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Ross SB, Popover J, Sucandy I, Christodoulou M, Pattilachan TM, Rosemurgy AS. The Oncological Stress Test of Neoadjuvant Therapy: A Systematic Review in Outcomes of Neoadjuvant Therapy Compared to Upfront Resection Approach for Borderline Resectable Pancreatic Adenocarcinoma. Am Surg 2024; 90:3061-3073. [PMID: 38635295 DOI: 10.1177/00031348241248703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/19/2024]
Abstract
Pancreatic adenocarcinoma, increasingly diagnosed in the United States, has a disheartening initial resection rate of 15%. Neoadjuvant therapy, particularly FOLFIRINOX and gemcitabine-based regimens, is gaining favor for its potential to improve resectability rates and achieving microscopically negative margins (R0) in borderline resectable cases, marked by intricate arterial or venous involvement. Despite surgery being the sole curative approach, actual benefit of neoadjuvant therapy remains debatable. This study scrutinizes current literature on oncological outcomes post-resection of borderline resectable pancreatic cancer. A MEDLINE/PubMed search was conducted to systematically compare oncological outcomes of patients treated with either neoadjuvant therapy with intent of curative resection or an "upfront resection" approach. A total of 1293 studies were initially screened and 30 were included (n = 1714) in this analysis. All studies included data on outcomes of patients with borderline resectable pancreatic adenocarcinoma being treated with neoadjuvant therapy (n = 1387) or a resection-first approach (n = 356). Patients treated with neoadjuvant therapy underwent resection 52% of the time, achieving negative margins of 43% (n = 601). Approximately 77% of patients who received an upfront resection underwent a successful resection, with 39% achieving negative margins. Neoadjuvant therapy remains marginally efficacious in treatment of borderline resectable pancreatic adenocarcinoma, as patients undergo an operation and successful resection less often when treated with neoadjuvant therapy. Rates of curative resection are comparable, despite neoadjuvant therapy being a primary recommendation in borderline resectable cases and employed more often than upfront resection. Upfront resection may offer improved resection rates by intention-to-treat, which can provide more patients with paths to curative resection.
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Affiliation(s)
- Sharona B Ross
- Digestive Health Institute, AdventHealth Tampa, Tampa, FL, USA
| | - Jesse Popover
- Digestive Health Institute, AdventHealth Tampa, Tampa, FL, USA
| | - Iswanto Sucandy
- Digestive Health Institute, AdventHealth Tampa, Tampa, FL, USA
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Aploks K, Kim M, Stroever S, Ostapenko A, Sim YB, Sooriyakumar A, Rahimi-Ardabily A, Seshadri R, Dong XD. Radiation therapy prior to a pancreaticoduodenectomy for adenocarcinoma is associated with longer operative times and higher blood loss. World J Gastrointest Surg 2023; 15:1663-1672. [PMID: 37701691 PMCID: PMC10494586 DOI: 10.4240/wjgs.v15.i8.1663] [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: 03/29/2023] [Revised: 05/12/2023] [Accepted: 06/12/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Pancreatic adenocarcinoma is currently the fourth leading cause of cancer-related deaths in the United States. In patients with "borderline resectable" disease, current National Comprehensive Cancer Center guidelines recommend the use of neoadjuvant chemoradiation prior to a pancreaticoduodenectomy. Although neoadjuvant radiotherapy may improve negative margin resection rate, it is theorized that its administration increases operative times and complexity. AIM To investigate the association between neoadjuvant radiotherapy and 30-d morbidity and mortality outcomes among patients receiving a pancreaticoduodenectomy for pancreatic adenocarcinoma. METHODS Patients listed in the 2015-2019 National Surgery Quality Improvement Program data set, who received a pancreaticoduodenectomy for pancreatic adenocarcinoma, were divided into two groups based off neoadjuvant radiotherapy status. Multivariable regression was used to determine if there is a significant correlation between neoadjuvant radiotherapy, perioperative blood transfusion status, total operative time, and other perioperative outcomes. RESULTS Of the 11458 patients included in the study, 1470 (12.8%) underwent neoadjuvant radiotherapy. Patients who received neoadjuvant radiotherapy were significantly more likely to require a perioperative blood transfusion [adjusted odds ratio (aOR) = 1.58, 95% confidence interval (CI): 1.37-1.82; P < 0.001] and have longer surgeries (insulin receptor-related receptor = 1.14, 95%CI: 1.11-1.16; P < 0.001), while simultaneously having lower rates of organ space infections (aOR = 0.80, 95%CI: 0.66-0.97; P = 0.02) and pancreatic fistula formation (aOR = 0.50, 95%CI: 0.40-0.63; P < 0.001) compared to those who underwent surgery alone. CONCLUSION Neoadjuvant radiotherapy, while not associated with increased mortality, will impact the complexity of surgical resection in patients with pancreatic adenocarcinoma.
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Affiliation(s)
- Krist Aploks
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Minha Kim
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Stephanie Stroever
- Department of Research and Innovation, Nuvance Health, Danbury, CT 06810, United States
| | - Alexander Ostapenko
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Young Bo Sim
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | | | | | - Ramanathan Seshadri
- Division of Surgical Oncology/Hepato-Pancreato-Biliary Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Xiang Da Dong
- Division of Surgical Oncology/Hepato-Pancreato-Biliary Surgery, Danbury Hospital, Danbury, CT 06810, United States
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Tsiotos GG, Ballian N, Milas F, Ziogou P, Papaioannou D, Salla C, Athanasiadis I, Stavridi F, Strimpakos A, Psomas M, Kostopanagiotou G. Portal-mesenteric vein resection for pancreatic cancer: Results in par with the defined benchmark outcomes. Front Surg 2023; 9:1069802. [PMID: 36704507 PMCID: PMC9871782 DOI: 10.3389/fsurg.2022.1069802] [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: 10/14/2022] [Accepted: 12/20/2022] [Indexed: 01/11/2023] Open
Abstract
Background Patients with pancreatic cancer (PC), which may involve major peripancreatic vessels, have been generally excluded from surgery, as resection was deemed futile. The purpose of this study was to analyze the results of portomesenteric vein resection in borderline resectable or locally advanced PC. This study comprises the largest series of such patients in Greece. Materials and Methods Investigator-initiated, retrospective, noncomparative study of patients with borderline resectable or locally advanced adenocarcinoma undergoing pancreatectomy en-block with portal and/or superior mesenteric vein resection in a tertiary referral center in Greece between January 2014 and October 2021. Follow-up was complete up to December 2021. Operative and outcome measures were determined. Results Forty patients were included. Neoadjuvant therapy was administered to only 58% and was associated with smaller tumor size (median: 2.9 cm vs. 4.2 cm, p = 0.004), but not with increased survival. Though venous wall infiltration was present in 55%, it was not associated with tumor size, or Eastern Cooperative Oncology Group (ECOG) status. Resection was extensive: a median of 27 LNs were retrieved, R0 resection rate (≥1 mm) was 87%, and median length of resected vein segments was 3 cm, requiring interposition grafts in 40% (polytetrafluoroethylene). Median ICU stay was 0 days and length of hospitalization 9 days. Postoperative mortality was 2.5%. Median follow-up was 46 months and median overall survival (OS) was 24 months. Two-, 3- and 5-year OS rates were 49%, 33%, and 22% respectively. All outcomes exceeded benchmark cutoffs. Lower ECOG status was positively correlated with longer survival (ECOG-0: 32 months, ECOG-1: 24 months, ECOG-2: 12 months, p = 0.02). Conclusion This series of portomesenteric resection in borderline resectable or locally advanced PC demonstrated a median survival of 2 years, extending to 32 months in patients with good performance status, which meet or exceed current outcome benchmarks.
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Affiliation(s)
- Gregory G. Tsiotos
- Departments of Surgery, Mitera-Hygeia Hospitals, Athens, Greece,Correspondence: Gregory G. Tsiotos
| | | | - Fotios Milas
- Departments of Surgery, Mitera-Hygeia Hospitals, Athens, Greece
| | - Panoraia Ziogou
- Departments of Surgery, Mitera-Hygeia Hospitals, Athens, Greece
| | | | - Charitini Salla
- Departments of Cytology, Mitera-Hygeia Hospitals, Athens, Greece
| | - Ilias Athanasiadis
- Departments of Medical Oncology, Mitera-Hygeia Hospitals, Athens, Greece
| | - Flora Stavridi
- Departments of Medical Oncology, Mitera-Hygeia Hospitals, Athens, Greece
| | - Alexios Strimpakos
- Departments of Medical Oncology, Mitera-Hygeia Hospitals, Athens, Greece
| | - Maria Psomas
- Departments of Anesthesiology, Mitera-Hygeia Hospitals, Athens, Greece
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Fossaert V, Mimmo A, Rhaiem R, Rached LJ, Brasseur M, Brugel M, Pegoraro F, Sanchez S, Bouché O, Kianmanesh R, Piardi T. Neoadjuvant chemotherapy for borderline resectable and upfront resectable pancreatic cancer increasing overall survival and disease-free survival? Front Oncol 2022; 12:980659. [PMID: 36387257 PMCID: PMC9640996 DOI: 10.3389/fonc.2022.980659] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 09/06/2022] [Indexed: 08/29/2023] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm. Surgery is the factual curative option, but most patients present with advanced disease. In order to increase resectability, results of neoadjuvant chemotherapy (NAC) on metastatic disease were extrapolated to the neoadjuvant setting by many centers. The aim of our study was to retrospectively evaluate the outcome of patients who underwent upfront surgery (US)-PDAC and borderline (BR)-PDAC, and those resected after NAC to determine prognostic factors that might affect the outcome in these resected patients. METHODS One hundred fifty-one patients between January 2012 and March 2021 in our department were reviewed. Epidemiological characteristics and pre-operative induction treatment were assessed. Pathological reports were analyzed to evaluate the quality of oncological resection (R0/R1). Post-operative mortality and morbidity and survival data were reviewed. RESULTS One hundred thirteen patients were addressed for US, and 38 were considered BR and referred for surgery after induction chemotherapy. The pancreatic resection R0 was 71.5% and R1 28.5%. pT3 rate was significantly higher in the US than BR (58,4% vs 34,2%, p= 0.005). The mean OS and DFS rates were 29.4 months 15.9 months respectively. There was no difference between OS and DFS of US vs BR patients. N0 patients had significantly longer OS and DFS (p=<0.001). R0 patients had significantly longer OS (p=0.03) and longer DFS (P=0.08). In the multivariate analysis, the presence of postoperative pancreatic fistula, R1 resection, N+ and not access to adjuvant chemotherapy were bad prognostic factors of OS. CONCLUSIONS Our study suggests the benefits of NAC for BR patients in downstaging tumors and rendering them amenable to resection, with same oncological result compared to US.
