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Chan AHY, Zhao Y, Tan HL, Chua DW, Ng KYY, Lee SY, Lee JJX, Tai D, Goh BKP, Koh YX. Clinical Outcomes of Neoadjuvant Therapy Versus Upfront Surgery in Resectable Pancreatic Cancer: Systematic Review and Meta-analysis of Latest Randomized Controlled Trials. Ann Surg Oncol 2025; 32:4094-4107. [PMID: 39987384 DOI: 10.1245/s10434-024-16674-y] [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: 07/23/2024] [Accepted: 11/23/2024] [Indexed: 02/24/2025]
Abstract
BACKGROUND Survival and surgical benefits of neoadjuvant treatments (NAT) in resectable pancreatic cancer (RPC) remains unclear. The role of NAT in providing additional benefits to reduce biological aggressiveness and recurrence is worth elucidating. We assessed the latest randomized controlled trials (RCTs). METHODS A systematic review and meta-analysis was performed including trials published from inception to February 2024 to evaluate survival, surgical, and short-term oncological benefits with RCTs for RPC, comparing NAT with upfront surgery. RESULTS Eight RCTs with 982 patients were analyzed. RPC treated with NAT conferred better median disease-free survival (DFS) compared to upfront surgery (HR = 0.66, p = 0.01) with a significantly improved R0 resection (RR = 1.20, p = 0.04) and pN0 rate (RR = 1.68, p < 0.001). These benefits did not translate into overall survival benefits (HR = 0.81, p = 0.06). Postoperative major morbidity and mortality did not differ significantly between treatment approaches. No significant difference was noted in resection rate (RR = 0.95, p = 0.21). However, a significantly lower surgical exploration rate was exhibited in the NAT group (RR = 0.84, p = 0.007). CONCLUSION NAT conferred better DFS with significantly improved R0 resection rate and pN0 rate compared with upfront surgery. Our findings highlight the potential benefits of NAT in enhancing survival, surgical, and short-term oncological outcomes without increasing postoperative risks.
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Affiliation(s)
- Anna Ho Yin Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
- Duke-National University of Singapore Graduate Medical School, Singapore, Singapore
| | - Yun Zhao
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
| | - Hwee Leong Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
| | - Darren Weiquan Chua
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
| | - Kennedy Yao Yi Ng
- Duke-National University of Singapore Graduate Medical School, Singapore, Singapore
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Suat Ying Lee
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Joycelyn Jie Xin Lee
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - David Tai
- Duke-National University of Singapore Graduate Medical School, Singapore, Singapore
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Brian Kim Poh Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
- Duke-National University of Singapore Graduate Medical School, Singapore, Singapore
- Division of Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore.
- Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
- Division of Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
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Tomita D, Matsumura M, Fujisawa K, Okubo S, Shindoh J, Tamura T, Imamura T, Miura Y, Takazawa Y, Hashimoto M. Pancreatic groove cancer with large cystic lesion. Clin J Gastroenterol 2025; 18:242-247. [PMID: 39612050 DOI: 10.1007/s12328-024-02071-1] [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: 07/01/2024] [Accepted: 11/17/2024] [Indexed: 11/30/2024]
Abstract
Groove pancreatic cancer is a malignant tumor that originates from the groove between the pancreas, duodenum, and bile duct. Groove pancreatic cancer shares similarities with groove pancreatitis in terms of clinical symptoms and imaging findings, which often makes it difficult to distinguish between the two diseases. We describe the case of a patient with a cystic lesion associated with groove pancreatic cancer. A 54-year-old male patient presented with sudden vomiting, hematemesis, and persistent epigastric pain. Enhanced computed tomography revealed a hypoenhanced, ill-defined lesion extending from the pancreatic head to the duodenum, with a large duodenal cystic formation. Despite various diagnostic efforts, a definitive diagnosis of malignancy before surgery remained elusive. Intraoperative findings revealed that the tumor was resectable. Subtotal stomach-preserving pancreaticoduodenectomy with portal vein resection and right hemicolectomy were performed. The resected specimen revealed groove pancreatic adenocarcinoma invading the duodenum and ascending colon. A large cyst was observed within the duodenal wall, the interior of which was lined with cancer cells. Despite postoperative chemotherapy, the patient succumbed to the disease 17 months after resection. This case emphasizes that when a groove area lesion with a huge paraduodenal cyst is observed, the possibility of groove pancreatic cancer should be considered.
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Affiliation(s)
- Daisuke Tomita
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Masaru Matsumura
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan.
| | - Kentoku Fujisawa
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Satoshi Okubo
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Junichi Shindoh
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Tetsuo Tamura
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Tsunao Imamura
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Yasuro Miura
- Department of Pathology, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Yutaka Takazawa
- Department of Pathology, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Masaji Hashimoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
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Ishizaki J, Okuwaki K, Watanabe M, Imaizumi H, Iwai T, Hasegawa R, Kurosu T, Tadehara M, Matsumoto T, Adachi K, Hanaoka T, Kida M, Kusano C. Effectiveness of endoscopic ultrasound-guided tissue acquisition with stereomicroscopic on-site evaluation for preoperative diagnosis of resectable or borderline resectable pancreatic cancer: a prospective study. Clin Endosc 2024; 57:807-813. [PMID: 38919058 PMCID: PMC11637653 DOI: 10.5946/ce.2023.277] [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: 10/25/2023] [Revised: 01/11/2024] [Accepted: 01/15/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND/AIMS To validate endoscopic ultrasound-guided tissue acquisition (EUS-TA) used in conjunction with stereomicroscopic on-site evaluation (SOSE) as a preoperative diagnostic tool for resectable pancreatic cancer (R-PC) and borderline resectable PC (BR-PC). METHODS Seventy-eight consecutive patients who underwent EUS-TA for suspected R-PC or BR-PC were enrolled. The primary endpoint was the sensitivity of EUS-TA together with SOSE based on the stereomicroscopically visible white core (SVWC) cutoff value. One or two sites were punctured by using a 22-gauge biopsy needle for EUS-TA, based on the SOSE findings. RESULTS We collected 99 specimens from 56 and 22 patients with R-PC and BR-PC, respectively. Based on the SOSE results, we performed 57 procedures with one puncture. The SVWC cutoff values were met in 73.7% and 73.1% of all specimens and in those obtained during the first puncture, respectively. The final diagnoses were malignant and benign tumors in 76 and two patients, respectively. The overall sensitivity, specificity, and accuracy of EUS-TA for the 78 lesions were 90.8%, 100%, and 91.0%, respectively. The sensitivity for malignant diagnosis based on the SVWC cutoff value were 89.5% and 90.4% for the first puncture and all specimens, respectively. CONCLUSIONS The sensitivity of EUS-TA in conjunction with SOSE for malignancy diagnosis in patients with suspected R-PC or BR-PC was 90.4%.
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Affiliation(s)
- Junro Ishizaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Kosuke Okuwaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Masafumi Watanabe
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Hiroshi Imaizumi
- Department of Gastroenterology, Japan Community Health Care Organization Sagamino Hospital, Sagamihara, Japan
| | - Tomohisa Iwai
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Rikiya Hasegawa
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Takahiro Kurosu
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Masayoshi Tadehara
- Department of Gastroenterology, Japan Community Health Care Organization Sagamino Hospital, Sagamihara, Japan
| | - Takaaki Matsumoto
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Kai Adachi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Taro Hanaoka
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Mitsuhiro Kida
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Chika Kusano
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
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Johnson R, McClelland PH, Ahmad SA. Neoadjuvant and Adjuvant Therapy in Resectable Pancreatic Adenocarcinoma. Surg Clin North Am 2024; 104:987-1005. [PMID: 39237173 DOI: 10.1016/j.suc.2024.04.002] [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: 09/07/2024]
Abstract
While pancreatic adenocarcinoma requires surgical resection definitive cure, treatment paradigms are shifting toward a neoadjuvant approach to systemic therapy. Rationale is twofold: micro-metastatic disease is likely present in a majority of patients, reinforcing the importance of systemic therapy regardless of resectability; moreover, systemic therapy is well-tolerated and improves surgical outcomes when delivered preoperatively. Second, a neoadjuvant approach allows for selection of biology and patients most likely to benefit from potentially morbid surgery. This review examines the increasing body of evidence in support of empiric neoadjuvant therapy in pancreatic adenocarcinoma.
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Affiliation(s)
- Ryan Johnson
- General Surgery, Division of Surgical Oncology, University of Cincinnati Cancer Institute, University of Cincinnati Medical Center, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267, USA
| | - Paul H McClelland
- General Surgery, Division of Surgical Oncology, University of Cincinnati Cancer Institute, University of Cincinnati Medical Center, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267, USA
| | - Syed A Ahmad
- Division of Surgical Oncology, University of Cincinnati Cancer Institute, University of Cincinnati Medical Center, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267, USA.
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5
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Vicente E, Quijano Y, Caruso R, Ferri V. Fully laparoscopic distal splenic pancreatectomy with prophylactic hyperthermic intraperitoneal chemotherapy (with video). BMJ Case Rep 2024; 17:e257974. [PMID: 39214583 DOI: 10.1136/bcr-2023-257974] [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: 09/04/2024] Open
Abstract
Peritoneal involvement represents one of the major difficulties that arise during the treatment of pancreatic adenocarcinoma. In fact, currently, there is a growing interest in the administration of intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) as an adjunct to surgical pancreatic resection, both with prophylactic or therapeutic intent. With this video, we report a case of pancreatic body adenocarcinoma treated with fully laparoscopic distal splenic pancreatectomy with intraoperative HIPEC with gemcitabine, administered initially with a prophylactic intent, based on a preliminary negative peritoneal washing cytology result. In our case, the association of HIPEC and surgical resection did not affect the postoperative recovery, and after 15 months of follow-up, the patient remains alive and has no signs of disease recurrence.
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Affiliation(s)
- Emilio Vicente
- General Surgery, HM Sanchinarro University Hospital, Health Sciences Faculty HM Hospitals, Camilo Jose Cela University, Madrid, Spain
| | - Yolanda Quijano
- General Surgery, HM Sanchinarro University Hospital, Health Sciences Faculty HM Hospitals, Camilo Jose Cela University, Madrid, Spain
| | - Riccardo Caruso
- General Surgery, HM Sanchinarro University Hospital, Health Sciences Faculty HM Hospitals, Camilo Jose Cela University, Madrid, Spain
| | - Valentina Ferri
- General Surgery, HM Sanchinarro University Hospital, Health Sciences Faculty HM Hospitals, Camilo Jose Cela University, Madrid, Spain
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Yamada Y, Yamamoto T, Tsutsumi C, Matsumoto T, Noguchi S, Shimada Y, Nakata K, Ohuchida K, Nakamura M, Oda Y. Immature stroma and high infiltration of CD15 + cells are predictive markers of poor prognosis in different subsets of patients with pancreatic cancer. Cancer Sci 2024; 115:1001-1013. [PMID: 38230840 PMCID: PMC10920995 DOI: 10.1111/cas.16060] [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: 09/06/2023] [Revised: 12/10/2023] [Accepted: 12/12/2023] [Indexed: 01/18/2024] Open
Abstract
Preoperative treatment is commonly carried out for borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, the relationship between the combination of immune cells in the tumor microenvironment and their intratumoral heterogeneity along with their association with histological findings remains unclear, especially in patients receiving preoperative chemotherapy. We aimed to explore the therapeutic strategies for patients with PDAC with poor prognosis after receiving chemotherapy based on histological and immunological microenvironmental classifications. We investigated the correlation between the prognosis and histological immune microenvironmental factors of patients who initially underwent surgery (n = 100) and were receiving gemcitabine plus nab-paclitaxel (GEM + nabPTX) as preoperative chemotherapy (n = 103). Immune profiles were generated based on immune cell infiltration into the tumor, and their correlation with patient outcomes and histological features was analyzed. Tumor-infiltrating neutrophils (TINs) were identified as independent poor prognostic factors using multivariate analysis in both surgery-first and preoperative chemotherapy groups. The patients were further classified into four groups based on immune cell infiltration into the tumor. Patients with high CD15 infiltration into the tumor and immature stroma at the cancer margins showed the worst prognosis in the preoperative chemotherapy group. The analysis of mRNA expression and immunohistochemical features revealed that CXCR2, the receptor for CXCL8, was correlated with disease-free and overall survival. We inferred that patients with immature stroma at the margins and high infiltration of CD15+ neutrophils within the tumor showed the worst prognosis and they could particularly benefit from treatment with inhibitors targeting CXCR2 or CXCL8.
