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1
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Yun WG, Kim D, Han Y, Kwon W, Lee SG, Jang JY, Park D. Multiomic quantification of the KRAS mutation dosage improves the preoperative prediction of survival and recurrence in patients with pancreatic ductal adenocarcinoma. Exp Mol Med 2025; 57:193-203. [PMID: 39779977 PMCID: PMC11799340 DOI: 10.1038/s12276-024-01382-0] [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: 11/13/2023] [Revised: 08/29/2024] [Accepted: 10/25/2024] [Indexed: 01/11/2025] Open
Abstract
Most cancer mutation profiling studies are laboratory-based and lack direct clinical application. For clinical use, it is necessary to focus on key genes and integrate them with relevant clinical variables. We aimed to evaluate the prognostic value of the dosage of the KRAS G12 mutation, a key pancreatic ductal adenocarcinoma (PDAC) variant and to investigate the biological mechanism of the prognosis associated with the dosage of the KRAS G12 mutation. In this retrospective cohort study, we analyzed 193 surgically treated patients with PDAC between 2009 and 2016. RNA, whole-exome, and KRAS-targeted sequencing data were used to estimate the dosage of the KRAS G12 mutant. Our prognostic scoring system included the mutation dosage from targeted sequencing ( > 0.195, 1 point), maximal tumor diameter at preoperative imaging ( > 20 mm, 1 point), and carbohydrate antigen 19-9 levels ( > 150 U/mL, 1 point). The KRAS mutation dosage exhibited comparable performance with clinical variables for survival prediction. High KRAS mutation dosages activated the cell cycle, leading to high mutation rates and poor prognosis. According to prognostic scoring systems that integrate mutation dosage with clinical factors, patients with 0 points had superior median overall survival of 97.0 months and 1-year, 3-year, and 5-year overall survival rates of 95.8%, 70.8%, and 66.4%, respectively. In contrast, patients with 3 points had worse median overall survival of only 16.0 months and 1-year, 3-year, and 5-year overall survival rates of 65.2%, 8.7%, and 8.7%, respectively. The incorporation of the KRAS G12 mutation dosage variable into prognostic scoring systems can improve clinical variable-based survival prediction, highlighting the feasibility of an integrated scoring system with clinical significance.
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Affiliation(s)
- Won-Gun Yun
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Daeun Kim
- Department of Molecular Science and Technology, Ajou University, Suwon, South Korea
- Ajou Energy Science Research Center, Ajou University, Suwon, South Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Seong-Geun Lee
- Department of Molecular Science and Technology, Ajou University, Suwon, South Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
| | - Daechan Park
- Department of Molecular Science and Technology, Ajou University, Suwon, South Korea.
- Advanced College of Bio-convergence Engineering, Ajou University, Suwon, South Korea.
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2
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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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3
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Fraunhoffer N, Teyssedou C, Pessaux P, Bigonnet M, Dusetti N, Iovanna J. Development of transcriptomic tools for predicting the response to individual drug of the mFOLFIRINOX regimen in patients with metastatic pancreatic cancer. Front Oncol 2024; 14:1437200. [PMID: 39323995 PMCID: PMC11422012 DOI: 10.3389/fonc.2024.1437200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 08/27/2024] [Indexed: 09/27/2024] Open
Abstract
Background The utilization of modified FOLFIRINOX (mFFX) therapy has shown notable advancements in patient outcomes in both localized and metastatic PDAC. Nevertheless, the effectiveness of mFFX treatment comes at the cost of elevated toxicity, leading to its restriction to patients with adequate performance status. Consequently, the administration of mFFX is contingent upon patient performance rather than rational criteria. The ideal scenario would involve the ability to assess the sensitivity of each drug within the mFFX regimen, minimizing unnecessary toxicity without compromising clinical benefits. Methods We developed transcriptomic signatures for each drug of the mFFX regimen (5FU, oxaliplatin and irinotecan) by integrating transcriptomic data from PDC, PDO and PDX with their corresponding chemo-response profiles to capture the biological components responsible for the response to each drug. We further validated the signatures in a cohort of 167 patients with advanced and metastatic PDAC. Results All three signatures captured high responder patients for OS and PFS in the mFFX arm exclusively. We then studied the response of patients to 0, 1, 2 and 3 drugs and we identified a positive correlation between the number of drugs predicted as sensitive and the OS and PFS, and the with objective response rate. Conclusions We developed three novel transcriptome-based signatures which define sensitivity for each mFFX components that can be used to rationalize the administration of the mFFX regimen in patients with metastatic pancreatic cancer and could help to avoid unnecessary toxic effects.