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Affiliation(s)
- Violette Fossaert
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Antonio Mimmo
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Rami Rhaiem
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Linda J. Rached
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Mathilde Brasseur
- Department of Digestive Medical Oncology, University Reims Champagne-Ardenne, Reims, France
| | - Mathias Brugel
- Department of Digestive Medical Oncology, University Reims Champagne-Ardenne, Reims, France
| | - Francesca Pegoraro
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
- Division of Hepato-Bilio-Pancreatic, Minimally Invasive, Robotic Surgery and Kidney Transplantation, Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy
| | - Stephane Sanchez
- Pôle Territorial Santé Publique et Performance des Hôpitaux Champagne Sud, University Reims Champagne-Ardenne, Troyes, France
| | - Olivier Bouché
- Department of Digestive Medical Oncology, University Reims Champagne-Ardenne, Reims, France
| | - Reza Kianmanesh
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Tullio Piardi
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
- Department of Surgery, Hepato-Bilio-Pancreatic and Metabolic Unit, University Reims Champagne-Ardenne, Troyes, France
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Katz MHG, Shi Q, Meyers J, Herman JM, Chuong M, Wolpin BM, Ahmad S, Marsh R, Schwartz L, Behr S, Frankel WL, Collisson E, Leenstra J, Williams TM, Vaccaro G, Venook A, Meyerhardt JA, O’Reilly EM. Efficacy of Preoperative mFOLFIRINOX vs mFOLFIRINOX Plus Hypofractionated Radiotherapy for Borderline Resectable Adenocarcinoma of the Pancreas: The A021501 Phase 2 Randomized Clinical Trial. JAMA Oncol 2022; 8:1263-1270. [PMID: 35834226 PMCID: PMC9284408 DOI: 10.1001/jamaoncol.2022.2319] [Citation(s) in RCA: 164] [Impact Index Per Article: 54.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 04/27/2022] [Indexed: 01/10/2023]
Abstract
Importance National guidelines endorse treatment with neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma (PDAC), but the optimal strategy remains unclear. Objective To compare treatment with neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) with or without hypofractionated radiation therapy with historical data and establish standards for therapy in borderline resectable PDAC. Design, Setting, and Participants This prospective, multicenter, randomized phase 2 clinical trial conducted from February 2017 to January 2019 among member institutions of National Clinical Trials Network cooperative groups used standardized quality control measures and included 126 patients, of whom 70 (55.6%) were registered to arm 1 (systemic therapy; 54 randomized, 16 following closure of arm 2 at interim analysis) and 56 (44.4%) to arm 2 (systemic therapy and sequential hypofractionated radiotherapy; all randomized before closure). Data were analyzed by the Alliance Statistics and Data Management Center during September 2021. Interventions Arm 1: 8 treatment cycles of mFOLFIRINOX (oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2) over 46 hours, administered every 2 weeks. Arm 2: 7 treatment cycles of mFOLFIRINOX followed by stereotactic body radiotherapy (33-40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions). Patients without disease progression underwent pancreatectomy, which was followed by 4 cycles of treatment with postoperative FOLFOX6 (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; bolus fluorouracil, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2 over 46 hours). Main Outcomes and Measures Each treatment arm's 18-month overall survival (OS) rate was compared with a historical control rate of 50%. A planned interim analysis mandated closure of either arm for which 11 or fewer of the first 30 accrued patients underwent margin-negative (R0) resection. Results Of 126 patients, 62 (49%) were women, and the median (range) age was 64 (37-83) years. Among the first 30 evaluable patients enrolled to each arm, 17 patients in arm 1 (57%) and 10 patients in arm 2 (33%) had undergone R0 resection, leading to closure of arm 2 but continuation to full enrollment in arm 1. The 18-month OS rate of evaluable patients was 66.7% (95% CI, 56.1%-79.4%) in arm 1 and 47.3% (95% CI 35.8%-62.5%) in arm 2. The median OS of evaluable patients in arm 1 and arm 2 was 29.8 (95% CI, 21.1-36.6) months and 17.1 (95% CI, 12.8-24.4) months, respectively. Conclusions and Relevance This randomized clinical trial found that treatment with neoadjuvant mFOLFIRINOX alone was associated with favorable OS in patients with borderline resectable PDAC compared with mFOLFIRINOX treatment plus hypofractionated radiotherapy; thus, mFOLFIRINOX represents a reference regimen in this setting. Trial Registration ClinicalTrials.gov Identifier: NCT02839343.
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Affiliation(s)
| | - Qian Shi
- Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, Minnesota
| | - Jeff Meyers
- Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, Minnesota
| | - Joseph M. Herman
- Northwell Cancer Institute, National Cancer Institute Community Oncology Research Program, Manhasset, New York
| | | | | | - Syed Ahmad
- University of Cincinnati, Cincinnati, Ohio
| | - Robert Marsh
- NorthShore University Health System, Evanston, Illinois
| | | | | | - Wendy L. Frankel
- The Ohio State University Arthur G James Cancer Hospital, Columbus
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Greco SH, August DA, Shah MM, Chen C, Moore DF, Masanam M, Turner AL, Jabbour SK, Javidian P, Grandhi MS, Kennedy TJ, Alexander HR, Carpizo DR, Langan RC. Neoadjuvant therapy is associated with lower margin positivity rates after Pancreaticoduodenectomy in T1 and T2 pancreatic head cancers: An analysis of the National Cancer Database. Surg Open Sci 2021; 3:22-28. [PMID: 33490937 PMCID: PMC7807160 DOI: 10.1016/j.sopen.2020.12.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 11/30/2020] [Accepted: 12/04/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Neoadjuvant therapy (NAT) for T1/T2 pancreatic adenocarcinoma (PDAC) prior to pancreaticoduodenectomy remains controversial. We compared positive margin rates in patients with clinical T1&T2 tumors who did and did not receive NAT. METHODS The National Cancer Database (NCDB) found clinical T1&T2 PDAC patients who underwent pancreaticoduodenectomy from 2004 to 2014. Univariate and multivariate regression determined factors associated with a positive margin and survival. RESULTS 9795 patients underwent surgery for clinical T1 or T2 pancreatic head adenocarcinoma. 8472 patients had data regarding use of neoadjuvant and adjuvant therapies; of which, 774 (9.1%) received NAT and 435 (5.1%) received both chemotherapy and radiation therapy. NAT was found to lower positive margin rates from 21.8 to 15.5% (p < 0.0001) and when radiation was added this rate dropped to 13.4%. Positive margins were associated with worse overall survival (14.9 vs. 23.9 months; HR 1.702, p < 0.0001). CONCLUSIONS NAT is associated with a reduced positive margin rate in patients with T1 and T2 tumors. These findings support ongoing and future clinical trials of NAT in T1 and T2, early stage PDAC to determine impacts on survival.