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Affiliation(s)
- Yutaka Yamada
- Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
- Department of Surgery and Oncology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Takeo Yamamoto
- Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
- Department of Surgery and Oncology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Chikanori Tsutsumi
- Department of Surgery and Oncology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Takashi Matsumoto
- Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
- Department of Surgery and Oncology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Shoko Noguchi
- Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
- Department of Surgery and Oncology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Yuki Shimada
- Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
- Department of Surgery and Oncology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Kohei Nakata
- Department of Surgery and Oncology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Kenoki Ohuchida
- Department of Surgery and Oncology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
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7
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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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Yang SQ, Zou RQ, Dai YS, Li FY, Hu HJ. Comparison of the upfront surgery and neoadjuvant therapy in resectable and borderline resectable pancreatic cancer: an updated systematic review and meta-analysis. Updates Surg 2024; 76:1-15. [PMID: 37639177 DOI: 10.1007/s13304-023-01626-0] [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: 05/17/2023] [Accepted: 08/02/2023] [Indexed: 08/29/2023]
Abstract
Pancreatic cancer is a malignant disease with a dismal prognosis. While neoadjuvant therapy has shown promise in the treatment of pancreatic cancer, its role remains a subject of controversy among physicians. We aimed to evaluate the benefits of neoadjuvant therapy in patients with resectable and borderline resectable pancreatic cancer. Eligible studies were identified from MEDLINE, Embase, Cochrane Library, and Web of Science. Studies comparing neoadjuvant therapy with upfront surgery (with or without adjuvant therapy) in resectable and borderline resectable pancreatic cancer were included. The primary endpoint assessed was overall survival. A total of 10,022 studies were identified, and the meta-analysis finally enrolled 50 revealed studies. The meta-analysis suggested that neoadjuvant therapy significantly improved the overall survival (HR 0.74, p < 0.001) and recurrence-free survival (HR 0.75, p = 0.006) compared to the upfront surgery approach. Furthermore, neoadjuvant therapy leads to favorable postoperative outcomes, with an enhanced R0 resection rate (OR 1.90, p < 0.001) and reduced lymph node metastasis (OR 0.36, p < 0.001) and perineural invasion (OR 0.42, p < 0.001), although it is associated with a reduced resection rate (OR 0.42, p < 0.001). In addition, patients treated with neoadjuvant therapy experience superior survival benefits compared to those undergoing adjuvant therapy (HR 0.87, p = 0.019). These results are further corroborated by the subgroup analysis of randomized controlled trials. Neoadjuvant therapy has the potential to provide survival benefits and improve postoperative long-term outcomes for patients with resectable and borderline resectable pancreatic cancer. However, to validate and reinforce these findings, further well-designed and large trials are required.
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Affiliation(s)
- Si-Qi Yang
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Rui-Qi Zou
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yu-Shi Dai
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Fu-Yu Li
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
| | - Hai-Jie Hu
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
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9
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Yang B, Chen K, Liu W, Long D, Wang Y, Liu X, Ma Y, Tian X, Yang Y. The benefits of neoadjuvant therapy for patients with resectable pancreatic cancer: an updated systematic review and meta-analysis. Clin Exp Med 2023; 23:3159-3169. [PMID: 37310659 DOI: 10.1007/s10238-023-01112-2] [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: 02/07/2023] [Accepted: 05/29/2023] [Indexed: 06/14/2023]
Abstract
Neoadjuvant therapy (NAT) was effective in improving overall survival (OS) of borderline resectable pancreatic cancer. However, its application in resectable pancreatic cancer remains controversial. This study aimed to determine whether NAT has a greater advantage over conventional upfront surgery (US) in terms of resection rate, R0 resection rate, positive lymph node rate, and OS. We identified articles before October 7, 2022, by searching four electronic databases. The studies included in the meta-analysis all met the inclusion and exclusion criteria. The Newcastle-Ottawa scale was used to evaluate the quality of the articles. OS, DFS, resection rate, R0 resection rate and positive lymph nodes rate were extracted. Odds ratio (OR), hazard ratio (HR) and 95% confidence intervals (CI) were calculated, and sensitivity analysis and publication bias were used to assess the sources of heterogeneity. In total, 24 studies, involving 1384 (35.66%) patients assigned to NAT and 2497 (64.43%) patients assigned to US, were included in the analysis. NAT could effectively prolong OS (HR 0.73, 95% CI 0.65-0.82, P < 0.001) and DFS (HR 0.72, 95% CI 0.62-0.84, P < 0.001). Subgroup analysis results of 6 randomized controlled trials (RCTs) also showed that RPC patients could benefit from NAT in the long term (HR 0.72, 95% CI 0.58-0.90, P = 0.003). NAT decreased resection rate (OR 0.43, 95% CI 0.33-0.55, P < 0.001), but was associated with increased R0 resection rate (OR 2.05, 95% CI 1.47-2.88, P < 0.001) and decreased positive lymph node rate (OR 0.38, 95% CI 0.27-0.52, P < 0.001). Although the application of NAT increases the risk of patients not being able to undergo surgical resection, it can prolong the OS and delay tumor progression in RPC. Therefore, we still expect larger and higher-quality RCTs to confirm the effectiveness of NAT.
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Affiliation(s)
- Bohan Yang
- Department of General Surgery, Peking University First Hospital, Beijing, 100034, China
| | - Kai Chen
- Department of General Surgery, Peking University First Hospital, Beijing, 100034, China
| | - Weikang Liu
- Department of General Surgery, Peking University First Hospital, Beijing, 100034, China
| | - Di Long
- Department of General Surgery, Peking University First Hospital, Beijing, 100034, China
| | - Yingjin Wang
- Department of General Surgery, Peking University First Hospital, Beijing, 100034, China
| | - Xinxin Liu
- Department of General Surgery, Peking University First Hospital, Beijing, 100034, China
| | - Yongsu Ma
- Department of General Surgery, Peking University First Hospital, Beijing, 100034, China
| | - Xiaodong Tian
- Department of General Surgery, Peking University First Hospital, Beijing, 100034, China.
| | - Yinmo Yang
- Department of General Surgery, Peking University First Hospital, Beijing, 100034, China.
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Ei S, Takahashi S, Ogasawara T, Mashiko T, Masuoka Y, Nakagohri T. Neoadjuvant and Adjuvant Treatments for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: The Current Status of Pancreatic Ductal Adenocarcinoma Treatment in Japan. Gut Liver 2023; 17:698-710. [PMID: 36843421 PMCID: PMC10502496 DOI: 10.5009/gnl220311] [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: 07/18/2022] [Revised: 10/30/2022] [Accepted: 10/30/2022] [Indexed: 02/28/2023] Open
Abstract
Resection is the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). Although the outcome of technically resectable PDAC has improved with advances in surgery and adjuvant therapy, the 5-year survival rate remains low at 20% to 40%. More effective therapy is needed. Almost 15 years ago, the National Comprehensive Cancer Network guidelines proposed a resectability classification of PDAC based on preoperative imaging. Since then, treatment strategies for PDAC have been devised based on resectability. The standard of care for resectable PDAC is adjuvant chemotherapy after R0 resection, as shown by the results of pivotal clinical trials. With regard to neoadjuvant treatment, several recent clinical trials comparing neoadjuvant treatment with upfront resection have been conducted on resectable PDAC and borderline resectable PDAC, and the benefits and efficacy of neoadjuvant treatment for pancreatic cancer has become clearer. The significance of neoadjuvant treatment for resectable PDAC remains controversial, but in borderline resectable PDAC the efficacy of neoadjuvant treatment has been further recognised, although the standard of care has not yet been established. Several promising clinical trials for PDAC are ongoing. This review presents previous and ongoing trials of perioperative treatment for resectable and borderline resectable PDAC, focusing on the difference between Asian and Western countries.
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Affiliation(s)
- Shigenori Ei
- Department of Gastroenterological Surgery, Tokai University School of Medicine, Isehara, Japan
| | - Shinichiro Takahashi
- Department of Gastroenterological Surgery, Tokai University School of Medicine, Isehara, Japan
| | - Toshihito Ogasawara
- Department of Gastroenterological Surgery, Tokai University School of Medicine, Isehara, Japan
| | - Taro Mashiko
- Department of Gastroenterological Surgery, Tokai University School of Medicine, Isehara, Japan
| | - Yoshihito Masuoka
- Department of Gastroenterological Surgery, Tokai University School of Medicine, Isehara, Japan
| | - Toshio Nakagohri
- Department of Gastroenterological Surgery, Tokai University School of Medicine, Isehara, Japan
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11
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Kwaśniewska D, Fudalej M, Nurzyński P, Badowska-Kozakiewicz A, Czerw A, Cipora E, Sygit K, Bandurska E, Deptała A. How A Patient with Resectable or Borderline Resectable Pancreatic Cancer should Be Treated-A Comprehensive Review. Cancers (Basel) 2023; 15:4275. [PMID: 37686551 PMCID: PMC10487031 DOI: 10.3390/cancers15174275] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/22/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high morbidity and mortality in which long-term survival rates remain disastrous. Surgical resection is the only potentially curable treatment for early pancreatic cancer; however, the right patient qualification is crucial for optimizing treatment outcomes. With the rapid development of radiographic and surgical techniques, resectability decisions are made by a multidisciplinary team. Upfront surgery (Up-S) can improve the survival of patients with potentially resectable disease with the support of adjuvant therapy (AT). However, early recurrences are quite common due to the often-undetectable micrometastases occurring before surgery. Adopted by international consensus in 2017, the standardization of the definitions of resectable PDAC (R-PDAC) and borderline resectable PDAC (BR-PDAC) disease was necessary to enable accurate interpretation of study results and define which patients could benefit from neoadjuvant therapy (NAT). NAT is expected to improve the resection rate with a negative margin to provide significant local control and eliminate micrometastases to prolong survival. Providing information about optimal sequential multimodal NAT seems to be key for future studies. This article presents a multidisciplinary concept for the therapeutic management of patients with R-PDAC and BR-PDAC based on current knowledge and our own experience.
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Affiliation(s)
- Daria Kwaśniewska
- Department of Oncology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (D.K.); (M.F.)
| | - Marta Fudalej
- Department of Oncology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (D.K.); (M.F.)
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Paweł Nurzyński
- Department of Oncology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (D.K.); (M.F.)
| | | | - Aleksandra Czerw
- Department of Health Economics and Medical Law, Medical University of Warsaw, 01-445 Warsaw, Poland
- Department of Economic and System Analyses, National Institute of Public Health NIH-National Research Institute, 00-791 Warsaw, Poland
| | - Elżbieta Cipora
- Medical Institute, Jan Grodek State University in Sanok, 38-500 Sanok, Poland
| | - Katarzyna Sygit
- Faculty of Health Sciences, Calisia University, 62-800 Kalisz, Poland
| | - Ewa Bandurska
- Centre for Competence Development, Integrated Care and e-Health, Medical University of Gdansk, 80-204 Gdansk, Poland
| | - Andrzej Deptała
- Department of Oncology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (D.K.); (M.F.)
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
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12
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Tong YT, Lai Z, Katz MHG, Prakash LR, Wang H, Chatterjee D, Kim M, Tzeng CWD, Lee JE, Ikoma N, Rashid A, Wolff RA, Zhao D, Koay EJ, Maitra A, Wang H. Prognosticators for Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel Therapy and Pancreatectomy. Cancers (Basel) 2023; 15:cancers15092608. [PMID: 37174073 PMCID: PMC10177033 DOI: 10.3390/cancers15092608] [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: 03/30/2023] [Revised: 04/24/2023] [Accepted: 04/28/2023] [Indexed: 05/15/2023] Open
Abstract
Neoadjuvant FOLFIRINOX and gemcitabine/nab-paclitaxel (GemNP) therapies are increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). However, limited data are available on their clinicopathologic prognosticators. We examined the clinicopathologic factors and survival of 213 PDAC patients who received FOLFIRINOX with 71 patients who received GemNP. The FOLFIRINOX group was younger (p < 0.01) and had a higher rate of radiation (p = 0.049), higher rate of borderline resectable and locally advanced disease (p < 0.001), higher rate of Group 1 response (p = 0.045) and lower ypN stage (p = 0.03) than the GemNP group. Within FOLFIRINOX group, radiation was associated with decreased lymph node metastasis (p = 0.01) and lower ypN stage (p = 0.01). The tumor response group, ypT, ypN, LVI and PNI, correlated significantly with both DFS and OS (p < 0.05). Patients with the ypT0/T1a/T1b tumor had better DFS (p = 0.04) and OS (p = 0.03) than those with ypT1c tumor. In multivariate analysis, the tumor response group and ypN were independently prognostic factors for DFS and OS (p < 0.05). Our study demonstrated that the FOLFIRINOX group was younger and had a better pathologic response than the GemNP group and that the tumor response group, ypN, ypT, LVI and PNI, are significant prognostic factors for survival in these patients. Our results also suggest that the tumor size of 1.0 cm is a better cut off for ypT2. Our study highlights the importance of systemic pathologic examination and the reporting of post-treatment pancreatectomies.