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Affiliation(s)
- Nicolas Fraunhoffer
- Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina, Buenos Aires, Argentina
| | - Carlos Teyssedou
- Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France
- Endocrine and Visceral Surgery Department, University Hospital Angers, Angers, France
| | - Patrick Pessaux
- Department of General, Digestive, and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg, France
| | - Martin Bigonnet
- PredictingMed, Luminy Science and Technology Park, Marseille, France
| | - Nelson Dusetti
- Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France
| | - Juan Iovanna
- Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France
- Hospital de Alta Complejidad El Cruce, Florencio Varela, Buenos Aires, Argentina
- University Arturo Jauretche, Florencio Varela, Buenos Aires, Argentina
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4
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Lucocq J, Hawkyard J, Robertson FP, Haugk B, Lye J, Parkinson D, White S, Mownah O, Zen Y, Menon K, Furukawa T, Inoue Y, Hirose Y, Sasahira N, Feretis M, Balakrishnan A, Zelga P, Ceresa C, Davidson B, Pande R, Dasari B, Tanno L, Karavias D, Helliwell J, Young A, Nunes Q, Urbonas T, Silva M, Gordon-Weeks A, Barrie J, Gomez D, van Laarhoven S, Doyle J, Bhogal R, Harrison E, Roalso M, Ciprani D, Aroori S, Ratnayake B, Koea J, Capurso G, Bellotti R, Stättner S, Alsaoudi T, Bhardwaj N, Jeffery F, Connor S, Cameron A, Jamieson N, Sheen A, Mittal A, Samra J, Gill A, Roberts K, Soreide K, Pandanaboyana S. Risk of Recurrence After Surgical Resection for Adenocarcinoma Arising From Intraductal Papillary Mucinous Neoplasia (IPMN) With Patterns of Distribution and Treatment: An International, Multicenter, Observational Study (ADENO-IPMN Study). Ann Surg 2024; 280:126-135. [PMID: 37873663 DOI: 10.1097/sla.0000000000006144] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2023]
Abstract
OBJECTIVE This international multicenter cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasm (IPMN). BACKGROUND Recurrence patterns and treatment of recurrence postresection of adenocarcinoma arising from IPMN are poorly explored. METHODS Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 and December 2020 at 18 pancreatic centers were identified. Survival analysis was performed using the Kaplan-Meier log-rank test and multivariable logistic regression by Cox-Proportional Hazards modeling. End points were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS Four hundred fifty-nine patients were included (median, 70 years; interquartile range, 64-76; male, 54%) with a median follow-up of 78.1 months. Recurrence occurred in 209 patients [45.5%; median time to recurrence, 12.8 months; early recurrence (within 1 years), 23.2%]. Eighty-three (18.1%) patients experienced a local regional recurrence, and 164 (35.7%) patients experienced a distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (hazard ratio 1.09; P =0.669) One hundred twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months ( P <0.001), with no significant difference between treatment modalities. There was no significant difference in survival between locations of recurrence ( P =0.401). CONCLUSIONS Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.
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Affiliation(s)
| | - Jake Hawkyard
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Francis P Robertson
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Beate Haugk
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Jonathan Lye
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Daniel Parkinson
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Steve White
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Omar Mownah
- Institute of Liver Studies, King's Healthcare Partners, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Yoh Zen
- Institute of Liver Studies, King's Healthcare Partners, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Krishna Menon
- Institute of Liver Studies, King's Healthcare Partners, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Takaaki Furukawa
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Inoue
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yuki Hirose
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoki Sasahira
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Michael Feretis
- Cambridge Hepatobiliary and Pancreatic Surgery Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Anita Balakrishnan
- Cambridge Hepatobiliary and Pancreatic Surgery Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Piotr Zelga
- Cambridge Hepatobiliary and Pancreatic Surgery Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Carlo Ceresa
- Hepatobiliary and Pancreatic Surgery Unit, The Royal Free Hospital, London, UK
| | - Brian Davidson
- Hepatobiliary and Pancreatic Surgery Unit, The Royal Free Hospital, London, UK
| | - Rupaly Pande
- Hepatobiliary and Pancreatic Surgery Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
| | - Bobby Dasari
- Hepatobiliary and Pancreatic Surgery Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
| | - Lulu Tanno
- Hepatobiliary and Pancreatic Surgery Unit, University Hospital Southampton, Southampton, UK
| | - Dimitrios Karavias
- Hepatobiliary and Pancreatic Surgery Unit, University Hospital Southampton, Southampton, UK
| | - Jack Helliwell
- Hepatobiliary and Pancreatic Surgery Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Alistair Young
- Hepatobiliary and Pancreatic Surgery Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Quentin Nunes
- Department of Hepatopancreatobiliary Surgery, East Lancashire Teaching Hospitals NHS Trust, UK
| | - Tomas Urbonas
- Oxford Hepato-Pancreato-Biliary (HPB) Surgical Unit, Oxford University Hospitals NHS Foundation Trust, UK
| | - Michael Silva
- Oxford Hepato-Pancreato-Biliary (HPB) Surgical Unit, Oxford University Hospitals NHS Foundation Trust, UK
| | - Alex Gordon-Weeks
- Oxford Hepato-Pancreato-Biliary (HPB) Surgical Unit, Oxford University Hospitals NHS Foundation Trust, UK