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Affiliation(s)
- Stephanie H. Greco
- Gastrointestinal and Hepatobiliary Oncology, Rutgers Cancer Institute of New, Jersey
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School
| | - David A. August
- Gastrointestinal and Hepatobiliary Oncology, Rutgers Cancer Institute of New, Jersey
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School
- Department of Surgery, RWJBarnabas Health, Saint Barnabas Medical Center
| | - Mihir M. Shah
- Division of Surgical Oncology, Department of Surgery, Emory University
| | - Chunxia Chen
- Biostatistics, Rutgers Cancer Institute of New, Jersey
| | - Dirk F. Moore
- Biostatistics, Rutgers Cancer Institute of New, Jersey
| | - Monika Masanam
- Gastrointestinal and Hepatobiliary Oncology, Rutgers Cancer Institute of New, Jersey
| | - Amber L. Turner
- Department of Surgery, RWJBarnabas Health, Saint Barnabas Medical Center
| | - Salma K. Jabbour
- Division of Radiation Oncology, Rutgers Cancer Institute of New, Jersey
| | - Parisa Javidian
- Department of Pathology, Rutgers Robert Wood Johnson University Hospital
| | - Miral S. Grandhi
- Gastrointestinal and Hepatobiliary Oncology, Rutgers Cancer Institute of New, Jersey
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School
- Department of Surgery, RWJBarnabas Health, Saint Barnabas Medical Center
| | - Timothy J. Kennedy
- Gastrointestinal and Hepatobiliary Oncology, Rutgers Cancer Institute of New, Jersey
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School
- Department of Surgery, RWJBarnabas Health, Saint Barnabas Medical Center
| | - H. Richard Alexander
- Gastrointestinal and Hepatobiliary Oncology, Rutgers Cancer Institute of New, Jersey
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School
- Department of Surgery, RWJBarnabas Health, Saint Barnabas Medical Center
| | - Darren R. Carpizo
- Gastrointestinal and Hepatobiliary Oncology, Rutgers Cancer Institute of New, Jersey
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School
- Department of Surgery, RWJBarnabas Health, Saint Barnabas Medical Center
| | - Russell C. Langan
- Gastrointestinal and Hepatobiliary Oncology, Rutgers Cancer Institute of New, Jersey
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School
- Department of Surgery, RWJBarnabas Health, Saint Barnabas Medical Center
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Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis. J Clin Med 2020; 9:jcm9072132. [PMID: 32640720 PMCID: PMC7408905 DOI: 10.3390/jcm9072132] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 06/29/2020] [Accepted: 07/01/2020] [Indexed: 12/24/2022] Open
Abstract
Background: Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT. Methods: The EMBASE, SCOPUS, PubMed, and Cochrane library databases were systematically searched to identify eligible studies that compare recurrence patterns between patients who had NAT (followed by resection) with those that had US. The primary outcome included site-specific recurrence. Results: 26 articles were identified including 4986 patients who underwent resection. Borderline resectable pancreatic cancer (BRPC, 47% 1074/2264) was the most common, followed by resectable pancreatic cancer (RPC 42%, 949/2264). The weighted overall recurrence rates were lower among the NAT group, 63.4% vs. 74% (US) (OR 0.67 (CI 0.52–0.87), p = 0.006). The overall weighted locoregional recurrence rate was lower amongst patients who received NAT when compared to US (12% vs. 27% OR 0.39 (CI 0.22–0.70), p = 0.004). In BRPC, locoregional recurrence rates improved with NAT (NAT 25.8% US 37.7% OR 0.62 (CI 0.44–0.87), p = 0.007). NAT was associated with a lower weighted liver recurrence rate (NAT 19.4% US 30.1% OR 0.55 (CI 0.34–0.89), p = 0.023). Lung and peritoneal recurrence rates did not differ between NAT and US cohorts (p = 0.705 and p = 0.549 respectively). NAT was associated with a significantly longer weighted mean time to first recurrence 18.8 months compared to US (15.7 months) (OR 0.18 (CI 0.05–0.32), p = 0.015). Conclusion: NAT was associated with lower overall recurrence rate and improved locoregional disease control particularly for those with BRPC. Although the burden of liver metastases was less, there was no overall effect upon distant metastatic disease.
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Basics and Frontiers on Pancreatic Cancer for Radiation Oncology: Target Delineation, SBRT, SIB technique, MRgRT, Particle Therapy, Immunotherapy and Clinical Guidelines. Cancers (Basel) 2020; 12:cancers12071729. [PMID: 32610592 PMCID: PMC7407382 DOI: 10.3390/cancers12071729] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/11/2020] [Accepted: 06/17/2020] [Indexed: 12/17/2022] Open
Abstract
Pancreatic cancer represents a modern oncological urgency. Its management is aimed to both distal and local disease control. Resectability is the cornerstone of treatment aim. It influences the clinical presentation’s definitions as up-front resectable, borderline resectable and locally advanced (unresectable). The main treatment categories are neoadjuvant (preoperative), definitive and adjuvant (postoperative). This review will focus on (i) the current indications by the available national and international guidelines; (ii) the current standard indications for target volume delineation in radiotherapy (RT); (iii) the emerging modern technologies (including particle therapy and Magnetic Resonance [MR]-guided-RT); (iv) stereotactic body radiotherapy (SBRT), as the most promising technical delivery application of RT in this framework; (v) a particularly promising dose delivery technique called simultaneous integrated boost (SIB); and (vi) a multimodal integration opportunity: the combination of RT with immunotherapy.
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Tran NH, Sahai V, Griffith KA, Nathan H, Kaza R, Cuneo KC, Shi J, Kim E, Sonnenday CJ, Cho CS, Lawrence TS, Zalupski MM. Phase 2 Trial of Neoadjuvant FOLFIRINOX and Intensity Modulated Radiation Therapy Concurrent With Fixed-Dose Rate-Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer. Int J Radiat Oncol Biol Phys 2020; 106:124-133. [PMID: 31494181 PMCID: PMC7245020 DOI: 10.1016/j.ijrobp.2019.08.057] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 08/11/2019] [Accepted: 08/26/2019] [Indexed: 01/05/2023]
Abstract
PURPOSE Preoperative therapy in borderline resectable pancreatic cancer (BRPC) is intended to increase R0 resection rates. An optimal approach in BRPC is yet to be defined. METHODS AND MATERIALS Patients with BRPC, confirmed adenocarcinoma, performance status ≤1, and adequate organ function enrolled in a single-institution, phase 2 trial. Patients received FOLFIRINOX × 6 cycles, then radiation therapy (50 Gy in 25 fractions) concurrent with fixed-dose rate gemcitabine (1 g/m2 over 100 minutes) followed by 2 additional gemcitabine infusions. Computed tomography scans were performed at 2-month intervals during treatment. Patients without distant disease were offered surgical exploration. The primary objective was R0 resection rate with an alternate hypothesis of 55%. Secondary objectives included median progression-free survival (PFS), median overall survival (OS), response rate, and safety. The trial registration number is NCT01661088. RESULTS Twenty-five patients with median age of 60 years (range, 47-77 years) enrolled from November 2011 through January 2017. Twenty-one (84%) completed FOLFIRINOX and 19 (76%) completed all protocol therapy. Treatment-related grade 3 to 4 toxicities included neutropenia (40%), nausea and vomiting (28%), diarrhea (16%), and fatigue (12%). Eighteen patients (72%) underwent laparotomy, 13 (52%) were resected (all R0). The median PFS and OS in 25 patients were 13.1 months (95% confidence interval [CI], 7.3-24.7) and 24.4 months (95% CI, 12.6-40.0), respectively. For resected patients, median PFS was 21.6 months (95% CI, 8.2-37.1) and OS was 37.1 months (95% CI, 15.4-not reached). CONCLUSIONS Neoadjuvant therapy with FOLFIRINOX, followed by intensity modulated radiation therapy concurrent with fixed-dose-rate gemcitabine in BRPC is feasible and tolerated. Although the alternate hypothesis was not met, the OS of the resected cohort was favorable.
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Affiliation(s)
| | | | | | | | - Ravi Kaza
- University of Michigan, Ann Arbor, Michigan
| | | | - Jiaqi Shi
- University of Michigan, Ann Arbor, Michigan
| | - Edward Kim
- Work completed at University of Michigan. Currently at University of California, Davis, California
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Wen Y, Tu J, Xue X, Shi W, Qin L, Qian H, Xu Y, Xu X. A CARE-compliant case report: total pancreatectomy and total gastrectomy to treat pancreatic ductal adenocarcinoma. Medicine (Baltimore) 2019; 98:e18151. [PMID: 31764857 PMCID: PMC6882560 DOI: 10.1097/md.0000000000018151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
RATIONALE Total pancreatectomy (TP) is performed in cases of multifocal and large invasive tumors of the pancreas, and is associated with high rates of mortality and morbidity. Previously, the limitations and unsatisfactory effect of this surgery rendered it rarely performed; however, with improvements in surgical techniques and blood sugar management, TP is now more frequently performed. TP has a similar long-term survival rate as that for pancreatoduodenectomy (PD). However, the application of TP plus total gastrectomy (TG) for the treatment of invasive pancreatic ductal adenocarcinoma has not been reported previously. PATIENT CONCERNS The patient was a 64-year-old man with epigastric discomfort. Physical examination showed a hard mass. Preoperative computed tomography and magnetic resonance imaging revealed a solid mass located in the pancreatic body and involving the portal vein and stomach. DIAGNOSIS Pancreatic cancer. INTERVENTIONS The patient was treated with TP combined with TG and portal vein reconstruction. OUTCOMES The patient had a smooth post-operative recovery but, regretfully, developed metastases 2 months after discharge. LESSONS Considering the poor outcome of the present case, the validity of the operation should be reevaluated. Although a single case does not elicit a convincing conclusion, the current case might serve as a warning against performing a similar surgery.
