- School of Pharmacy, Naval Medical University, Shanghai, 200433, China.
| | - Huojun Zhang
- Department of Radiation Oncology, Changhai Hospital affiliated to Naval Medical University, Shanghai, 200433, China.
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4
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Stoop TF, Wu YHA, Oba A, Ali M, Feld IM, Al-Musawi MH, Jain A, Saiura A, Sauvanet A, Coppola A, Javed AA, Groot Koerkamp B, Miller BN, Hashimoto D, Caputo D, Kleive D, Sereni E, Kazemier G, Belfiori G, Ishida H, van Dam JL, Dembinski J, Akahoshi K, Roberts KJ, Tanaka K, Labori KJ, Falconi M, House MG, Sugimoto M, Tanabe M, Gotohda N, Chatzizacharias N, Krohn PS, Dokmak S, Rodriguez Franco S, Hirano S, Burgdorf SK, Crippa S, Satoi S, Nguyen TK, Yamamoto T, Nakamura T, Ushida Y, Bachu V, Burns WR, Inoue Y, Takahashi Y, Aslami Z, Schulick RD, He J, Messersmith W, Besselink MG, Burkhart RA, Wilmink JW, Del Chiaro M. Survival after neoadjuvant and induction FOLFIRINOX versus gemcitabine-nab-paclitaxel in patients with resected localised pancreatic adenocarcinoma: an international multicentre study. Br J Cancer 2025:10.1038/s41416-025-03025-1. [PMID: 40328917 DOI: 10.1038/s41416-025-03025-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 03/15/2025] [Accepted: 04/08/2025] [Indexed: 05/08/2025] Open
Abstract
BACKGROUND It remains unclear whether there is a difference in overall survival (OS) benefit between (m)FOLFIRINOX and gemcitabine-nab-paclitaxel as preoperative regimens for localised pancreatic adenocarcinoma. This study aimed to investigate the outcome of patients with resected localised pancreatic adenocarcinoma following (m)FOLFIRINOX versus gemcitabine-nab-paclitaxel. METHODS International multicentre retrospective study (16 centres, 8 countries, 3 continents), including consecutive patients after pancreatic resection for localised pancreatic adenocarcinoma following 2-6 months preoperative (m)FOLFIRINOX or gemcitabine-nab-paclitaxel (2010-2018). Primary endpoint was OS from start of preoperative chemotherapy. Cox regression analysis was performed to investigate the association of the preoperative chemotherapy regimen with OS, adjusted for confounders at diagnosis. RESULTS Overall, 935 patients were included after resection of localised pancreatic adenocarcinoma following preoperative (m)FOLFIRINOX (65%) or gemcitabine-nab-paclitaxel (35%). Preoperative chemotherapy regimen (m)FOLFIRINOX was not associated with OS (HR = 0.83 [95% CI 0.64-1.08]), compared to gemcitabine-nab-paclitaxel. Interaction analysis showed stronger effect of (m)FOLFIRINOX in patients with a lower (i.e., non-elevated/marginally elevated) serum CA19-9 at diagnosis (pinteraction = 0.032). CONCLUSION This international study found no OS benefit of preoperative (m)FOLFIRINOX in patients with resected localised pancreatic adenocarcinoma compared to gemcitabine-nab-paclitaxel.
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Affiliation(s)
- Thomas F Stoop
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands.
- Cancer Center Amsterdam, Amsterdam, The Netherlands.
| | - Y H Andrew Wu
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
| | - Atsushi Oba
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Mahsoem Ali
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
| | - Isabel M Feld
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Mohammed H Al-Musawi
- Clinical Trials of Office, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Ajay Jain
- Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Akio Saiura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Alain Sauvanet
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, University Paris Cité, INSERM Unité Mixte de Recherche 1149, Clichy, France
| | | | - Ammar A Javed
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
- Division of Surgical Oncology, Department of Surgery, New York University Medical Center, New York City, NY, USA
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Braden N Miller
- Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | | | - Damiano Caputo
- Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
- Research Unit of General Surgery, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Dyre Kleive
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Elisabetta Sereni
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
- Department of General and Pancreatic Surgery, The Pancreas Institute University of Verona, Hospital Trust, Verona, Italy
| | - Geert Kazemier
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
| | - Giulio Belfiori
- Pancreatic Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milano, Italy
| | - Hirofumi Ishida
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Jacob L van Dam
- Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jeanne Dembinski
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, University Paris Cité, INSERM Unité Mixte de Recherche 1149, Clichy, France
| | - Keiichi Akahoshi
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Keith J Roberts
- Hepato-Pancreato-Biliary Unit, Department of Surgery, University Hospitals of Birmingham, Birmingham, UK
| | - Kimitaka Tanaka
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, Hokkaido, Japan
| | - Knut J Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Massimo Falconi
- Pancreatic Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milano, Italy
| | - Michael G House
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Motokazu Sugimoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Minoru Tanabe
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Naoto Gotohda
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Nikolaos Chatzizacharias
- Hepato-Pancreato-Biliary Unit, Department of Surgery, University Hospitals of Birmingham, Birmingham, UK
| | - Paul S Krohn
- Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Safi Dokmak
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, University Paris Cité, INSERM Unité Mixte de Recherche 1149, Clichy, France
| | - Salvador Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, Hokkaido, Japan
| | - Stefan K Burgdorf
- Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Stefano Crippa
- Pancreatic Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milano, Italy
| | - Sohei Satoi
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - Trang K Nguyen
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Tomohisa Yamamoto
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, Hokkaido, Japan
| | - Toru Nakamura
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, Hokkaido, Japan
| | - Yuta Ushida
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Vismaya Bachu
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
| | - William R Burns
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
| | - Yosuke Inoue
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Yu Takahashi
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Zohra Aslami
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
| | - Richard D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Jin He
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
| | - Wells Messersmith
- Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Marc G Besselink
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Richard A Burkhart
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
| | - Johanna W Wilmink
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Amsterdam UMC, Location University of Amsterdam, Department of Medical Oncology, Amsterdam, The Netherlands
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
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5
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He Y, Zhu Y, Wang W, Yi Y, Wang Z, Zhao C, Li J, Huang X, Zheng L. Clinical efficacy and chemoresistance analysis of precision neoadjuvant chemotherapy for borderline resectable pancreatic cancer: a prospective, single-arm pilot study. Int J Surg 2025; 111:3269-3280. [PMID: 40146255 DOI: 10.1097/js9.0000000000002342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 03/06/2025] [Indexed: 03/28/2025]
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) can improve the survival outcomes of patients with pancreatic cancer, but for borderline resectable pancreatic cancer (BRPC) the proportion of conversion to surgery remains unsatisfactory. This single-arm pilot study aimed to assess the clinical efficacy and safety of NAC based on patient-derived organoids (PDOs) for BRPC. METHODS Biopsy samples from BRPC patients were collected for generating PDOs. Gemcitabine plus nab-paclitaxel as NAC was initially administrated for one cycle, and then the treatment regimen was adjusted based on the PDO drug sensitivity testing. The primary endpoint was the objective response rate (ORR). Secondary endpoints included R0 resection rate, NAC-related adverse events (AEs), and postoperative complications. Exploratory objectives were to assess the chemoresistance to gemcitabine. RESULTS Totally 19 of 25 patients were eligible for the study, among whom 16 achieved partial response and received surgical resection, with the ORR of 84.2% (16/19). The R0 resection rate was 81.3% (13/16). During NAC, 8 (42.1%, 8/19) patients experienced different grades of AEs, mainly including grade 2 myelosuppression (26.3%), cutaneous pruritus (5.3%), and diarrhea (5.3%). scRNA-seq analysis of duct cells showed that the transcriptome in aneuploid cells may affect gemcitabine resistance via multiple pathways, among which upregulation of drug-resistant genes ( OLFM4, AGR2, MUC5AC, MUC1, HMGA1, REG4, IL17RB, GCNT3, AKR1B10, ITGA6, HMGCS2 , and SQLE ) and downregulation of sensitive genes ( SIK1, HEXIM1, SPINT2, GADD45 , and TIMP2 ) played crucial roles. Changes in the interactions between cancer cells and other cell groups may also involve in gemcitabine resistance. CONCLUSION PDO-based NAC shows a promising resectable rate in BRPC patients, with good tolerance. Potential drug-resistant and sensitive genes and cell-cell interaction changes may participate in the development of gemcitabine resistance.
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Affiliation(s)
- Yonggang He
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Yinan Zhu
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Weiwei Wang
- Department of Hepatobiliary and Pancreatic Surgery, Chongqing Tongliang District People's Hospital, Chongqing, China
| | - Yuanyue Yi
- Department of Pathology, The Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Zheng Wang
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Chongyu Zhao
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Jing Li
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Xiaobing Huang
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Lu Zheng
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing, China
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6
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Kim HS, Chae H, Lim SY, Jeong H, Yoon SJ, Shin SH, Han IW, Heo JS, Kim H. Prognostic Accuracy of ypTNM Stage in Patients with Pancreatic Cancer in the Era of Modern Neoadjuvant Therapy. Ann Surg Oncol 2025; 32:2799-2808. [PMID: 39757338 DOI: 10.1245/s10434-024-16792-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 12/16/2024] [Indexed: 01/07/2025]
Abstract
BACKGROUND The American Joint Committee on Cancer (AJCC) 8th edition TNM staging manual, which provided ypTNM for patients undergoing neoadjuvant therapy (NAT), has not been comparatively assessed against pTNM for prognosis in pancreatic cancer. This study aimed to compare the prognosis between ypTNM and pTNM stages. PATIENTS AND METHODS Clinicopathological data from 586 patients who underwent pancreatic cancer surgery at a tertiary center between 2018 and 2022 were analyzed to compare survival outcomes between ypTNM and pTNM stages and identify prognostic factors. RESULTS The analysis included 541 patients (100 ypTNM, 441 pTNM). Significant differences in overall survival (OS) were observed among patients stratified by TNM stage (p < 0.001). However, no significant difference in OS was found between the ypTNM and pTNM groups (2-year survival rate (YSR): 76.8% vs. 66.7%, p = 0.094). Subgroup analysis by stage I (82.4% vs. 76.2%, p = 0.577) and II (68.8% vs. 61.6%, p = 0.715), and III (53.0% vs. 49.8%, p = 0.596) revealed similar survival rates. Multivariate analysis identified factors associated with OS: age > 65 years (HR 1.763, p < 0.001), CA19-9 > 150 U/mL (HR 1.439, p = 0.014), preoperative biliary drainage (HR 1.405, p = 0.029), pathologic T2 stage (HR 1.961, p = 0.004) and T3/4 stage (HR 2.830, p < 0.001) versus T0/1 stage, lymphovascular invasion (HR 2.220, p < 0.001), and adjuvant treatment (HR 0.251, p < 0.001). CONCLUSIONS This study confirms comparable survival outcomes between ypTNM and pTNM stages in surgically resected pancreatic cancer, affirming the applicability of the TNM staging system after NAT. The results highlight the utility of TNM staging in guiding therapeutic decisions for patients undergoing NAT.
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Affiliation(s)
- Hyeong Seok Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hochang Chae
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Soo Yeun Lim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea
| | - HyeJeong Jeong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University School of Medicine, Daejeon, South Korea
| | - So Jeong Yoon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sang Hyun Shin
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - In Woong Han
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jin Seok Heo
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hongbeom Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
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7
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Addeo P, Muzzolini M, Laurent C, Heyd B, Sauvanet A, Garnier J, Alfano MS, Gaujoux S, De Ponthaud C, Marchese U, Da Silva D, Buc E, Souche R, Fabre JM, Colombo PE, Ferre L, Foguenne M, Hubert C, El Amrani M, Truant S, Schwartz L, Regenet N, Dupre A, Brustia R, Cherif R, Navez J, Darnis B, Facy O, Grellet R, Piessen G, Veziant J, Rhaiem R, Kianmanesh R, Fernandez-De-Sevilla E, Gelli M, Taibi A, Georges P, Mabrut JY, Lesurtel M, Doussot A, Bachellier P. ASO Author Reflections: Complete Pathological Response after Neoadjuvant Treatment for Pancreatic Ductal Adenocarcinomas-Curative Surgery in Cured Patients? Ann Surg Oncol 2025; 32:2861-2863. [PMID: 39893336 DOI: 10.1245/s10434-025-16925-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 01/04/2025] [Indexed: 02/04/2025]
Affiliation(s)
- Pietro Addeo
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives et Hépatiques, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France.
| | - Milena Muzzolini
- Department of HBP Surgery, AP-HP, Hôpital Beaujon, University of Paris, Clichy, France
| | - Christophe Laurent
- Department of Digestive Surgery, Centre Magellan, CHU Bordeaux, Bordeaux, France
| | - Bruno Heyd
- Department of Digestive Surgical Oncology, University Hospital of Besançon, Besançon, France
| | - Alain Sauvanet
- Department of HBP Surgery, AP-HP, Hôpital Beaujon, University of Paris, Clichy, France
| | - Jonathan Garnier
- Department of Oncological Surgery, Institut Paoli Calmettes, Marseille University, Marseille, France
| | - Marie Sophie Alfano
- Department of Oncological Surgery, Institut Paoli Calmettes, Marseille University, Marseille, France
| | - Sebastien Gaujoux
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
| | - Charles De Ponthaud
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
| | - Ugo Marchese
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Hospital, AP-HP, Université de Paris, Paris, France
| | - Doris Da Silva
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Hospital, AP-HP, Université de Paris, Paris, France
| | - Emmanuel Buc
- Department of Digestive and Hepatobiliary Surgery, Liver Transplantation, University Hospital Clermont-Ferrand, Clermont-Ferrand, France
| | - Regis Souche
- Department of Surgery, Hopital Saint Eloi, Montpellier, France
| | | | | | - Lorenzo Ferre
- Department of Surgical Oncology, Institut du Cancer de Montpellier, Montpellier, France
| | - Maxime Foguenne
- Department of Abdominal Surgery and Transplantation, Cliniques universitaires Saint-Luc, Brussels, Belgium
| | - Catherine Hubert
- Department of Abdominal Surgery and Transplantation, Cliniques universitaires Saint-Luc, Brussels, Belgium
| | - Mehdi El Amrani
- Department of Digestive Surgery and Transplantation, Lille University Hospital, Lille, France
| | - Stephanie Truant
- Department of Digestive Surgery and Transplantation, Lille University Hospital, Lille, France
| | - Lilian Schwartz
- Department of Digestive Surgery, Rouen University Hospital and Université de Rouen Normandie, Rouen, France
| | - Nicolas Regenet
- Department of Digestive Surgery, Nantes Hospital, Nantes, France
| | - Aurelien Dupre
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Raffaele Brustia
- Department of Digestive and Hepato-Pancreatic-Biliary Surgery, Hôpital Henri-Mondor, AP-HP, Paris Est Créteil University, UPEC, Créteil, France
| | - Rim Cherif
- Department of Digestive and Hepato-Pancreatic-Biliary Surgery, Hôpital Henri-Mondor, AP-HP, Paris Est Créteil University, UPEC, Créteil, France
| | - Julie Navez
- Department of Abdominal Surgery and Transplantation, Hôpitaux Universitaires de Bruxelles, Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Benjamin Darnis
- Department of Digestive Surgery, Clinique de La Sauvegarde, Lyon, France
| | - Olivier Facy
- Department of Digestive and Surgical Oncology, University Hospital, Dijon, France
| | - Robin Grellet
- Department of Digestive and Surgical Oncology, University Hospital, Dijon, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France
| | - Julie Veziant
- Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France
| | - Rami Rhaiem
- Department of HBP and Digestive Oncological Surgery, Robert Debré University Hospital, University Reims Champagne-Ardenne, Reims, France
| | - Reza Kianmanesh
- Department of HBP and Digestive Oncological Surgery, Robert Debré University Hospital, University Reims Champagne-Ardenne, Reims, France
| | | | | | - Abdelkader Taibi
- Department of Digestive Surgery, Dupuytren Limoges University Hospital, Limoges, France
| | - Pauline Georges
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France
| | - Jean Yves Mabrut
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France
| | - Mickael Lesurtel
- Department of HBP Surgery, AP-HP, Hôpital Beaujon, University of Paris, Clichy, France
| | - Alexandre Doussot
- Department of Digestive Surgical Oncology, University Hospital of Besançon, Besançon, France
| | - Philippe Bachellier
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives et Hépatiques, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France
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8
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Addeo P, Muzzolini M, Laurent C, Heyd B, Sauvanet A, Garnier J, Alfano MS, Gaujoux S, De Ponthaud C, Marchese U, Da Silva D, Buc E, Souche R, Fabre JM, Colombo PE, Ferre L, Foguenne M, Hubert C, El Amrani M, Truant S, Schwartz L, Regenet N, Dupre A, Brustia R, Cherif R, Navez J, Darnis B, Facy O, Grellet R, Piessen G, Veziant J, Rhaiem R, Kianmanesh R, Fernandez-De-Sevilla E, Gelli M, Taibi A, Georges P, Mabrut JY, Lesurtel M, Doussot A, Bachellier P. Prognosis Associated with Complete Pathological Response Following Neoadjuvant Treatment for PancreaTic AdenOcarciNOma in the FOFLIRINOX Era: the Multicenter TONO Study. Ann Surg Oncol 2025; 32:2809-2818. [PMID: 39777595 DOI: 10.1245/s10434-024-16735-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND The use of multiagent FOLFIRINOX chemotherapy for pancreatic adenocarcinoma in a neoadjuvant setting has been associated with an increased rate of complete pathological response (CPR) after surgery. This study investigated the long-term outcomes of patients with CPR in a multicenter setting to identify prognostic factors for overall survival (OS) and recurrence-free survival (RFS). METHODS This retrospective cohort study examined biopsy-proven pancreatic adenocarcinomas with CPR after neoadjuvant chemotherapy or chemoradiotherapy and surgery, between January 2006 and December 2023 across 22 French and 2 Belgian centers. Cox analyses were used to identify prognostic factors of OS and RFS. RESULTS There were 101 patients with CPR after chemotherapy (n = 58, 57.4%) and chemoradiotherapy (n = 43, 42.6%) followed by surgery. Neoadjuvant FOLFIRINOX was used in 90% of patients. The median OS after surgery was 177 months (95% confidence interval (CI) 58.9-177 months) with 1-, 3-, 5-, and 10-year OS rates of 93%, 75%, 63%, and 51%, respectively. The median RFS was 67.8 months (95% CI:34.4-NR) with 1-, 3-, 5-, and 10-year RFS rates of 83%, 58%, 54%, and 49%, respectively. The multivariate Cox analysis of OS and RFS showed that preoperative radiotherapy was an independent negative prognostic factor for OS (hazard ratio (HR) 2.51; 95% CI 1.00-6.30; p = 0.03) and RFS (HR 2.62; 95% CI 1.27-5.41; p = 0.009). CONCLUSIONS Complete pathologic response after neoadjuvant treatment is associated with remarkable long-term survival that is usually not seen after the resection of pancreatic adenocarcinomas. One-third of the patients still experienced disease recurrence, which was more common in those receiving preoperative chemoradiotherapy.