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Affiliation(s)
- Yi Tat Tong
- Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Zongshan Lai
- Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Laura R Prakash
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Hua Wang
- Department Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Deyali Chatterjee
- Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Michael Kim
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Jeffrey E Lee
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Naruhiko Ikoma
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Asif Rashid
- Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Robert A Wolff
- Department Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Dan Zhao
- Department Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Eugene J Koay
- Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Anirban Maitra
- Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
- Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Huamin Wang
- Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
- Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
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13
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Murakami Y, Sakamoto T, Hanaki T, Tokuyasu N, Fujiwara Y. Current Value of Perioperative Therapies for Resectable or Borderline Resectable Pancreatic Cancer. Yonago Acta Med 2023; 66:202-207. [PMID: 37229366 PMCID: PMC10203636 DOI: 10.33160/yam.2023.05.014] [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: 03/22/2023] [Accepted: 04/17/2024] [Indexed: 05/27/2023]
Abstract
Invasive pancreatic ductal carcinoma is a representative refractory malignant tumor, and even with the development of early diagnosis and treatment techniques, the treatment outcome has been remarkably poor. Surgical resection is the curative treatment for resectable pancreatic cancer and borderline resectable pancreatic cancer. However, the survival rate in patients with pancreatic cancer treated by resection alone is low because of the high postoperative recurrence rate. In this review article, we report recent studies on perioperative treatment for pancreatic cancer. Perioperative therapy is the addition of chemotherapy or radiation therapy before or after surgery to improve resectability and curative effects. Because it is difficult to cure redsecttable pancreatic cancer by surgery alone, multidisciplinary treatment combined with perioperative adjuvant chemotherapy is the current standard of care. Although perioperative chemotherapy and chemoradiotherapy have been investigated for borderline resectable pancreatic cancer, the effectiveness of preoperative treatment has not been sufficiently proven. Potentially curative pancreatic cancer is treated by surgery plus perioperative therapy; treatment cannot be either alone. We regard the successful completion of surgery and perioperative care as the key to improving treatment outcomes. Therefore, ongoing randomized controlled trials for the treatment of BR-pancreatic cancer are expected to induce further improvements survival outcomes of patients with BR-pancreatic cancer.
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Affiliation(s)
- Yuki Murakami
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Teruhisa Sakamoto
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Takehiko Hanaki
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Naruo Tokuyasu
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Yoshiyuki Fujiwara
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
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14
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Wu HY, Li JW, Li JZ, Zhai QL, Ye JY, Zheng SY, Fang K. Comprehensive multimodal management of borderline resectable pancreatic cancer: Current status and progress. World J Gastrointest Surg 2023; 15:142-162. [PMID: 36896309 PMCID: PMC9988647 DOI: 10.4240/wjgs.v15.i2.142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/23/2022] [Accepted: 01/12/2023] [Indexed: 02/27/2023] Open
Abstract
Borderline resectable pancreatic cancer (BRPC) is a complex clinical entity with specific biological features. Criteria for resectability need to be assessed in combination with tumor anatomy and oncology. Neoadjuvant therapy (NAT) for BRPC patients is associated with additional survival benefits. Research is currently focused on exploring the optimal NAT regimen and more reliable ways of assessing response to NAT. More attention to management standards during NAT, including biliary drainage and nutritional support, is needed. Surgery remains the cornerstone of BRPC treatment and multidisciplinary teams can help to evaluate whether patients are suitable for surgery and provide individualized management during the perioperative period, including NAT responsiveness and the selection of surgical timing.
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Affiliation(s)
- Hong-Yu Wu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Jin-Wei Li
- Department of Neurosurgery, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou 545000, Guangxi Province, China
| | - Jin-Zheng Li
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Qi-Long Zhai
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Jing-Yuan Ye
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Si-Yuan Zheng
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Kun Fang
- Department of Surgery, Yinchuan Maternal and Child Health Hospital, Yinchuan 750000, Ningxia, China
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15
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Sumiyoshi T, Uemura K, Takasaki T, Kondo N, Katayama K, Okada K, Seo S, Otsuka H, Serikawa M, Ishii Y, Tomofumi T, Takahashi S. Hepatic artery resection in distal cholangiocarcinoma. Langenbecks Arch Surg 2023; 408:58. [PMID: 36688973 DOI: 10.1007/s00423-022-02749-5] [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: 02/15/2022] [Accepted: 10/18/2022] [Indexed: 01/24/2023]
Abstract
PURPOSE This study aimed to elucidate the safety and oncological outcomes of surgery with hepatic artery resection (HAR) for patients with distal cholangiocarcinoma. METHODS The clinical data of patients with distal cholangiocarcinoma who underwent curative intent surgery at Hiroshima University between March 2009 and January 2021 were retrospectively analyzed. Eligible patients were classified according to the presence or absence of HAR (HAR and non-HAR group), and clinicopathological features and disease-free survival rates were compared between the two groups. RESULTS Among the 60 patients analyzed, eight patients had received HAR, and the remaining 52 patients had not. The rate of portal vein resection, T stage, and the number of metastasized lymph nodes in the HAR group were significantly greater than those in the non-HAR group (p < 0.001, p = 0.00695, and p = 0.0480, respectively). Postoperative severe complication was confirmed in one patient, and there were no in-hospital deaths in the HAR group. Seven of 8 patients in the HAR group showed recurrence during follow-up, and of those, six patients showed early recurrence within 1 year postoperatively. The disease-free survival time in the HAR group was significantly shorter than that in the non-HAR group (median: 7.4 m vs. 34.2 m, respectively) (p < 0.001). Multivariate analysis revealed that lymph node metastasis and HAR were significant risk factors for predicting the adverse disease-free survival time (hazard ratio (HR), 3.21; p = 0.0142; HR, 4.47; p = 0.0346, respectively). CONCLUSIONS Patients with distal cholangiocarcinoma who underwent surgery with HAR tended to show early recurrences, although HAR could be performed safely.
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Affiliation(s)
- Tatsuaki Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kenichiro Uemura
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Taiichi Takasaki
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Naru Kondo
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Keijiro Katayama
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kenjiro Okada
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shingo Seo
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroyuki Otsuka
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Yasutaka Ishii
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Tsuboi Tomofumi
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Shinya Takahashi
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
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16
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Possibility of Neoadjuvant Treatment for Radiologically Judged Resectable Pancreatic Cancer. J Clin Med 2022; 11:jcm11226792. [PMID: 36431269 PMCID: PMC9698623 DOI: 10.3390/jcm11226792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/07/2022] [Accepted: 11/11/2022] [Indexed: 11/19/2022] Open
Abstract
Survival remains poor even after resection of pancreatic cancer and the postoperative recurrence rate is extremely high. Thus, neoadjuvant treatment may improve outcomes for resectable pancreatic cancer (RPC). This study evaluated the efficacy of neoadjuvant therapy for radiologically judged RPC. A prospectively maintained institutional database was reviewed to identify patients who underwent potentially curative resection of radiologically judged RPC. Patient characteristics and intermediate-term outcomes were compared between groups that received neoadjuvant treatment or upfront surgery (UFS). We identified 353 eligible patients, including 55 patients who received neoadjuvant chemoradiotherapy (CRT group), 53 patients who received neoadjuvant gemcitabine plus nab-paclitaxel (GnP group), and 245 patients who underwent UFS (UFS group). The cumulative rates of pancreatic cancer recurrence at 2 years after pancreatic surgery were 49.5% in the UFS, 48.1% in the CRT group, and 52.7% in the GnP group. The recurrence rate tended to be improved after neoadjuvant treatment, although the difference was not significant at this follow-up point. While the clinical TNM classifications were noticeably different from the final pathological findings, the clinical and pathological TNM classifications were more similar in the groups that underwent neoadjuvant treatment. Neoadjuvant treatment can help identify good surgical candidates and avoid unnecessary laparotomy. Our results also suggest that neoadjuvant therapy might help improve the preoperative diagnostic accuracy for patients with RPC.
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17
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Oncologic Benefits of Neoadjuvant Treatment versus Upfront Surgery in Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2022; 14:cancers14184360. [PMID: 36139520 PMCID: PMC9497278 DOI: 10.3390/cancers14184360] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 08/31/2022] [Accepted: 09/03/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Borderline resectable pancreatic cancer (BRPC) has been primarily indicated for neoadjuvant treatment (NAT) in the last decade. This study is the updated meta-analysis for only patients with BRPC including recent NAT regimens such as FOLFIRINOX. The OS, R0 resection rate, and node-negativity rate was improved in NAT group compared with upfront surgery. Providing high-quality evidence is important to standardize the treatment protocol and help physicians decide the appropriate pancreatic cancer treatment. Abstract Neoadjuvant treatment (NAT) followed by surgery is the primary treatment for borderline resectable pancreatic cancer (BRPC). However, there is limited high-level evidence supporting the efficacy of NAT in BRPC. PubMed was searched to identify studies that compared the survival between BRPC patients who underwent NAT and those who underwent upfront surgery (UFS). The overall survival (OS) was compared using intention-to-treat (ITT) analysis. A total of 1204 publications were identified, and 19 publications with 21 data sets (2906 patients; NAT, 1516; UFS, 1390) were analyzed. Two randomized controlled trials and two prospective studies were included. Thirteen studies performed an ITT analysis, while six presented the data of resected patients. The NAT group had significantly better OS than the UFS group in the ITT analyses (HR: 0.63, 95% CI = 0.53–0.76) and resected patients (HR: 0.68, 95% CI = 0.60–0.78). Neoadjuvant chemotherapy with gemcitabine or S-1 and FOLFIRINOX improved the survival outcomes. Among the resected patients, the R0 resection and node-negativity rates were significantly higher in the NAT group. NAT improved the OS, R0 resection rate, and node-negativity rate compared with UFS. Standardizing treatment regimens based on high-quality evidence is fundamental for developing an optimal protocol.
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18
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Ingram MA, Lauren BN, Pumpalova Y, Park J, Lim F, Bates SE, Kastrinos F, Manji GA, Kong CY, Hur C. Cost-effectiveness of neoadjuvant FOLFIRINOX versus gemcitabine plus nab-paclitaxel in borderline resectable/locally advanced pancreatic cancer patients. Cancer Rep (Hoboken) 2022; 5:e1565. [PMID: 35122419 PMCID: PMC9458514 DOI: 10.1002/cnr2.1565] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/11/2021] [Accepted: 09/21/2021] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND The 2020 National Comprehensive Cancer Network guidelines recommend neoadjuvant FOLFIRINOX or neoadjuvant gemcitabine plus nab-paclitaxel (G-nP) for borderline resectable/locally advanced pancreatic ductal adenocarcinoma (BR/LA PDAC). AIM The purpose of our study was to compare treatment outcomes, toxicity profiles, costs, and quality-of-life measures between these two treatments to further inform clinical decision-making. METHODS AND RESULTS We developed a decision-analytic mathematical model to compare the total cost and health outcomes of neoadjuvant FOLFIRINOX against G-nP over 12 years. The model inputs were estimated using clinical trial data and published literature. The primary endpoint was incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100 000 per quality-adjusted-life-year (QALY). Secondary endpoints included overall (OS) and progression-free survival (PFS), total cost of care, QALYs, PDAC resection rate, and monthly treatment-related adverse events (TRAE) costs (USD). FOLFIRINOX was the cost-effective strategy, with an ICER of $60856.47 per QALY when compared to G-nP. G-nP had an ICER of $44639.71 per QALY when compared to natural history. For clinical outcomes, more patients underwent an "R0" resection with FOLFIRINOX compared to G-nP (84.9 vs. 81.0%), but FOLFIRINOX had higher TRAE costs than G-nP ($10905.19 vs. $4894.11). A one-way sensitivity analysis found that the ICER of FOLFIRINOX exceeded the threshold when TRAE costs were higher or PDAC recurrence rates were lower. CONCLUSION Our modeling analysis suggests that FOLFIRNOX is the cost-effective treatment compared to G-nP for BR/LA PDAC despite having a higher cost of total care due to TRAE costs. Trial data with sufficient follow-up are needed to confirm our findings.
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Affiliation(s)
- Myles A. Ingram
- Division of General MedicineColumbia University Irving Medical Cancer and the Vagelos College of Physicians and SurgeonsNew YorkNew YorkUSA
| | - Brianna N. Lauren
- Division of General MedicineColumbia University Irving Medical Cancer and the Vagelos College of Physicians and SurgeonsNew YorkNew YorkUSA
| | - Yoanna Pumpalova
- Department of Medicine, Vagelos College of Physicians and SurgeonsColumbia UniversityNew YorkNew YorkUSA
| | - Jiheum Park
- Division of General MedicineColumbia University Irving Medical Cancer and the Vagelos College of Physicians and SurgeonsNew YorkNew YorkUSA
| | - Francesca Lim
- Division of General MedicineColumbia University Irving Medical Cancer and the Vagelos College of Physicians and SurgeonsNew YorkNew YorkUSA
| | - Susan E. Bates
- Herbert Irving Comprehensive Cancer CenterColumbia University Irving Medical CenterNew YorkNew YorkUSA
| | - Fay Kastrinos
- Herbert Irving Comprehensive Cancer CenterColumbia University Irving Medical CenterNew YorkNew YorkUSA
- Division of Digestive and Liver DiseasesColumbia University Irving Medical Cancer and the Vagelos College of Physicians and SurgeonsNew YorkNew YorkUSA
| | - Gulam A. Manji
- Herbert Irving Comprehensive Cancer CenterColumbia University Irving Medical CenterNew YorkNew YorkUSA
| | - Chung Yin Kong
- Division of General MedicineMount Sinai School of MedicineNew YorkNew YorkUSA
| | - Chin Hur
- Division of General MedicineColumbia University Irving Medical Cancer and the Vagelos College of Physicians and SurgeonsNew YorkNew YorkUSA
- Herbert Irving Comprehensive Cancer CenterColumbia University Irving Medical CenterNew YorkNew YorkUSA
- Division of Digestive and Liver DiseasesColumbia University Irving Medical Cancer and the Vagelos College of Physicians and SurgeonsNew YorkNew YorkUSA
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19
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Du J, Gao X, Zhang H, Wan Z, Yu H, Wang D. Stent Selection in Preoperative Biliary Drainage for Patients With Operable Pancreatic Cancer Receiving Neoadjuvant Therapy: A Meta-Analysis and Systematic Review. Front Surg 2022; 9:875504. [PMID: 35846957 PMCID: PMC9280034 DOI: 10.3389/fsurg.2022.875504] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 05/31/2022] [Indexed: 12/29/2022] Open
Abstract
With the increasing use of neoadjuvant therapy (NAT) in patients with pancreatic cancer to reduce tumor burden on prognosis, preoperative biliary drainage (PBD) is becoming increasingly necessary. The aim of this study was to summarize the latest evidence and compare the clinical efficacy of metal stents (MS) and plastic stents (PS) in patients undergoing neoadjuvant therapy for operable pancreatic cancer. Eligible studies were searched in PubMed, Embase and Cochrane Library from their inception to September 2021. In this study, RevMan 5.4 was used to perform the analyses. Two randomized controlled trials (RCTs) and six retrospective studies with 316 patients were included. All patients had pancreatic cancer and received NAT before surgical resection. Meta-analysis showed that the rate of endoscopic reintervention in MS (26/143, 18%) group was lower than that of PS (122/153, 80%) group (P < 0.05). The rate of stent-related complications in MS group was lower (18/118, 15%) than that of PS (52/117, 44%) group (P = 0.02). But there were no significant differences in operative time, operative blood loss, overall postoperative complications, postoperative hospitalization days and total medical costs between the two groups. For operable pancreatic cancer patients undergoing NAT surgery, MS was preferred over PS in terms of the incidence of endoscopic reintervention and stent-related complications. More clinical trials are needed in the future to confirm these data with higher levels of evidence.