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Affiliation(s)
- Yanghui Wen
- Department of General Surgery, The First Affiliated Hospital of Soochow University
| | - Junhao Tu
- Department of General Surgery, Suzhou Wuzhong People's Hospital, Jiangsu Province, China
| | - Xiaofeng Xue
- Department of General Surgery, The First Affiliated Hospital of Soochow University
| | - Weiqiang Shi
- Department of Pathology, The First Affiliated Hospital of Soochow University
| | - Lei Qin
- Department of General Surgery, The First Affiliated Hospital of Soochow University
| | - Haixin Qian
- Department of General Surgery, The First Affiliated Hospital of Soochow University
| | - Yinkai Xu
- Department of General Surgery, The First Affiliated Hospital of Soochow University
| | - Xiaolan Xu
- Department of Gastroenterology, Xiangcheng People's Hospital, Suzhou, China
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11
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Tsiotos GG, Ballian N, Michelakos T, Milas F, Ziogou P, Papaioannou D, Salla C, Athanasiadis I, Razis E, Stavridi F, Psomas M. Portal-Mesenteric Vein Resection in Borderline Pancreatic Cancer; 33 Month-Survival in Patients with Good Performance Status. J Pancreat Cancer 2019; 5:43-50. [PMID: 31559380 PMCID: PMC6761582 DOI: 10.1089/pancan.2019.0013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background: Patients with pancreatic cancer (PC), which is not upfront resectable, but borderline, involving major peripancreatic vessels, have not been generally considered for surgery, considering that resection in such a setting may be futile. Materials and Methods: Retrospective analysis of prospectively collected data on patients with borderline pancreatic adenocarcinoma undergoing pancreatectomy en-block with portal and/or superior mesenteric vein resection in a tertiary referral center in Greece between January 2012 and February 2017. Follow-up was complete up to January 2018. Results: Twenty-four patients were included. Neoadjuvant therapy (NAT) was administered to only 38%, but more commonly in the second half of the group (58% vs. 17%, p = 0.035). It was associated with smaller tumor size (median: 2.5 vs. 4.2 cm, p < 0.001), fewer positive lymph nodes (LNs) in the resected specimen (median: 2 vs. 5, p = 0.04), and higher likelihood of adjuvant therapy (78% vs. 40%, p = 0.01), but not with survival. Resection was extensive: a median of 26 LNs were retrieved, R0 resection rate (≥1 mm) was 79%, and median length of vein segments was 4 cm, requiring interposition grafts in 58% (mostly polytetrafluoroethylene). Median intensive care unit stay was 0 days and length of hospital stay was 9 days. Post-operative mortality was 12.5%. Median overall survival was 24 months. Eastern Cooperative Oncology Group (ECOG) status was significantly associated with survival (p < 0.001) with ECOG-0: 33 months, ECOG-1: 12 months, and ECOG-2: 6 months. Conclusion: This first Greek national series of portomesenteric vein resection in borderline PC demonstrates that it results to 2 years of median survival, extending to 33 months in patients with good performance status, especially if NAT is uniformly administered.
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Affiliation(s)
| | | | | | - Fotios Milas
- Department of Surgery, Mitera-Hygeia Hospitals, Marousi, Greece
| | - Panoraia Ziogou
- Department of Surgery, Mitera-Hygeia Hospitals, Marousi, Greece
| | | | - Charitini Salla
- Department of Cytology, Mitera-Hygeia Hospitals, Marousi, Greece
| | - Ilias Athanasiadis
- Department of Medical Oncology, Mitera-Hygeia Hospitals, Marousi, Greece
| | - Evangelia Razis
- Department of Medical Oncology, Mitera-Hygeia Hospitals, Marousi, Greece
| | - Flora Stavridi
- Department of Medical Oncology, Mitera-Hygeia Hospitals, Marousi, Greece
| | - Maria Psomas
- Department of Anesthesiology, Mitera-Hygeia Hospitals, Marousi, Greece
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12
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Phase 2 Study of Neoadjuvant Treatment of Sequential S-1-Based Concurrent Chemoradiation Therapy Followed by Systemic Chemotherapy with Gemcitabine for Borderline Resectable Pancreatic Adenocarcinoma (HOPS-BR 01). Int J Radiat Oncol Biol Phys 2019; 105:606-617. [PMID: 31306735 DOI: 10.1016/j.ijrobp.2019.07.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2018] [Revised: 06/21/2019] [Accepted: 07/04/2019] [Indexed: 01/24/2023]
Abstract
PURPOSE Preoperative treatment is recommended for borderline resectable pancreatic ductal adenocarcinoma. However, the standard treatment has not yet been determined. We conducted a multicenter phase 2 study to investigate the efficacy of neoadjuvant treatment of sequential chemoradiation followed by chemotherapy. METHODS AND MATERIALS All enrolled patients were treated by preoperative chemoradiation (a total dose of 50.4 Gy in 28 fractions and orally administered S-1 at 80 mg/m2 on the day of irradiation) followed by chemotherapy (administration of gemcitabine at 1000 mg/m2/dose on days 1, 8, and 15 in 3 cycles of 4 weeks) and attempted curative resection. The primary outcome was an R0 resection rate among patients who completed preoperative treatment and pancreatectomy. The threshold of the R0 resection rate was defined as 74% based on a previous study of up-front surgery. RESULTS Forty-five patients were included. Twenty-one patients could not undergo pancreatectomy because of progressive diseases (n = 14), adverse events (n = 5), or consent withdrawal (n = 2), and 4 patients underwent additional resection after dropping out. The resection rates were 53.3% and 62.2% in the per-protocol set (PPS) and full analysis set (FAS) populations, respectively. The R0 resection rates were 95.8% (95% confidence interval, 78.9%-99.9%) and 96.4% (81.7%-99.9%) in the PPS and FAS populations, respectively. The median overall survival and progression-free survival of all the included patients were 17.3 and 10.5 months, respectively. The median survival time of the patients with pancreatectomy was significantly longer than that of the patients without pancreatectomy in the PPS (27.9 vs 12.3 months; P = .001) and FAS populations (32.2 vs 11.8 months; P < .001). CONCLUSIONS This study revealed that a long duration of preoperative treatment of sequential chemoradiation followed by systemic chemotherapy provides a high rate of R0 resection and sufficient survival time in patients undergoing pancreatectomy.
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13
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Clinical Characteristics of Patients Experiencing Pathologic Complete Response Following Neoadjuvant Therapy for Borderline Resectable/Locally Advanced Pancreatic Adenocarcinoma. Am J Clin Oncol 2019; 41:982-985. [PMID: 28968257 DOI: 10.1097/coc.0000000000000409] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES The purpose of this study is to describe clinical characteristics and outcomes of patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) who achieved pathologic complete response (pCR) following neoadjuvant therapy. MATERIALS AND METHODS A single institution clinical database for patients with pancreatic ductal adenocarcinoma was queried. Between 2008 and 2014 patients were identified with BRPC and LAPC, who underwent surgical resection after receiving neoadjuvant treatment. Clinical and pathologic features of the patients who achieved pCR were acquired retrospectively. RESULTS Six patients were identified to have pCR on pathology of the postoperative specimen. On the basis of pretreatment clinical staging, 2 patients were considered to have BRPC and 4 LAPC. Four patients received gemcitabine-based chemotherapy and 2 patients received FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, and leucovorin). Five of 6 patients received radiation therapy before operative resection. Operative procedures included distal pancreatectomy (n=3) and pancreatoduodenectomy (n=3). Pancreatic intraepithelial neoplasia 1 to 2 was present in 3 cases, and pancreatic intraepithelial neoplasia 3 in 1 case. During a median follow-up of 21.3 months, 2 patients died, with a median survival of 11.0 months (range, 10.4 to 11.6 mo). Four patients are alive and continue to follow-up with median survival of 28.7 months (range, 20.1 to 42.4 mo). CONCLUSIONS Multimodality neoadjuvant therapy may lead to complete pathologic response in a small number of patients with borderline resectable/locally advanced pancreatic adenocarcinoma. pCR to neoadjuvant therapy does not lead to cure in most cases, and the majority of patients appear to relapse locally or systemically.
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14
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Han S, Choi SH, Choi DW, Heo JS, Han IW, Park DJ, Ryu Y. Neoadjuvant therapy versus upfront surgery for borderline-resectable pancreatic cancer. MINERVA CHIR 2019; 75:15-24. [PMID: 31115240 DOI: 10.23736/s0026-4733.19.07958-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Neoadjuvant therapy is recommended for patients with borderline-resectable pancreatic cancer (BRPC). In this study, we compare survival outcomes of neoadjuvant therapy with upfront surgery. METHODS From January 2011 to June 2016, 1415 patients underwent treatments for pancreatic cancer in Samsung Medical Center. Among them, 112 (7.9%) patients were categorized as BRPC by the NCCN 2016 guideline. They were classified by type of initial treatments into neoadjuvant group (NA, N.=26) and upfront surgery group (US, N.=86). RESULTS The median survival duration of all patients was 18.3 months. Patients in the NA group had more T4 disease than those in the US group (38.5% in NA versus 15.1% in the US group; P=0.010). Arterial involvement was more frequent in the NA group (42.3% versus 15.1%; P=0.003). In the NA group, ten (38.5%) patients underwent surgery, and seven of them had complete R0 resection. In the US group, 83 (96.5%) patients received radical surgery, and 42 (48.8%) had R0 resection. In survival analysis according to intent to treat, the overall two-year survival rate was 51.1% in the US group and 36.7% in the NA group (P=0.001). However, among patients who underwent surgery (N.=96), the two-year overall survival rate was not significantly different between the two groups (P=0.089). According to involved vessels, the survival rate was not different between patients with arterial or both arterial and venous involvement and in patients with only venous involvement (P=0.649). CONCLUSIONS It is necessary to demonstrate the efficacy of neoadjuvant therapy and to standardize the regimens through large-scale, multicenter, randomized controlled studies.