| | - Jenifer Barrie
- Nottingham Hepato-Pancreatico-Biliary (HPB) Service, Nottingham University Hospitals NHS Foundation Trust, UK
| | - Dhanny Gomez
- Nottingham Hepato-Pancreatico-Biliary (HPB) Service, Nottingham University Hospitals NHS Foundation Trust, UK
| | - Stijn van Laarhoven
- Department of General Surgery, University Hospitals Bristol & Weston NHS Foundation trust, UK
| | - Joseph Doyle
- Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - Ricky Bhogal
- Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - Ewen Harrison
- Department of Clinical Surgery, University of Edinburgh, UK
| | - Marcus Roalso
- Department of Gastrointestinal Surgery, HPB unit, Stavanger University Hospital, Norway
- Department of Quality and Health Technology, University of Stavanger, Stavanger, Norway
| | - Debora Ciprani
- Hepatopancreatobiliary Unit, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Somaiah Aroori
- Hepatopancreatobiliary Unit, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Bathiya Ratnayake
- Hepato-Pancreatico-Biliary/Upper Gastrointestinal Unit, North Shore Hospital, Auckland, NZ
| | - Jonathan Koea
- Hepato-Pancreatico-Biliary/Upper Gastrointestinal Unit, North Shore Hospital, Auckland, NZ
| | - Gabriele Capurso
- San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
- Digestive and Liver Disease Unit, S. Andrea Hospital, Rome, Italy
| | - Ruben Bellotti
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Austria
| | - Stefan Stättner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Austria
| | - Tareq Alsaoudi
- Leicester Hepatopancreatobiliary Unit, University Hospitals of Leicester NHS Trust, UK
| | - Neil Bhardwaj
- Leicester Hepatopancreatobiliary Unit, University Hospitals of Leicester NHS Trust, UK
| | - Fraser Jeffery
- Department of General and Vascular Surgery, Christchurch Hospital, New Zealand
| | - Saxon Connor
- Department of General and Vascular Surgery, Christchurch Hospital, New Zealand
| | - Andrew Cameron
- Wolfson Wohl Cancer Research Centre, University of Glasgow, UK
| | - Nigel Jamieson
- Wolfson Wohl Cancer Research Centre, University of Glasgow, UK
| | - Amy Sheen
- Department of Anatomical Pathology, New South Wales Health Pathology, Royal North Shore Hospital, Sydney, NSW, Australia
| | | | - Jas Samra
- Royal North Shore Hospital, Sydney, NSW, Australia
| | - Anthony Gill
- Department of Anatomical Pathology, New South Wales Health Pathology, Royal North Shore Hospital, Sydney, NSW, Australia
- Royal North Shore Hospital, Sydney, NSW, Australia
- Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - Keith Roberts
- Hepatobiliary and Pancreatic Surgery Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
| | - Kjetil Soreide
- Department of Gastrointestinal Surgery, HPB unit, Stavanger University Hospital, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Sanjay Pandanaboyana
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
- Population Health Sciences Institute, Newcastle University, Newcastle Upon Tyne, UK
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5
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Giulia O, Alessandro B, Angelo C, Paolo M, Rosa C, Marina M, Umberto P, Catia C, Giulia V, Massimo F, Michele R. Isolated lung metastases from pancreatic ductal adenocarcinoma (PDAC): Diagnostic and therapeutic challenges of a different disease. Semin Oncol 2024; 51:69-76. [PMID: 38879350 DOI: 10.1053/j.seminoncol.2024.04.001] [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: 09/28/2023] [Revised: 04/11/2024] [Accepted: 04/17/2024] [Indexed: 08/04/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, mostly due to the high rate of distant dissemination. However, growing evidence shows that isolated lung recurrence or metastases (ILM) from PDAC are not only less common, but also correlated with a better prognosis. Lung-only recurrence after surgery occurs later in time and is associated with more favorable prognostic characteristics of the primary tumor. Moreover, recent findings suggest that this specific site of metastases is characterized by an immunologically "hot" microenvironment and a more favorable molecular profile that could possibly justify its clinical behavior. Thus, ILM from PDAC emerge as a distinct entity, that might also benefit from a different therapeutic approach, possibly with the integration of surgery and de-intensified chemotherapy regimens, especially in selected patients. In this review we delve into the current scientific evidence on the clinical and biological characteristics of isolated LM from PDAC, also focusing on concerns with their diagnostic process and the therapeutic options for the management of this subset of patients.
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Affiliation(s)
- Orsi Giulia
- Department of Medical Oncology, Vita-Salute University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Bandiera Alessandro
- Department of Thoracic Surgery, Vita- Salute University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carretta Angelo
- Department of Thoracic Surgery, Vita- Salute University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Migliori Paolo
- Medical Sciences, Sant'Anna School of Advanced Studies, Pisa, Italy
| | - Chavez Rosa
- Department of Medical Oncology, Vita-Salute University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Macchini Marina
- Department of Medical Oncology, Vita-Salute University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Peretti Umberto
- Department of Medical Oncology, Vita-Salute University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carconi Catia
- Department of Medical Oncology, Vita-Salute University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Veronesi Giulia
- Department of Thoracic Surgery, Vita- Salute University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Falconi Massimo
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, Vita -Salute University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Reni Michele
- Department of Medical Oncology, Vita-Salute University, IRCCS San Raffaele Scientific Institute, Milan, Italy.