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Affiliation(s)
- Pietro Addeo
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives et Hépatiques, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France.
| | - Milena Muzzolini
- Department of HBP Surgery, AP-HP, Hôpital Beaujon, University of Paris, Clichy, France
| | - Christophe Laurent
- Department of Digestive Surgery, Centre Magellan-CHU Bordeaux, Bordeaux, France
| | - Bruno Heyd
- Department of Digestive Surgical Oncology, University Hospital of Besançon, Besançon, France
| | - Alain Sauvanet
- Department of HBP Surgery, AP-HP, Hôpital Beaujon, University of Paris, Clichy, France
| | - Jonathan Garnier
- Department of Oncological Surgery, Institut Paoli Calmettes, Marseille University, Marseille, France
| | - Marie Sophie Alfano
- Department of Oncological Surgery, Institut Paoli Calmettes, Marseille University, Marseille, France
| | - Sebastien Gaujoux
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
| | - Charles De Ponthaud
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
| | - Ugo Marchese
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Hospital, AP-HP, Université de Paris, Paris, France
| | - Doris Da Silva
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Hospital, AP-HP, Université de Paris, Paris, France
| | - Emmanuel Buc
- Department of Digestive and Hepatobiliary Surgery-Liver Transplantation, University Hospital Clermont-Ferrand, Clermont-Ferrand, France
| | - Regis Souche
- Department of Surgery, Hopital Saint Eloi, Montpellier, France
| | | | - Pierre-Emanuel Colombo
- Department of Surgical Oncology, Institut du Cancer de Montpellier (ICM), Montpellier, France
| | - Lorenzo Ferre
- Department of Surgical Oncology, Institut du Cancer de Montpellier (ICM), Montpellier, France
| | - Maxime Foguenne
- Department of Abdominal Surgery and Transplantation, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Catherine Hubert
- Department of Abdominal Surgery and Transplantation, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Mehdi El Amrani
- Department of Digestive Surgery and Transplantation, Lille University Hospital, Lille, France
| | - Stephanie Truant
- Department of Digestive Surgery and Transplantation, Lille University Hospital, Lille, France
| | - Lilian Schwartz
- Department of Digestive Surgery, Rouen University Hospital and Université de Rouen Normandie, Rouen, France
| | - Nicolas Regenet
- Department of Digestive Surgery, Nantes Hospital, Nantes, France
| | - Aurelien Dupre
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Raffaele Brustia
- Department of Digestive and Hepato-Pancreatic-Biliary Surgery, Hôpital Henri-Mondor, AP-HP, Paris Est Créteil University, UPEC, Créteil, France
| | - Rim Cherif
- Department of Digestive and Hepato-Pancreatic-Biliary Surgery, Hôpital Henri-Mondor, AP-HP, Paris Est Créteil University, UPEC, Créteil, France
| | - Julie Navez
- Department of Abdominal Surgery and Transplantation, Hôpitaux Universitaires de Bruxelles (HUB), Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Benjamin Darnis
- Department of Digestive Surgery, Clinique de La Sauvegarde, Lyon, France
| | - Olivier Facy
- Department of Digestive and Surgical Oncology, University Hospital, Dijon, France
| | - Robin Grellet
- Department of Digestive and Surgical Oncology, University Hospital, Dijon, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France
| | - Julie Veziant
- Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France
| | - Rami Rhaiem
- Department of HBP and Digestive Oncological Surgery, Robert Debré University Hospital, University Reims Champagne-Ardenne, Reims, France
| | - Reza Kianmanesh
- Department of HBP and Digestive Oncological Surgery, Robert Debré University Hospital, University Reims Champagne-Ardenne, Reims, France
| | | | | | - Abdelkader Taibi
- Department of Digestive Surgery, Dupuytren Limoges University Hospital, Limoges, France
| | - Pauline Georges
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France
| | - Jean Yves Mabrut
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France
| | - Mickael Lesurtel
- Department of HBP Surgery, AP-HP, Hôpital Beaujon, University of Paris, Clichy, France
| | - Alexandre Doussot
- Department of Digestive Surgical Oncology, University Hospital of Besançon, Besançon, France
| | - Philippe Bachellier
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives et Hépatiques, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France
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9
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Renouf T. The Role of Prehabilitation in Oncology Patients Undergoing Complex Systemic Anticancer Therapy. Semin Oncol Nurs 2025; 41:151812. [PMID: 39939205 DOI: 10.1016/j.soncn.2025.151812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 01/13/2025] [Accepted: 01/14/2025] [Indexed: 02/14/2025]
Abstract
OBJECTIVES To review the recent literature around the role of patient-centric prehabilitation for oncology patients undergoing complex systemic anticancer therapy (SACT) and the nurse's role in this area. METHOD A narrative review of recent peer-reviewed literature, national guidance, and government strategy for prehabilitation in oncology patients undergoing complex SACT. RESULTS/CONCLUSION Prehabilitation interventions in people receiving complex SACT are feasible and benefit patient outcomes. These results must still be viewed with caution; however, as of now, there are only small-scale studies in this area, although larger-scale studies are now being done. The role of the nurse is key here (as part of the interdisciplinary team) through the establishment of the therapeutic relationship underpinning patient screening, assessment, intervention implementation, and patient reassessment, ensuring care is dynamic, consistent, and tailored to patient needs. IMPLICATIONS FOR NURSING PRACTICE The review has discussed the beneficial patient outcomes from prehabilitation in patients receiving complex SACT, but more research is warranted in the form of larger multisite trials to increase the validity of the prehabilitation interventions. The review advocates for the role of the nurse in the provision of prehabilitation in SACT oncology patients through the provision of personalized patient care.
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10
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Gayibov E, Sychra T, Souček P, Oliverius M. A current knowledge of the undifferentiated carcinoma of the pancreas with osteoclast-like giant cells: a narrative review. J Gastrointest Oncol 2025; 16:281-291. [PMID: 40115925 PMCID: PMC11921273 DOI: 10.21037/jgo-24-780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 01/06/2025] [Indexed: 03/23/2025] Open
Abstract
Background and Objective Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is a rare variant of malignant pancreatic tumor. There is still no standardized treatment for this uncommon subtype, as surgical resection with lymphadenectomy is the only potentially curative treatment so far. In this paper, we describe the current knowledge of this very rare specific subtype of pancreatic cancer (PC) as a narrative review. Methods For this review, we did not specify the time range of studies referred to due to limited data availability. Our inclusion criteria comprised previous studies, which specifically focused on the rare UCOGC subtype of PC as a confirmed histopathology, either pure or present together with other subtypes. We disregarded the studies involving any other PC subtype but not UCOGC, including undifferentiated and anaplastic carcinomas without osteoclast-like giant cell components. Key Content and Findings The limited available data precludes a definitive assessment of the efficacy of both neoadjuvant and adjuvant chemotherapy in the treatment of UCOGC. Monoclonal antibody pembrolizumab has been proven to be effective in metastatic cases. Multiple cases demonstrate a better overall survival rate for patients with UCOGC only versus those having UCOGC as a component with a pancreatic ductal adenocarcinoma (PDAC) histopathological subtype. The same conclusion can be also drawn comparing the survival rate of patients having pure UCOGC versus UCOGC with associated PDAC. Programmed cell death ligand-1 expression has been shown to be an important determinant, which shortens the survival period of patients diagnosed with UCOGC. Conclusions The rarity of UCOGC limits data for clinical courses and treatment plans. We need more data to better understand the relationship between pathogenic mutations, histological subtypes, and prognosis in PC, including UCOGC. Understanding UCOGC's molecular, clinical, radiological, and pathological characteristics can lead to earlier, more accurate diagnoses and better management.
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Affiliation(s)
- Emin Gayibov
- Third Faculty of Medicine, Charles University, Prague, Czech Republic
- Department of General Surgery, University Hospital Královské Vinohrady, Prague, Czech Republic
| | - Tomáš Sychra
- Third Faculty of Medicine, Charles University, Prague, Czech Republic
- Department of General Surgery, University Hospital Královské Vinohrady, Prague, Czech Republic
- Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic
| | - Pavel Souček
- Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic
| | - Martin Oliverius
- Third Faculty of Medicine, Charles University, Prague, Czech Republic
- Department of General Surgery, University Hospital Královské Vinohrady, Prague, Czech Republic
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11
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Rasenberg DWM, Ramaekers M, Jacobs I, Pluyter JR, Geurts LJF, Yu B, van der Ven JCP, Nederend J, de Hingh IHJT, Bonsing BA, Vahrmeijer AL, van der Harst E, den Dulk M, van Dam RM, Groot Koerkamp B, Erdmann JI, Daams F, Busch OR, Besselink MG, te Riele WW, Reinhard R, Jansen FW, Dankelman J, Mieog JSD, Luyer MDP. Computer-Aided Decision Support and 3D Models in Pancreatic Cancer Surgery: A Pilot Study. J Clin Med 2025; 14:1567. [PMID: 40099616 PMCID: PMC11899912 DOI: 10.3390/jcm14051567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 02/07/2025] [Accepted: 02/20/2025] [Indexed: 03/20/2025] Open
Abstract
Background: Preoperative planning of patients diagnosed with pancreatic head cancer is difficult and requires specific expertise. This pilot study assesses the added value of three-dimensional (3D) patient models and computer-aided detection (CAD) algorithms in determining the resectability of pancreatic head tumors. Methods: This study included 14 hepatopancreatobiliary experts from eight hospitals. The participants assessed three radiologically resectable and three radiologically borderline resectable cases in a simulated setting via crossover design. Groups were divided in controls (using a CT scan), a 3D group (using a CT scan and 3D models), and a CAD group (using a CT scan, 3D and CAD). For the perceived fulfillment of preoperative needs, the quality and confidence of clinical decision-making were evaluated. Results: A higher perceived ability to determine degrees and the length of tumor-vessel contact was reported in the CAD group compared to controls (p = 0.022 and p = 0.003, respectively). Lower degrees of tumor-vessel contact were predicted for radiologically borderline resectable tumors in the CAD group compared to controls (p = 0.037). Higher confidence levels were observed in predicting the need for vascular resection in the 3D group compared to controls (p = 0.033) for all cases combined. Conclusions: "CAD (including 3D) improved experts' perceived ability to accurately assess vessel involvement and supports the development of evolving techniques that may enhance the diagnosis and treatment of pancreatic cancer".
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Affiliation(s)
- Diederik W. M. Rasenberg
- Faculty of BioMechanical Engineering, Delft University of Technology, 2628 CE Delft, The Netherlands; (D.W.M.R.); (F.W.J.); (J.D.)
- Department of Experience Design, Philips, 5656 AE Eindhoven, The Netherlands; (J.R.P.); (L.J.F.G.); (B.Y.)
| | - Mark Ramaekers
- Department of Surgery, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; (I.H.J.T.d.H.); (M.D.P.L.)
| | - Igor Jacobs
- Department of Hospital Services & Informatics, Philips Research, 5656 AE Eindhoven, The Netherlands; (I.J.); (J.C.P.v.d.V.)
| | - Jon R. Pluyter
- Department of Experience Design, Philips, 5656 AE Eindhoven, The Netherlands; (J.R.P.); (L.J.F.G.); (B.Y.)
| | - Luc J. F. Geurts
- Department of Experience Design, Philips, 5656 AE Eindhoven, The Netherlands; (J.R.P.); (L.J.F.G.); (B.Y.)
| | - Bin Yu
- Department of Experience Design, Philips, 5656 AE Eindhoven, The Netherlands; (J.R.P.); (L.J.F.G.); (B.Y.)
| | - John C. P. van der Ven
- Department of Hospital Services & Informatics, Philips Research, 5656 AE Eindhoven, The Netherlands; (I.J.); (J.C.P.v.d.V.)
| | - Joost Nederend
- Department of Radiology, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands;
| | - Ignace H. J. T. de Hingh
- Department of Surgery, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; (I.H.J.T.d.H.); (M.D.P.L.)
- GROW—School for Oncology and Developmental Biology, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - Bert A. Bonsing
- Department of Surgery, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; (B.A.B.); (A.L.V.); (J.S.D.M.)
| | - Alexander L. Vahrmeijer
- Department of Surgery, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; (B.A.B.); (A.L.V.); (J.S.D.M.)
| | - Erwin van der Harst
- Department of Surgery, Maasstad Hospital, 3079 DZ Rotterdam, The Netherlands;
| | - Marcel den Dulk
- Department of Surgery, Maastricht University Medical Centre+, 6229 ER Maastricht, The Netherlands; (M.d.D.); (R.M.v.D.)
| | - Ronald M. van Dam
- Department of Surgery, Maastricht University Medical Centre+, 6229 ER Maastricht, The Netherlands; (M.d.D.); (R.M.v.D.)
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus Medical Centre, 3015 GD Rotterdam, The Netherlands;
| | - Joris I. Erdmann
- Department of Surgery, Amsterdam University Medical Centers, 1081 HV Amsterdam, The Netherlands; (J.I.E.); (F.D.); (O.R.B.); (M.G.B.)
| | - Freek Daams
- Department of Surgery, Amsterdam University Medical Centers, 1081 HV Amsterdam, The Netherlands; (J.I.E.); (F.D.); (O.R.B.); (M.G.B.)
| | - Olivier R. Busch
- Department of Surgery, Amsterdam University Medical Centers, 1081 HV Amsterdam, The Netherlands; (J.I.E.); (F.D.); (O.R.B.); (M.G.B.)
| | - Marc G. Besselink
- Department of Surgery, Amsterdam University Medical Centers, 1081 HV Amsterdam, The Netherlands; (J.I.E.); (F.D.); (O.R.B.); (M.G.B.)
| | - Wouter W. te Riele
- Department of Surgery, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands;
| | - Rinze Reinhard
- Department of Radiology, Onze Lieve Vrouwe Gasthuis (loc. West), 1091 AC Amsterdam, The Netherlands;
| | - Frank Willem Jansen
- Faculty of BioMechanical Engineering, Delft University of Technology, 2628 CE Delft, The Netherlands; (D.W.M.R.); (F.W.J.); (J.D.)
- Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Jenny Dankelman
- Faculty of BioMechanical Engineering, Delft University of Technology, 2628 CE Delft, The Netherlands; (D.W.M.R.); (F.W.J.); (J.D.)
| | - J. Sven D. Mieog
- Department of Surgery, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; (B.A.B.); (A.L.V.); (J.S.D.M.)
| | - Misha D. P. Luyer
- Department of Surgery, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; (I.H.J.T.d.H.); (M.D.P.L.)
- Department of Electrical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands
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Pham TD, Metropulos AE, Mubin N, Becker JH, Shah D, Spaulding C, Shields MA, Bentrem DJ, Munshi HG. Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells. Mol Cancer Ther 2024; 23:1854-1865. [PMID: 39162011 PMCID: PMC11614707 DOI: 10.1158/1535-7163.mct-23-0833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 05/07/2024] [Accepted: 08/08/2024] [Indexed: 08/21/2024]
Abstract
Despite advances in immune checkpoint inhibitors, chemotherapy remains the standard therapy for patients with pancreatic ductal adenocarcinoma (PDAC). As the combinations of chemotherapy, including the FOLFIRINOX [5-fluorouracil, F; irinotecan, I; and oxaliplatin, O (FIO)] regimen, and immune checkpoint inhibitors have failed to demonstrate clinical benefit in patients with metastatic PDAC tumors, there is increasing interest in identifying therapeutic approaches to potentiate ICI efficacy in patients with PDAC. In this study, we report that neoadjuvant FOLFIRINOX-treated human PDAC tumors exhibit increased MEK/ERK activation. We also show elevated MEK/ERK signaling in ex vivo PDAC slice cultures and cell lines treated with a combination of FIO. In addition, we find that the KPC-FIO cells, established from repeated treatment of mouse PDAC cell lines with six to eight cycles of FIO, display enhanced ERK phosphorylation and demonstrate increased sensitivity to MEK inhibition in vitro and in vivo. Significantly, the KPC-FIO cells develop tumors with a proinflammatory immune profile similar to human PDAC tumors after neoadjuvant FOLFIRINOX treatment. Furthermore, we found that the MEK inhibitor trametinib enables additional infiltration of highly functional CD8+ T cells into the KPC-FIO tumors and potentiates the efficacy of anti-PD-1 antibody in syngeneic mouse models. Our findings provide a rationale for combining trametinib and anti-PD-1 antibodies in patients with PDAC after neoadjuvant or short-term FOLFIRINOX treatment to achieve effective antitumor responses.
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Affiliation(s)
- Thao D. Pham
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- The Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA
| | - Anastasia E. Metropulos
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Jesse Brown VA Medical Center, Chicago, IL, USA
| | - Nida Mubin
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Jeffrey H. Becker
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Jesse Brown VA Medical Center, Chicago, IL, USA
| | - Dhavan Shah
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Christina Spaulding
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Jesse Brown VA Medical Center, Chicago, IL, USA
| | - Mario A. Shields
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- The Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA
| | - David J. Bentrem
- The Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA
- Jesse Brown VA Medical Center, Chicago, IL, USA
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Hidayatullah G. Munshi
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- The Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA
- Jesse Brown VA Medical Center, Chicago, IL, USA
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13
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Mastrantoni L, Chiaravalli M, Spring A, Beccia V, Di Bello A, Bagalà C, Bensi M, Barone D, Trovato G, Caira G, Giordano G, Bria E, Tortora G, Salvatore L. Comparison of first-line chemotherapy regimens in unresectable locally advanced or metastatic pancreatic cancer: a systematic review and Bayesian network meta-analysis. Lancet Oncol 2024; 25:1655-1665. [PMID: 39542008 DOI: 10.1016/s1470-2045(24)00511-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 09/08/2024] [Accepted: 09/09/2024] [Indexed: 11/17/2024]
Abstract
BACKGROUND In advanced pancreatic ductal adenocarcinoma (PDAC), first-line chemotherapy is the standard of care. Due to the absence of head-to-head comparisons in clinical trials, we performed this systematic review and network meta-analysis to compare treatment options for PDAC in terms of their efficacy and toxicity. METHODS PubMed, the Cochrane Central Register of Controlled Trials, Embase, and oncological meetings websites were searched until Nov 15, 2023. We included phase 2-3 randomised controlled trials published after Jan 1, 2000, evaluating first-line treatments in patients with previously untreated, unresectable, locally advanced or metastatic PDAC. Primary endpoints assessed were progression-free survival and overall survival. Summary data were extracted from published reports. The deviance information criterion was used to choose between a random-effects or fixed-effects model. Hazard ratios (HRs) with 95% credible intervals were estimated using a Bayesian approach. The risk of bias was evaluated using the Cochrane Risk of Bias 2 (RoB 2) tool and studies were graded as low, some concerns, or high risk of bias. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. This systematic review and network meta-analysis is registered with PROSPERO, CRD42023450330. FINDINGS 6050 records were screened and 79 randomised controlled trials (22 168 patients) were included in the analysis. Gemcitabine was the most frequent comparator (in 50 [63%] of 79 trials) and was considered as the reference treatment. A fixed-effect model was used to analyse the primary outcomes. Regarding progression-free survival (71 trials, 19 479 patients), the most effective treatments were gemcitabine plus nab-paclitaxel alternating folinic acid, fluorouracil, and oxaliplatin ([FOLFOX] HR 0·32, 95% credible interval 0·22-0·47), cisplatin, nab-paclitaxel, capecitabine, and gemcitabine ([PAXG] 0·35, 0·22-0·55), and liposomal irinotecan in combination with fluorouracil, leucovorin, and oxaliplatin ([NALIRIFOX] 0·43, 0·34-0·54), followed by fluorouracil, leucovorin, irinotecan, and oxaliplatin ([FOLFIRINOX] 0·55, 0·47-0·65) and gemcitabine plus nab-paclitaxel (0·62, 0·54-0·72). Similar results were observed for overall survival (79 trials, 22 104 patients): PAXG (HR 0·40, 95% credible interval 0·25-0·65), gemcitabine plus nab-paclitaxel alternating FOLFOX (0·46, 0·32-0·66), and NALIRIFOX (0·56, 0·45-0·70) had the highest benefit, followed by FOLFIRINOX (0·66, 0·56-0·78) and gemcitabine plus nab-paclitaxel (0·67, 0·59-0·77). The overall risk of bias was low to some concerns. Certainty of evidence was low. INTERPRETATION Our findings suggest that NALIRIFOX and FOLFIRINOX should be the preferred options for patients who can tolerate these regimens, with gemcitabine plus nab-paclitaxel remaining a viable alternative, particularly in patients unfit for triplet therapy. Phase 3 randomised controlled trials investigating concomitant or sequential quadruplets are warranted. FUNDING None.
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Affiliation(s)
- Luca Mastrantoni
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy
| | - Marta Chiaravalli
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy
| | - Alexia Spring
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy
| | - Viria Beccia
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy
| | - Armando Di Bello
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy
| | - Cinzia Bagalà
- Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy
| | - Maria Bensi
- Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy
| | - Diletta Barone
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy
| | - Giovanni Trovato
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy
| | - Giulia Caira
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy
| | - Giulia Giordano
- Department of Aging, Orthopedics and Rheumatological Sciences, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Emilio Bria
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy; Medical Oncology Unit, Ospedale Isola Tiberina-Gemelli Isola, Rome, Italy
| | - Giampaolo Tortora
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy
| | - Lisa Salvatore
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy.
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14
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Li P, Zhang H, Dai M. Current status and prospect of gut and oral microbiome in pancreatic cancer: Clinical and translational perspectives. Cancer Lett 2024; 604:217274. [PMID: 39307411 DOI: 10.1016/j.canlet.2024.217274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 09/18/2024] [Accepted: 09/19/2024] [Indexed: 09/27/2024]
Abstract
Pancreatic cancer is a highly lethal malignancy, and its diagnosis and treatment continue to pose significant challenges. Despite advancements in surgical and comprehensive treatment methods, the five-year survival rate remains below 12 %. With the rapid development of microbiome science, the gut and oral microbiota, which are readily accessible and can be sampled non-invasively, have emerged as a novel area of interest in pancreatic cancer research. Dysbiosis in these microbial communities can induce persistent inflammatory responses and affect the host's immune system, promoting cancer development and impacting the efficacy of treatments like chemotherapy and immunotherapy. This review provides an up-to-date overview of the roles of both gut and oral microbiota in the onset, progression, diagnosis, and treatment of pancreatic cancer. It analyzes the potential of utilizing these microbiomes as biomarkers and therapeutic targets from a clinical application perspective. Furthermore, it discusses future research directions aimed at harnessing these insights to advance the diagnosis and treatment strategies for pancreatic cancer. By focusing on the microbiome's role in clinical and translational medicine, this review offers insights into improving pancreatic cancer diagnosis and treatment outcomes.
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Affiliation(s)
- Pengyu Li
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Hanyu Zhang
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Menghua Dai
- Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
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15
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Jia Q, Zhu Y, Yao H, Yin Y, Duan Z, Zheng J, Ma D, Yang M, Yang J, Zhang J, Liu D, Hua R, Huo Y, Fu X, Sun Y, Liu W. Oncogenic GALNT5 confers FOLFIRINOX resistance via activating the MYH9/ NOTCH/ DDR axis in pancreatic ductal adenocarcinoma. Cell Death Dis 2024; 15:767. [PMID: 39433745 PMCID: PMC11493973 DOI: 10.1038/s41419-024-07110-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 09/16/2024] [Accepted: 09/24/2024] [Indexed: 10/23/2024]
Abstract
Chemotherapy resistance has been a great challenge in pancreatic ductal adenocarcinoma(PDAC) treatments. Current first-line chemotherapy regimens for PDAC include gemcitabine-based regimens such as AG regimen (albumin paclitaxel and gemcitabine), fluorouracil-based regiments such as FOLFIRINOX regimen ((5-fluorouracil5-FU), oxaliplatin, Irinotecan) and platinum-based regimens for patients with BRCA mutations. large amounts of work have been done on exploring the mechanism underlying resistance of gemcitabine-based and platinum-based regimens, while little research has been achieved on the mechanism of FOLFIRINOX regimens resistance. Hence, we identified Polypeptide N-Acetylgalactosaminyltransferase 5, (GALNT5) as a vital regulator and a potential therapeutic target in FOLFIRINOX regimens resistance. Colony formation assays and flow cytometry assays were performed to explore the roles of GALNT5 in cell proliferation and apoptosis in PDAC treated with FOLFIRINOX. IC50 alterations were calculated in GALNT5 knockdown and overexpressed cell lines. RNA-seq followed by GSEA (gene set enrichment analysis) was displayed to explore the potential mechanism. WB (western blotting), real-time PCR, and IF (immunofluorescence) were performed to validate relative pathways. The mouse orthotopic xenograft PDAC model was established to examine GALNT5 functions in vivo. GALNT5 was highly expressed in PDAC tissues and predicted poor prognosis in PDAC. Upregulation of GALNT5 in PDAC cells conferred FOLFIRINOX resistance on PDAC by inhibiting DNA damage. Moreover, GALNT5 interacted with MYH9, thus participating in the activation of the NOTCH pathways, resulting in hampering FOI-induced DNA damage. Functions of GALNT5 promoting FOLFIRINOX resistance were validated in vivo. In this study, we found that aberrantly overexpressed GALNT5 in PDAC took part in the activation of the NOTCH pathway by interacting with MYH9, thus inhibiting the DDR to achieve FOLFIRINOX resistance and causing poor prognosis. We identified GALNT5 as a potential therapeutic target for PDAC patients resistant to FOLFIRINOX chemotherapy.
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MESH Headings
- Humans
- Carcinoma, Pancreatic Ductal/drug therapy
- Carcinoma, Pancreatic Ductal/genetics
- Carcinoma, Pancreatic Ductal/metabolism
- Carcinoma, Pancreatic Ductal/pathology
- Drug Resistance, Neoplasm/drug effects
- Drug Resistance, Neoplasm/genetics
- N-Acetylgalactosaminyltransferases/metabolism
- N-Acetylgalactosaminyltransferases/genetics
- Oxaliplatin/pharmacology
- Oxaliplatin/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/pharmacology
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Animals
- Fluorouracil/pharmacology
- Fluorouracil/therapeutic use
- Leucovorin/pharmacology
- Leucovorin/therapeutic use
- Mice
- Cell Line, Tumor
- Polypeptide N-acetylgalactosaminyltransferase
- Pancreatic Neoplasms/drug therapy
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/metabolism
- Receptors, Notch/metabolism
- Irinotecan/pharmacology
- Irinotecan/therapeutic use
- Mice, Nude
- Cell Proliferation/drug effects
- Apoptosis/drug effects
- Signal Transduction/drug effects
- Gene Expression Regulation, Neoplastic/drug effects
- Female
- Xenograft Model Antitumor Assays
- Myosin Heavy Chains
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Affiliation(s)
- Qinyuan Jia
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China
| | - Yuheng Zhu
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China
| | - Hongfei Yao
- Department of Hepato-Biliary-Pancreatic Surgery, General Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, P.R. China
| | - Yifan Yin
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China
| | - Zonghao Duan
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China
| | - Jiahao Zheng
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China
| | - Ding Ma
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China
| | - Minwei Yang
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China
| | - Jianyu Yang
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China
| | - Junfeng Zhang
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China
| | - Dejun Liu
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China
| | - Rong Hua
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China
| | - Yanmiao Huo
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
| | - Xueliang Fu
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
| | - Yongwei Sun
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
| | - Wei Liu
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
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16
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Hagerty BL, Fekrmandi F, Schneider T, Fountzilas C, Stiles Z, Kukar M, Calvo B, Cherkassky L. Chemotherapy switch for nonresponse or progression on neoadjuvant chemotherapy for pancreatic adenocarcinoma. J Surg Oncol 2024; 130:1014-1022. [PMID: 39155683 DOI: 10.1002/jso.27803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 07/21/2024] [Indexed: 08/20/2024]
Abstract
BACKGROUND AND OBJECTIVES Patients with localized pancreatic adenocarcinoma who do not respond to neoadjuvant therapy present a challenge. We sought to define the characteristics and outcomes of those patients to guide clinical practice. METHODS Patients included were those without evidence of biochemical or radiographic response and no evidence of distant progression at the first reassessment after initiation of therapy. RESULTS Of the 45 patients in the cohort, 23 (51.1%) proceeded to surgical exploration with all but one of those undergoing resection. The median overall survival of the study cohort was 28.6 and 48.6 months in those who underwent resection. A total of 13 patients (28.9%) underwent chemotherapy switch (CS) during their course of neoadjuvant therapy. The CS cohort demonstrated higher rates of radiologic progression (25% vs. 10%, p = 0.329), new or worse vascular involvement (58.3% vs. 30%, p = 0.082), and CA 19-9 increase (30.8% vs. 12.9%, p = 0.209) at initial re-staging. Despite this, overall survival was similar between the two groups (20.7 vs. 28.7 months, p = 0.674). CONCLUSION Non-responders to first-line neoadjuvant therapy have poor rates of curative-intent resection. However, resection should be undertaken when feasible. CS may be considered in patients who do not respond to first-line chemotherapy.
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Affiliation(s)
- Brendan L Hagerty
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Fatemeh Fekrmandi
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Tyce Schneider
- Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Christos Fountzilas
- Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Zachary Stiles
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Moshim Kukar
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Benjamin Calvo
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Leonid Cherkassky
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
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17
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Jung HS, Kwon W, Yun WG, Paik WH, Hyub Lee S, Ryu JK, Oh DY, Lee KB, Chie EK, Jang JY. Optimal timing of surgery after neoadjuvant treatment in borderline resectable pancreatic cancer. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2024; 31:737-746. [PMID: 39034526 DOI: 10.1002/jhbp.12049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/23/2024]
Abstract
BACKGROUND Neoadjuvant treatment (NAT) is standard for borderline resectable pancreatic cancer (BRPC). However, consensus is lacking on the optimal surgical timing for patients with BRPC undergoing NAT. The aim of this study was to investigate the long-term outcomes of patients undergoing NAT for BRPC and suggest optimal resection timing. METHODS Prospectively collected data for 282 patients with BRPC between January 2007 and December 2019 were retrospectively reviewed. There were 164 patients who underwent NAT followed by surgery, 45 for chemotherapy only, and 73 for upfront surgery. Among them, 150 patients who underwent R0 or R1 resection following NAT were investigated to identify prognostic factors. RESULTS Patients receiving NAT followed by surgery showed the best survival (median overall survival [OS]; NAT followed by surgery vs. upfront surgery vs. chemotherapy only; 35 vs. 23 vs. 16 months). In the NAT group, 54 (36.0%) patients received less than 3 months of NAT, 68 (45.3%) received ≥3, <6 months, and 28 (18.7%) received longer than 6 months. Patients receiving ≥3 months of NAT showed an improved OS compared to <3 months (median; not reached vs. 27 months). In the FOLFIRINOX group, patients who received more than eight FOLFIRINOX cycles showed a good prognosis (<6 vs. 6-7 vs. ≥8 cycles; median survival, 26 vs. 41 months vs. not-reached). However, >12 cycles did not carry a survival benefit compared to 8-11 cycles. CONCLUSION The optimal resection timing following NAT is once a patient undergoes at least 3 months of neoadjuvant chemotherapy or at least eight FOLFIRINOX cycles.