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Affiliation(s)
- Sunjong Han
- Departments of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, South Korea
| | - Seong H Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea -
| | - Dong W Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jin S Heo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - In W Han
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Dae-Joon Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Youngju Ryu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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15
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Verbeke C, Häberle L, Lenggenhager D, Esposito I. Pathology assessment of pancreatic cancer following neoadjuvant treatment: Time to move on. Pancreatology 2018; 18:467-476. [PMID: 29843972 DOI: 10.1016/j.pan.2018.04.010] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Revised: 04/20/2018] [Accepted: 04/24/2018] [Indexed: 02/06/2023]
Abstract
Neoadjuvant treatment has increasingly become an integral part of the multimodal management of patients with pancreatic cancer. In patients who are able to undergo surgery following preoperative therapy, tumour regression grading remains the diagnostic gold standard for the histomorphological assessment of the effect of neoadjuvant treatment. In recent years, however, there has been growing concern about inherent flaws of tumour regression grading systems as well as their imprecise and impractical criteria that result in divergence of practice and lack of interobserver agreement. Furthermore, existing tumour regression systems differ in their defining criteria and thresholds, leading to incomparability of data. In this review, the principles and limitations of the main existing tumour regression systems are discussed, and potential alternative assessment approaches and novel markers are presented.
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Affiliation(s)
- Caroline Verbeke
- Dept of Pathology, Institute of Clinical Medicine, University of Oslo, Norway; Dept of Pathology, Oslo University Hospital, Norway.
| | - Lena Häberle
- Institute of Pathology, Heinrich-Heine University and University Hospital of Düsseldorf, Germany
| | - Daniela Lenggenhager
- Dept of Pathology, Institute of Clinical Medicine, University of Oslo, Norway; Dept of Pharmacology, Institute of Clinical Medicine, University of Oslo, Norway; Institute of Pathology and Molecular Pathology, University of Zürich and University Hospital Zürich, Switzerland
| | - Irene Esposito
- Institute of Pathology, Heinrich-Heine University and University Hospital of Düsseldorf, Germany.
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16
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Gilbert JW, Wolpin B, Clancy T, Wang J, Mamon H, Shinagare AB, Jagannathan J, Rosenthal M. Borderline resectable pancreatic cancer: conceptual evolution and current approach to image-based classification. Ann Oncol 2018; 28:2067-2076. [PMID: 28407088 DOI: 10.1093/annonc/mdx180] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Diagnostic imaging plays a critical role in the initial diagnosis and therapeutic monitoring of pancreatic adenocarcinoma. Over the past decade, the concept of 'borderline resectable' pancreatic cancer has emerged to describe a distinct subset of patients existing along the spectrum from resectable to locally advanced disease for whom a microscopically margin-positive (R1) resection is considered relatively more likely, primarily due to the relationship of the primary tumor with surrounding vasculature. Materials and methods This review traces the conceptual evolution of borderline resectability from a radiological perspective, including the debates over the key imaging criteria that define the thresholds between resectable, borderline resectable, and locally advanced or metastatic disease. This review also addresses the data supporting neoadjuvant therapy in this population and discusses current imaging practices before and during treatment. Results A growing body of evidence suggests that the borderline resectable group of patients may particularly benefit from neoadjuvant therapy to increase the likelihood of an ultimately margin-negative (R0) resection. Unfortunately, anatomic and imaging criteria to define borderline resectability are not yet universally agreed upon, with several classification systems proposed in the literature and considerable variance in institution-by-institution practice. As a result of this lack of consensus, as well as overall small patient numbers and lack of established clinical trials dedicated to borderline resectable patients, accurate evidence-based diagnostic categorization and treatment selection for this subset of patients remains a significant challenge. Conclusions Clinicians and radiologists alike should be cognizant of evolving imaging criteria for borderline resectability given their profound implications for treatment strategy, follow-up recommendations, and prognosis.
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Affiliation(s)
- J W Gilbert
- Department of Imaging, Dana-Farber Cancer Institute.,Department of Radiology, Brigham and Women's Hospital.,Harvard Medical School
| | - B Wolpin
- Harvard Medical School.,Department of Medical Oncology, Dana-Farber Cancer Institute
| | - T Clancy
- Harvard Medical School.,Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital
| | - J Wang
- Harvard Medical School.,Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital.,Gastrointestinal Surgical Center, Dana-Farber/Brigham and Women's Cancer Center
| | - H Mamon
- Harvard Medical School.,Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, USA
| | - A B Shinagare
- Department of Imaging, Dana-Farber Cancer Institute.,Department of Radiology, Brigham and Women's Hospital.,Harvard Medical School
| | - J Jagannathan
- Department of Imaging, Dana-Farber Cancer Institute.,Department of Radiology, Brigham and Women's Hospital.,Harvard Medical School
| | - M Rosenthal
- Department of Imaging, Dana-Farber Cancer Institute.,Department of Radiology, Brigham and Women's Hospital.,Harvard Medical School
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17
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Toesca DAS, Koong AJ, Poultsides GA, Visser BC, Haraldsdottir S, Koong AC, Chang DT. Management of Borderline Resectable Pancreatic Cancer. Int J Radiat Oncol Biol Phys 2018; 100:1155-1174. [PMID: 29722658 DOI: 10.1016/j.ijrobp.2017.12.287] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 11/07/2017] [Accepted: 12/27/2017] [Indexed: 12/13/2022]
Abstract
With the rapid development of imaging modalities and surgical techniques, the clinical entity representing tumors that are intermediate between resectable and unresectable pancreatic adenocarcinoma has been identified has been termed "borderline resectable" (BR). These tumors are generally amenable for resection but portend an increased risk for positive margins after surgery and commonly necessitate vascular resection and reconstruction. Although there is a lack of consensus regarding the appropriate definition of what constitutes a BR pancreatic tumor, it has been demonstrated that this intermediate category carries a particular prognosis that is in between resectable and unresectable disease. In order to downstage the tumor and increase the probability of clear surgical margins, neoadjuvant therapy is being increasingly utilized and studied. There is a lack of high-level evidence to establish the optimal treatment regimen for BR tumors. When resection with negative margins is achieved after neoadjuvant therapy, the prognosis for BR tumors approaches and even exceeds that for resectable disease. This review presents the current definitions, different treatment approaches, and the clinical outcomes of BR pancreatic cancer.
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Affiliation(s)
- Diego A S Toesca
- Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California
| | - Amanda J Koong
- Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California
| | | | - Brendan C Visser
- Department of Surgery, Stanford Cancer Institute, Stanford, California
| | | | - Albert C Koong
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Daniel T Chang
- Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California.
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18
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Lee SH, Hwang HK, Kang CM, Lee WJ. The Yonsei criteria as a clinically detectable parameter for excellent prognosis in resected left-sided pancreatic cancer: outcomes of a propensity score-matched analysis. Surg Endosc 2017; 31:4656-4664. [PMID: 28389802 DOI: 10.1007/s00464-017-5529-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2016] [Accepted: 03/15/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND This study aimed to identify that Yonsei criteria (YC) can be regarded as a preoperative clinical parameter to predict biological behavior of the left-sided pancreatic cancer. METHODS Between June 2007 and December 2014, 135 patients who underwent minimally invasive (MIS) or open distal pancreatectomy for left-sided pancreatic cancer were enrolled in this study consecutively. Perioperative short-term and long-term oncologic outcomes were analyzed according to the YC retrospectively. RESULTS Fifty-four and 81 patients did and did not meet the YC, respectively. Short-term oncologic outcomes were favorable among those meeting the YC even after propensity score matching. Patients within the YC also had better disease-free and disease-specific overall survival (p < 0.05). In analysis for receiver operating characteristic curve, area under curve of CA19-9 was satisfactory only within YC group. Multivariate analysis for disease-free survival identified the YC as a strong independent prognostic factor (p < 0.05). In preoperative clinical setting, patients' survival was clearly different based on following clinical groups, such as within YC, beyond YC, and unresectable. CONCLUSIONS Preoperative CT-based determined YC can predict excellent short-term and long-term oncologic outcomes. YC might have a potential role as a preoperative clinical staging for left-sided pancreatic cancer. External validations of YC based on multicenter cohorts are mandatory to confirm this oncologic significance of YC.
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Affiliation(s)
- Sung Hwan Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Ludlow Faculty Research Building #201, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea
- Pancreatobiliary Cancer Clinic, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Ho Kyoung Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Ludlow Faculty Research Building #201, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea
- Pancreatobiliary Cancer Clinic, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Chang Moo Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Ludlow Faculty Research Building #201, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea.