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6
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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: 21] [Impact Index Per Article: 21.0] [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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7
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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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8
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Akkaya H, Özdemir S, Dilek O, Topaloglu AC, Bayhan AZ, Taş ZA, Gökler C, Gülek B. Evaluation of the performance of and interobserver agreement on postoperative baseline CT findings in the identification of locoregional recurrence in patients with pancreatic ductal adenocarcinoma. Abdom Radiol (NY) 2023; 48:3135-3146. [PMID: 37517056 DOI: 10.1007/s00261-023-04012-x] [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: 05/26/2023] [Revised: 07/13/2023] [Accepted: 07/15/2023] [Indexed: 08/01/2023]
Abstract
PURPOSE To evaluate interobserver agreement on the findings of baseline contrast-enhanced multidetector computed tomography (CE-MDCT) performed at the postoperative third month in patients who underwent surgery due to ductal adenocarcinoma of the pancreatic head and investigate the value of these findings in predicting locoregional recurrence. MATERIAL AND METHODS The baseline CE-MDCT images of 198 patients who underwent the Whipple procedure due to pancreatic head tumors were evaluated independently by three radiologists at the postoperative third month. The radiologists were asked to note suspicious findings in terms of locoregional recurrence, including postoperative fat stranding, the presence of perivascular contrast-enhanced solid tissue, short diameter of solid tissue if present, the shape of solid tissue (convex/concave), presence of peritoneal implants, diameter (mm) of pancreatic duct dilatation if present, the presence of lymph nodes larger than 5 mm, portal vein stenosis (≥50 and <50%), the presence of ascites, and the presence of distant metastases, as specified by the Society of Abdominal Radiology in October 2022. The agreement between the radiologists and the value of these parameters in predicting locoregional recurrence were investigated. RESULTS Among the CE-MDCT findings evaluated, the radiologists had a moderate-to-high level of agreement concerning the presence of perivascular contrast-enhanced solid tissue. However, there was a poor interobserver agreement on the shape of solid tissue. A very high level of agreement was found among the radiologists in the evaluation of pancreatic duct dilatation, peritoneal implants, ascites, and the presence of distant metastases. According to the univariate analysis, the rates of portal vein stenosis had a 1.419 -fold effect [odds ratio (OR)=1.419, [95% confidence interval (CI)= 0.548-3.679, p=0.041], lymph node presence had a 2.337 -fold effect [odds ratio (OR)=2.337, [95% confidence interval (CI)= 1.165-4.686, p=0.015], perivascular contrast-enhanced solid tissue had 2.241 -fold effect [odds ratio (OR)=2.241, [95% confidence interval (CI)= 1.072-4.684, p=0.005]. In the multivariate analysis, perivascular contrast-enhanced solid tissue had 2.241 -fold effect [odds ratio (OR)=2.519, [95% confidence interval (CI)= 1.132-5.605, p=0.024]. CONCLUSION In the postoperative baseline CE-MDCT examination, the presence of solid tissue, lymph node presence, and portal vein stenosis in the surgical bed are among the findings that may indicate early locoregional recurrence in patients with pancreatic ductal adenocarcinoma.
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Affiliation(s)
- Hüseyin Akkaya
- Department of Radiology, Adana City Training and Research Hospital, University of Health Sciences, Kışla District, Dr. Mithat Özsan Boulevard, 4522. Street No. 1, 01230, Yüreğir, Adana, Turkey.
| | - Selim Özdemir
- Department of Radiology, Adana City Training and Research Hospital, University of Health Sciences, Kışla District, Dr. Mithat Özsan Boulevard, 4522. Street No. 1, 01230, Yüreğir, Adana, Turkey
| | - Okan Dilek
- Department of Radiology, Adana City Training and Research Hospital, University of Health Sciences, Kışla District, Dr. Mithat Özsan Boulevard, 4522. Street No. 1, 01230, Yüreğir, Adana, Turkey
| | - Ali Can Topaloglu
- Department of Radiology, Adana City Training and Research Hospital, University of Health Sciences, Kışla District, Dr. Mithat Özsan Boulevard, 4522. Street No. 1, 01230, Yüreğir, Adana, Turkey
| | - Ahmet Ziya Bayhan
- Department of Medical Oncology, Adana City Training and Research Hospital, University of Health Sciences, Kışla District, Dr. Mithat Özsan Boulevard, 4522. Street No. 1, 01230, Yüreğir, Adana, Turkey
| | - Zeynel Abidin Taş
- Department of Pathology, Adana City Training and Research Hospital, University of Health Sciences, Kışla District, Dr. Mithat Özsan Boulevard, 4522. Street No. 1, 01230, Yüreğir, Adana, Turkey