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Affiliation(s)
- Hye-Sol Jung
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Won-Gun Yun
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Woo Hyun Paik
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ji Kon Ryu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Do-Youn Oh
- Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea
| | - Kyoung Bun Lee
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
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18
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Lee SH. [Neoadjuvant Therapy for Resectable or Borderline Resectable Pancreatic Cancer]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 84:103-110. [PMID: 39319431 DOI: 10.4166/kjg.2024.079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 08/13/2024] [Accepted: 08/14/2024] [Indexed: 09/26/2024]
Abstract
Surgical resection of a primary tumor is the only effective curative treatment for patients with localized pancreatic cancer without a distant metastasis. Nevertheless, most patients eventually develop postoperative recurrence caused by micrometastases. The risk increases if a complete resection is not achieved. Three surgical stages have emerged for a preoperative assessment based on resectability: resectable, borderline resectable, and unresectable. Although controversial, considerable research has focused on the role of neoadjuvant therapy in all forms of potentially resectable pancreatic cancer. While upfront surgery with adjuvant chemotherapy remains the standard of care for patients with resectable pancreatic cancer, there is growing evidence that neoadjuvant chemotherapy improves overall survival without increasing the resection rate in patients with borderline resectable pancreatic cancer. This review describes the current treatment strategies for resectable and borderline resectable pancreatic cancer and summarizes the results of the latest clinical trials.
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Affiliation(s)
- Sang Hoon Lee
- Division of Gastroenterology, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
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19
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Keum J, Lee HS, Park CS, Kim J, Jang W, Shin KI, Kang H, Lee SH, Jo JH, Jang SI, Chung MJ, Park JY, Park SW, Cho JH, Bang S. Survival predictors in patients with pancreatic cancer on liposomal irinotecan plus fluorouracil/leucovorin: a multicenter observational study. Ther Adv Med Oncol 2024; 16:17588359241279688. [PMID: 39328901 PMCID: PMC11425736 DOI: 10.1177/17588359241279688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 08/15/2024] [Indexed: 09/28/2024] Open
Abstract
Background Approximately half of the patients with advanced pancreatic ductal adenocarcinoma (PDAC) receive subsequent lines of chemotherapy. Recently, the liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) regimen is recommended as subsequent lines of chemotherapy. However, little is known about the predictive factors for the nal-IRI + 5-FU/LV regimen, especially in patients with previous irinotecan (IRI) exposure. Objectives We investigated the predictive factors associated with nal-IRI + 5-FU/LV treatment in patients with PDAC. Design Multicenter, retrospective cohort study. Methods This study included patients with advanced PDAC who received the nal-IRI + 5-FU/LV regimen for palliative purposes. Results Overall, 268 patients were treated with nal-IRI + 5-FU/LV. The median overall survival (OS) was 7.9 months (95% confidence interval (CI): 7.0-8.8), while the median progression-free survival (PFS) was 2.6 months (95% CI: 1.9-3.2). An albumin level of<4.0 g/dL, neutrophil-to-lymphocyte ratio (NLR) of ⩾3.5, liver or peritoneal metastasis, and a history of >3 lines of palliative chemotherapy were associated with worse OS. An NLR of ⩾3.5 and liver metastasis were significant predictive factors for worse PFS. Previous exposure to IRI was not a significant predictor. Patients without prior IRI (no-IRI) treatment showed relatively longer OS and PFS compared to IRI responders and nonresponders, but these differences were not significant when compared specifically to the responders (OS: 8.8 vs 8.1 months, p = 0.388; PFS: 3.6 vs 2.6 months, p = 0.126). Conclusion An NLR of ⩾3.5 and liver metastasis were associated with worse PFS. Prior IRI exposure was not a significant predictive factor for OS and PFS, especially in IRI responders.
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Affiliation(s)
- Jiyoung Keum
- Division of Gastroenterology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Hee Seung Lee
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Chan Su Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
- Division of Gastroenterology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, South Korea
| | - Jeehoon Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Wonjoon Jang
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Kyung In Shin
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Huapyong Kang
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea
| | - Sang Hoon Lee
- Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea
| | - Jung Hyun Jo
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Sung Ill Jang
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seo
| | - Moon Jae Chung
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Jeong Youp Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung Woo Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Hee Cho
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 712 Eonju-ro, Gangnam-gu, Seoul 135-720, South Korea
| | - Seungmin Bang
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, South Korea
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20
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Boggi U, Kauffmann EF, Napoli N, Barreto SG, Besselink MG, Fusai GK, Hackert T, Hilal MA, Marchegiani G, Salvia R, Shrikhande SV, Truty M, Werner J, Wolfgang C, Bannone E, Capretti G, Cattelani A, Coppola A, Cucchetti A, De Sio D, Di Dato A, Di Meo G, Fiorillo C, Gianfaldoni C, Ginesini M, Hidalgo Salinas C, Lai Q, Miccoli M, Montorsi R, Pagnanelli M, Poli A, Ricci C, Sucameli F, Tamburrino D, Viti V, Cameron J, Clavien PA, Asbun HJ. REDISCOVER guidelines for borderline-resectable and locally advanced pancreatic cancer: management algorithm, unanswered questions, and future perspectives. Updates Surg 2024; 76:1573-1591. [PMID: 38684573 PMCID: PMC11455680 DOI: 10.1007/s13304-024-01860-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 04/10/2024] [Indexed: 05/02/2024]
Abstract
The REDISCOVER guidelines present 34 recommendations for the selection and perioperative care of borderline-resectable (BR-PDAC) and locally advanced ductal adenocarcinoma of the pancreas (LA-PDAC). These guidelines represent a significant shift from previous approaches, prioritizing tumor biology over anatomical features as the primary indication for resection. Condensed herein, they provide a practical management algorithm for clinical practice. However, the guidelines also highlight the need to redefine LA-PDAC to align with modern treatment strategies and to solve some contradictions within the current definition, such as grouping "difficult" and "impossible" to resect tumors together. Furthermore, the REDISCOVER guidelines highlight several areas requiring urgent research. These include the resection of the superior mesenteric artery, the management strategies for patients with LA-PDAC who are fit for surgery but unable to receive multi-agent neoadjuvant chemotherapy, the approach to patients with LA-PDAC who are fit for surgery but demonstrate high serum Ca 19.9 levels even after neoadjuvant treatment, and the optimal timing and number of chemotherapy cycles prior to surgery. Additionally, the role of primary chemoradiotherapy versus chemotherapy alone in LA-PDAC, the timing of surgical resection post-neoadjuvant/primary chemoradiotherapy, the efficacy of ablation therapies, and the management of oligometastasis in patients with LA-PDAC warrant investigation. Given the limited evidence for many issues, refining existing management strategies is imperative. The establishment of the REDISCOVER registry ( https://rediscover.unipi.it/ ) offers promise of a unified research platform to advance understanding and improve the management of BR-PDAC and LA-PDAC.
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Affiliation(s)
- Ugo Boggi
- Division of General and Transplant Surgery, University of Pisa, Via Savi 10, 56126, Pisa, PI, Italy.
| | - Emanuele F Kauffmann
- Division of General and Transplant Surgery, University of Pisa, Via Savi 10, 56126, Pisa, PI, Italy
| | - Niccolò Napoli
- Division of General and Transplant Surgery, University of Pisa, Via Savi 10, 56126, Pisa, PI, Italy
| | - S George Barreto
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Division of Surgery and Perioperative Medicine, Flinders Medical Center, Beadfor Park, Australia
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | | | - Thilo Hackert
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Mohammad Abu Hilal
- Department of Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Giovanni Marchegiani
- Hepatopancreatobiliary and Liver Transplant Surgery, Department of Surgery, Oncology and Gastroenterology, DiSCOG, University of Padua, Padua, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Shailesh V Shrikhande
- Tata Memorial Centre, Gastrointestinal and HPB Service, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Mark Truty
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic Rochester, Rochester, MN, USA
| | - Jens Werner
- Department of General, Visceral, and Transplant Surgery, LMU, University of Munich, Munich, Germany
| | - Christopher Wolfgang
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Elisa Bannone
- Department of Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | | | - Alice Cattelani
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | | | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences - DIMEC, Alma Mater Studiorum Università di Bologna, Bologna, Italy
| | - Davide De Sio
- Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Armando Di Dato
- Division of General and Transplant Surgery, University of Pisa, Via Savi 10, 56126, Pisa, PI, Italy
| | - Giovanna Di Meo
- Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari, Bari, Italy
| | - Claudio Fiorillo
- Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Cesare Gianfaldoni
- Division of General and Transplant Surgery, University of Pisa, Via Savi 10, 56126, Pisa, PI, Italy
| | - Michael Ginesini
- Division of General and Transplant Surgery, University of Pisa, Via Savi 10, 56126, Pisa, PI, Italy
| | | | - Quirino Lai
- Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umberto I of Rome, Rome, Italy
| | - Mario Miccoli
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Roberto Montorsi
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | | | - Andrea Poli
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Claudio Ricci
- Division of Pancreatic Surgery, Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, IRCCS, Azienda Ospedaliero-Universitaria di Bologna (IRCCS AOUBO), Bologna, Italy
| | - Francesco Sucameli
- Department of Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Domenico Tamburrino
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy
| | - Virginia Viti
- Division of General and Transplant Surgery, University of Pisa, Via Savi 10, 56126, Pisa, PI, Italy
| | - John Cameron
- Department of Surgery, John Hopkins University School of Medicine, Baltimore, MD, USA
| | - Pierre-Alain Clavien
- Department of Surgery and Transplantation, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Horacio J Asbun
- Division of Hepatobiliary and Pancreas Surgery, Miami Cancer Institute, Miami, FL, USA
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21
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Timmer FEF, Geboers B, Scheffer HJ, Bruynzeel AME, Meijerink MR. Ablative treatments for locally advanced pancreatic cancer: the CROSSFIRE trial: Authors' reply. Lancet Gastroenterol Hepatol 2024; 9:687-688. [PMID: 38971162 DOI: 10.1016/s2468-1253(24)00162-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 05/22/2024] [Indexed: 07/08/2024]
Affiliation(s)
- Florentine E F Timmer
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands.
| | - Bart Geboers
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Hester J Scheffer
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands; Department of Radiology and Nuclear Medicine, Noordwest Ziekenhuisgroep, Alkmaar, Netherlands
| | - Anna M E Bruynzeel
- Department of Radiation Oncology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Martijn R Meijerink
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands
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22
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Fromer MW, Mouw TJ, Scoggins CR, Egger ME, Philips P, McMasters KM, Martin RCG. Barriers to resection following neoadjuvant chemotherapy for resectable pancreatic adenocarcinoma: A national and local perspective. J Surg Oncol 2024; 130:284-292. [PMID: 38828742 DOI: 10.1002/jso.27697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 03/26/2024] [Accepted: 05/14/2024] [Indexed: 06/05/2024]
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) use for pancreatic ductal adenocarcinoma (PDAC) has increased, but some patients never get resection following NAC. METHODS Data from January 2012 to December 2019 for all clinically resectable patients across two health networks were utilized, as well as data from the ACS NCDB registry. Univariate testing, multivariable logistic regression, and survival analyses were employed to evaluate failure to resection after neo-adjuvant chemotherapy. RESULTS Of the 10 007 registry patients eligible for resection, the resected group was younger (64.6 vs. 69.5 years; p < 0.001) and had a slightly lower mean comorbidity index (0.41 vs. 0.45; p < 0.001) than the nonsurgical group. The nonsurgical group was composed of a higher percentage of Black and Hispanic patients (17.5 vs. 13.1%; p < 0.001). After adjusting for age and comorbidities, the factors associated with decreased probability of resection after NAC were evaluation at a community hospital (OR 2.4), Black or Hispanic race (OR 1.6), areas of increased high school drop-out rates (OR 1.4), and lack of private health insurance (OR 1.3). The median overall survival for nonsurgery was markedly worse than the surgical cohort (10.6 vs. 26.6 months; p < 0.001). The most frequent reasons for a lack of definitive resection were operative upstaging to unresectable (39.6%), patient preference (14.5%), progression on NAC (13.2%), deconditioning or comorbidity severity (12.5%), and nonreferral to a surgeon (8.8%). CONCLUSIONS Racial, economic, and educational disparities have a considerable influence on the successful completion of a neoadjuvant approach for resectable PDAC. A comprehensive closed or highly collaborative/communicative multidisciplinary neoadjuvant program is optimal for treatment success and completion.
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Affiliation(s)
- Marc W Fromer
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky, USA
| | - Tyler J Mouw
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky, USA
| | - Charles R Scoggins
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky, USA
| | - Michael E Egger
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky, USA
| | - Prejesh Philips
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky, USA
| | - Kelly M McMasters
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky, USA
| | - Robert C G Martin
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky, USA
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Pathak P, Weekes CD, Shroff RT. The Sequencing Conundrum in Localized Pancreatic Adenocarcinoma-Progress or Passive Acceptance? JAMA Oncol 2024; 10:1036-1037. [PMID: 38900451 DOI: 10.1001/jamaoncol.2024.0870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2024]
Affiliation(s)
| | - Colin D Weekes
- Division of Hematology-Oncology, Massachusetts General Hospital, Boston
| | - Rachna T Shroff
- Division of Hematology/Oncology, University of Arizona Cancer Center, Tucson
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24
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Guillot Morales M, Visa L, Brozos Vázquez E, Feliu Batlle J, Khosravi Shahi P, Laquente Sáez B, de San Vicente Hernández BL, Macarulla T, Gironés Sarrió R. Update on the management of older patients with pancreatic adenocarcinoma: a perspective from medical oncology. Clin Transl Oncol 2024; 26:1570-1583. [PMID: 38329611 PMCID: PMC11178577 DOI: 10.1007/s12094-024-03386-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 01/04/2024] [Indexed: 02/09/2024]
Abstract
In the context of pancreatic cancer, surgical intervention is typically recommended for localized tumours, whereas chemotherapy is the preferred approach in the advanced and/or metastatic setting. However, pancreatic cancer is closely linked to ageing, with an average diagnosis at 72 years. Paradoxically, despite its increased occurrence among older individuals, this population is often underrepresented in clinical studies, complicating the decision-making process. Age alone should not determine the therapeutic strategy but, given the high comorbidity and mortality of this disease, a comprehensive geriatric assessment (CGA) is necessary to define the best treatment, prevent toxicity, and optimize older patient care. In this review, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica, SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours (Grupo Español de Tratamiento de los Tumores Digestivos, TTD), and the Multidisciplinary Spanish Group of Digestive Cancer (Grupo Español Multidisciplinar en Cáncer Digestivo, GEMCAD) have assessed the available scientific evidence and propose a series of recommendations on the management and treatment of the older population with pancreatic cancer.