- Pancreatobiliary Cancer Clinic, Yonsei Cancer Center, Severance Hospital, Seoul, Korea.
| | - Woo Jung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Ludlow Faculty Research Building #201, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea
- Pancreatobiliary Cancer Clinic, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
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19
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Dhir M, Malhotra GK, Sohal DP, Hein NA, Smith LM, O’Reilly EM, Bahary N, Are C. Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta-analysis of 5520 patients. World J Surg Oncol 2017; 15:183. [PMID: 29017581 PMCID: PMC5634869 DOI: 10.1186/s12957-017-1240-2] [Citation(s) in RCA: 106] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2017] [Accepted: 08/25/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recent years have seen standardization of the anatomic definitions of pancreatic adenocarcinoma, and increasing utilization of neoadjuvant therapy (NAT). The aim of the current review was to summarize the evidence for NAT in pancreatic adenocarcinoma since 2009, when consensus criteria for resectable (R), borderline resectable (BR), and locally advanced (LA) disease were endorsed. METHODS PubMed search was undertaken along with extensive backward search of the references of published articles to identify studies utilizing NAT for pancreatic adenocarcinoma. Abstracts from ASCO-GI 2014 and 2015 were also searched. RESULTS A total of 96 studies including 5520 patients were included in the final quantitative synthesis. Pooled estimates revealed 36% grade ≥ 3 toxicities, 5% biliary complications, 21% hospitalization rate and low mortality (0%, range 0-16%) during NAT. The majority of patients (59%) had stable disease. On an intention-to-treat basis, R0-resection rates varied from 63% among R patients to 23% among LA patients. R0 rates were > 80% among all patients who were resected after NAT. Among R and BR patients who underwent resection after NAT, median OS was 30 and 27.4 months, respectively. CONCLUSIONS The current study summarizes the recent literature for NAT in pancreatic adenocarcinoma and demonstrates improving outcomes after NAT compared to those historically associated with a surgery-first approach for pancreatic adenocarcinoma.
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Affiliation(s)
- Mashaal Dhir
- Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210 USA
| | - Gautam K. Malhotra
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE 98198 USA
| | - Davendra P.S. Sohal
- Division of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195 USA
| | - Nicholas A. Hein
- Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198 USA
| | - Lynette M. Smith
- Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198 USA
| | - Eileen M. O’Reilly
- David M. Rubenstein Center for Pancreatic Cancer, Memorial Sloan Kettering Cancer Center, New York, NY 10065 USA
| | - Nathan Bahary
- Department of Medicine, Division of Hematology and Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 15232 USA
| | - Chandrakanth Are
- Department of Surgery, Division of Surgical Oncology, University of Nebraska Medical Center, Omaha, NE 98198 USA
- Department of Surgery/Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198 USA
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20
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Adamska A, Domenichini A, Falasca M. Pancreatic Ductal Adenocarcinoma: Current and Evolving Therapies. Int J Mol Sci 2017; 18:E1338. [PMID: 28640192 PMCID: PMC5535831 DOI: 10.3390/ijms18071338] [Citation(s) in RCA: 412] [Impact Index Per Article: 51.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 06/01/2017] [Accepted: 06/13/2017] [Indexed: 02/07/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC), which constitutes 90% of pancreatic cancers, is the fourth leading cause of cancer-related deaths in the world. Due to the broad heterogeneity of genetic mutations and dense stromal environment, PDAC belongs to one of the most chemoresistant cancers. Most of the available treatments are palliative, with the objective of relieving disease-related symptoms and prolonging survival. Currently, available therapeutic options are surgery, radiation, chemotherapy, immunotherapy, and use of targeted drugs. However, thus far, therapies targeting cancer-associated molecular pathways have not given satisfactory results; this is due in part to the rapid upregulation of compensatory alternative pathways as well as dense desmoplastic reaction. In this review, we summarize currently available therapies and clinical trials, directed towards a plethora of pathways and components dysregulated during PDAC carcinogenesis. Emerging trends towards targeted therapies as the most promising approach will also be discussed.
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Affiliation(s)
- Aleksandra Adamska
- Metabolic Signalling Group, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia.
| | - Alice Domenichini
- Metabolic Signalling Group, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia.
| | - Marco Falasca
- Metabolic Signalling Group, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia.
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21
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Shrestha B, Sun Y, Faisal F, Kim V, Soares K, Blair A, Herman JM, Narang A, Dholakia AS, Rosati L, Hacker-Prietz A, Chen L, Laheru DA, De Jesus-Acosta A, Le DT, Donehower R, Azad N, Diaz LA, Murphy A, Lee V, Fishman EK, Hruban RH, Liang T, Cameron JL, Makary M, Weiss MJ, Ahuja N, He J, Wolfgang CL, Huang CY, Zheng L. Long-term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer. Cancer Med 2017. [PMID: 28639410 PMCID: PMC5504321 DOI: 10.1002/cam4.1104] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
The use of neoadjuvant chemotherapy or radiation for borderline resectable pancreatic adenocarcinoma (BL-PDAC) is increasing. However, the impact of neoadjuvant chemotherapy and radiation therapy on the outcome of BL-PDAC remains to be elucidated. We performed a retrospective analysis of 93 consecutive patients who were diagnosed with BL-PDAC and primarily followed at Johns Hopkins Hospital between February 2007 and December 2012. Among 93 patients, 62% received upfront neoadjuvant chemotherapy followed by chemoradiation, whereas 20% received neoadjuvant chemoradiation alone and 15% neoadjuvant chemotherapy alone. Resectability following all neoadjuvant therapy was 44%. Patients who underwent resection with a curative intent had a median overall survival (mOS) of 25.8 months, whereas those who did not undergo surgery had a mOS of 11.9 months. However, resectability and overall survival were not significantly different between the three types of neoadjuvant therapy. Nevertheless, 22% (95% CI, 0.13-0.36) of the 58 patients who received upfront chemotherapy followed by chemoradiation remained alive for a minimum of 48 months compared to none of the 19 patients who received upfront chemoradiation. Among patients who underwent curative surgical resection, 32% (95% CI, 0.19-0.55) of those who received upfront chemotherapy remained disease free at least 48 months following surgical resection, whereas none of the eight patients who received upfront chemoradiation remained disease free beyond 24 months following surgical resection. Neoadjuvant therapy with upfront chemotherapy may result in long-term survival in a subpopulation of patients with BL-PDAC.
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Affiliation(s)
- Bikram Shrestha
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Yifei Sun
- Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Farzana Faisal
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Victoria Kim
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kevin Soares
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Alex Blair
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Joseph M Herman
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Radiation Oncology, M.D. Anderson Cancer Center, Houston, Texas
| | - Amol Narang
- Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Avani S Dholakia
- Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Lauren Rosati
- Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Amy Hacker-Prietz
- Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Linda Chen
- Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Daniel A Laheru
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ana De Jesus-Acosta
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Dung T Le
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ross Donehower
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Nilofar Azad
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Luis A Diaz
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Adrian Murphy
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Valerie Lee
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Elliot K Fishman
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ralph H Hruban
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Tingbo Liang
- The Second Affiliated Hospital of Zhejiang University, Hangzhou, China
| | - John L Cameron
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Martin Makary
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Matthew J Weiss
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Nita Ahuja
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Jin He
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Christopher L Wolfgang
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Chiung-Yu Huang
- Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Lei Zheng
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
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22
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Schorn S, Demir IE, Reyes CM, Saricaoglu C, Samm N, Schirren R, Tieftrunk E, Hartmann D, Friess H, Ceyhan GO. The impact of neoadjuvant therapy on the histopathological features of pancreatic ductal adenocarcinoma - A systematic review and meta-analysis. Cancer Treat Rev 2017; 55:96-106. [PMID: 28342938 DOI: 10.1016/j.ctrv.2017.03.003] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 03/04/2017] [Accepted: 03/06/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND Due to increased rates of curative tumor resections exceeding 60% after FOLFIRINOX-treatment, neoadjuvant therapy/NTx is increasingly recognized as an effective therapy option for downstaging borderline or locally advanced pancreatic ductal adenocarcinoma/PDAC. Yet, the effects of NTx on the common histopathological features of PDAC have not been systematically analysed. Therefore, the aim of the current study was to assess the impact of NTx on relevant histopathological features of PDAC. PATIENTS AND METHODS Biomedical databases were systematically screened for predefined searching terms related to NTx and PDAC. The Preferred-Reporting-Items-for-Systematic-review-and-Meta-Analysis/PRISMA-guidelines were used to perform a systematic review and meta-analysis. Articles meeting the predefined criteria were analysed on relevance, and a meta-analysis was performed. RESULTS A total of 9031 studies could be identified that analysed the effect of NTx on PDAC. Only 35 studies presented comparative data on the histological features of neoadjuvantly treated vs. upfront resected PDAC patients. In meta-analyses, the beneficial effect of NTx was reflected by reduced tumor size (T1/2: RR 2.87, 95%-CI: 1.52-5.42, P=0.001, T3/4: RR 0.78, 95%-CI: 0.69-0.89, P=0.0002), lower N-Stage (N0: RR 2.14, 95%-CI: 1.85-2.46, P<0.00001, N1: RR 0.59, 95%-CI: 0.53-0.65, P<0.00001), higher R0-rates (R0: RR 1.13, 95%-CI: 1.08-1.18, P<0.00001, R1: RR 0.66, 95%-CI: 0.58-0.76, P<0.00001), less perineural invasion (Pn1: RR 0.78, 95%-CI: 0.73-0.83, P<0.00001), less lymphatic vessel invasion (RR: 0.50, 95%-CI: 0.36-0.70, P<0.0001) and fewer G3-tumors (RR 0.82, 95%-CI: 0.71-0.94, P=0.005). CONCLUSIONS NTx in PDAC seems to exert its beneficial effect in borderline or locally advanced PDAC over genuine tumor downstaging. Thus, although at least 40% of all NTx treated patients remain unresectable even with modern NTx regimes, neoadjuvantly treated PDAC showed not only increasing resectability rates especially after FOLFIRINOX, but even reach a lower tumor stage than primarily resected PDAC.