| | - Cihan Gökler
- Department of Surgical Oncology, Adana City Training and Research Hospital, University of Health Sciences, Kışla District, Dr. Mithat Özsan Boulevard, 4522. Street No. 1, 01230, Yüreğir, Adana, Turkey
| | - Bozkurt Gülek
- Department of Radiology, Adana City Training and Research Hospital, University of Health Sciences, Kışla District, Dr. Mithat Özsan Boulevard, 4522. Street No. 1, 01230, Yüreğir, Adana, Turkey
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9
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Herpels M, Ishihara J, Sadanandam A. The clinical terrain of immunotherapies in heterogeneous pancreatic cancer: unravelling challenges and opportunities. J Pathol 2023; 260:533-550. [PMID: 37550956 DOI: 10.1002/path.6171] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 06/20/2023] [Accepted: 06/22/2023] [Indexed: 08/09/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer and has abysmal survival rates. In the past two decades, immunotherapeutic agents with success in other cancer types have gradually been trialled against PDACs at different stages of cancer progression, either as a monotherapy or in combination with chemotherapy. Unfortunately, to this day, chemotherapy still prolongs the survival rates the most and is prescribed in clinics despite the severe side effects in other cancer types. The low success rates of immunotherapy against PDAC have been attributed most frequently to its complex and multi-faceted tumour microenvironment (TME) and low mutational burden. In this review, we give a comprehensive overview of the immunotherapies tested in PDAC clinical trials thus far, their limitations, and potential explanations for their failure. We also discuss the existing classification of heterogenous PDACs into cancer, cancer-associated fibroblast, and immune subtypes and their potential opportunity in patient selection as a form of personalisation of PDAC immunotherapy. © 2023 The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Melanie Herpels
- Division of Molecular Pathology, Institute of Cancer Research, London, UK
- Department of Bioengineering, Imperial College London, London, UK
| | - Jun Ishihara
- Department of Bioengineering, Imperial College London, London, UK
| | - Anguraj Sadanandam
- Division of Molecular Pathology, Institute of Cancer Research, London, UK
- Centre for Global Oncology, Division of Molecular Pathology, Institute of Cancer Research, London, UK
- Centre for Translational Immunotherapy, Division of Radiotherapy and Imaging, Institute of Cancer Research, London, UK
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10
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Halle-Smith JM, Powell-Brett S, Roberts K, Chatzizacharias NA. Resection of isolated liver oligometastatic disease in pancreatic ductal adenocarcinoma: Is there a survival benefit? A systematic review. World J Gastrointest Surg 2023; 15:1512-1521. [PMID: 37555114 PMCID: PMC10405113 DOI: 10.4240/wjgs.v15.i7.1512] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 02/22/2023] [Accepted: 05/05/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND Presence of liver metastatic disease in pancreatic ductal adenocarcinoma (PDAC), either synchronous or metachronous after pancreatic resection, is a terminal diagnosis that warrants management with palliative intent as per all international practice guidelines. However, there is an increasing interest on any potential value of surgical treatment of isolated oligometastatic disease in selected cases. AIM To present the published evidence on surgical management of PDAC liver metastases, synchronous and metachronous, and compare the outcomes of these treatments to the current standard of care. METHODS A systematic review was performed in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to compare the outcomes of both synchronous and metachronous liver metastases resection to standard care. RESULTS 356 studies were identified, 31 studies underwent full-text review and of these 10 were suitable for inclusion. When synchronous resection of liver metastases was compared to standard care, most studies did not demonstrate a survival benefit with the exception of one study that utilised neoadjuvant treatment. However, resection of metachronous disease appeared to confer a survival advantage when compared to treatment with chemotherapy alone. CONCLUSION A survival benefit may exist in resection of selected cases of metachronous liver oligometastatic PDAC disease, after disease biology has been tested with time and systemic treatment. Any survival benefit is less clear in synchronous cases; however an approach with neoadjuvant treatment and consideration of resection in some selected cases may confer some benefit. Future studies should focus on pathways for selection of cases that may benefit from an aggressive approach.