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Affiliation(s)
- Mónica Guillot Morales
- Spanish Society of Medical Oncology (SEOM) Oncogeriatrics Section, Department of Medical Oncology, Son Espases University Hospital, Carretera de Valldemossa, 79, Islas Baleares, 07120, Palma de Mallorca, Spain.
| | - Laura Visa
- Spanish Society of Medical Oncology (SEOM) Oncogeriatrics Section, Mar-Parc de Salut Mar Hospital, Barcelona, Spain
| | - Elena Brozos Vázquez
- Spanish Society of Medical Oncology (SEOM) Oncogeriatrics Section, A Coruña University Clinical Hospital, A Coruña, Spain
| | - Jaime Feliu Batlle
- Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD), La Paz University Hospital, IDIPAZ, CIBERONC, Cathedra UAM-AMGEN, Madrid, Spain
| | - Parham Khosravi Shahi
- Spanish Society of Medical Oncology (SEOM) Oncogeriatrics Section, Gregorio Marañón University Hospital, Madrid, Spain
| | - Berta Laquente Sáez
- Spanish Society of Medical Oncology (SEOM) Oncogeriatrics Section, ICO L´Hospitalet-IDIBELL, Barcelona, Spain
| | | | - Teresa Macarulla
- Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD), Hebron University Hospital, Vall d, Barcelona, Spain
| | - Regina Gironés Sarrió
- Spanish Society of Medical Oncology (SEOM), Polytechnic la Fe University Hospital, Valencia, Spain
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25
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Saúde-Conde R, El Ghali B, Navez J, Bouchart C, Van Laethem JL. Total Neoadjuvant Therapy in Localized Pancreatic Cancer: Is More Better? Cancers (Basel) 2024; 16:2423. [PMID: 39001485 PMCID: PMC11240662 DOI: 10.3390/cancers16132423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 06/24/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge in oncology due to its advanced stage upon diagnosis and limited treatment options. Surgical resection, the primary curative approach, often results in poor long-term survival rates, leading to the exploration of alternative strategies like neoadjuvant therapy (NAT) and total neoadjuvant therapy (TNT). While NAT aims to enhance resectability and overall survival, there appears to be potential for improvement, prompting consideration of alternative neoadjuvant strategies integrating full-dose chemotherapy (CT) and radiotherapy (RT) in TNT approaches. TNT integrates chemotherapy and radiotherapy prior to surgery, potentially improving margin-negative resection rates and enabling curative resection for locally advanced cases. The lingering question: is more always better? This article categorizes TNT strategies into six main groups based on radiotherapy (RT) techniques: (1) conventional chemoradiotherapy (CRT), (2) the Dutch PREOPANC approach, (3) hypofractionated ablative intensity-modulated radiotherapy (HFA-IMRT), and stereotactic body radiotherapy (SBRT) techniques, which further divide into (4) non-ablative SBRT, (5) nearly ablative SBRT, and (6) adaptive ablative SBRT. A comprehensive analysis of the literature on TNT is provided for both borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC), with detailed sections for each.
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Affiliation(s)
- Rita Saúde-Conde
- Digestive Oncology Department, Hôpitaux Universitaires de Bruxelles (HUB), Université Libre de Bruxelles, 1070 Brussels, Belgium;
| | - Benjelloun El Ghali
- Department of Radiation Oncology, Hôpitaux Universitaires de Bruxelles (HUB), Institut Jules Bordet, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium; (B.E.G.); (C.B.)
| | - Julie Navez
- Department of Abdominal Surgery and Transplantation, Hôpitaux Universitaires de Bruxelles (HUB), Hopital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium;
| | - Christelle Bouchart
- Department of Radiation Oncology, Hôpitaux Universitaires de Bruxelles (HUB), Institut Jules Bordet, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium; (B.E.G.); (C.B.)
| | - Jean-Luc Van Laethem
- Digestive Oncology Department, Hôpitaux Universitaires de Bruxelles (HUB), Université Libre de Bruxelles, 1070 Brussels, Belgium;
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Domagała-Haduch M, Gorzelak-Magiera A, Michalecki Ł, Gisterek-Grocholska I. Radiochemotherapy in Pancreatic Cancer. Curr Oncol 2024; 31:3291-3300. [PMID: 38920733 PMCID: PMC11202861 DOI: 10.3390/curroncol31060250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 05/23/2024] [Accepted: 06/03/2024] [Indexed: 06/27/2024] Open
Abstract
Despite the advancements made in oncology in recent years, the treatment of pancreatic cancer remains a challenge. Five-year survival rates for this cancer do not exceed 10%. Among the reasons contributing to poor treatment outcomes are the oligosymptomatic course of the tumor, diagnostic difficulties due to the anatomical location of the organ, and the unique biological features of pancreatic cancer. The mainstay of treatment for resectable cancer is surgery and adjuvant chemotherapy. For unresectable and metastatic cancers, chemotherapy remains the primary method of treatment. At the same time, for about thirty years, there have been attempts to improve treatment outcomes by using radiotherapy combined with systemic treatment. Unlike chemotherapy, radiotherapy has no established place in the treatment of pancreatic cancer. This paper addresses the topic of radiotherapy in pancreatic cancer as a valuable method that can improve treatment outcomes alongside chemotherapy.
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Affiliation(s)
- Małgorzata Domagała-Haduch
- Department of Oncology and Radiotherapy, Medical University of Silesia, 40-514 Katowice, Poland; (A.G.-M.); (Ł.M.); (I.G.-G.)
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27
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Safyan RA, Kim E, Dekker E, Homs M, Aguirre AJ, Koerkamp BG, Chiorean EG. Multidisciplinary Standards and Evolving Therapies for Patients With Pancreatic Cancer. Am Soc Clin Oncol Educ Book 2024; 44:e438598. [PMID: 38781541 DOI: 10.1200/edbk_438598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDA) is a challenging disease that presents at an advanced stage and results in many symptoms that negatively influence patients' quality of life and reduce their ability to receive effective treatment. Early implementation of expert multidisciplinary care with nutritional support, exercise, and palliative care for both early-stage and advanced disease promises to maintain or improve the patients' physical, social, and psychological well-being, decrease aggressive interventions at the end of life, and ultimately improve survival. Moreover, advances in treatment strategies in the neoadjuvant and metastatic setting combined with novel therapeutic agents targeting the key drivers of the disease are leading to improvements in the care of patients with pancreatic cancer. Here, we emphasize the multidisciplinary supportive and therapeutic care of patients with PDA, review current guidelines and new developments of neoadjuvant and perioperative treatments for localized disease, as well as the treatment standards and the evolving field of precision oncology and immunotherapies for advanced PDA.
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Affiliation(s)
- Rachael A Safyan
- University of Washington School of Medicine, Department of Medicine, Division of Hematology-Oncology, Seattle, WA
- Fred Hutchinson Cancer Center, Clinical Research Division, Seattle, WA
| | - Eejung Kim
- Dana-Farber Cancer Center, Department of Medical Oncology, Boston, MA
- Harvard Medical School, Boston, MA
| | - Emmelie Dekker
- Erasmus MC Cancer Institute, Department of Surgery, Rotterdam, the Netherlands
| | - Marjolein Homs
- Erasmus MC Cancer Institute, Department of Medical Oncology, Rotterdam, the Netherlands
| | - Andrew J Aguirre
- Dana-Farber Cancer Center, Department of Medical Oncology, Boston, MA
- Harvard Medical School, Boston, MA
| | - Bas Groot Koerkamp
- Erasmus MC Cancer Institute, Department of Surgery, Rotterdam, the Netherlands
| | - E Gabriela Chiorean
- University of Washington School of Medicine, Department of Medicine, Division of Hematology-Oncology, Seattle, WA
- Fred Hutchinson Cancer Center, Clinical Research Division, Seattle, WA
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28
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Mahmood U, Carrier E, Khan K. Neoadjuvant management of locally advanced pancreatic ductal adenocarcinoma - Heading towards a promising change in treatment paradigm. Cancer Treat Rev 2024; 127:102750. [PMID: 38703592 DOI: 10.1016/j.ctrv.2024.102750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 04/27/2024] [Accepted: 04/29/2024] [Indexed: 05/06/2024]
Abstract
Traditional chemotherapy-based adjuvant therapies for locally advanced pancreatic ductal adenocarcinoma (PDAC) have been associated with poor clinical outcomes driven partly by its complex anatomy and molecular heterogeneity. Treatment for PDAC is challenged by presence of a dense tumour microenvironment involving an interplay of multiple tumoural and stromal components which promote metastatic oncogenic behaviour. PDAC also involves aberrations in multiple signalling pathways with paucity of treatment options against the most common mutations including KRAS, TP53, CDKN2A andSMAD4. However, recent discovery of new mechanisms implicated in pancreatic carcinogenesis have led to identification of promising mechanistic therapeutic targets such as NET1 and ULK1. Early evidence also suggests the utility of targeting multiple DNA repair processes, modulators of DNA replication and major DNA damage response regulators. We explore the clinical rationale behind a neoadjuvant therapeutic strategy and emerging predictors of survival benefit associated with this approach. We also discuss challenges and opportunities originating from recent clinical trials evaluating neoadjuvant treatments composed of various combinations of radiotherapy, chemotherapy and immunotherapeutic regimens that have aimed to address some of these biological challenges. Selective treatment of patients harbouring specific genomic aberrations with targeted agents and immunotherapy can translate into optimum survival outcomes in PDAC. We also share perspectives on emerging prospective clinical evidence regarding stromal modifying agents, such as Tumour Growth Factor-Beta and Connective Tissue Growth Factor inhibitors along with novel vaccination-based approaches in improving PDAC outcomes.
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Affiliation(s)
- Umair Mahmood
- Department of Gastrointestinal Oncology, University College Hospital NHS Foundation Trust (UCLH), London NW1 2BU, UK
| | - Ewa Carrier
- Department of Clinical Development, FibroGen, Inc., San Francisco, CA, USA
| | - Khurum Khan
- Department of Gastrointestinal Oncology, University College Hospital NHS Foundation Trust (UCLH), London NW1 2BU, UK; University College London Cancer Institute, London WC1E 6DD, UK.
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29
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Zohar N, Kowal L, Moskal D, Ponzini F, Sun G, Lamm RJ, Williamson J, Nevler A, Lavu H, Maley WR, Yeo CJ, Bowne WB. Contemporary report of surgical outcomes after single-stage total pancreatectomy: A 10-year experience. J Surg Oncol 2024; 129:1235-1244. [PMID: 38419193 DOI: 10.1002/jso.27614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 01/25/2024] [Accepted: 02/11/2024] [Indexed: 03/02/2024]
Abstract
BACKGROUND Surgeons rarely perform elective total pancreatectomy (TP). Our study seeks to report surgical outcomes in a contemporary series of single-stage (SS) TP patients. METHODS Between the years 2013 to 2023 we conducted a retrospective review of 60 consecutive patients who underwent SSTP. Demographics, pathology, treatment-related variables, and survival were recorded and analyzed. RESULTS SSTP consisted of 3% (60/1859) of elective pancreas resections conducted. Patient median age was 68 years. Ninety percent of these patients (n = 54) underwent SSTP for pancreatic ductal adenocarcinoma (PDAC). Conversion from a planned partial pancreatectomy to TP occurred intraoperatively in 31 (52%) patients. Fifty-nine patients (98%) underwent an R0 resection. Median length of hospital stay was 6 days. The majority of morbidities were minor, with 27% patients (n = 16) developing severe complications (Clavien-Dindo ≥3). Thirty and ninety-day mortality rates were 1.67% (one patient) and 5% (three patients), respectively. Median survival for the entire cohort was 24.4 months; 22.7 months for PDAC patients, with 1-, 3-, and 5-year survival of 68%, 43%, and 16%, respectively. No mortality occurred in non-PDAC patients (n = 6). CONCLUSION Elective single-stage total pancreatectomy can be a safe and appropriate treatment option. SSTP should be in the armamentarium of surgeons performing pancreatic resection.
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Affiliation(s)
- Nitzan Zohar
- Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Luke Kowal
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - David Moskal
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Francesca Ponzini
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - George Sun
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Ryan J Lamm
- Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - John Williamson
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Avinoam Nevler
- Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Harish Lavu
- Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Warren R Maley
- Department of Surgery, Jefferson Transplant Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Charles J Yeo
- Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Wilbur B Bowne
- Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
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30
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Waugh E, Glinka J, Breadner D, Liu R, Tang E, Allen L, Welch S, Leslie K, Skaro A. Survival benefit of neoadjuvant FOLFIRINOX for patients with borderline resectable pancreatic cancer. Ann Hepatobiliary Pancreat Surg 2024; 28:229-237. [PMID: 38296221 PMCID: PMC11128787 DOI: 10.14701/ahbps.23-107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 12/05/2023] [Accepted: 12/09/2023] [Indexed: 05/25/2024] Open
Abstract
Backgrounds/Aims While patients with borderline resectable pancreatic cancer (BRPC) are a target population for neoadjuvant chemotherapy (NAC), formal guidelines for neoadjuvant therapy are lacking. We assessed the perioperative and oncological outcomes in patients with BRPC undergoing NAC with FOLFIRINOX for patients undergoing upfront surgery (US). Methods The AHPBA criteria for borderline resectability and/or a CA19-9 level > 100 μ/mL defined borderline resectable tumors retrieved from a prospectively populated institutional registry from 2007 to 2020. The primary outcome was overall survival (OS) at 1 and 3 years. A Cox Proportional Hazard model based on intention to treat was used. A receiver-operator characteristics (ROC) curve was constructed to assess the discriminatory capability of the use of CA19-9 > 100 μ/mL to predict resectability and mortality. Results Forty BRPC patients underwent NAC, while 46 underwent US. The median OS with NAC was 19.8 months (interquartile range [IQR], 10.3-44.24) vs. 10.6 months (IQR, 6.37-17.6) with US. At 1 year, 70% of the NAC group and 41.3% of the US group survived (p = 0.008). At 3 years, 42.5 % of the NAC group and 10.9% of the US group survived (p = 0.001). NAC significantly reduced the hazard of death (adjusted hazard ratio, 0.20; 95% confidence interval, 0.07-0.54; p = 0.001). CA19-9 > 100 μ/mL showed poor discrimination in predicting mortality, but was a moderate predictor of resectability. Conclusions We found a survival benefit of NAC with FOLFIRINOX for BRPC. Greater pre-treatment of CA19-9 and multivessel involvement on initial imaging were associated with progression of the disease following NAC.
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Affiliation(s)
- Evelyn Waugh
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Juan Glinka
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Daniel Breadner
- Division of Medical Oncology, Department of Oncology, Western University, London, ON, Canada
| | - Rachel Liu
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Ephraim Tang
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Laura Allen
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Stephen Welch
- Division of Medical Oncology, Department of Oncology, Western University, London, ON, Canada
| | - Ken Leslie
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Anton Skaro
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
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31
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Mendis S, Lipton L, To YH, Ananda S, Michael M, McLachlan SA, Thomson B, Loveday B, Knowles B, Fox A, Nikfarjam M, Usatoff V, Shapiro J, Clarke K, Pattison S, Chee CE, Zielinski R, Wong R, Gibbs P, Lee B. Early onset pancreatic cancer-exploring contemporary treatment and outcomes using real-world data. Br J Cancer 2024; 130:1477-1484. [PMID: 38448752 PMCID: PMC11058801 DOI: 10.1038/s41416-024-02619-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 02/01/2024] [Accepted: 02/09/2024] [Indexed: 03/08/2024] Open
Abstract
BACKGROUND Pancreatic cancer incidence is increasing in younger populations. Differences between early onset pancreatic cancer (EOPC) and later onset pancreatic cancer (LOPC), and how these should inform management warrant exploration in the contemporary setting. METHODS A prospectively collected multi-site dataset on consecutive pancreatic adenocarcinoma patients was interrogated. Patient, tumour, treatment, and outcome data were extracted for EOPC (≤50 years old) vs LOPC (>50 years old). RESULTS Of 1683 patients diagnosed between 2016 and 2022, 112 (6.7%) were EOPC. EOPC more frequently had the tail of pancreas tumours, earlier stage disease, surgical resection, and trended towards increased receipt of chemotherapy in the curative setting compared to LOPC. EOPC more frequently received 1st line chemotherapy, 2nd line chemotherapy, and chemoradiotherapy than LOPC in the palliative setting. Recurrence-free survival was improved for the tail of pancreas EOPC vs LOPC in the resected setting; overall survival was superior for EOPC compared to LOPC across the resected, locally advanced unresectable and metastatic settings. CONCLUSIONS EOPC remains a small proportion of pancreatic cancer diagnoses. The more favourable outcomes in EOPC suggest these younger patients are overall deriving benefits from increased treatment in the curative setting and increased therapy in the palliative setting.