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Affiliation(s)
- Stephan Schorn
- Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
| | - Ihsan Ekin Demir
- Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
| | - Carmen Mota Reyes
- Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
| | - Cemil Saricaoglu
- Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
| | - Nicole Samm
- Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
| | - Rebekka Schirren
- Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
| | - Elke Tieftrunk
- Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
| | - Daniel Hartmann
- Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
| | - Helmut Friess
- Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
| | - Güralp Onur Ceyhan
- Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
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23
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Abstract
OBJECTIVES We evaluated whether neoadjuvant therapy followed by surgical resection improves the clinical outcome for patients with borderline resectable pancreatic cancer with radiologic artery involvement (BRPC-A). METHODS We reviewed 143 BRPC-A patients from among 330 pancreatic cancer patients, including 111 potentially resectable pancreatic cancer patients and 76 borderline resectable pancreatic cancer with portal/superior mesenteric vein involvement patients, who underwent surgery at Wakayama Medical University Hospital. We compared the clinicopathological factors of 40 BRPC-A patients treated with neoadjuvant therapy followed by surgery and those of 103 BRPC-A patients treated with upfront surgery. RESULTS The R0 rate and progression-free survival of BRPC-A patients who received neoadjuvant therapy and subsequent surgical resection were significantly better compared to those who received upfront surgery (R0: P = 0.041; progression-free survival: P = 0.033), but overall survival was not significantly different. A multivariate analysis showed that intraoperative transfusion (P = 0.007), moderately or poorly differentiated pathological adenocarcinoma (P = 0.019), and failure to complete postoperative adjuvant therapy (P < 0.001) independently predicted a poor prognosis for BRPC-A patients who underwent surgical resection. CONCLUSIONS Neoadjuvant treatment followed by surgery might provide clinical benefits for BRPC-A patients; however, the establishment of the most appropriate neoadjuvant therapy is needed by further studies.
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24
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Younan G, Tsai S, Evans DB, Christians KK. Techniques of Vascular Resection and Reconstruction in Pancreatic Cancer. Surg Clin North Am 2016; 96:1351-1370. [PMID: 27865282 DOI: 10.1016/j.suc.2016.07.005] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Multimodality therapy has become the standard approach for the treatment of pancreatic cancer. With improved response rates to newer chemotherapeutic agents, tumors that used to be considered unresectable are now being considered for operation. Neoadjuvant therapy for borderline resectable pancreatic cancer is considered standard of care and venous resection/reconstruction is no longer controversial. Arterial resection and reconstruction in select patients has also proven to be safe when done in highly specialized centers by high-volume surgeons. This article reviews indications for, and technical aspects of, vascular resection/reconstruction and shunting procedures during pancreatectomy, including critical elements of perioperative care.
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Affiliation(s)
- George Younan
- Pancreatic Cancer Program, Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226, USA
| | - Susan Tsai
- Pancreatic Cancer Program, Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226, USA
| | - Douglas B Evans
- Pancreatic Cancer Program, Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226, USA
| | - Kathleen K Christians
- Pancreatic Cancer Program, Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226, USA.
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25
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Gostimir M, Bennett S, Moyana T, Sekhon H, Martel G. Complete pathological response following neoadjuvant FOLFIRINOX in borderline resectable pancreatic cancer - a case report and review. BMC Cancer 2016; 16:786. [PMID: 27724927 PMCID: PMC5057443 DOI: 10.1186/s12885-016-2821-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 09/29/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Pancreatic cancer is among the top 5 most common cancers worldwide, but is particularly devastating due to its insidious nature. Complete surgical resection remains the only potential curative treatment, although only 20 % of patients present with a resectable tumor. Patients may alternatively present with borderline resectable pancreatic cancer or locally advanced pancreatic cancer and can be offered treatment with neoadjuvant intent. The effectiveness of these treatments is unclear and there is a paucity of data to suggest one optimal treatment approach. CASE PRESENTATION We describe a 61-year-old female who presented with a two-week history of obstructive jaundice in the context of vague abdominal pain that had been ongoing for years prior to her visit. CT scan of the abdomen confirmed a hypovascular mass in the uncinate process consistent with borderline resectable pancreatic cancer. Pancreatic adenocarcinoma was confirmed with endoscopic ultrasound guided fine-needle aspiration cytology. Following multidisciplinary discussion, it was recommended that she undergo treatment with FOLFIRINOX. After a total of 13 cycles, follow up CT revealed that the lesion had decreased in size and she was offered resection as a potentially curative treatment. She underwent pancreaticoduodenectomy. Final pathology report revealed no evidence of residual adenocarcinoma (ypT0 ypN0 (0/23)). The patient remains disease-free 15 months following surgery. CONCLUSION To date, there have been very few reports of a complete pathological response following neoadjuvant therapy in borderline resectable or locally advanced pancreatic cancer. This report describes a unique case of a complete pathological remission in a patient with borderline resectable pancreatic cancer following FOLFIRINOX therapy alone and adds to the growing base of evidence meriting the initiation of clinical trials to assess the efficacy of FOLFIRINOX in these subsets of pancreatic cancer.
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Affiliation(s)
- Mišo Gostimir
- Faculty of Medicine, University of Ottawa, 451 Smyth Rd, K1H 8 M5 Ottawa, Canada
| | - Sean Bennett
- Department of Surgery, Division of General Surgery, University of Ottawa, 451 Smyth Rd, K1H 8 M5 Ottawa, Canada
| | - Terence Moyana
- Department of Pathology and Laboratory Medicine, University of Ottawa, 501 Smyth Rd, K1H 8 L6 Ottawa, Canada
| | - Harman Sekhon
- Department of Pathology and Laboratory Medicine, University of Ottawa, 501 Smyth Rd, K1H 8 L6 Ottawa, Canada
| | - Guillaume Martel
- Department of Surgery, Liver and Pancreas Unit, University of Ottawa, 501 Smyth Rd, K1H 8 L6 Ottawa, Canada
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26
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Russo S, Wasif Saif M. Neoadjuvant therapy for pancreatic cancer: an ongoing debate. Therap Adv Gastroenterol 2016; 9:429-36. [PMID: 27366211 PMCID: PMC4913343 DOI: 10.1177/1756283x16646524] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Suzanne Russo
- Case Western Reserve University School of Medicine, Cleveland, OH, USA
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27
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Liu W, Fu XL, Yang JY, Liu DJ, Li J, Zhang JF, Huo YM, Yang MW, Hua R, Sun YW. Efficacy of Neo-Adjuvant Chemoradiotherapy for Resectable Pancreatic Adenocarcinoma: A PRISMA-Compliant Meta-Analysis and Systematic Review. Medicine (Baltimore) 2016; 95:e3009. [PMID: 27082545 PMCID: PMC4839789 DOI: 10.1097/md.0000000000003009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
We have conducted a meta-analysis and systematic review to determine the overall survival, mortality rate, and complete resection rate of neo-adjuvant chemoradiotherapy (CRT) compared with pancreaticoduodenectomy alone in patients with pancreatic adenocarcinoma. Whether neo-adjuvant CRT is beneficial in the treatment of resectable pancreatic cancer or not, it is still a controversial issue. Medline and Cochrane were searched with relevant terms. Eight studies with a total of 833 participants were selected. The meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The analysis revealed neo-adjuvant group may have a benefit in the overall survival, as compared with the resection group, although it did not reach statistical significance (pooled hazard ratio = 0.87, 95% confidence interval [CI] = 0.75-1.00, P = 0.051). We found no difference in the in-hospital mortality rate (pooled odds ratio [OR] = 1.27, 95% CI = 0.35-4.58, P = 0.710). The complete resection rate was significantly higher in the neo-adjuvant group than in the resection group (pooled OR = 2.39, 95% CI = 1.21-4.74, P = 0.012). This meta-analysis found that there was no significant difference in the overall survival between patients treated with neo-adjuvant CRT or pancreaticduodenectomy.
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Affiliation(s)
- Wei Liu
- From the Biliary-Pancreatic Surgery Department, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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28
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Russo S, Ammori J, Eads J, Dorth J. The role of neoadjuvant therapy in pancreatic cancer: a review. Future Oncol 2016; 12:669-85. [PMID: 26880384 DOI: 10.2217/fon.15.335] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Controversy remains regarding neoadjuvant approaches in the treatment of pancreatic cancer. Neoadjuvant therapy has several potential advantages over adjuvant therapy including earlier delivery of systemic treatment, in vivo assessment of response, increased resectability rate in borderline resectable patients and increased margin-negative resection rate. At present, there are no randomized data favoring neoadjuvant over adjuvant therapy and multiple neoadjuvant approaches are under investigation. Combination chemotherapy regimens including 5-fluorouracil, irinotecan and oxaliplatin, gemcitabine with or without abraxane, or docetaxel and capecitabine have been used in the neoadjuvant setting. Radiation and chemoradiation have also been incorporated into neoadjuvant strategies, and delivery of alternative fractionation regimens is being explored. This review provides an overview of neoadjuvant therapies for pancreatic cancer.