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Affiliation(s)
- James M Halle-Smith
- Department of HPB and Liver Transplant, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Sarah Powell-Brett
- Department of HPB and Liver Transplant, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Keith Roberts
- Department of HPB and Liver Transplant, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Nikolaos A Chatzizacharias
- Department of HPB and Liver Transplant, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2GW, United Kingdom
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11
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Kubo H, Ohgi K, Sugiura T, Ashida R, Yamada M, Otsuka S, Yamazaki K, Todaka A, Sasaki K, Uesaka K. The Association Between Neoadjuvant Therapy and Pathological Outcomes in Pancreatic Cancer Patients After Resection: Prognostic Significance of Microscopic Venous Invasion. Ann Surg Oncol 2022; 29:4992-5002. [PMID: 35368218 DOI: 10.1245/s10434-022-11628-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 03/04/2022] [Indexed: 12/17/2023]
Abstract
BACKGROUND The impact of neoadjuvant therapy (NAT) on pathological outcomes, including microscopic venous invasion (MVI), remains unclear in pancreatic cancer. METHODS A total of 456 patients who underwent pancreatectomy for resectable and borderline resectable pancreatic cancer between July 2012 and February 2020 were retrospectively reviewed. Patients were divided into two groups: patients with NAT (n = 120, 26%) and those without NAT (n = 336, 74%). Clinicopathological factors, survival outcomes and recurrence patterns were analyzed. RESULTS Regarding pathological findings, the proportion of MVI was significantly lower in patients with NAT than in those without NAT (43% vs 62%, P = 0.001). The 5-year survival rate in patients with NAT was significantly better than that in those without NAT (54% vs 45%, P = 0.030). A multivariate analysis showed that MVI was an independent prognostic factor for the overall survival (OS) (hazard ratio 2.86, P = 0.003) in patients who underwent NAT. MVI was an independent risk factor for liver recurrence (odds ratio [OR] 2.38, P = 0.016) and multiple-site recurrence (OR 1.92, P = 0.027) according to a multivariate analysis. The OS in patients with liver recurrence was significantly worse than that in patients with other recurrence patterns (vs lymph node, P = 0.047; vs local, P < 0.001; vs lung, P < 0.001). The absence of NAT was a significant risk factor for MVI (OR 1.93, P = 0.007). CONCLUSION MVI was a crucial prognostic factor associated with liver and multiple-site recurrence in pancreatic cancer patients with NAT. MVI may be reduced by NAT, which may contribute to the improvement of survival in pancreatic cancer patients.
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Affiliation(s)
- Hidemasa Kubo
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhisa Ohgi
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Mihoko Yamada
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Shimpei Otsuka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kentaro Yamazaki
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Akiko Todaka
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Keiko Sasaki
- Division of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
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12
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Murakami M, Fujimori N, Ohno A, Matsumoto K, Teramatsu K, Takamatsu Y, Takeno A, Oono T, Abe T, Ideno N, Ikenaga N, Nakata K, Nakamura M, Ishigami K, Ogawa Y. Predictive factors of operability after neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer: a single-center retrospective study. Discov Oncol 2022; 13:2. [PMID: 35201490 PMCID: PMC8777497 DOI: 10.1007/s12672-021-00462-1] [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: 11/08/2021] [Accepted: 12/22/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND/AIMS Recently neoadjuvant chemotherapy (NAC) for pancreatic cancer has been shown to be superior to upfront surgery, but it remains a matter of debate for resectable cases. In clinical practice, some resectable cases may become unresectable after NAC. This study aimed to reveal the outcomes after NAC and to clarify the characteristics of unresected cases. METHODS The medical records of 142 patients who underwent NAC between 2016 and 2020 were retrospectively reviewed. Patient characteristics, effectiveness of NAC, and outcomes were compared between the surgical group and non-surgical group (NSG). Furthermore, the risk of recurrence limited to in the patients who received NAC with gemcitabine plus nab-paclitaxel, which were mostly administered in this cohort, following R0/R1 resection was assessed. RESULTS The overall and R0 resection rates after NAC were 89.1% and 79.7%, respectively. The neutrophil to lymphocyte ratio (NLR) > 2.78 (p = 0.0120) and anatomical borderline resectable pancreatic cancer (p = 0.0044) revealed a statistically significantly correlation with the NSG. On the other hand, NAC week < 8 (p = 0.0285), radiological response, stable disease or progression disease (p = 0.0212), and pathological stage > IIA (P = 0.0003) were significantly associated with recurrence. The tumor response rate was approximately 26.1%, and three patients with ≥ 30% reduction of primary tumor lost excision opportunities because of metastasis, interstitial pneumonia, and vascular invasion. CONCLUSIONS This study shows incomplete tumor shrinkage benefits, but pre-NAC NLR is a predictive factor for predicting operability after NAC. The NLR can be easily calculated by normal blood test, and can be considered as a suitable marker of operability.