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Affiliation(s)
- Shehara Mendis
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
| | | | - Yat Hang To
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- University of Melbourne, Parkville, VIC, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
| | - Sumitra Ananda
- University of Melbourne, Parkville, VIC, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
| | - Michael Michael
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
| | - Sue-Anne McLachlan
- University of Melbourne, Parkville, VIC, Australia
- Department of Medical Oncology, St Vincent's Hospital, Fitzroy, VIC, Australia
| | - Benjamin Thomson
- Department of Surgery, Royal Melbourne Hospital, Parkville, VIC, Australia
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
| | - Benjamin Loveday
- Department of Surgery, Royal Melbourne Hospital, Parkville, VIC, Australia
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
| | - Brett Knowles
- Department of Surgery, Royal Melbourne Hospital, Parkville, VIC, Australia
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
- Epworth Healthcare, Melbourne, VIC, Australia
| | - Adrian Fox
- Department of Hepatobiliary Surgery, St Vincent's Hospital, Fitzroy, VIC, Australia
| | - Mehrdad Nikfarjam
- University of Melbourne, Parkville, VIC, Australia
- Department of Hepatobiliary Surgery, Austin Health, Heidelberg, VIC, Australia
| | | | - Julia Shapiro
- Department of Medicine, Alfred Hospital, Prahran, VIC, Australia
| | - Kate Clarke
- Department of Medical Oncology, Wellington Hospital, Wellington, New Zealand
| | - Sharon Pattison
- Department of Medicine, Dunedin School of Medicine, University of Otago, Otago, New Zealand
| | - Cheng Ean Chee
- Department of Hematology-Oncology, National University Cancer Institute, Singapore, Singapore
| | - Rob Zielinski
- Department of Medical Oncology, Orange Hospital, Orange, NSW, Australia
- Department of Medical Oncology, Dubbo Base Hospital, Dubbo, NSW, Australia
- Department of Medical Oncology, Bathurst Base Hospital, West Bathurst, NSW, Australia
| | - Rachel Wong
- Epworth Healthcare, Melbourne, VIC, Australia
- Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia
- Department of Medical Oncology, Eastern Health, Box Hill, VIC, Australia
| | - Peter Gibbs
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- University of Melbourne, Parkville, VIC, Australia
| | - Belinda Lee
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- University of Melbourne, Parkville, VIC, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
- Department of Medical Oncology, Northern Hospital, Epping, VIC, Australia
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32
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Shimizu T, Maeda S, Link J, Deranteriassian A, Premji A, Verma A, Chervu N, Park J, Girgis M, Benharash P, Hines J, Wainberg Z, Wolfgang C, Burns W, Yu J, Fernandez-Del Castillo C, Lillemoe K, Ferrone C, Donahue T. Clinical and pathological factors associated with survival in patients with pancreatic cancer who receive adjuvant therapy after neoadjuvant therapy: A retrospective multi-institutional analysis. Surgery 2024; 175:1377-1385. [PMID: 38365548 DOI: 10.1016/j.surg.2024.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 12/29/2023] [Accepted: 01/08/2024] [Indexed: 02/18/2024]
Abstract
BACKGROUND Neoadjuvant therapy is being increasingly used for patients with pancreatic cancer. The role of adjuvant therapy in these patients is unclear. The purpose of this study was to identify clinical and pathologic characteristics that are associated with longer overall survival in patients with pancreatic cancer who receive adjuvant therapy after neoadjuvant therapy. METHODS This study was conducted using multi-institutional data. All patients underwent surgery after at least 1 cycle of neoadjuvant therapy for pancreatic cancer. Patients who died within 3 months after surgery and were known to have distant metastasis or macroscopic residual disease were excluded. Mann-Whitney U test, χ2 analysis, Kaplan-Meier plot, and univariate and multivariate Cox regression analysis were performed as statistical analyses. RESULTS In the present study, 529 patients with resected pancreatic cancer after neoadjuvant therapy were reviewed. For neoadjuvant therapy, 177 (33.5%) patients received neoadjuvant chemotherapy, and 352 (66.5%) patients received neoadjuvant chemoradiotherapy. The median duration of neoadjuvant therapy was 7.0 months (interquartile range, 5.0-8.7). Patients were followed for a median of 23.0 months after surgery. Adjuvant therapy was administered to 297 (56.1%) patients and was not associated with longer overall survival for the entire cohort (24 vs 22 months, P = .31). Interaction analysis showed that adjuvant therapy was associated with longer overall survival in patients who received less than 4 months neoadjuvant therapy (hazard ratio 0.40; 95% confidence interval 0.17-0.95; P = .03) or who had microscopic margin positive surgical resections (hazard ratio 0.56; 95% confidence interval 0.33-0.93; P = .03). CONCLUSION In this retrospective study, there was a survival benefit associated with adjuvant therapy for patients who received less than 4 months of neoadjuvant therapy or had microscopic positive margins.
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Affiliation(s)
- Takayuki Shimizu
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Shimpei Maeda
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Jason Link
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | | | - Alykhan Premji
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Arjun Verma
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Nikhil Chervu
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Joon Park
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Mark Girgis
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Peyman Benharash
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Joe Hines
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Zev Wainberg
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Christopher Wolfgang
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - William Burns
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - Jun Yu
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD
| | | | - Keith Lillemoe
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Cristina Ferrone
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Timothy Donahue
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.
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33
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Yoon H, Shin Y, Ryoo BY, Jeong H, Park I, Seo DW, Lee SS, Park DH, Song TJ, Oh D, Hwang DW, Lee JH, Song KB, Park Y, Kwak BJ, Hong SM, Park JH, Kim SC, Kim KP, Yoo C. Clinical outcomes of second-line therapy following disease progression on first-line modified FOLFIRINOX for borderline resectable and locally advanced pancreatic adenocarcinoma. Pancreatology 2024; 24:424-430. [PMID: 38395676 DOI: 10.1016/j.pan.2024.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 01/21/2024] [Accepted: 02/09/2024] [Indexed: 02/25/2024]
Abstract
BACKGROUND Modified FOLFIRINOX (mFOLFIRINOX) is one of the standard first-line therapies in borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). However, there is no globally accepted second-line therapy following progression on mFOLFIRINOX. METHODS Patients with BRPC and LAPC (n = 647) treated with first-line mFOLFIRINOX between January 2017 and December 2020 were included in this retrospective analysis. The details of the treatment outcomes and patterns of subsequent therapy after mFOLFIRINOX were reviewed. RESULTS With a median follow-up duration of 44.2 months (95% confidence interval [CI], 42.3-47.6), 322 patients exhibited disease progression on mFOLFIRINOX-locoregional progression only in 177 patients (55.0%) and distant metastasis in 145 patients (45.0%). The locoregional progression group demonstrated significantly longer post-progression survival (PPS) than that of the distant metastasis group (10.1 vs. 7.3 months, p = 0.002). In the locoregional progression group, survival outcomes did not differ between second-line chemoradiation/radiotherapy and systemic chemotherapy (progression-free survival with second-line therapy [PFS-2], 3.2 vs. 4.3 months; p = 0.649; PPS, 10.7 vs. 10.2 months; p = 0.791). In patients who received second-line systemic chemotherapy following progression on mFOLFIRINOX (n = 211), gemcitabine plus nab-paclitaxel was associated with better disease control rates (69.2% vs. 42.3%, p = 0.005) and PFS-2 (3.8 vs. 1.7 months, p = 0.035) than gemcitabine monotherapy. CONCLUSIONS The current study showed the real-world practice pattern of subsequent therapy and clinical outcomes following progression on first-line mFOLFIRINOX in BRPC and LAPC. Further investigation is necessary to establish the optimal therapy after failure of mFOLFIRINOX.
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Affiliation(s)
- Hyunseok Yoon
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yeokyeong Shin
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Baek-Yeol Ryoo
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Hyehyun Jeong
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Inkeun Park
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dong-Wan Seo
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sang Soo Lee
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Do Hyun Park
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Tae Jun Song
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dongwook Oh
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dae Wook Hwang
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jae Hoon Lee
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ki Byung Song
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yejong Park
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Bong Jun Kwak
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Seung-Mo Hong
- Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jin-Hong Park
- Departments of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Song Cheol Kim
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Kyu-Pyo Kim
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Changhoon Yoo
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
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34
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Jethwa KR, Kim E, Berlin J, Anker CJ, Tchelebi L, Abood G, Hallemeier CL, Jabbour S, Kennedy T, Kumar R, Lee P, Sharma N, Small W, Williams V, Russo S. Executive Summary of the American Radium Society Appropriate Use Criteria for Neoadjuvant Therapy for Nonmetastatic Pancreatic Adenocarcinoma: Systematic Review and Guidelines. Am J Clin Oncol 2024; 47:185-199. [PMID: 38131628 DOI: 10.1097/coc.0000000000001076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]
Abstract
For patients with locoregionally confined pancreatic ductal adenocarcinoma (PDAC), margin-negative surgical resection is the only known curative treatment; however, the majority of patients are not operable candidates at initial diagnosis. Among patients with resectable disease who undergo surgery alone, the 5-year survival remains poor. Adjuvant therapies, including systemic therapy or chemoradiation, are utilized as they improve locoregional control and overall survival. There has been increasing interest in the use of neoadjuvant therapy to obtain early control of occult metastatic disease, allow local tumor response to facilitate margin-negative resection, and provide a test of time and biology to assist with the selection of candidates most likely to benefit from radical surgical resection. However, limited guidance exists regarding the relative effectiveness of treatment options. In this systematic review, the American Radium Society multidisciplinary gastrointestinal expert panel convened to develop Appropriate Use Criteria evaluating the evidence regarding neoadjuvant treatment for patients with PDAC, including surgery, systemic therapy, and radiotherapy, in terms of oncologic outcomes and quality of life. The evidence was assessed using the Population, Intervention, Comparator, Outcome, and Study (PICOS) design framework and "Preferred Reporting Items for Systematic Reviews and Meta-analyses" 2020 methodology. Eligible studies included phases 2 to 3 trials, meta-analyses, and retrospective analyses published between January 1, 2012 and December 30, 2022 in the Ovid Medline database. A summary of recommendations based on the available literature is outlined to guide practitioners in the management of patients with PDAC.
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Affiliation(s)
- Krishan R Jethwa
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, MN
| | - Ed Kim
- Department of Radiation Oncology, University of Washington, Seattle, WA
| | - Jordan Berlin
- Department of Medicine, Division of Hematology-Oncology, Vanderbilt-Ingram Cancer Center, Nashville, TN
| | - Christopher J Anker
- Department of Radiation Oncology, University of Vermont Larner College of Medicine, Burlington, VT
| | - Leila Tchelebi
- Department of Radiation Oncology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead
| | | | | | | | - Timothy Kennedy
- Department of Surgery, Rutgers Cancer Institute, New Brunswick, NJ
| | - Rachit Kumar
- Department of Radiation Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Sibley Memorial Hospital, Washington DC
| | - Percy Lee
- Department of Radiation Oncology, City of Hope National Medical Center, Los Angeles, CA
| | - Navesh Sharma
- Department of Radiation Oncology, WellSpan Cancer Center, York, PA
| | - William Small
- Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, IL
| | - Vonetta Williams
- Department of Radiation Oncology, Memorial Sloan Kettering, New York, NY
| | - Suzanne Russo
- Department of Radiation Oncology, University Hospitals Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH
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Dias E Silva D, Chung V. Neoadjuvant treatment for pancreatic cancer: Controversies and advances. Cancer Treat Res Commun 2024; 39:100804. [PMID: 38508132 DOI: 10.1016/j.ctarc.2024.100804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 02/28/2024] [Accepted: 03/02/2024] [Indexed: 03/22/2024]
Abstract
Despite the advancements in the treatment of localized pancreatic cancer, several unresolved issues persist in clinical practice, especially in the neoadjuvant setting. These include determining the criteria for selecting patients for treatment, identifying the most effective chemotherapy regimens, understanding the role of radiotherapy, and accurately assessing how patients respond to treatment. Current strategies for assessing patients before surgery involve thoroughly evaluating their overall health status, analyzing tumor markers, and using advanced imaging techniques. However, existing methods for staging the disease still have limitations when it comes to accurately detecting metastatic cancer. The ongoing debate between performing surgery upfront or administering neoadjuvant therapy highlights the need for robust clinical evidence to guide treatment decisions effectively. This review analyzes the evidence regarding controversial topics in neoadjuvant pancreatic cancer treatment and discusses further research efforts to enhance patient outcomes. To improve the outcomes found with surgery alone, multimodal treatment with chemotherapy.
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Affiliation(s)
| | - Vincent Chung
- City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, United States.
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van Eijck CWF, Sabroso-Lasa S, Strijk GJ, Mustafa DAM, Fellah A, Koerkamp BG, Malats N, van Eijck CHJ. A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapy. Neoplasia 2024; 49:100975. [PMID: 38335839 PMCID: PMC10873733 DOI: 10.1016/j.neo.2024.100975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 01/31/2024] [Indexed: 02/12/2024]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is often treated with FOLFIRINOX, a chemotherapy associated with high toxicity rates and variable efficacy. Therefore, it is crucial to identify patients at risk of early progression during treatment. This study aims to explore the potential of a multi-omics biomarker for predicting early PDAC progression by employing an in-depth mathematical modeling approach. METHODS Blood samples were collected from 58 PDAC patients undergoing FOLFIRINOX before and after the first cycle. These samples underwent gene (GEP) and inflammatory protein expression profiling (IPEP). We explored the predictive potential of exclusively IPEP through Stepwise (Backward) Multivariate Logistic Regression modeling. Additionally, we integrated GEP and IPEP using Bayesian Kernel Regression modeling, aiming to enhance predictive performance. Ultimately, the FOLFIRINOX IPEP (FFX-IPEP) signature was developed. RESULTS Our findings revealed that proteins exhibited superior predictive accuracy than genes. Consequently, the FFX-IPEP signature consisted of six proteins: AMN, BANK1, IL1RL2, ITGB6, MYO9B, and PRSS8. The signature effectively identified patients transitioning from disease control to progression early during FOLFIRINOX, achieving remarkable predictive accuracy with an AUC of 0.89 in an independent test set. Importantly, the FFX-IPEP signature outperformed the conventional CA19-9 tumor marker. CONCLUSIONS Our six-protein FFX-IPEP signature holds solid potential as a liquid biomarker for the early prediction of PDAC progression during toxic FOLFIRINOX chemotherapy. Further validation in an external cohort is crucial to confirm the utility of the FFX-IPEP signature. Future studies should expand to predict progression under different chemotherapies to enhance the guidance of personalized treatment selection in PDAC.
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Affiliation(s)
- Casper W F van Eijck
- Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain.
| | - Sergio Sabroso-Lasa
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain; Centro de Investigación Biomédica en Red-Cáncer (CIBERONC), Madrid, Spain
| | - Gaby J Strijk
- Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Dana A M Mustafa
- Department of Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Amine Fellah
- Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Núria Malats
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain; Centro de Investigación Biomédica en Red-Cáncer (CIBERONC), Madrid, Spain
| | - Casper H J van Eijck
- Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain.
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Ruff SM, Stevens L, Bressler L, Khatri R, Sarna A, Ejaz AM, Dillhoff M, Pawlik TM, Rose K, Cloyd JM. Evaluating the caregiver experience during neoadjuvant therapy for pancreatic ductal adenocarcinoma. J Surg Oncol 2024; 129:775-784. [PMID: 38063046 DOI: 10.1002/jso.27558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 11/10/2023] [Accepted: 11/25/2023] [Indexed: 02/17/2024]
Abstract
INTRODUCTION Neoadjuvant therapy (NT) is increasingly recommended for patients with localized pancreatic ductal adenocarcinoma (PDAC). Recent research has highlighted the significant treatment burden that patients experience during NT, but caregiver well-being during NT is poorly understood. METHODS A cross-sectional mixed-methods analysis of primary caregivers of patients with localized PDAC receiving NT was undertaken. All patients completed the Caregiver Quality of Life Index-Cancer (CQOLC) survey, while semi-structured interviews were conducted among a convenience sample of participants. RESULTS Among 28 caregivers, the mean age was 60.1 years, and most were patient spouses/significant others (71.4%). Patients had resectable (18%), borderline resectable (46%), or locally advanced (36%) PDAC with a mean treatment duration of 2.9 months at the time of their caregiver's enrollment. Most caregivers felt that they received adequate emotional/psychosocial support (80%) and understood the rationale for NT (93%). A majority (60%) reported that caregiving responsibilities impacted their daily lives and required a decrease in their work hours, leading to financial challenges (47%). While overall QOL was moderate (mean 83 ± 21.1, range 0-140), "emotional burden" (47.3 ± 20.9), and "positive adaption" (57.3 ± 13.9) were the lowest ranked CQOLC subsection scores. DISCUSSION Caregivers of patients with PDAC undergoing NT experience significant emotional symptoms and impact on their daily lives. Assessing caregiver needs and providing resources during NT should be a priority.