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Affiliation(s)
- Jianbing Du
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Xiangyu Gao
- Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Hongtao Zhang
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Zhuo Wan
- Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
| | - Hengchao Yu
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- Correspondence: Hengchao Yu Desheng Wang
| | - Desheng Wang
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- Correspondence: Hengchao Yu Desheng Wang
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20
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Wang C, Tan G, Zhang J, Fan B, Chen Y, Chen D, Yang L, Chen X, Duan Q, Maimaiti F, Du J, Lin Z, Gu J, Luo H. Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma: Where Do We Go? Front Oncol 2022; 12:828223. [PMID: 35785193 PMCID: PMC9245892 DOI: 10.3389/fonc.2022.828223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 05/09/2022] [Indexed: 11/15/2022] Open
Abstract
The incidence of pancreatic ductal adenocarcinoma (PDAC) has been on the rise in recent years; however, its clinical diagnosis and treatment remain challenging. Although surgical resection remains the only chance for long-term patient survival, the likelihood of initial resectability is no higher than 20%. Neoadjuvant therapy (NAT) in PDAC aims to transform the proportion of inoperable PDACs into operable cases and reduce the likelihood of recurrence to improve overall survival. Ongoing phase 3 clinical trial aims to validate the role of NAT in PDAC therapy, including prolongation of survival, increased R0 resection, and a higher proportion of negative lymph nodes. Controversies surrounding the role of NAT in PDAC treatment include applicability to different stages of PDAC, chemotherapy regimens, radiation, duration of treatment, and assessment of effect. This review aims to summarize the current progress and controversies of NAT in PDAC.
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Affiliation(s)
- Chenqi Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Guang Tan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jie Zhang
- Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Bin Fan
- Department of General Surgery, The First Hospital of Northwest University (Xi’an No. 1 Hospital), Xi’an, China
| | - Yunlong Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Dan Chen
- Department of Pathology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Lili Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xiang Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Qingzhu Duan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Feiliyan Maimaiti
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jian Du
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Zhikun Lin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jiangning Gu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- *Correspondence: Haifeng Luo, ; Jiangning Gu,
| | - Haifeng Luo
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- *Correspondence: Haifeng Luo, ; Jiangning Gu,
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21
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Vivarelli M, Mocchegiani F, Nicolini D, Vecchi A, Conte G, Dalla Bona E, Rossi R, Benedetti Cacciaguerra A. Neoadjuvant Treatment in Resectable Pancreatic Cancer. Is It Time for Pushing on It? Front Oncol 2022; 12:914203. [PMID: 35712487 PMCID: PMC9195424 DOI: 10.3389/fonc.2022.914203] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 04/28/2022] [Indexed: 11/13/2022] Open
Abstract
Pancreatic resection still represents the only curative option for patients affected by pancreatic ductal adenocarcinoma (PDAC). However, the association with modern chemotherapy regimens is a key factor in improving the inauspicious oncological outcome. The benefit of neoadjuvant treatment (NAT) for borderline resectable/locally advanced PDAC has been demonstrated; this evidence raises the question of whether even resectable PDAC should undergo NAT rather than upfront surgery. NAT may avoid futile surgery because of undetected distant metastases or aggressive tumor biology, providing more effective systemic control of the disease, which is hampered when adjuvant chemotherapy is delayed or precluded. However, recent data show controversial results regarding the efficacy and safety of NAT in resectable PDAC compared to upfront surgery. Although several prospective studies and meta-analyses indicate better oncologic outcomes after NAT, there are some biases, such as the methodological approaches used to capture the events of interest, which could make these results hardly reproducible. For instance, per-protocol studies, considering only the postoperative outcomes, tend to overestimate the performance of NAT by excluding patients who will never be suitable for surgery due to the development of chemotoxicity or tumor progression. To draw reliable conclusions, the studies should capture the events of interest of both strategies (NAT/upfront surgery) from the time of allocation to a specific treatment in an intention-to-treat fashion. This critical review highlights the current literature data concerning the use of NAT in resectable PDAC, summarizing the results of high-quality studies and focusing on the methodological issues of the most recent pieces of evidence.
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22
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Ielpo B, Burdio F, Martinez A, Sanchez-Velazquez P. Pancreatectomy with concomitant portal vein resection in the current neoadjuvant era. Hepatobiliary Surg Nutr 2022; 11:295-298. [PMID: 35464289 PMCID: PMC9023828 DOI: 10.21037/hbsn-21-547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 02/10/2022] [Indexed: 08/30/2023]
Affiliation(s)
- Benedetto Ielpo
- Hepato-Biliary and Pancreatic Surgery Unit, Hospital del Mar, Universitat Pompeu Fabra, Barcelona, Spain
| | - Fernando Burdio
- Hepato-Biliary and Pancreatic Surgery Unit, Hospital del Mar, Universitat Pompeu Fabra, Barcelona, Spain
| | - Ana Martinez
- Hepato-Biliary and Pancreatic Surgery Unit, Hospital del Mar, Universitat Pompeu Fabra, Barcelona, Spain
| | - Patricia Sanchez-Velazquez
- Hepato-Biliary and Pancreatic Surgery Unit, Hospital del Mar, Universitat Pompeu Fabra, Barcelona, Spain
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23
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Nehme F, Lee JH. Preoperative biliary drainage for pancreatic cancer. Dig Endosc 2022; 34:428-438. [PMID: 34275165 DOI: 10.1111/den.14081] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 07/15/2021] [Indexed: 12/15/2022]
Abstract
Pancreatic adenocarcinoma is currently one of the leading causes of cancer-related morbidity and mortality with dismal long term survival after diagnosis. Nearly 85% of pancreatic cancer patients present with advanced disease precluding curative surgical resection. In those who are candidates for surgery, preoperative biliary drainage (PBD) has been developed since the 1960s in order to improve surgical outcomes. While obstructive jaundice in resectable pancreatic cancer has been traditionally treated before surgical resection in all patients, data over the past decade demonstrated increased perioperative complications and morbidity with systematic PBD compared to direct surgery. With new evidence of potential adverse events, the role of routine PBD is being reassessed. Current indications for PBD include cholangitis, delayed surgery, and relief of jaundice in patients planned to receive neoadjuvant therapy (NAT). NAT is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer and a higher proportion of patients with likely require PBD in the future. The evidence for endoscopic retrograde cholangiopancreatography as first line for PBD is robust with supporting data from endoscopic ultrasound assisted biliary drainage. Self-expanding metal stent was shown to be cost-effective in recent studies without increase in morbidity compared to plastic stents in this setting. In this review, we will summarize the current evidence for PBD in patients with pancreatic cancer.
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Affiliation(s)
- Fredy Nehme
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - Jeffrey H Lee
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, USA
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24
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Amintas S, Fernandez B, Chauvet A, Chiche L, Laurent C, Belleannée G, Marty M, Buscail E, Dabernat S. KRAS gene mutation quantification in the resection or venous margins of pancreatic ductal adenocarcinoma is not predictive of disease recurrence. Sci Rep 2022; 12:2976. [PMID: 35194118 PMCID: PMC8864048 DOI: 10.1038/s41598-022-07004-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 02/07/2022] [Indexed: 11/24/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) patients eligible for curative surgery undergo unpredictable disease relapse. Even patients with a good pathological response after neoadjuvant treatment (NAT) remain susceptible to recurrent PDAC. Molecular analysis of R0 margins may identify patients with a worse prognosis. The molecular status of mutant KRAS (exon 2, codon 12/13) was analysed retrospectively by digital droplet PCR in tumour areas, venous and resection margins of resected tumours, either undergoing up-front surgery (UFS) or after NAT with a good pathological response. Expectedly, tumour tissues or remnants from patients who underwent NAT presented lower KRAS mutant allele frequencies (MAF) than patients eligible for UFS. Similarly, ypT1 tumour MAFs were greater than the ypT0 tumour remnant MAFs in the NAT group. Mutant KRAS status in margins did not distinguish NAT subgroups. It was not predictive of shorter recurrence-free or overall survival within or between groups. KRAS-double negativity in both venous and resection margins did not identify patients with a better prognosis, regardless of the groups. The cohorts ‘sizes were small due to limited numbers of patients meeting the inclusion criteria, but KRAS-positivity or MAFs in resection and venous margins did not carry prognostic value. Comparison of margins from good versus bad responders receiving NAT may provide better clinical value.
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Affiliation(s)
- Samuel Amintas
- Université de Bordeaux, 33000, Bordeaux, France.,Inserm U1312 «BoRdeaux Institute of onCology», BRIC, Team Biotherapy Genetics and Oncology, 33000, Bordeaux, France.,Centre Hospitalier Universitaire (CHU) de Bordeaux, 33000, Bordeaux, France
| | - Benjamin Fernandez
- Université de Bordeaux, 33000, Bordeaux, France.,Inserm U1312 «BoRdeaux Institute of onCology», BRIC, Team Biotherapy Genetics and Oncology, 33000, Bordeaux, France.,Centre Hospitalier Universitaire (CHU) de Bordeaux, 33000, Bordeaux, France
| | - Alexandre Chauvet
- Centre Hospitalier Universitaire (CHU) de Bordeaux, 33000, Bordeaux, France
| | - Laurence Chiche
- Université de Bordeaux, 33000, Bordeaux, France.,Inserm U1312 «BoRdeaux Institute of onCology», BRIC, Team Biotherapy Genetics and Oncology, 33000, Bordeaux, France.,Centre Hospitalier Universitaire (CHU) de Bordeaux, 33000, Bordeaux, France
| | - Christophe Laurent
- Université de Bordeaux, 33000, Bordeaux, France.,Inserm U1312 «BoRdeaux Institute of onCology», BRIC, Team Biotherapy Genetics and Oncology, 33000, Bordeaux, France.,Centre Hospitalier Universitaire (CHU) de Bordeaux, 33000, Bordeaux, France
| | | | - Marion Marty
- Inserm U1312 «BoRdeaux Institute of onCology», BRIC, Team Biotherapy Genetics and Oncology, 33000, Bordeaux, France
| | - Etienne Buscail
- Centre Hospitalier Universitaire (CHU) de Toulouse, 31000, Toulouse, France.,Inserm, UMR-1220, IRSD, 31000, Toulouse, France.,Université de Toulouse III, 31000, Toulouse, France
| | - Sandrine Dabernat
- Université de Bordeaux, 33000, Bordeaux, France. .,Inserm U1312 «BoRdeaux Institute of onCology», BRIC, Team Biotherapy Genetics and Oncology, 33000, Bordeaux, France. .,Centre Hospitalier Universitaire (CHU) de Bordeaux, 33000, Bordeaux, France.
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25
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Yoon MS, Lee HS, Kang CM, Lee WJ, Keum J, Sung MJ, Kim SS, Park MS, Jo JH, Chung MJ, Park JY, Park SW, Song SY, Hwang HK, Bang S. Response to Neoadjuvant Therapy and Prognosis in Patients with Resectable Pancreatic Cancer: A Propensity Score Matching Analysis. Gut Liver 2022; 16:118-128. [PMID: 34140428 PMCID: PMC8761915 DOI: 10.5009/gnl20301] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 03/12/2021] [Accepted: 03/15/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND/AIMS : Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC. METHODS We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC: 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 1:3 propensity score matching (PSM) was performed to reduce selection bias. RESULTS Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis. CONCLUSIONS We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.