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Affiliation(s)
- Masatoshi Murakami
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Nao Fujimori
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Akihisa Ohno
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kazuhide Matsumoto
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Katsuhito Teramatsu
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yu Takamatsu
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Ayumu Takeno
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Takamasa Oono
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Toshiya Abe
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noboru Ideno
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Naoki Ikenaga
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kohei Nakata
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kousei Ishigami
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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13
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Bouchart C, Engelholm JL, Closset J, Navez J, Loi P, Gökburun Y, De Grez T, Mans L, Hendlisz A, Bali MA, Eisendrath P, Van Gestel D, Hein M, Moretti L, Van Laethem JL. Isotoxic high-dose stereotactic body radiotherapy integrated in a total multimodal neoadjuvant strategy for the treatment of localized pancreatic ductal adenocarcinoma. Ther Adv Med Oncol 2021; 13:17588359211045860. [PMID: 34691244 PMCID: PMC8529314 DOI: 10.1177/17588359211045860] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 08/25/2021] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Our aim was to evaluate the feasibility and safety of isotoxic high-dose (iHD) stereotactic body radiation therapy (SBRT) in a total neoadjuvant sequence for the treatment of localized pancreatic adenocarcinoma. MATERIALS AND METHODS Biopsy-proven borderline resectable/locally advanced pancreatic cancer (BR/LAPC) patients were included in this observational prospective analysis from August 2017 to April 2020 without excluding tumours showing a radiological direct gastrointestinal (GI) invasion. An induction chemotherapy by modified fluorouracil, irinotecan and oxaliplatin was performed for a median of six cycles. In case of non-progression, an isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) was delivered in 5 fractions followed by a surgical exploration. The primary endpoint was acute/late gastrointestinal grade ⩾3 toxicity. Secondary endpoints were overall survival (OS), progression-free survival (PFS) and local control (LC). RESULTS A total of 39 consecutive patients (21 BR and 18 LAPC) were included: 34 patients (87.2%, 18 BR and 16 LAPC) completed the planned neoadjuvant sequence. After iHD-SBRT, 19 patients [55.9% overall, 13/18 BR (72.2%) and 6/16 LAPC (37.5%)] underwent an oncological resection among the 25 patients surgically explored (73.5%). The median follow up was 18.2 months. The rates of acute and late GI grade 3 toxicity were, respectively, 2.9% and 4.2%. The median OS and PFS from diagnosis were, respectively, 24.5 and 15.6 months. The resected patients had improved median OS and PFS in comparison with the non-resected patients (OS: 32.3 versus 18.2 months, p = 0.02; PFS: 24.1 versus 7.1 months, p < 0.001). There was no survival difference between the BR and LAPC patients. The 1-year LC from SBRT was 74.1% and the median locoregional PFS was not reached for both BR and LAPC patients. CONCLUSIONS iHD-SBRT displays an excellent toxicity profile, also for potentially high-risk patients with radiological direct GI invasion at diagnosis and can be easily integrated in a total neoadjuvant strategy. The oncological outcomes are promising and emphasise the need for further exploration of iHD-SBRT in phase II/III trials.
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Affiliation(s)
- Christelle Bouchart
- Department of Radiation-Oncology, Institut
Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo, 121,
Brussels 1000, Belgium
| | - Jean-Luc Engelholm
- Department of Radiology, Institut Jules Bordet,
Université Libre de Bruxelles, Brussels, Belgium
| | - Jean Closset
- Department of Hepato-Biliary-Pancreatic
Surgery, Hopital Erasme, Université Libre de Bruxelles, Brussels,
Belgium
| | - Julie Navez
- Department of Hepato-Biliary-Pancreatic
Surgery, Hopital Erasme, Université Libre de Bruxelles, Brussels,
Belgium
| | - Patrizia Loi
- Department of Hepato-Biliary-Pancreatic
Surgery, Hopital Erasme, Université Libre de Bruxelles, Brussels,
Belgium
| | - Yeter Gökburun
- Department of Gastroenterology, CHR Namur,
Namur, Belgium
| | | | - Laura Mans
- Department of Gastroenterology, Hepatology and
Digestive Oncology, Hopital Erasme, Université Libre de Bruxelles, Brussels,
Belgium
| | - Alain Hendlisz
- Department of Medical Oncology, Institut Jules
Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Maria Antonietta Bali
- Department of Radiology, Institut Jules
Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Pierre Eisendrath
- Department of Gastroenterology, CHU St Pierre,
Université Libre de Bruxelles, Brussels, Belgium
| | - Dirk Van Gestel
- Department of Radiation-Oncology, Institut
Jules Bordet,Université Libre de Bruxelles, Brussels, Belgium
| | - Matthieu Hein
- Sleep Laboratory, Hopital Erasme, Université
Libre de Bruxelles, Brussels, Belgium
| | - Luigi Moretti
- Department of Radiation-Oncology, Institut
Jules Bordet,Université Libre de Bruxelles, Brussels, Belgium
| | - Jean-Luc Van Laethem
- Department of Gastroenterology, Hepatology and
Digestive Oncology, Hopital Erasme, Université Libre de Bruxelles, Brussels,
Belgium
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14
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Windsor JA, Callery MP. Is Margin Status Less Prognostic After Neoadjuvant Chemoradiotherapy for Pancreatic Adenocarcinoma? Ann Surg Oncol 2021; 29:20-22. [PMID: 34654987 DOI: 10.1245/s10434-021-10885-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 09/27/2021] [Indexed: 11/18/2022]
Affiliation(s)
- John A Windsor
- Surgical and Translational Research Centre, The University of Auckland, Building 507-2004, 22-30 Park Avenue, Grafton, 1142, Auckland, New Zealand.