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Affiliation(s)
- Samantha M Ruff
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Lena Stevens
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Luke Bressler
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Rakhsha Khatri
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Angela Sarna
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Aslam M Ejaz
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Mary Dillhoff
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Karen Rose
- College of Nursing, The Ohio State University, Columbus, Ohio, USA
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
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Riviere D, Aarntzen E, van Geenen E, Chang D, de Geus-Oei LF, Brosens L, van Laarhoven K, Gotthardt M, Hermans J. Qualitative flow metabolic phenotype of pancreatic cancer. A new prognostic biomarker? HPB (Oxford) 2024; 26:389-399. [PMID: 38114400 DOI: 10.1016/j.hpb.2023.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 10/26/2023] [Accepted: 11/17/2023] [Indexed: 12/21/2023]
Abstract
BACKGROUND Retrospective analysis to investigate the relationship between the flow-metabolic phenotype and overall survival (OS) of pancreatic ductal adenocarcinoma (PDAC) and its potential clinical utility. METHODS Patients with histopathologically proven PDAC between 2005 and 2014 using tumor attenuation on routine pre-operative CECT as a surrogate for the vascularity and [18F]FDG-uptake as a surrogate for metabolic activity on [18F]FDG-PET. RESULTS In total, 93 patients (50 male, 43 female, median age 63) were included. Hypoattenuating PDAC with high [18F]FDG-uptake has the poorest prognosis (median OS 7 ± 1 months), compared to hypoattenuating PDAC with low [18F]FDG-uptake (median OS 11 ± 3 months; p = 0.176), iso- or hyperattenuating PDAC with high [18F]FDG-uptake (median OS 15 ± 5 months; p = 0.004) and iso- or hyperattenuating PDAC with low [18F]FDG-uptake (median OS 23 ± 4 months; p = 0.035). In multivariate analysis, surgery combined with tumor differentiation, tumor stage, systemic therapy and flow metabolic phenotype remained independent predictors for overall survival. DISCUSSION The novel qualitative flow-metabolic phenotype of PDAC using a combination of CECT and [18F]FDG-PET features, predicted significantly worse survival for hypoattenuating-high uptake pancreatic cancers compared to the other phenotypes.
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Affiliation(s)
- Deniece Riviere
- Department of Medical Imaging, Radboud University Medical Center, Nijmegen, the Netherlands.
| | - Erik Aarntzen
- Department of Medical Imaging, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Erwin van Geenen
- Department of Gastroenterology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - David Chang
- Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Bearsden, Glasgow, Scotland, United Kingdom; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom
| | - Lioe-Fee de Geus-Oei
- Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Lodewijk Brosens
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Kees van Laarhoven
- Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Martin Gotthardt
- Department of Medical Imaging, Radboud University Medical Center, Nijmegen, the Netherlands
| | - John Hermans
- Department of Medical Imaging, Radboud University Medical Center, Nijmegen, the Netherlands.
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Aoki T, Mori S, Kubota K. Neoadjuvant and Adjuvant Chemotherapy for Pancreatic Adenocarcinoma: Literature Review and Our Experience of NAC-GS. Cancers (Basel) 2024; 16:910. [PMID: 38473272 DOI: 10.3390/cancers16050910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 02/16/2024] [Accepted: 02/21/2024] [Indexed: 03/14/2024] Open
Abstract
In addition to established evidence of the efficacy of adjuvant chemotherapy (AC) for pancreatic ductal adenocarcinoma (PDAC), evidence of the effects of neoadjuvant treatments (NATs), including chemotherapy and chemoradiotherapy, has also been accumulating. Recent results from prospective studies and meta-analyses suggest that NATs may be beneficial not only for borderline resectable PDAC, but also for resectable PDAC, by increasing the likelihood of successful R0 resection, decreasing the likelihood of the development of lymph node metastasis, and improving recurrence-free and overall survival. In addition, response to NAT may be informative for predicting the clinical course after preoperative NAT followed by surgery; in this way, the postoperative treatment strategy can be revised based on the effect of NAT and the post-neoadjuvant therapy/surgery histopathological findings. On the other hand, the response to NAT and AC is also influenced by the tumor biology and the patient's immune/nutritional status; therefore, planning of the treatment strategy and meticulous management of NAT, surgery, and AC is required on a patient-by-patient basis. Our experience of using gemcitabine plus S-1 showed that this NAT regimen achieved tumor shrinkage and decreased the levels of tumor markers but failed to provide a survival benefit. Our results also suggested that response/adverse events to NAT may be predictive of the efficacy of AC, as well as survival outcomes.
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Affiliation(s)
- Taku Aoki
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Mibu 321-0293, Tochigi, Japan
| | - Shozo Mori
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Mibu 321-0293, Tochigi, Japan
| | - Keiichi Kubota
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Mibu 321-0293, Tochigi, Japan
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Stoop TF, Theijse RT, Seelen LWF, Groot Koerkamp B, van Eijck CHJ, Wolfgang CL, van Tienhoven G, van Santvoort HC, Molenaar IQ, Wilmink JW, Del Chiaro M, Katz MHG, Hackert T, Besselink MG. Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer. Nat Rev Gastroenterol Hepatol 2024; 21:101-124. [PMID: 38036745 DOI: 10.1038/s41575-023-00856-2] [Citation(s) in RCA: 51] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/05/2023] [Indexed: 12/02/2023]
Abstract
Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda.
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Affiliation(s)
- Thomas F Stoop
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Rutger T Theijse
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands
- Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Leonard W F Seelen
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, Netherlands
| | - Casper H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, Netherlands
| | - Christopher L Wolfgang
- Division of Surgical Oncology, Department of Surgery, New York University Medical Center, New York City, NY, USA
| | - Geertjan van Tienhoven
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Radiation Oncology, Amsterdam, Netherlands
| | - Hjalmar C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - Johanna W Wilmink
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Medical Oncology, Amsterdam, Netherlands
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Marc G Besselink
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands.
- Cancer Center Amsterdam, Amsterdam, Netherlands.
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Zhang R, Wang J, Zhang P, Zhang Z, Miao R. Pancreatic cancer progression and mortality predicted by depression and anxiety: a systematic review and meta-analysis protocol. Front Psychiatry 2024; 14:1266502. [PMID: 38274428 PMCID: PMC10808776 DOI: 10.3389/fpsyt.2023.1266502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 12/29/2023] [Indexed: 01/27/2024] Open
Abstract
Although the relationship between psychological factors and pancreatic cancer outcomes has been widely discussed, controversy remains. We will for the first time systematically summarize the literature to explore the correlation of anxiety and depression to the prognosis of patients with pancreatic cancer. The findings will fill existing research gaps, informing healthcare providers about better psychological care and medical treatment. The following databases will be retrieved from their inception to July 2023: Cochrane Library, MEDLINE (PubMed), Web of Science, EMBASE, and four Chinese databases (Chinese National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, and Chongqing VIP Chinese Science and Technology Periodical Database). The World Health Organization Clinical Trials Registry, Chinese Clinical Registry, and ClinicalTrials.gov will be searched to identify other related studies. A manual search will be performed to identify missing eligible studies based on the reference list of selected articles. The search will focus on studies published in Chinese or English. To assess the risk of bias in the selected articles, Newcastle-Ottawa Quality Assessment Scale (NOS) will be used for the cohort study. Funnel plots and Egger's test will be used to assess whether publication bias exists. Moreover, the Grading of Recommendations Assessment Development and Evaluation (GRADE) will be utilized to analyze the credibility of the results from selected articles. Two independent evaluators will implement the study selection and data extraction, as well as evaluate the risk of bias and evidence quality. Data will be analyzed using Stata 16.0. Trial registration: PROSPERO registration number is CRD42022366232.
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Affiliation(s)
- Ruoqi Zhang
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate College, Beijing University of Chinese Medicine, Beijing, China
| | - Jing Wang
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate College, Beijing University of Chinese Medicine, Beijing, China
| | - Peitong Zhang
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zheng Zhang
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate College, Beijing University of Chinese Medicine, Beijing, China
| | - Rui Miao
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate College, Beijing University of Chinese Medicine, Beijing, China
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van Eijck CWF, Strijk G, Vietsch EE, van der Sijde F, Verheij M, Mustafa DAM, Vink M, Aerts JGJV, van Eijck CHJ, Willemsen M. FOLFIRINOX chemotherapy modulates the peripheral immune landscape in pancreatic cancer: Implications for combination therapies and early response prediction. Eur J Cancer 2024; 196:113440. [PMID: 37988843 DOI: 10.1016/j.ejca.2023.113440] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 11/01/2023] [Indexed: 11/23/2023]
Abstract
BACKGROUND FOLFIRINOX chemotherapy has improved outcomes for pancreatic cancer patients, but poor long-term survival outcomes and high toxicity remain challenges. This study investigates the impact of FOLFIRINOX on plasma proteins and peripheral immune cells to guide immune-based combination therapies and, ideally, to identify a potential biomarker to predict early disease progression during FOLFIRINOX. METHODS Blood samples were collected from 86 pancreatic cancer patients before and two weeks after the first FOLFIRINOX cycle and subjected to comprehensive immune cell and proteome profiling. Principal Component Analysis and Linear Mixed Effect Regression models were used for data analysis. FOLFIRINOX efficacy was radiologically evaluated after the fourth cycle. RESULTS One cycle of FOLFIRINOX diminished tumour-cell-related pathways and enhanced pathways related to immune activation, illustrated by an increase in pro-inflammatory IL-18, IL-15, and TNFRSF4. Similarly, FOLFIRINOX promoted the activation of CD4 + and CD8 + T cells, the proliferation of NK(T), and the activation of antigen-presenting cells. Furthermore, high pre-treatment levels of VEGFA and PRDX3 and an elevation in FCRL3 levels after one cycle predicted early progression under FOLFIRINOX. Finally, patients with progressive disease exhibited high levels of inhibitory markers on B cells and CD8 + T cells, while responding patients exhibited high levels of activation markers on CD4 + and CD8 + T cell subsets. CONCLUSION FOLFIRINOX has immunomodulatory effects, providing a foundation for clinical trials exploring immune-based combination therapies that harness the immune system to treat pancreatic cancer. In addition, several plasma proteins hold potential as circulating predictive biomarkers for early prediction of FOLFIRINOX response in patients with pancreatic cancer.
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Affiliation(s)
- Casper W F van Eijck
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre, Madrid, Spain
| | - Gaby Strijk
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Eveline E Vietsch
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands; Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Fleur van der Sijde
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Maaike Verheij
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Dana A M Mustafa
- Department of Pathology, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Madelief Vink
- Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, the Netherlands; Department of Pulmonary Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Joachim G J V Aerts
- Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, the Netherlands; Department of Pulmonary Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Casper H J van Eijck
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre, Madrid, Spain
| | - Marcella Willemsen
- Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, the Netherlands; Department of Pulmonary Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands.
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Smart AC, Niemierko A, Wo JY, Ferrone CR, Tanabe KK, Lillemoe KD, Clark JW, Blaszkowsky LS, Allen JN, Weekes C, Ryan DP, Warshaw AL, Castillo CFD, Hong TS, Keane FK. Portal Vein or Superior Mesenteric Vein Thrombosis with Dose-Escalated Radiation for Borderline or Locally Advanced Pancreatic Cancer. J Gastrointest Surg 2023; 27:2464-2473. [PMID: 37578568 DOI: 10.1007/s11605-023-05796-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 07/29/2023] [Indexed: 08/15/2023]
Abstract
PURPOSE Portal vein and superior mesenteric vein thrombosis (PVT/SMVT) are potentially morbid complications of radiation dose-escalated local therapy for pancreatic cancer. We retrospectively reviewed records for patients treated with and without intraoperative radiation (IORT) to identify risk factors for PVT/SMVT. METHODS Ninety-six patients with locally advanced or borderline resectable pancreatic adenocarcinoma received neoadjuvant therapy followed by surgical exploration from 2009 to 2014. Patients at risk for close or positive surgical margins received IORT boost to a biologically effective dose (BED10) > 100. Prognostic factors for PVT/SMVT were evaluated using competing risks regression. RESULTS Median follow-up was 79 months for surviving patients. Fifty-six patients (58%) received IORT. Twenty-nine patients (30%) developed PVT/SMVT at a median time of 18 months. On univariate competing risks regression, operative blood loss and venous repair with a vascular interposition graft, but not IORT dose escalation or diabetes history, were significantly associated with PVT/SMVT. The development of thrombosis in the absence of recurrence was significantly associated with a longstanding diabetes history, post-neoadjuvant treatment CA19-9, and operative blood loss. All 4 patients who underwent both IORT and vascular repair with a graft developed PVT/SMVT. PVT/SMVT in the absence of recurrence is not associated with significantly worsened overall survival but led to frequent medical interventions. CONCLUSIONS Approximately 30% of patients who underwent neoadjuvant chemoradiation for PDAC developed PVT/SMVT a median of 18 months following surgery. This was significantly associated with venous reconstruction with vascular grafts, but not with escalating radiation dose. PVT/SMVT in the absence of recurrence was associated with significant morbidity.
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Affiliation(s)
- Alicia C Smart
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Andrzej Niemierko
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
| | | | - Kenneth K Tanabe
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Keith D Lillemoe
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Jeffrey W Clark
- Division of Medical Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Lawrence S Blaszkowsky
- Division of Medical Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Jill N Allen
- Division of Medical Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Colin Weekes
- Division of Medical Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - David P Ryan
- Division of Medical Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Andrew L Warshaw
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | | | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Florence K Keane
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.
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Quispel R, Schutz HM, Keultjes AWP, Erler NS, Janssen QP, van Hooft JE, Venneman NG, Honkoop P, Hol L, Scheffer RC, Bisseling TM, Voermans RP, Vleggaar FP, Schwartz MP, Verdonk RC, Hoge CV, Kuiken SD, Curvers WL, van Vilsteren FGI, Poen AC, Spanier MB, Bruggink AH, Smedts FM, van Velthuysen MLF, van Eijck CH, Besselink MG, Veldt BJ, Koerkamp BG, van Driel LMJW, Bruno MJ. Diagnostic accuracy of endoscopic ultrasonography-guided tissue acquisition prior to resection of pancreatic carcinoma: a nationwide analysis. HPB (Oxford) 2023; 25:1438-1445. [PMID: 37550169 DOI: 10.1016/j.hpb.2023.07.900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 05/18/2023] [Accepted: 07/20/2023] [Indexed: 08/09/2023]
Abstract
INTRODUCTION Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM). AIM assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands. PATIENTS AND METHODS Results of all EUS + TA prior to resection of pancreatic carcinoma from 2014-2018, were extracted from the national Dutch Pathology Registry (PALGA). Pathology reports were classified as: insufficient for analysis (b1), benign (b2), atypia (b3), neoplastic other (b4), suspected malignant (b5), and malignant (b6). RAS was defined as the proportion of EUS procedures yielding specimen sufficient for analysis. SFM was calculated using a strict definition (malignant only, SFM-b6), and a broader definition (SFM-b5+6). RESULTS 691 out of 1638 resected patients (42%) underwent preoperative EUS + TA. RAS was 95% (range 89-100%), SFM-b6 was 44% (20-77%), and SFM-b5+6 was 65% (53-90%). All centers met the performance target RAS>85%. Only 9 out of 17 met the performance target SFM-b5+6 > 85%. CONCLUSION This nationwide study detected significant practice variation regarding KPI of EUS + TA procedures prior to surgical resection of pancreatic carcinoma. Therefore, quality improvement of EUS + TA is indicated.