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Affiliation(s)
- Min Sung Yoon
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hee Seung Lee
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Chang Moo Kang
- Department of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Woo Jung Lee
- Department of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jiyoung Keum
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Min Je Sung
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seung-seob Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Mi-Suk Park
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Hyun Jo
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Moon Jae Chung
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jeong Youp Park
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Woo Park
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Si Young Song
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Ho Kyoung Hwang
- Department of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Seungmin Bang
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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26
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Kondo N, Uemura K, Sudo T, Hashimoto Y, Sumiyoshi T, Okada K, Seo S, Otsuka H, Murakami Y, Takahashi S. A phase II study of gemcitabine/nab-paclitaxel/S-1 combination neoadjuvant chemotherapy for patients with borderline resectable pancreatic cancer with arterial contact. Eur J Cancer 2021; 159:215-223. [PMID: 34781169 DOI: 10.1016/j.ejca.2021.10.012] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 10/04/2021] [Accepted: 10/11/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND The prognosis of patients with borderline resectable pancreatic cancer with arterial contact (BRPC-A) is extremely poor, and effective preoperative treatment is indispensable. We evaluated the clinical efficacy and safety of neoadjuvant chemotherapy, including gemcitabine, nab-paclitaxel and S-1 (GAS), for patients with BRPC-A. MATERIAL AND METHODS A multicentre, single-arm, phase II study was performed. Patients were administered 1000 mg/m2 gemcitabine on day 1, 125 mg/m2 nab-paclitaxel on day 1 and 60-100 mg/day S-1 on days 1-7 during a 14-day cycle. Patients were then assessed for resectability and response to treatment after six cycles. The primary end-points were 2-year overall survival (OS) rate and median OS time (trial registration: jRCTs061180045, UMIN000016630). RESULTS Forty-seven patients with BRPC-A were eligible for the present study. Six courses of neoadjuvant GAS regimen were completed in all eligible patients. The rate of grade III/IV toxicities occurred in 14 (30%) patients during the neoadjuvant GAS regimen. The response and disease control rates were 43% and 96%, respectively. Forty-five (96%) patients received potentially curative pancreatectomy, whereas two did not owing to disease progression. R0 resection was performed in 40 (86%) of 47 eligible patients. Eleven (24%) patients experienced postoperative major complications (>grade III), including one mortality. The 2-year OS rate and median OS time among 47 eligible patients were 70.1% and 41.0 months, respectively. CONCLUSIONS The neoadjuvant GAS chemotherapy regimen for BRPC-A showed good efficacy with mild toxicity, resulting in a high R0 resection rate and prolonged survival in patients with BRPC-A.
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Affiliation(s)
- Naru Kondo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
| | - Kenichiro Uemura
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
| | - Takeshi Sudo
- Department of Surgery, Kure Medical Center and Chugoku Cancer Center, 3-1, Aoyama-cho, Kure 737-0023, Japan
| | - Yasushi Hashimoto
- Department of Surgery, Hiroshima Memorial Hospital, 1-4-3, Honkawa-cho, Naka-ku, Hiroshima 730-0802, Japan
| | - Tatsuaki Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
| | - Kenjiro Okada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
| | - Shingo Seo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
| | - Hiroyuki Otsuka
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
| | - Yoshiaki Murakami
- Department of Surgery, Hiroshima Memorial Hospital, 1-4-3, Honkawa-cho, Naka-ku, Hiroshima 730-0802, Japan; Department of Advanced Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
| | - Shinya Takahashi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
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27
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Tamura T, Itonaga M, Ashida R, Yamashita Y, Hatamaru K, Kawaji Y, Emori T, Kitahata Y, Miyazawa M, Hirono S, Okada KI, Kawai M, Shimokawa T, Yamaue H, Kitano M. Covered self-expandable metal stents versus plastic stents for preoperative biliary drainage in patient receiving neo-adjuvant chemotherapy for borderline resectable pancreatic cancer: Prospective randomized study. Dig Endosc 2021; 33:1170-1178. [PMID: 33410564 DOI: 10.1111/den.13926] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 12/21/2020] [Accepted: 01/05/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVES This single-center comparative randomized superiority study compared biliary stenting using fully covered self-expandable metal stents (FCSEMS) and biliary stenting using plastic stents (PS) in preoperative biliary drainage of patients with borderline resectable pancreatic cancer (BRPC) who are planned to undergo a single regimen of neo-adjuvant chemotherapy (NAC). METHODS Twenty-two patients with BRPC who required preoperative biliary drainage before NAC (Gemcitabine plus Nab-paclitaxel) were randomly assigned 1:1 to the FCSEMS or PS group. The primary endpoint was the rate of stent dysfunction until surgery or tumor progression. Secondary endpoints were stent patency, number of re-interventions, adverse events of endoscopic retrograde biliary drainage (EBD), operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs. RESULTS Eleven patients in each of the groups reached the primary endpoint. The FCSEMS group showed a significantly lower rate of stent dysfunction (18.2% vs. 72.8%, P = 0.015), longer stent patency (P = 0.02), and lower number of re-interventions for stent dysfunction (0.27 ± 0.65 vs. 1.27 ± 1.1, P = 0.001) than the PS group. The adverse events of EBD, operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs did not significantly differ between the two groups. CONCLUSIONS In patients with BRPC for preoperative biliary drainage, stent dysfunction occurred less frequently with FCSEMSs than with PSs. In addition, FCSEMS and PS provided similar preoperative management of BRPC in terms of the safety of surgery and medical costs. (UMIN ID000030473).
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Affiliation(s)
- Takashi Tamura
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Masahiro Itonaga
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Reiko Ashida
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Yasunobu Yamashita
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Keiichi Hatamaru
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Yuki Kawaji
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Tomoya Emori
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Yuji Kitahata
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Motoki Miyazawa
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Seiko Hirono
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Ken-Ichi Okada
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Manabu Kawai
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Toshio Shimokawa
- Clinical Study Support Center, Wakayama Medical University Hospital, Wakayama, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Masayuki Kitano
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
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28
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Okada K, Uemura K, Kondo N, Sumiyoshi T, Seo S, Otsuka H, Serikawa M, Ishii Y, Tsuboi T, Murakami Y, Takahashi S. Neoadjuvant therapy contributes to nodal downstaging of pancreatic cancer. Langenbecks Arch Surg 2021; 407:623-632. [PMID: 34609618 DOI: 10.1007/s00423-021-02339-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: 02/16/2021] [Accepted: 09/21/2021] [Indexed: 11/27/2022]
Abstract
PURPOSE This study aimed to assess the impact of neoadjuvant therapy (NAT) for borderline resectable or locally advanced pancreatic cancer (BR/LAPC) on the American Joint Commission on Cancer (AJCC) nodal status. METHODS The medical records of BR/LAPC patients who underwent surgery with curative intent were retrospectively reviewed. The nodal status was compared between patients who underwent upfront surgery (UFS) and those who received NAT. Moreover, clinicopathological factors and prognostic factors for overall survival were analyzed. RESULTS In all, 200 patients with BR/LAPC, 78 with UFS, and 122 with NAT were enrolled. The nodal status was significantly lower in patients after NAT than after UFS (p = 0.011). A multivariate analysis of overall survival showed that UFS (hazard ratio (HR) 1.61, p = 0.024) and N2 status (HR 2.69, p < 0.001) were independent poor prognostic factors. The median serum carbohydrate antigen (CA) 19-9 level after NAT in N2 patients was 105 U/mL, which was significantly higher than that of patients with N0 (p = 0.004) and N1 (p = 0.008) status. CONCLUSION Patients with BR/LAPC who underwent surgery after NAT had significantly lower N2 status and better prognosis than patients who underwent UFS. Elevated CA19-9 levels after NAT indicated a higher nodal status.
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Affiliation(s)
- Kenjiro Okada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kenichiro Uemura
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Naru Kondo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tatsuaki Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shingo Seo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroyuki Otsuka
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yasutaka Ishii
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomofumi Tsuboi
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshiaki Murakami
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shinya Takahashi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
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Korean clinical practice guideline for pancreatic cancer 2021: A summary of evidence-based, multi-disciplinary diagnostic and therapeutic approaches. Pancreatology 2021; 21:1326-1341. [PMID: 34148794 DOI: 10.1016/j.pan.2021.05.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/20/2021] [Accepted: 05/04/2021] [Indexed: 02/08/2023]
Abstract
Pancreatic cancer is the eighth most common cancer and the fifth most common cause of cancer-related death in Korea. To enable standardization of management and facilitate improvements in outcome, a total of 53 multi-disciplinary experts in gastroenterology, surgery, medical oncology, radiation oncology, radiology, nuclear medicine, and pathology in Korea developed new recommendations that integrate the most up-to-date, evidence-based research findings and expert opinions. Recommendations were made on imaging diagnosis, endoscopic management, surgery, radiotherapy, palliative chemotherapy, and specific management procedures, including neoadjuvant treatment or adjuvant treatment for patients with resectable, borderline resectable, and locally advanced unresectable pancreatic cancer. This is the English version of the Korean clinical practice guideline for pancreatic cancer 2021. This guideline includes 20 clinical questions and 32 statements. This guideline represents the most standard guideline for the diagnosis and treatment of patients with pancreatic ductal adenocarcinoma in adults at this time in Korea. The authors believe that this guideline will provide useful and informative advice.
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Yang L, Bai Y, Li Q, Chen J, Liu F, Weng X, Xu F. Analysis of the Curative Effect of Neoadjuvant Therapy on Pancreatic Cancer. Front Oncol 2021; 11:695645. [PMID: 34485131 PMCID: PMC8416459 DOI: 10.3389/fonc.2021.695645] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 07/30/2021] [Indexed: 12/24/2022] Open
Abstract
The prevalence of pancreatic cancer is sharply increasing recently, which significantly increases the economic burden of the population. At present, the primary treatment of resectable pancreatic cancer is surgical resection, followed by chemotherapy with or without radiation. However, the recurrence rates remain high even after R0 resection. This treatment strategy does not distinguish undetected metastatic disease, and it is prone to postoperative complications. Neoadjuvant therapies, including neoadjuvant chemotherapy and radiotherapy, is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer. This review summarized and discussed clinical trials of neoadjuvant therapy for pancreatic cancer, comparing resection rates, outcome measures, and adverse reactions between neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy.
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Affiliation(s)
- Liqiong Yang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Yun Bai
- Department of Public Health, Chengdu Medical College, Chengdu, China
| | - Qing Li
- Department of Anesthesiology, Gulinxian People's Hospital of Sichuan Province, Luzhou, China
| | - Jie Chen
- Department of Digestive Surgery, School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.,Department of Orthopedics, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Fangfang Liu
- Department of Art, Art College, Southwest Minzu University, Chengdu, China
| | - Xiechuan Weng
- Department of Neuroscience, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Fan Xu
- Department of Public Health, Chengdu Medical College, Chengdu, China
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van Dongen JC, Wismans LV, Suurmeijer JA, Besselink MG, de Wilde RF, Groot Koerkamp B, van Eijck CHJ. The effect of preoperative chemotherapy and chemoradiotherapy on pancreatic fistula and other surgical complications after pancreatic resection: a systematic review and meta-analysis of comparative studies. HPB (Oxford) 2021; 23:1321-1331. [PMID: 34099372 DOI: 10.1016/j.hpb.2021.04.027] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 04/27/2021] [Accepted: 04/29/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Preoperative chemo- or chemoradiotherapy is recommended for borderline-resectable pancreatic cancer. The aim of this study was to determine the impact of preoperative therapy on surgical complications in patients with resected pancreatic cancer. METHODS This systematic review and meta-analysis included studies reporting on the rate of surgical complications after preoperative chemo- or chemoradiotherapy versus immediate surgery in pancreatic cancer patients. The primary endpoint was the rate of grade B/C POPF. Pooled odds ratios were calculated using random-effects models. RESULTS Forty-one comparative studies including 25,389 patients were included. Vascular resections were more often performed after preoperative therapy (29.4% vs. 15.7%, p < 0.001). Preoperative therapy was associated with a lower rate of grade B/C POPF as compared to immediate surgery (pooled OR 0.47, 95%CI 0.38-0.58). This reduction was mostly obtained by preoperative chemoradiotherapy (OR 0.46, 95%CI 0.29-0.73), but not by preoperative chemotherapy alone (OR 0.83, 95%CI 0.59-1.16). No difference was demonstrated for major morbidity, mortality, postpancreatectomy haemorrhage, delayed gastric emptying and overall morbidity. CONCLUSION Preoperative chemo- and chemoradiotherapy in patients with pancreatic cancer appears to be safe with respect to POPF and other surgical complications as compared to immediate surgery. The reduced rate of POPF appears to be attributable to preoperative chemoradiation.