| | - Mark P Callery
- Harvard Medical School, 185 Pilgrim Road, Palmer 6, Boston, MA, 02215, USA
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15
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Ratnayake B, Al-Leswas D, Mohammadi-Zaniani G, Littler P, Sen G, Manas D, Pandanaboyana S. Margin Accentuation Irreversible Electroporation in Stage III Pancreatic Cancer: A Systematic Review. Cancers (Basel) 2021; 13:cancers13133212. [PMID: 34199031 PMCID: PMC8268790 DOI: 10.3390/cancers13133212] [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: 05/14/2021] [Revised: 06/14/2021] [Accepted: 06/24/2021] [Indexed: 11/17/2022] Open
Abstract
Simple Summary This literature review shows preliminary evidence to suggest that electroporation, the use of electricity to cause the death of cells around the tumour, may be associated with an improved survival and complete resection rates following pancreatic surgery for higher stage pancreatic cancer. However, one in five patients have a complication from the procedure that alters their normal course in hospital. Moreover, the number of patients who underwent this technique is small and further data is needed to support the preliminary evidence. The results therefore should be interpreted with caution. Abstract The present systematic review aimed to summarise the available evidence on indications and oncological outcomes after MA IRE for stage III pancreatic cancer (PC). A literature search was performed in the Pubmed, MEDLINE, EMBASE, SCOPUS databases using the PRISMA framework to identify all MA IRE studies. Nine studies with 235 locally advanced (LA) (82%, 192/235) or Borderline resectable (BR) PC (18%, 43/235) patients undergoing MA IRE pancreatic resection were included. Patients were mostly male (56%) with a weighted-mean age of 61 years (95% CI: 58–64). Pancreatoduodenectomy was performed in 51% (120/235) and distal pancreatectomy in 49% (115/235). R0 resection rate was 73% (77/105). Clavien Dindo grade 3–5 postoperative complications occurred in 19% (36/187). Follow-up intervals ranged from 3 to 29 months. Local and systematic recurrences were noted in 8 and 43 patients, respectively. The weighted-mean progression free survival was 11 months (95% CI: 7–15). The weighted-mean overall survival was 22 months (95% CI 20–23 months) and 8 months (95% CI 1–32 months) for MA IRE and IRE alone, respectively. Early non-randomised data suggest MA IRE during pancreatic surgery for stage III pancreatic cancer may result in increased R0 resection rates and improved OS with acceptable postoperative morbidity. Further, larger studies are warranted to corroborate this evidence.
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Affiliation(s)
- Bathiya Ratnayake
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand;
| | - Dhya Al-Leswas
- Hepato-Pancreato-Biliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK; (D.A.-L.); (G.M.-Z.); (G.S.); (D.M.)
| | - Ghazaleh Mohammadi-Zaniani
- Hepato-Pancreato-Biliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK; (D.A.-L.); (G.M.-Z.); (G.S.); (D.M.)
| | - Peter Littler
- Department of Interventional Radiology, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK;
| | - Gourab Sen
- Hepato-Pancreato-Biliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK; (D.A.-L.); (G.M.-Z.); (G.S.); (D.M.)
| | - Derek Manas
- Hepato-Pancreato-Biliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK; (D.A.-L.); (G.M.-Z.); (G.S.); (D.M.)
| | - Sanjay Pandanaboyana
- Hepato-Pancreato-Biliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK; (D.A.-L.); (G.M.-Z.); (G.S.); (D.M.)
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE2 4AX, UK
- Correspondence:
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Narayanan S, AlMasri S, Zenati M, Nassour I, Chopra A, Rieser C, Smith K, Oyefusi V, Daum T, Bahary N, Bartlett D, Lee K, Zureikat A, Paniccia A. Predictors of early recurrence following neoadjuvant chemotherapy and surgical resection for localized pancreatic adenocarcinoma. J Surg Oncol 2021; 124:308-316. [PMID: 33893740 DOI: 10.1002/jso.26510] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 03/22/2021] [Accepted: 04/12/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES Neoadjuvant chemotherapy (NAT) for pancreatic adenocarcinoma (PDAC) is increasingly being utilized. However, a significant number of patients will experience early recurrence, possibly negating the benefit of surgery. We aimed to identify factors implicated in early disease recurrence. METHODS A retrospective review of pancreaticoduodenectomies performed between 2005 and 2017 at our institution for PDAC following NAT was performed. A 6-month cut-off was used to stratify patients into early/late recurrence groups. Multivariate analysis was performed to identify predictors of recurrence. RESULTS Of 273 patients, 64 (23%) developed early recurrence or died within 90 days of surgery. The median time to recurrence was 4 months (95% confidence interval [CI]: 2.2-4.3) in the early group versus 16 months (95% CI: 13.7-19.9) in the late group. The former had higher baseline and post-NAT Ca19-9 levels than the latter (472 vs. 153 IU/ml, p = 0.001 and 71 vs. 39 IU/ml, p = 0.005, respectively). A higher positive lymph node ratio significantly increased the risk of early recurrence (hazard ratio [HR]: 15.9, p < 0.001) while adjuvant chemotherapy was protective (HR: 0.4, p < 0.001). CONCLUSION Our findings acknowledge the limitations of clinically measured factors used to ascertain response to NAT and underline the need for individualized molecular markers that take into consideration the specific tumor biology.
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Affiliation(s)
- Sowmya Narayanan
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Samer AlMasri
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Mazen Zenati
- Department of Surgery and Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Ibrahim Nassour
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Asmita Chopra
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Caroline Rieser
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Katelyn Smith
- Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Vivianne Oyefusi
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Tracy Daum
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Nathan Bahary
- Department of Internal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - David Bartlett
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Kenneth Lee
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Amer Zureikat
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Alessandro Paniccia
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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