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Affiliation(s)
- Rutger Quispel
- Department of Gastroenterology and Hepatology, Reinier de Graaf Gasthuis, Delft, the Netherlands; Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, the Netherlands.
| | - Hannah M Schutz
- Department of Gastroenterology and Hepatology, Reinier de Graaf Gasthuis, Delft, the Netherlands; Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Augustinus W P Keultjes
- Department of Gastroenterology and Hepatology, Reinier de Graaf Gasthuis, Delft, the Netherlands
| | - Nicole S Erler
- Department of Biostatistics, Erasmus University Medical Centre, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Quisette P Janssen
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, the Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, the Netherlands
| | - Niels G Venneman
- Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, Enschede, the Netherlands
| | - Pieter Honkoop
- Department of Gastroenterology and Hepatology, Albert Schweitzer Ziekenhuis, Dordrecht, the Netherlands
| | - Lieke Hol
- Department of Gastroenterology and Hepatology, Maasstad Ziekenhuis, Rotterdam, the Netherlands
| | - Robert C Scheffer
- Department of Gastroenterology and Hepatology, Jeroen Bosch Ziekenhuis, 's Hertogenbosch, the Netherlands
| | - Tanya M Bisseling
- Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Rogier P Voermans
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, the Netherlands
| | - Frank P Vleggaar
- Department of Gastroenterology and Hepatology, Utrecht University Medical Centre, Utrecht, the Netherlands
| | - Matthijs P Schwartz
- Department of Gastroenterology and Hepatology, Meander Medical Centre, Amersfoort, the Netherlands
| | - Robert C Verdonk
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Chantal V Hoge
- Department of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Sjoerd D Kuiken
- Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands
| | - Wouter L Curvers
- Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands
| | - Frederike G I van Vilsteren
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, the Netherlands
| | - Alexander C Poen
- Department of Gastroenterology and Hepatology, Isala Hospital, Zwolle, the Netherlands
| | - Marcel B Spanier
- Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, the Netherlands
| | | | - Frank M Smedts
- Department of Pathology, Reinier de Graaf Gasthuis, Delft, the Netherlands
| | | | - Casper H van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, the Netherlands
| | - Marc G Besselink
- Department of Surgery, Amsterdam University Medical Centre, Amsterdam, the Netherlands
| | - Bart J Veldt
- Department of Gastroenterology and Hepatology, Reinier de Graaf Gasthuis, Delft, the Netherlands
| | - Bas G Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, the Netherlands
| | - Lydi M J W van Driel
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, the Netherlands
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Farnes I, Kleive D, Verbeke CS, Aabakken L, Issa-Epe A, Småstuen MC, Fosby BV, Dueland S, Line PD, Labori KJ. Resection rates and intention-to-treat outcomes in borderline and locally advanced pancreatic cancer: real-world data from a population-based, prospective cohort study (NORPACT-2). BJS Open 2023; 7:zrad137. [PMID: 38155512 PMCID: PMC10755199 DOI: 10.1093/bjsopen/zrad137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 10/17/2023] [Accepted: 10/20/2023] [Indexed: 12/30/2023] Open
Abstract
BACKGROUND Systemic chemotherapy is the initial treatment strategy for borderline resectable and locally advanced pancreatic cancer to facilitate curative resection. The aim of this study was to investigate the resection rates and overall survival in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer. METHODS Consecutive patients with borderline resectable pancreatic cancer/locally advanced pancreatic cancer discussed by Oslo University Hospital multidisciplinary team between 2018 and 2020, serving a population of 3.1 million within a geographically defined area in south-eastern Norway, were included in this prospective Norwegian Pancreatic Cancer Trial-2 study, according to intention-to-treat principles. The total number of patients with pancreatic cancer was sought from the Cancer Registry of Norway. RESULTS A total of 1178 patients were diagnosed with pancreatic cancer, of whom 618 were referred to Oslo University Hospital. After multidisciplinary team evaluation, 230 patients were considered to have borderline resectable pancreatic cancer/locally advanced pancreatic cancer. The final study group consisted of 188 patients (borderline resectable pancreatic cancer n = 96, locally advanced pancreatic cancer n = 92) who were fit to receive primary chemotherapy. Resection rates were 46.9% (45 of 96) for borderline resectable pancreatic cancer and 13% (12 of 92) for locally advanced pancreatic cancer (P <0.001). Median overall survival was 14.6 months (borderline resectable pancreatic cancer 16.4 months; locally advanced pancreatic cancer 13.7 months, (P = 0.2)). Adjusted for immortal time bias, median overall survival for patients undergoing resection versus only chemotherapy was 24.4 months versus 10.1 months (P <0.001) for borderline resectable pancreatic cancer and 28.4 months versus 12.6 months for locally advanced pancreatic cancer (P = 0.001). CONCLUSION Resection rates and survival in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer treated at a high-volume centre in a universal healthcare system compare well with those treated at international expert centres.Registration number: NCT04423731 (http://www.clinicaltrials.gov).
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Affiliation(s)
- Ingvild Farnes
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Dyre Kleive
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Caroline S Verbeke
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Lars Aabakken
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Aart Issa-Epe
- Department of Radiology, Oslo University Hospital, Oslo, Norway
| | | | - Bjarte V Fosby
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Svein Dueland
- Department of Oncology, Oslo University Hospital, Oslo, Norway
| | - Pål-Dag Line
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Knut J Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Shrikhande SV, Kunte AR, Chopde AN, Chaudhari VA, Bhandare MS. Big data and RCT's in surgical oncology: Impact on improving hepatopancreatobiliary cancer surgical care on the global stage. J Surg Oncol 2023; 128:1003-1010. [PMID: 37818909 DOI: 10.1002/jso.27467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 09/13/2023] [Accepted: 09/14/2023] [Indexed: 10/13/2023]
Abstract
Randomized controlled clinical trials (RCTs) are at the heart of "evidence-based" medicine. Conducting well-designed RCTs for surgical procedures is often challenged by inadequate recruitment accrual, blinding, or standardization of the surgical procedure, as well as lack of funding and evolution of the treatment strategy during the many years over which such trials are conducted. In addition, most clinical trials are performed in academic high-volume centers with highly selected patients, which may not necessarily reflect a "real-world" practice setting. Large databases provide easy and inexpensive access to data on a large and diverse patient population at a variety of treatment centers. Furthermore, large database studies provide the opportunity to answer questions that would be impossible or very arduous to answer using RCTs, including questions regarding health policy efficacy, trends in surgical practice, access to health care, the impact of hospital volume, and adherence to practice guidelines, as well as research questions regarding rare disease, infrequent surgical outcomes, and specific subpopulations. Prospective data registries may also allow for quality benchmarking and auditing. There are several high-quality RCTs providing evidence to support current practices in hepatopancreatobiliary (HPB) oncology. Evidence from big data bridges the gap in several instances where RCTs are lacking. In this article, we review the evidence from RCTs and big data in HPB oncology identify the existing lacunae, and discuss the future directions of research in HPB oncology.
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Affiliation(s)
- Shailesh V Shrikhande
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Aditya R Kunte
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Amit N Chopde
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Vikram A Chaudhari
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Manish S Bhandare
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
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Okada K, Kimura K, Yamashita Y, Shibuya K, Matsumoto I, Satoi S, Yoshida K, Kodera Y, Akahori T, Hirono S, Eguchi H, Asakuma M, Tani M, Hatano E, Ikoma H, Ohira G, Hayashi H, Wan K, Shimokawa T, Kawai M, Yamaue H, The NAC‐GA investigators. Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial). Ann Gastroenterol Surg 2023; 7:997-1008. [PMID: 37927936 PMCID: PMC10623952 DOI: 10.1002/ags3.12712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/06/2023] [Accepted: 06/20/2023] [Indexed: 11/07/2023] Open
Abstract
Background Nab-paclitaxel plus gemcitabine is a standard treatment for metastatic/locally advanced pancreatic cancer. The effectiveness of neoadjuvant therapy with nab-paclitaxel plus gemcitabine (GnP-NAT) in patients with borderline resectable pancreatic cancer (BRPC) remains unclear. Patients and Methods This single-arm phase II trial included 61 patients with BRPC that were treated with two cycles of GnP-NAT, (nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2), on days 1, 8, and 15 over a 4-week period, which comprised one cycle. The primary endpoint was overall survival time. In the absence of disease progression, patients underwent planned pancreatectomy. Results Median overall survival, the primary endpoint, was 25.2 months, and the median recurrence-free survival was 12.3 months. The overall rate of grade 3/4 events was 73.8%. One patient, who had a history of radiation therapy for past esophageal cancer, died from exacerbation via pneumonia. The overall resection rate was 73.8% (n = 45), and the R0 resection rate was 63.9% (n = 39). Overall, postoperative complications were found in 19 patients (42%) with 24 events, and nine patients (20%) with nine events ≥ grade IIIa, based on Dindo's classification. Conclusions This protocol treatment is thought to be a feasible, safe, and promising treatment regimen, but we caution against its use in patients with a history of interstitial lung disease and/or prior pulmonary irradiation. The survival data from this study suggest the need for further investigations of GnP-NAT efficacy in patients with BRPC, as well as prospective evaluation of adverse events. Clinical Trial Registration UMIN Clinical Trials Registry, UMIN000024154 and ClinicalTrials.gov, NCT02926183.
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Affiliation(s)
- Ken‐ichi Okada
- Second Department of SurgeryWakayama Medical UniversityWakayamaJapan
| | - Kenjiro Kimura
- Department of Hepato‐Biliary‐Pancreatic SurgeryOsaka Metropolitan University Graduate School of MedicineOsakaJapan
| | - Yo‐Ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Kazuto Shibuya
- Department of Surgery and Science, Faculty of Medicine, Academic AssemblyUniversity of ToyamaToyamaJapan
| | - Ippei Matsumoto
- Department of SurgeryKindai University Faculty of MedicineOsaka‐SayamaJapan
| | - Sohei Satoi
- Department of SurgeryKansai Medical UniversityHirakataJapan
| | - Kazuhiro Yoshida
- Department of Surgical OncologyGifu University Graduate School of MedicineGifuJapan
| | - Yasuhiro Kodera
- Department of Gastroenterological SurgeryNagoya University Graduate School of MedicineNagoyaJapan
| | | | - Seiko Hirono
- Second Department of SurgeryWakayama Medical UniversityWakayamaJapan
- Division of Hepato‐Biliary‐Pancreatic Surgery, Department of Gastroenterological SurgeryHyogo Medical UniversityNishinomiyaJapan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaJapan
| | - Mitsuhiro Asakuma
- Department of General and Gastroenterological SurgeryOsaka Medical and Pharmaceutical UniversityTakatsukiJapan
| | - Masaji Tani
- Department of SurgeryShiga University of Medical ScienceŌtsuJapan
| | - Etsuro Hatano
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Hisashi Ikoma
- Division of Digestive Surgery, Department of SurgeryKyoto Prefectural University of MedicineKyotoJapan
| | - Go Ohira
- Department of Hepato‐Biliary‐Pancreatic SurgeryOsaka Metropolitan University Graduate School of MedicineOsakaJapan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Ke Wan
- Clinical Study Support CenterWakayama Medical UniversityWakayamaJapan
| | - Toshio Shimokawa
- Clinical Study Support CenterWakayama Medical UniversityWakayamaJapan
| | - Manabu Kawai
- Second Department of SurgeryWakayama Medical UniversityWakayamaJapan
| | - Hiroki Yamaue
- Department of Cancer ImmunologyWakayama Medical UniversityWakayamaJapan
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Khasawneh H, Ferreira Dalla Pria HR, Miranda J, Nevin R, Chhabra S, Hamdan D, Chakraborty J, Biachi de Castria T, Horvat N. CT Imaging Assessment of Pancreatic Adenocarcinoma Resectability after Neoadjuvant Therapy: Current Status and Perspective on the Use of Radiomics. J Clin Med 2023; 12:6821. [PMID: 37959287 PMCID: PMC10649102 DOI: 10.3390/jcm12216821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/13/2023] [Accepted: 10/20/2023] [Indexed: 11/15/2023] Open
Abstract
Pancreatic adenocarcinoma (PDAC) is the most common pancreatic cancer and is associated with poor prognosis, a high mortality rate, and a substantial number of healthy life years lost. Surgical resection is the primary treatment option for patients with resectable disease; however, only 10-20% of all patients with PDAC are eligible for resection at the time of diagnosis. In this context, neoadjuvant therapy has the potential to increase the number of patients who are eligible for resection, thereby improving the overall survival rate. For patients who undergo neoadjuvant therapy, computed tomography (CT) remains the primary imaging tool for assessing treatment response. Nevertheless, the interpretation of imaging findings in this context remains challenging, given the similarity between viable tumor and treatment-related changes following neoadjuvant therapy. In this review, following an overview of the various treatment options for PDAC according to its resectability status, we will describe the key challenges regarding CT-based evaluation of PDAC treatment response following neoadjuvant therapy, as well as summarize the literature on CT-based evaluation of PDAC treatment response, including the use of radiomics. Finally, we will outline key recommendations for the management of PDAC after neoadjuvant therapy, taking into consideration CT-based findings.
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Affiliation(s)
- Hala Khasawneh
- Department of Radiology, University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX 75390, USA;
| | | | - Joao Miranda
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; (J.M.); (R.N.); (S.C.)
- Department of Radiology, University of Sao Paulo, R. Dr. Ovidio Pires de Campos, 75-Cerqueira Cesar, Sao Paulo 05403-010, SP, Brazil
| | - Rachel Nevin
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; (J.M.); (R.N.); (S.C.)
| | - Shalini Chhabra
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; (J.M.); (R.N.); (S.C.)
| | - Dina Hamdan
- Department of Radiology, The Mount Sinai Hospital, 1468 Madison Ave, New York, NY 10029, USA;
| | - Jayasree Chakraborty
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA;
| | - Tiago Biachi de Castria
- Department of Gastrointestinal Oncology, Moffit Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA;
- Morsani College of Medicine, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620, USA
| | - Natally Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; (J.M.); (R.N.); (S.C.)
- Department of Radiology, University of Sao Paulo, R. Dr. Ovidio Pires de Campos, 75-Cerqueira Cesar, Sao Paulo 05403-010, SP, Brazil
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Paulino J, Mansinho H. Recent Developments in the Treatment of Pancreatic Cancer. ACTA MEDICA PORT 2023; 36:670-678. [PMID: 37788655 DOI: 10.20344/amp.19957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 08/22/2023] [Indexed: 10/05/2023]
Abstract
Pancreatic duct adenocarcinoma is currently the sixth-leading cause of cancer death worldwide and the fourth in Europe, with a continuous increase in annual lethality in Portugal during the last two decades. Surgical en-bloc resection of the tumor with microscopic-negative margins and an adequate lymphadenectomy is the only possibility of long-term survival. As this type of cancer is a systemic disease, there is a high rate of recurrence even after curative resection, turning systemic therapy the core of its management, mostly based on chemotherapy. Neoadjuvant strategies for nonmetastatic disease showed significant improvement in overall survival compared with upfront surgery, namely in borderline resectable disease. Moreover, these strategies provided downstaging in several situations allowing R0 resections. Under these new oncologic strategies, several recent surgical issues were introduced, namely more aggressive vascular resections and even tumor resections in oligometastatic disease. This review revisits the state-of-the-art of surgical and oncological interventions in pancreatic duct adenocarcinoma and highlights recent advances in the field aiming to achieve higher survival rates.
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Affiliation(s)
- Jorge Paulino
- General Surgery Department. Hospital da Luz. Lisboa. Portugal
| | - Hélder Mansinho
- Oncology Department. Hospital Garcia de Orta. Almada. Portugal
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50
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Donisi G, Nappo G, Pacilli M, Capretti GL, Spaggiari P, Sollai M, Bozzarelli S, Zerbi A. Pathologic tumor response to neoadjuvant therapy in resected pancreatic cancer: does it affect prognosis? Updates Surg 2023; 75:1497-1508. [PMID: 37578734 DOI: 10.1007/s13304-023-01628-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 08/04/2023] [Indexed: 08/15/2023]
Abstract
Neoadjuvant therapy (NAT) + surgical resection for pancreatic cancer (PC) has gained consensus in recent years. Pathological response (PR) is generally assessed according to the College of American Pathologists grading system, ranging from 0 (complete response) to 3 (no response). The aim of our study is to evaluate the PR in a series of resections for PC after NAT and its prognostic implication. 112 patients undergone NAT and resection for PC between 2011 and 2020 were retrospectively evaluated. PR was 0/1, 2 and 3 in 18 (15%), 79 (61%) and 29 (24%) cases, respectively. Chemotherapy regimens different from FOLFIRINOX and gemcitabine + nab-paclitaxel (OR 11.61 (2.53-53.36), p = 0.002) and lymphovascular invasion (OR 11.28 (1.89-67.23), p = 0.008) were associated to PR-3. Median follow-up was 25.8 (3.6-130.5) months. For PR-0/1, PR-2 and PR-3, median DFS was 45.8, 11.5, 4.6 months (p < 0.0001), respectively, while median OS was not reached, 27.1 and 17.5 months (p = 0.0006), respectively. At univariate analysis, PR-0/1 was significantly associated to better DFS and OS (HR 0.33 (0.17-0.67), p = 0.002; HR 0.20 (0.07-0.54), p = 0.002, respectively). At multivariate analysis, pancreaticoduodenectomy (HR 0.50 (0.30-0.84), p = 0.009), LNR (HR 27.14 (1.21-608.9), p = 0.038) and lymphovascular invasion (HR 1.99 (1.06-3.76), p = 0.033) were independently associated to DFS; pre-treatment CA 19.9 value (HR 1.00 (1.00-1.00), p = 0.025), post-treatment resectability status (HR 0.51 (0.28-0.95), p = 0.035), pancreaticoduodenectomy (HR 0.56 (0.32-0.99), p = 0.050), severe morbidity (2.99 (1.22-7.55), p = 0.017), LNR (HR 56.8 (2.08-1548.3), p = 0.017), lymphovascular invasion (HR 2.18 (1.08-4.37), p = 0.029) were independently associated to OS. PR did not reach statistical significance at multivariate analysis. A favorable PR is observed only in a limited number of cases. The prognostic role of PR, despite being promising, remains unclear and further multicentric studies are needed.
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Affiliation(s)
- G Donisi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Milan, Pieve Emanuele, Italy
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
| | - G Nappo
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Milan, Pieve Emanuele, Italy.
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy.
| | - M Pacilli
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
| | - G L Capretti
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Milan, Pieve Emanuele, Italy
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
| | - P Spaggiari
- Department of Pathology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
| | - M Sollai
- Department of Pathology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
| | - S Bozzarelli
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
| | - A Zerbi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Milan, Pieve Emanuele, Italy
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
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