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Affiliation(s)
- Jelle C van Dongen
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Leonoor V Wismans
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - J Annelie Suurmeijer
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Roeland F de Wilde
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
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Damm M, Efremov L, Birnbach B, Terrero G, Kleeff J, Mikolajczyk R, Rosendahl J, Michl P, Krug S. Efficacy and Safety of Neoadjuvant Gemcitabine Plus Nab-Paclitaxel in Borderline Resectable and Locally Advanced Pancreatic Cancer-A Systematic Review and Meta-Analysis. Cancers (Basel) 2021; 13:cancers13174326. [PMID: 34503138 PMCID: PMC8430874 DOI: 10.3390/cancers13174326] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/18/2021] [Accepted: 08/23/2021] [Indexed: 12/20/2022] Open
Abstract
Simple Summary Due to the availability of effective combination chemotherapies such as gemcitabine/nab-paclitaxel (GNP) or FOLFIRINOX, neoadjuvant treatment of borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) has been increasingly investigated in recent years. However, due to toxicity, FOLFIRINOX is only available for selected patients and data on GNP are scarce. The aim of this systematic review and meta-analysis, which is to our knowledge the first addressing this question, is to evaluate the value of GNP in patients with BRPC and LAPC. We provide a comprehensive overview on data of 21 studies, comprising 950 patients treated with neoadjuvant GNP. The pooled overall and R0 resection rates were 36% and 26%, respectively. Resection rates were higher in BRPC (49%) compared to LAPC (16%). With acceptable toxicity and a median overall survival rate ranging from 12 to 30 months, neoadjuvant GNP has considerable value in this setting, with more prospective trials being warranted. Abstract Therapy with gemcitabine and nab-paclitaxel (GNP) is the most commonly used palliative chemotherapy, but its advantage in the neoadjuvant setting remains unclear. Accordingly, our aim is to evaluate the impact of first-line neoadjuvant therapy with GNP in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). A systematic search for published studies until August 2020 was performed. The primary endpoint included resection and R0 resection rates in the intention-to-treat population. Secondary endpoints were response rate, survival and toxicity. Among 21 studies, 950 patients who received neoadjuvant GNP were evaluated. Treatment with GNP resulted in surgical resection and R0 resection rates as follows: 49% (95% CI 30–68%) and 36% (95% CI 17–58%) for BRPC and 16% (95% CI 7–26%) and 11% (95% CI 5–19%) for LAPC, respectively. The objective response rates and the median overall survival (mOS) ranged from 0 to 67% and 12 to 30 months, respectively. Neutropenia (range 5–77%) and neuropathy (range 0–22%) were the most commonly reported grade 3 to 4 adverse events. Neoadjuvant chemotherapy with GNP can be performed safely and with valuable effects in patients with BRPC and LAPC. The utility of GNP in comparison to FOLFIRINOX in the neoadjuvant setting requires further investigation in prospective randomized trials.
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Affiliation(s)
- Marko Damm
- Department of Internal Medicine I, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, D-06120 Halle (Saale), Germany; (M.D.); (J.R.); (S.K.)
| | - Ljupcho Efremov
- Institute for Medical Epidemiology, Biometrics and Informatics (IMEBI), Interdisciplinary Center for Health Sciences, Martin-Luther-University Halle-Wittenberg, D-06112 Halle (Saale), Germany; (L.E.); (B.B.); (R.M.)
- Department of Radiation Oncology, Martin-Luther-University Halle-Wittenberg, D-06120 Halle (Saale), Germany
| | - Benedikt Birnbach
- Institute for Medical Epidemiology, Biometrics and Informatics (IMEBI), Interdisciplinary Center for Health Sciences, Martin-Luther-University Halle-Wittenberg, D-06112 Halle (Saale), Germany; (L.E.); (B.B.); (R.M.)
| | - Gretel Terrero
- Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA;
| | - Jörg Kleeff
- Department of Surgery, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, D-06120 Halle (Saale), Germany;
| | - Rafael Mikolajczyk
- Institute for Medical Epidemiology, Biometrics and Informatics (IMEBI), Interdisciplinary Center for Health Sciences, Martin-Luther-University Halle-Wittenberg, D-06112 Halle (Saale), Germany; (L.E.); (B.B.); (R.M.)
| | - Jonas Rosendahl
- Department of Internal Medicine I, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, D-06120 Halle (Saale), Germany; (M.D.); (J.R.); (S.K.)
| | - Patrick Michl
- Department of Internal Medicine I, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, D-06120 Halle (Saale), Germany; (M.D.); (J.R.); (S.K.)
- Correspondence: ; Tel.: +49-345-557-2661; Fax: +49-345-557-2653
| | - Sebastian Krug
- Department of Internal Medicine I, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, D-06120 Halle (Saale), Germany; (M.D.); (J.R.); (S.K.)
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Furukawa T, Sasaki T, Ono Y, Kawano F, Takamatsu M, Mori C, Mie T, Yamada Y, Okamoto T, Takeda T, Kasuga A, Matsuyama M, Ozaka M, Takahashi Y, Sasahira N. A case of necrotic enteritis during neoadjuvant chemotherapy with gemcitabine and S-1 for resectable pancreatic ductal adenocarcinoma. Clin J Gastroenterol 2021; 14:1571-1577. [PMID: 34255287 DOI: 10.1007/s12328-021-01480-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 07/09/2021] [Indexed: 11/25/2022]
Abstract
Pancreatic cancer is the fourth leading cause of cancer-related death in Japan. Pancreatic cancer is categorized as resectable, borderline resectable, or unresectable based on the degree of adjacent vascular invasion and the presence of distant metastases. Neoadjuvant chemotherapy with gemcitabine and S-1 (NAC-GS) has recently become a standard option for resectable pancreatic cancer in Japanese patients. According to previous reports, GS is considered to be relatively safe and feasible treatment for Japanese patients, including the elderly. However, NAC-GS is occasionally associated with severe adverse events which may ultimately render the patient unfit for surgery. A 60-year-old man with resectable pancreatic cancer suffered from severe necrotic enteritis during NAC-GS, which required surgical resection. Considering the time course and histological findings of the resected bowel, S-1 was believed to be the causative agent. The low urinary dihydrouracil to uracil ratio also suggested possible dihydropyrimidine dehydrogenase deficiency, which may have hindered the metabolism of S-1 and contributed to the development of necrotic enteritis. Life-threatening enteritis occurs in approximately 0.3% of all patients who receive S-1. As initial symptoms are non-specific, patients should be instructed to lower the hurdle for contacting the hospital during NAC-GS.
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Affiliation(s)
- Takaaki Furukawa
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Takashi Sasaki
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan.
| | - Yoshihiro Ono
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Fumihiro Kawano
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Manabu Takamatsu
- Department of Pathology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Chinatsu Mori
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Takafumi Mie
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Yuto Yamada
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Takeshi Okamoto
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Tsuyoshi Takeda
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Akiyoshi Kasuga
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Masato Matsuyama
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Masato Ozaka
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Yu Takahashi
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Naoki Sasahira
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
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Evangelista L, Zucchetta P, Moletta L, Serafini S, Cassarino G, Pegoraro N, Bergamo F, Sperti C, Cecchin D. The role of FDG PET/CT or PET/MRI in assessing response to neoadjuvant therapy for patients with borderline or resectable pancreatic cancer: a systematic literature review. Ann Nucl Med 2021; 35:767-776. [PMID: 34047926 PMCID: PMC8197718 DOI: 10.1007/s12149-021-01629-0] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 05/11/2021] [Indexed: 02/05/2023]
Abstract
The aim of the present systematic review is to examine the role of fluorodeoxyglucose (FDG) positron emission tomography (PET) associated with computed tomography (CT) or magnetic resonance imaging (MRI) in assessing response to preoperative chemotherapy or chemoradiotherapy (CRT) for patients with borderline and resectable pancreatic ductal adenocarcinoma (PDAC). Three researchers ran a database query in PubMed, Web of Science and EMBASE. The total number of patients considered was 488. The most often used parameters of response to therapy were the reductions in the maximum standardized uptake value (SUVmax) or the peak standardized uptake lean mass (SULpeak). Patients whose SUVs were higher at the baseline (before CRT) were associated with a better response to therapy and a better overall survival. SUVs remaining high after neoadjuvant therapy correlated with a poor prognosis. Available data indicate that FDG PET/CT or PET/MRI can be useful for predicting and assessing response to CRT in patients with resectable or borderline PDAC.
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Affiliation(s)
- Laura Evangelista
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, Via Giustiniani 2, 35128, Padua, Italy.
| | - Pietro Zucchetta
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Lucia Moletta
- Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Simone Serafini
- Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Gianluca Cassarino
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Nicola Pegoraro
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Francesca Bergamo
- Medical Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128, Padua, Italy
| | - Cosimo Sperti
- Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Diego Cecchin
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
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Hepatic artery resection and reconstruction using the right gastroepiploic artery during pancreaticoduodenectomy in advanced pancreatic cancer. Langenbecks Arch Surg 2021; 406:2075-2080. [PMID: 33847784 DOI: 10.1007/s00423-021-02120-0] [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: 08/31/2020] [Accepted: 02/04/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE Surgical resection is the only curative treatment for pancreatic cancer. Arterial resection and reconstruction during pancreaticoduodenectomy for advanced pancreatic cancer remain controversial due to a high rate of complications. METHODS We report two cases of pancreatic cancer with hepatic artery resection and reconstruction using the right gastroepiploic artery during pancreaticoduodenectomy after neoadjuvant therapy. RESULTS The patients underwent pancreaticoduodenectomy with resection of the right hepatic and common hepatic arteries. Achieving direct anastomosis was difficult; therefore, we planned hepatic artery reconstruction using the right gastroepiploic artery. We performed the reconstruction using an interrupted suture with end-to-end anastomosis. The first patient developed a postoperative pancreatic fistula, while the postoperative course of the second patient was uneventful. However, there were no adverse events related to the arterial reconstruction. R0 resection was achieved, and postoperative computed tomography revealed good patency of the reconstructed artery. CONCLUSION Hepatic artery reconstruction using the right gastroepiploic artery in pancreatic cancer might be technically safe and might become one of the alternative options.
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Sugarbaker PH, Stuart OA. Intraperitoneal gemcitabine chemotherapy is safe for patients with resected pancreatic cancer: final clinical and pharmacologic data from a phase II protocol and recommended future directions. J Gastrointest Oncol 2021; 12:S99-S109. [PMID: 33968430 DOI: 10.21037/jgo-2020-02] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Worldwide, the surgical management of pancreas cancer using the Whipple procedure results in long-term survival in approximately 20% of patients when there is a R0 resection. Local recurrence within the resection site and peritoneal metastases are a prominent part of this treatment failure. Gemcitabine was used for a regional chemotherapy treatment strategy. Doses and schedules of chemotherapy routinely used for systemic treatment were administered as hyperthermic intraperitoneal chemotherapy (HIPEC) in the operating room. Then patients went on to receive 6 months of long-term normothermic intraperitoneal chemotherapy (NIPEC) with gemcitabine. Data was gathered to determine a pharmacologic rationale and safety of this monotherapy with gemcitabine. The use of intraperitoneal gemcitabine was well supported by pharmacologic data. The peritoneal surface exposure as measured by pharmacokinetic studies showed the area under the curve (AUC) of intraperitoneal concentration times time divided by plasma concentration times time to be 95-507. Regarding the safety of HIPEC gemcitabine in 12 patients, a single class III adverse event that resolved by radiologic intervention occurred. In patients with resected pancreas cancer treated with HIPEC gemcitabine the morbidity and mortality rate was not increased over historical data of resection alone. Also, six cycles of NIPEC gemcitabine were well tolerated in eight of eight eligible patients with seven patients completing 6 months of long-term intraperitoneal treatment. Local recurrence and peritoneal metastases were absent. Median survival was 29 months and five patients survived longer than 2 years. These early data suggest that intraperitoneal gemcitabine given under hyperthermic conditions in the operating theater and long-term through an intraperitoneal port is safe. Also, in this pilot study long-term local control with intraperitoneal gemcitabine occurred. Intraperitoneal gemcitabine may improve local-regional control of resected pancreas cancer. This may lead to more successful multimodality strategies.
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Affiliation(s)
- Paul H Sugarbaker
- Center for Gastrointestinal Malignancies, MedStar Washington Hospital Center, Washington, DC, USA
| | - O Anthony Stuart
- Center for Gastrointestinal Malignancies, MedStar Washington Hospital Center, Washington, DC, USA
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Preoperative risk factors for para-aortic lymph node positivity in pancreatic cancer. Pancreatology 2021; 21:606-612. [PMID: 33648880 DOI: 10.1016/j.pan.2021.01.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 01/27/2021] [Accepted: 01/29/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE This study aimed to identify the preoperative risk factors for para-aortic lymph node (PALN) positivity, including micrometastasis, in pancreatic cancer. METHODS Medical records of patients with pancreatic cancer who underwent curative resection were retrospectively reviewed, and the relationships between preoperative risk factors and PALN positivity were identified. Clinicopathological and prognostic factors for overall survival were analyzed. Micrometastasis was investigated by immunohistochemistry. RESULTS 400 patients were enrolled. PALN positivity by hematoxylin and eosin staining, micrometastasis, and negative were found in 46 (11%), 32 (8%), and 322 (81%) patients, respectively. The median overall survival times of patients with PALN positivity, including micrometastasis, was 22.5 months. Multivariate logistic regression identified borderline or locally advanced status (p=0.037), elevated preoperative carbohydrate antigen (CA) 19-9 level (p<0.001), larger tumor size ≥30 mm (p=0.001) and larger PALN size ≥10 mm (p=0.019) as independent preoperative risk factors of PALN positivity. Multivariate overall survival analysis demonstrated borderline or locally advanced status (p=0.013), elevated preoperative CA19-9 level (p<0.001) and PALN positivity (p=0.048) were independent poor prognostic factors. CONCLUSIONS Borderline or locally advanced status, elevated preoperative CA19-9 level, and larger tumor and PALN size were risk factors for PALN positivity, and thus, they may contribute to the optimization of preoperative treatments for patients with potential PALN positivity.
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Lindemann J, du Toit L, Kotze U, Bernon M, Krige J, Jonas E. Survival equivalence in patients treated for borderline resectable and unresectable locally advanced pancreatic ductal adenocarcinoma: a systematic review and network meta-analysis. HPB (Oxford) 2021; 23:173-186. [PMID: 33268268 DOI: 10.1016/j.hpb.2020.09.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 08/04/2020] [Accepted: 09/29/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The clinical relevance of subdivision of non-metastatic pancreatic ductal adenocarcinoma (PDAC) into locally advanced borderline resectable (LA-BR) and locally advanced unresectable (LA-UR) has been questioned. We assessed equivalence of overall survival (OS) in patients with LA-BR and LA-UR PDAC. METHODS A systematic review was performed of studies published January 1, 2009 to August 21, 2019, reporting OS for LA-BR and LA-UR patients treated with or without neoadjuvant therapy (NAT), with or without surgical resection. A frequentist network meta-analysis was used to assess the primary outcome (hazard ratio for OS) and secondary outcomes (OS in LA-BR, LA-UR, and upfront resectable (UFR) PDAC). RESULTS Thirty-nine studies, comprising 14,065 patients in a network of eight unique treatment subgroups were analysed. Overall survival was better for LA-BR than LA-UR patients following surgery both with and without NAT. Neoadjuvant therapy prior to surgery was associated with longer OS for UFR, LA-BR, and LA-UR tumours, compared to upfront surgery. CONCLUSION Survival between the LA-BR and LA-UR subgroups was not equivalent. This subdivision is useful for prognostication, but likely unhelpful in treatment decision making. Our data supports NAT regardless of initial disease extent. Individual patient data assessment is needed to accurately estimate the benefit of NAT.
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Affiliation(s)
- Jessica Lindemann
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Anzio Road, Observatory, 7925, Cape Town, South Africa; Department of Surgery, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, 63110, USA
| | - Leon du Toit
- Department of Anaesthesia and Perioperative Medicine, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Anzio Road, Observatory, 7925, Cape Town, South Africa
| | - Urda Kotze
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Anzio Road, Observatory, 7925, Cape Town, South Africa
| | - Marc Bernon
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Anzio Road, Observatory, 7925, Cape Town, South Africa
| | - Jake Krige
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Anzio Road, Observatory, 7925, Cape Town, South Africa
| | - Eduard Jonas
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Anzio Road, Observatory, 7925, Cape Town, South Africa.
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Yu Q, Jobin C, Thomas RM. Implications of the microbiome in the development and treatment of pancreatic cancer: Thinking outside of the box by looking inside the gut. Neoplasia 2021; 23:246-256. [PMID: 33418277 PMCID: PMC7804346 DOI: 10.1016/j.neo.2020.12.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 12/23/2020] [Accepted: 12/23/2020] [Indexed: 12/19/2022]
Abstract
Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related death in the United States. As one of the most lethal cancer types, the prognosis for patients diagnosed with pancreatic cancer remains dismal and novel investigations are urgently needed. Evidence for an association of microbes with pancreatic cancer risk, development, treatment response, and post-treatment survivorship is rapidly developing. Herein, we provide an overview on the role of the microbiome as it relates to the natural history of pancreatic cancer, including host immune interactions, alterations in metabolism, direct carcinogenic effect, and its role in treatment response.
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Affiliation(s)
- Qin Yu
- Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA
| | - Christian Jobin
- Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA; Department of Infectious Diseases and Immunology, University of Florida College of Medicine, Gainesville, FL, USA; Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL, USA
| | - Ryan M Thomas
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA; Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA.
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Ueno M, Morinaga S, Hashimoto Y, Umemoto K, Sasahira N, Saiura A, Seyama Y, Honda G, Ioka T, Takahashi H, Miyamoto A, Nakamori S, Unno M, Takadate T, Mizuno N, Shimizu Y, Ueno H, Sugiyama M, Fukutomi A, Shimizu S, Okusaka T, Furuse J. Tolerability of Nab-Paclitaxel Plus Gemcitabine as Adjuvant Setting in Japanese Patients With Resected Pancreatic Cancer: Phase I Study. Pancreas 2021; 50:83-88. [PMID: 33370027 PMCID: PMC7748052 DOI: 10.1097/mpa.0000000000001702] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 10/23/2020] [Indexed: 12/24/2022]
Abstract
OBJECTIVE The combination of gemcitabine plus nab-paclitaxel (GnP) has not been studied in Japanese patients with resectable pancreatic cancer (PC). This study aimed to assess the tolerability of adjuvant GnP in Japanese patients with resected PC. METHODS This was a Phase I, open-label, multicenter, single-arm study of patients with resected PC in Japan. Patients received 125 mg/m2 of nab-paclitaxel and 1000 mg/m2 of gemcitabine on days 1, 8, and 15 of a 28-day cycle for a total of 6 cycles. The primary end point was tolerability, defined as the absence of specific grade 3 or higher treatment-related adverse events by the end of cycle 2. Secondary end points included safety, disease-free survival, and overall survival. RESULTS Forty-one patients were enrolled between June 2016 and February 2017 (median age, 68 years; 51% male; stage II, 95%). Gemcitabine plus nab-paclitaxel met the tolerability criteria in 39 of the 40 patients included in the tolerability analysis set (97.5%). The most common treatment-related adverse events were leukopenia, neutropenia, alopecia, and peripheral sensory neuropathy. After a follow-up of 30.1 months, median disease-free survival was 17.0 months and median overall survival was not reached. CONCLUSIONS These results show that adjuvant GnP is tolerable in Japanese patients with resected PC.Clinical Trial Registration No.: JapicCTI-163179.
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Affiliation(s)
- Makoto Ueno
- From the Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center
| | - Soichiro Morinaga
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama
| | - Yusuke Hashimoto
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa
| | - Kumiko Umemoto
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa
| | - Naoki Sasahira
- Department of Hepatobiliary and Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research
| | - Akio Saiura
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research
| | - Yasuji Seyama
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery
| | - Goro Honda
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo
| | - Tatsuya Ioka
- Departments of Cancer Survey and Gastrointestinal Oncology
| | | | - Atsushi Miyamoto
- Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka
| | - Shoji Nakamori
- Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Miyagi
| | - Tatsuyuki Takadate
- Department of Surgery, Tohoku University Graduate School of Medicine, Miyagi
| | | | - Yasuhiro Shimizu
- Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya
| | - Hideki Ueno
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo
| | - Masanori Sugiyama
- Department of Surgery, Kyorin University, School of Medicine, Mitaka
| | - Akira Fukutomi
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka
| | - Satoshi Shimizu
- Department of Gastroenterology, Saitama Cancer Center, Saitama
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo
| | - Junji Furuse
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Japan
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Ishido K, Hakamada K, Kimura N, Miura T, Wakiya T. Essential updates 2018/2019: Current topics in the surgical treatment of pancreatic ductal adenocarcinoma. Ann Gastroenterol Surg 2021; 5:7-23. [PMID: 33532676 PMCID: PMC7832965 DOI: 10.1002/ags3.12379] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 06/23/2020] [Accepted: 06/25/2020] [Indexed: 12/17/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is highly malignant. While cancers in other organs have shown clear improvements in 5-year survival, the 5-year survival rate of pancreatic cancer is approximately 10%. Early relapse and metastasis are not uncommon, making it difficult to achieve an acceptable prognosis even after complete surgical resection of the pancreas. Studies have been performed on various treatments to improve the prognosis of PDAC, and multidisciplinary approaches including non-surgical treatments have led to gradual improvement. In the present literature review, we have described the significance of anatomical and biological resectability criteria, the concept of R0 resection in surgical treatment, the feasibility of minimally invasive surgery, the remarkable development of perioperative chemotherapy, the effectiveness of conversion surgery for unresectable PDAC, and ongoing challenges in PDAC treatment. We also provide an essential update on these subjects by focusing on recent trends and topics.
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Affiliation(s)
- Keinosuke Ishido
- Department of Gastroenterological SurgeryHirosaki University Graduate School of MedicineHirosakiJapan
| | - Kenichi Hakamada
- Department of Gastroenterological SurgeryHirosaki University Graduate School of MedicineHirosakiJapan
| | - Norihisa Kimura
- Department of Gastroenterological SurgeryHirosaki University Graduate School of MedicineHirosakiJapan
| | - Takuya Miura
- Department of Gastroenterological SurgeryHirosaki University Graduate School of MedicineHirosakiJapan
| | - Taiichi Wakiya
- Department of Gastroenterological SurgeryHirosaki University Graduate School of MedicineHirosakiJapan
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Yu Y, Zheng P, Chen Y, Wang B, Paul ME, Tao P, Wang D, Li H, Gu B, Gao L, Wang D, Chen H. Advances and challenges of neoadjuvant therapy in pancreatic cancer. Asia Pac J Clin Oncol 2020; 17:425-434. [PMID: 33164329 DOI: 10.1111/ajco.13504] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 07/10/2020] [Indexed: 01/06/2023]
Abstract
Pancreatic cancer has been becoming the second cause of cancer death in the western world, and its disease burden has increased. Neoadjuvant therapy is one of the current research hotspots in the field of pancreatic cancer, aiming to improve the surgical rate and prognosis of pancreatic cancer. Based on the latest evidence, this review discussed neoadjuvant therapy in pancreatic cancer from the following three aspects: patient selection, protocols selection of neoadjuvant therapy, and treatment response evaluation and resectability prediction. A big controversy existed on the indications of neoadjuvant treatment, but it was agreed that any patient who is likely to achieve R0 resection due to neoadjuvant therapy should be the targeted population. A variety of chemotherapy regimens were tried for neoadjuvant therapy in pancreatic cancer, and FOLFIRINOX and Nab-Paclitaxel plus Gemcitabine are two preferred regimens at present. It was challenging to evaluate treatment response and predict resectability after neoadjuvant therapy, although imaging by CT is widely used. Based on new findings of the remarkable performance of several chemotherapy regimens with or without radiotherapy, the neoadjuvant indications of pancreatic cancer have extended in recent years. However, it is still a challenge to assess the neoadjuvant treatment response and determine the timing of surgery.
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Affiliation(s)
- Yang Yu
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Peng Zheng
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Yajing Chen
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Bofang Wang
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Maswikiti Ewetse Paul
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Pengxian Tao
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Dengfeng Wang
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Haiyuan Li
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Baohong Gu
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Lei Gao
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Dan Wang
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Hao Chen
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Key Laboratory of the Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P. R. China
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43
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Okada K, Uemura K, Kondo N, Sumiyoshi T, Nakagawa N, Seo S, Otsuka H, Urabe K, Murakami Y, Takahashi S. Prognostic significance of dissecting the nerve plexus around the common hepatic artery in pancreatic cancer. Langenbecks Arch Surg 2020; 406:679-689. [DOI: 10.1007/s00423-020-02025-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 11/03/2020] [Indexed: 01/08/2023]
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Laura A, Anna C, Cinquepalmi M, Giovanni M, Sole MM, Nava AK, Niccolò P, Giuseppe N, Stefano V, Paolo A, Francesco D, Giovanni R. Is Complete Pathologic Response in Pancreatic Cancer Overestimated? A Systematic Review of Prospective Studies. J Gastrointest Surg 2020; 24:2336-2348. [PMID: 32583324 DOI: 10.1007/s11605-020-04697-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 06/11/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND In literature, percentages of pathologic complete response (pCR) in patients presenting with resectable (RES), borderline resectable (BLR) or locally advanced (LA) pancreatic cancer (PaC) after neoadjuvant treatment (NADT) are variable, ranging 0-33%. Those data come mostly from retrospective reviews of single centres. The objective of this systematic review is to assess the incidence of pCR. METHODS Following the criteria of the PRISMA statement, a literature search was conducted looking for prospective papers focusing on neoadjuvant treatment in PaC. Retrospective papers, other than ductal carcinoma histologies and trials including metastatic patients, were excluded from the present review. Data extraction was carried out by 3 independent investigators. Meta-analysis was performed with ProMeta3 Software (Internovi, 2015). PROSPERO registry: CRD42018095641. RESULTS The literature search of Embase, Cochrane and Medline with the terms "neoadjuvant OR preoperative", "pancreatic OR pancreas" and "cancer OR adenocarcinoma OR tumor" led to the identification of 3128 papers. We restricted the search to humans, last 10 years and English language articles resulting in 1158 eligible articles to review. Extended paper revision led to the inclusion of 27 papers. Complete pathologic response ranged 0-11.11%, at the meta-analysis 4% (95% CI 3-5%), in prospective studies 0-9.09% and in prospective databases 1.63-11.11%. CONCLUSIONS Pathologic complete response in pancreatic cancer is actually infrequent: high-quality studies provide a more reliable picture of neoadjuvant effects, high rates of pCR are reported in selected retrospective studies but it is overestimated.
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Affiliation(s)
- Antolino Laura
- General Surgery Unit, Department of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University of Rome, Via di Grottorassa 1035, 00168, Rome, Italy
| | - Crovetto Anna
- General Surgery Unit, Department of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University of Rome, Via di Grottorassa 1035, 00168, Rome, Italy
| | - Matteo Cinquepalmi
- General Surgery Unit, Department of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University of Rome, Via di Grottorassa 1035, 00168, Rome, Italy.
| | - Moschetta Giovanni
- General Surgery Unit, Department of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University of Rome, Via di Grottorassa 1035, 00168, Rome, Italy
| | - Mattei Maria Sole
- General Surgery Unit, Department of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University of Rome, Via di Grottorassa 1035, 00168, Rome, Italy
| | - Andrea Kazemi Nava
- Hepatopancreaticobiliary Group, Saint Vincent's University Hospital, Dublin, Ireland
| | - Petrucciani Niccolò
- General Surgery Unit, Department of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University of Rome, Via di Grottorassa 1035, 00168, Rome, Italy
| | - Nigri Giuseppe
- General Surgery Unit, Department of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University of Rome, Via di Grottorassa 1035, 00168, Rome, Italy
| | - Valabrega Stefano
- General Surgery Unit, Department of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University of Rome, Via di Grottorassa 1035, 00168, Rome, Italy
| | - Aurello Paolo
- General Surgery Unit, Department of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University of Rome, Via di Grottorassa 1035, 00168, Rome, Italy
| | - D'Angelo Francesco
- General Surgery Unit, Department of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University of Rome, Via di Grottorassa 1035, 00168, Rome, Italy
| | - Ramacciato Giovanni
- General Surgery Unit, Department of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University of Rome, Via di Grottorassa 1035, 00168, Rome, Italy
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Okada K, Murakami Y, Uemura K, Kondo N, Nakagawa N, Seo S, Otsuka H, Takahashi S. Neoadjuvant therapy for pancreatic cancer: an intention-to-treat analysis. Langenbecks Arch Surg 2020; 405:623-633. [PMID: 32592044 DOI: 10.1007/s00423-020-01914-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 06/22/2020] [Indexed: 01/13/2023]
Abstract
PURPOSE This study aimed to reassess the duration of neoadjuvant therapy (NAT) for patients with borderline resectable pancreatic cancer (BRPC). METHODS The medical records of patients with BRPC who received NAT before intended curative resection were retrospectively reviewed. Patient demographics, clinicopathological factors, and prognostic factors for overall survival were analyzed. The serum carbohydrate antigen (CA) 19-9 level was examined monthly during NAT. RESULTS A total of 118 patients with BRPC were enrolled. The median survival time and 5-year overall survival were 28.0 months and 31%, respectively. Three months after NAT, the CA19-9 levels were normal in 57% of the patients, and 92% underwent resection. Multivariate analysis showed that radiological partial response (hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.26-0.99; p = 0.047); a normal CA19-9 level after NAT (HR, 0.30; 95% CI, 0.22-0.66; p = 0.006); and tumor resection (HR, 0.29; 95% CI, 0.13-0.67; p = 0.005) were independent predictors of better survival. The median CA19-9 level and the rate of normal CA19-9 levels before and after NAT were 256 (interquartile range (IQR), 23-1197) U/mL and 33%, and 27 (IQR, 7-176) U/mL and 57%, respectively. CONCLUSION A normal CA19-9 level after NAT was an independent predictor of better survival in patients with BRPC. A longer NAT duration might contribute to improved prognosis of patients with elevated CA19-9 levels.
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Affiliation(s)
- Kenjiro Okada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Yoshiaki Murakami
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kenichiro Uemura
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Naru Kondo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Naoya Nakagawa
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shingo Seo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroyuki Otsuka
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shinya Takahashi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
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A contemporary evidence basis for neoadjuvant chemotherapy in upfront resectable pancreatic adenocarcinoma: a systematic review of the literature. JOURNAL OF PANCREATOLOGY 2020. [DOI: 10.1097/jp9.0000000000000037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Irie H, Suzuki R, Takagi T, Sugimoto M, Konno N, Sato Y, Hikichi T, Nakamura J, Hashimoto M, Ohira H. Interstitial lung disease in advanced pancreatic ductal adenocarcinoma patients treated with gemcitabine and nab-paclitaxel combination therapy: a retrospective analysis. Cancer Chemother Pharmacol 2020; 85:517-523. [PMID: 31691078 DOI: 10.1007/s00280-019-03983-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 10/22/2019] [Indexed: 12/30/2022]
Abstract
PURPOSE Gemcitabine and nab-paclitaxel (GnP) combination therapy is a standard regimen for advanced pancreatic ductal adenocarcinoma (PDAC) worldwide; however, concerns regarding the unexpectedly high incidence of interstitial lung disease (ILD) have emerged. We investigated the incidence and predictive factors of ILD in PDAC patients who were treated with GnP combination therapy. METHODS Thirty-seven patients treated with GnP therapy as either 1st or 2nd line treatment were included, among whom seven developed ILD (18.9%). The clinical characteristics (age, etc.) were compared between patients with and without ILD. The diagnostic yield of the markers to predict the presence of ILD was calculated. The clinical course of the seven patients with ILD was summarized. Survival analysis was performed using the Kaplan-Meier method and log-rank test. RESULTS The median age was higher in patients with ILD (73.0 vs. 65.0 years old, p = 0.03), while no differences were observed in the other clinical characteristics. Among the three investigated markers, SP-D showed the best diagnostic yield (AUC = 0.94) for diagnosing ILD. Though one patient required steroid therapy and the discontinuation of GnP therapy, all patients could undergo subsequent treatment. In the survival analysis, the median survival time of PDAC patients with ILD was comparable to that of patients without ILD (25.1 vs. 24.5 months, p = 0.98). CONCLUSION ILD was observed in 18.9% of PDAC patients treated with GnP therapy. With appropriate management, no prognostic influence was observed.
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Affiliation(s)
- Hiroki Irie
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan
| | - Rei Suzuki
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
| | - Tadayuki Takagi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan
| | - Mitsuru Sugimoto
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan
| | - Naoki Konno
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan
| | - Yuki Sato
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan
| | - Takuto Hikichi
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
| | - Jun Nakamura
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
| | - Minami Hashimoto
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan
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Pan L, Fang J, Tong C, Chen M, Zhang B, Juengpanich S, Wang Y, Cai X. Survival benefits of neoadjuvant chemo(radio)therapy versus surgery first in patients with resectable or borderline resectable pancreatic cancer: a systematic review and meta-analysis. World J Surg Oncol 2019; 18:1. [PMID: 31892339 PMCID: PMC6937851 DOI: 10.1186/s12957-019-1767-5] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 12/02/2019] [Indexed: 12/28/2022] Open
Abstract
Background Pancreatic adenocarcinoma is a highly lethal malignancy. Neoadjuvant chemo(radio)therapy [NAC(R)T] is recommended to use for borderline resectable pancreatic cancer (BRPC) and high-risk resectable pancreatic cancer (RPC), but no high-level evidence exists. Methods We searched PubMed, EMBASE, Web of Science, and Cochrane library to identify trials comparing survival data of NAC(R)T with SF for RPC or BRPC. Overall survival (OS) was synthesized in analysis of all the patients (intention-to-treat [ITT] analysis) and resected patients respectively. Results The meta-analysis included 17 trials with 2286 participants. For BRPC, NAC(R)T improved OS both in ITT analysis (HR, 0.49; 95% CI, 0.37–0.65; P < 0.001) and in analysis of resected patients (HR, 0.66; 95% CI, 0.51–0.85; P = 0.001) in comparison to SF, accompanied with comparable overall resection rate [odds ratio (OR), 0.69; 95% Cl, 0.41–1.16; P = 0.159]. Disease-free survival, R0 rate, and recurrence were also in favor of NAC(R)T. For RPC, OS in analysis of resected patients was higher with NAC(R)T (HR, 0.75; 95% CI, 0.63–0.89; P = 0.001), but OS in ITT analysis was similar (HR, 1.02; 95% CI, 0.85–1.22; P = 0.818). The overall resection rate (OR, 0.50; 95% Cl, 0.25–0.99; P = 0.048) was lower, but R0 rate was higher with NAC(R)T. No differences in disease-free survival and recurrence between NAC(R)T and SF. Survival benefits of NAC(R)T basically persisted across sensitivity and subgroup analyses. Conclusions This meta-analysis demonstrates that NAC(R)T can provide survival benefits in BRPC patients and a subgroup of RPC patients compared with SF. Future research should focus on investigating the potential biomarkers to screen the subgroup of RPC patients who can benefit from neoadjuvant therapy. Trial registration CRD42018103086.
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Affiliation(s)
- Long Pan
- Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.,Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou, 310016, China.,Institute of Minimally Invasive Surgery of Zhejiang University, Hangzhou, 310016, China
| | - Jing Fang
- Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.,Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou, 310016, China
| | - Chenhao Tong
- Department of General Surgery, Shaoxing People's Hospital, Zhejiang University School of Medicine, Shaoxing, 312000, China
| | - Mingyu Chen
- Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.,Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou, 310016, China.,Institute of Minimally Invasive Surgery of Zhejiang University, Hangzhou, 310016, China
| | - Bin Zhang
- Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.,Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou, 310016, China.,Institute of Minimally Invasive Surgery of Zhejiang University, Hangzhou, 310016, China
| | - Sarun Juengpanich
- Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China
| | - Yifan Wang
- Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China. .,Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou, 310016, China. .,Institute of Minimally Invasive Surgery of Zhejiang University, Hangzhou, 310016, China.
| | - Xiujun Cai
- Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China. .,Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou, 310016, China. .,Institute of Minimally Invasive Surgery of Zhejiang University, Hangzhou, 310016, China.
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Chen X, Yu Q, Liu Y, Sheng Q, Shi K, Wang Y, Li M, Zhang Z, He Q. Synergistic cytotoxicity and co-autophagy inhibition in pancreatic tumor cells and cancer-associated fibroblasts by dual functional peptide-modified liposomes. Acta Biomater 2019; 99:339-349. [PMID: 31499197 DOI: 10.1016/j.actbio.2019.09.003] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 08/17/2019] [Accepted: 09/04/2019] [Indexed: 12/12/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDA) is a highly fatal disease with 5-year survival of ∼8.5%. Nanoplatforms such as nab-paclitaxel and nanoliposomal irinotecan demonstrate superiority and utility in treating different progressions of PDA by prolonging the median overall survival by only a few months. Due to the dense surrounding stroma and the high autophagy in pancreatic cancer, integrin ɑvβ3 targeting, acid environmental sensitive, TR peptide-modified liposomal platforms loaded with combined autophagy inhibiting hydroxychloroquine (HCQ), and cytotoxic paclitaxel (PTX) were designed (TR-PTX/HCQ-Lip) to accomplish the aim of synergistically killing tumor cells while inhibiting stroma fibrosis. The results showed that TR peptide-modified liposomes (TR-Lip) have superior targeting and penetrating effects both in vitro and in vivo. TR-PTX/HCQ-Lip efficiently inhibited autophagy in pancreatic cells and surrounding cancer-associated fibroblasts. The synergistic anti-fibrosis roles were also confirmed both in vitro and in vivo, all of which contributes to the enhanced curative effects of TR-PTX/HCQ-Lip in both heterogenetic and orthotopic pancreatic cancer models. STATEMENT OF SIGNIFICANCE: Autophagy plays a significant role in pancreatic ductal adenocarcinoma, especially in activating cancer associated fibroblasts which is also related to collagen generation that promotes the formation of dense stroma, which hinder the cytotoxic drugs to target and kill cancer cells. In this study, we designed integrin ɑvβ3 targeting, acid environmental sensitive liposomal platforms to co-loaded paclitaxel and the autophagy inhibitor hydroxychloroquine. The results showed that the muti-functional liposomes can target to the pancreatic tumor and efficiently kill tumor cells and inhibit stroma fibrosis, thus improve the therapeutic effect in orthotopic pancreatic cancer models.
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Affiliation(s)
- Xiaoxiao Chen
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China
| | - Qianwen Yu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China
| | - Yinke Liu
- West China School of Stomotology, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, PR China
| | - Qinglin Sheng
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China
| | - Kairong Shi
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China
| | - Yang Wang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China
| | - Man Li
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China
| | - Zhirong Zhang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China
| | - Qin He
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.
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50
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Lee YS, Lee JC, Yang SY, Kim J, Hwang JH. Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer according to intention-to-treat and per-protocol analysis: A systematic review and meta-analysis. Sci Rep 2019; 9:15662. [PMID: 31666626 PMCID: PMC6821820 DOI: 10.1038/s41598-019-52167-9] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 10/14/2019] [Indexed: 12/11/2022] Open
Abstract
The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US). The aim of this study was to investigate the survival gain of NAT over US in resectable PC. PubMed and EMBASE were searched for studies comparing survival outcomes between NAT and US for resectable PC until June 2018. Overall survival (OS) was analyzed according to treatment strategy (NAT versus US) and analytic methods (intention-to-treat analysis (ITT) and per-protocol analysis (PP)). In 14 studies, 2,699 and 6,992 patients were treated with NAT and US, respectively. Although PP analysis showed the survival gain of NAT (HR 0.72, 95% CI 0.68-0.76), ITT analysis did not show the statistical significance (HR 0.96, 95% CI 0.82-1.12). However, NAT completed with subsequent surgery showed better survival over US completed with adjuvant therapy (HR 0.82, 95% CI 0.71-0.93). In conclusion, the supporting evidence for NAT in resectable PC was insufficient because the benefit was not demonstrated in ITT analysis. However, among the patients who completed both surgery and chemotherapy, NAT showed survival benefit over adjuvant therapy. Therefore, NAT could have a role of triaging the patients for surgery even in resectable PC.
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Affiliation(s)
- Yoon Suk Lee
- Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Republic of Korea
| | - Jong-Chan Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Se Yeol Yang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jaihwan Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
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