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Affiliation(s)
- Suzanne Russo
- Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA
| | - John Ammori
- Department of Surgery, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA
| | - Jennifer Eads
- Department of Medicine, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA
| | - Jennifer Dorth
- Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA
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29
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Preoperative Biliary Drainage in Cases of Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Chemotherapy and Surgery. Gastroenterol Res Pract 2016; 2016:7968201. [PMID: 26880897 PMCID: PMC4736763 DOI: 10.1155/2016/7968201] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Accepted: 12/07/2015] [Indexed: 01/02/2023] Open
Abstract
Objective. To elucidate the optimum preoperative biliary drainage method for patients with pancreatic cancer treated with neoadjuvant chemotherapy (NAC). Material and Methods. From January 2010 through December 2014, 20 patients with borderline resectable pancreatic cancer underwent preoperative biliary drainage and NAC with a plastic or metallic stent and received NAC at Hiroshima University Hospital. We retrospectively analyzed delayed NAC and complication rates due to biliary drainage, effect of stent type on perioperative factors, and hospitalization costs from diagnosis to surgery. Results. There were 11 cases of preoperative biliary drainage with plastic stents and nine metallic stents. The median age was 64.5 years; delayed NAC occurred in 9 cases with plastic stent and 1 case with metallic stent (p = 0.01). The complication rates due to biliary drainage were 0% (0/9) with metallic stents and 72.7% (8/11) with plastic stents (p = 0.01). Cumulative rates of complications determined with the Kaplan-Meier method on day 90 were 60% with plastic stents and 0% with metallic stents (log-rank test, p = 0.012). There were no significant differences between group in perioperative factors or hospitalization costs from diagnosis to surgery. Conclusions. Metallic stent implantation may be effective for preoperative biliary drainage for pancreatic cancer treated with NAC.
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30
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Tang K, Lu W, Qin W, Wu Y. Neoadjuvant therapy for patients with borderline resectable pancreatic cancer: A systematic review and meta-analysis of response and resection percentages. Pancreatology 2015; 16:28-37. [PMID: 26687001 DOI: 10.1016/j.pan.2015.11.007] [Citation(s) in RCA: 103] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Revised: 11/08/2015] [Accepted: 11/10/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND We systematically reviewed and performed a meta-analysis of the available data regarding neoadjuvant chemo- and/or radiotherapy with special emphasis on tumor response/progression rates, toxicities, and clinical benefit, i.e. resection probabilities and survival estimates. METHODS AND FINDINGS Trials were identified by searching PUBMED, MEDLINE, and the Cochrane Central Register of Controlled Trials from 1966 to Feb 2015. A total of 18 studies (n = 959) were analyzed. the estimated fraction of patients with complete response was 2.8% (CI 0.8-4.7%) and with partial response 28.7% (CI 18.9%-38.5%). Stable disease was averaged to 45.9% (CI 32.9%-58.9%) in all patients and tumor progression under therapy occurred by estimation in 16.9% (CI 10.2%-23.6%) of the patients. The weighted frequency of those who underwent resection was 65.3% (CI 54.2%-76.5%), and the proportion of R0 resection amounted to 57.4% (CI 48.2%-66.5%). The weighted mean of median survival amounted to 17.9 months (range: 14.7-21.2 months) for the overall cohort of patients, 25.9 months (range: 21.1-30.7 months) for those who were resected, and 11.9 months (range: 10.4-13.5 months) for unresected patients. CONCLUSIONS The resection and R0 resection rates in the group of borderline resectable tumor patients after neoadjuvant therapy are similar to the resectable tumor patients, much higher than those in unresectable tumor patients. The survival estimates of borderline resectable tumor patients after neoadjuvant therapy were similar to resectable tumor patients. Patients with borderline resectable pancreatic cancer should be included in neoadjuvant protocols and subsequently be reevaluated for resection. How to find chemo-responsiveness before neoadjuvant chemotherapy so as to give individualized treatment is still an important issue.
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Affiliation(s)
- Kezhong Tang
- Department of Surgery, 2nd Affiliated Hospital of Zhejiang University Medical College, Hangzhou 310009, PR China
| | - Wenjie Lu
- Department of Surgery, 2nd Affiliated Hospital of Zhejiang University Medical College, Hangzhou 310009, PR China
| | - Wenjie Qin
- Department of Surgery, 2nd Affiliated Hospital of Zhejiang University Medical College, Hangzhou 310009, PR China
| | - Yulian Wu
- Department of Surgery, 2nd Affiliated Hospital of Zhejiang University Medical College, Hangzhou 310009, PR China.
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31
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Lee SH, Kang CM, Kim H, Hwang HK, Song SY, Seong J, Kim MJ, Lee WJ. Pathological Complete Remission of Pancreatic Cancer Following Neoadjuvant Chemoradiation Therapy; Not the End of Battles. Medicine (Baltimore) 2015; 94:e2168. [PMID: 26717359 PMCID: PMC5291600 DOI: 10.1097/md.0000000000002168] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Revised: 10/12/2015] [Accepted: 10/19/2015] [Indexed: 01/15/2023] Open
Abstract
In spite of controversial issues, pancreatectomy following neoadjuvant chemoradiation therapy (NeoCRT) has been applied in treating advanced pancreatic cancer. Cases of pathological complete remission (pCR) following NeoCRT is rare, and its long-term follow-up data are still lacking.From January 2000 to December 2012, medical records of the patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma were retrospectively reviewed. Characteristics of the patients with pCR were summarized and their long-term follow-up data were analyzed.Among 86 patients with pancreatic cancer who underwent radical pancreatectomy following NeoCRT, 10 patients (11.6%) were reported to pCR. Nine out of 10 patients received gemcitabine-based chemoradiation therapy. Median pre-NeoCRT serum CA 19-9 was 313.5 U/ml, and post-NeoCRT serum CA 19-9 was 9.9 U/ml, which was shown to be significant difference between 2 serum CA 19-9 level (P = 0.005). Pylorus-preserving pancreaticoduodenectomy was done in 8 patients, and the others received distal pancreatosplenectomy. Postoperative chemotherapy was received in 6 patients. Disease-free survival was statistically superior in patients with pCR than patients without pCR (P < 0.05). However, 5 patients experienced cancer recurrence and no clinicopathologic variables including preoperative resectability could not predict the potential recurrence of tumor in patients with pCR (P > 0.05).pCR is rarely reported following NeoCRT, but this condition is not telling the cure of the disease. Early recurrence in the pattern of liver metastasis and peritoneal seeding can be expected. However, long-term survival could be maintained in patients without recurrence. Further investigation is necessary for predicting failure of treatment.
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Affiliation(s)
- Sung Hwan Lee
- From the Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea (SHL, CMK, HKH, WJL); Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea (HK); Department of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea (SYS); Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea (JSS); Department of Radiology, Yonsei University College of Medicine, Seoul, South Korea (MJK)
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Lee JH, Kang CM, Bang SM, Choi JY, Seong JS, Hwang HK, Choi SH, Lee WJ. The Role of Neoadjuvant Chemoradiation Therapy in Patients With Borderline Resectable Pancreatic Cancer With Isolated Venous Vascular Involvement. Medicine (Baltimore) 2015; 94:e1233. [PMID: 26252282 PMCID: PMC4616587 DOI: 10.1097/md.0000000000001233] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 05/28/2015] [Accepted: 07/06/2015] [Indexed: 12/12/2022] Open
Abstract
The rationale for neoadjuvant chemoradiation therapy (Neo-CRT) and the definition of borderline resectable pancreatic cancer (BRPC) are still controversial. In particular, surgical treatment of BRPC with isolated venous vascular involvement (IVVI) is debatable.From January 2000 to December 2013, 84 patients diagnosed with BRPC according to NCCN guidelines were identified, and 70 patients were found to have BRPC with IVVI. We divided all 70 patients into 3 groups: surgery first without Neo-CRT (Group 1); pancreatectomy following Neo-CRT (Group 2); and no operation following Neo-CRT (Group 3). Patient characteristics including oncologic outcomes were analyzed for each of the 3 patients groups.Thirty-seven patients were female and 33 were male, with a mean age of 61.7 ± 9.74 years. Among the 70 BRPC patients with IVVI, 28 patients (40%) belonged to Group 1, 30 patients (42.9%) belonged to Group 2, and 12 patients (17.1%) belonged to Group 3. Pathological tumor size (P < 0.001), pT stage (P = 0.001), pTNM stage (P=0.002), combined vascular resection (P = 0.003), completeness of adjuvant therapy (P = 0.004) were found to be statistically significantly different between Groups 1 and 2. In addition, disease-free survival (P = 0.055) and disease-specific survival (DSS) (P=0.006) were improved in Group 2. Interestingly, when comparing DSS, there was no statistically significant difference between Groups 1 and 3 (P = 0.991).The clinical practice of pancreatectomy following Neo-CRT in BRPC with IVVI provided favorable oncologic outcomes. The effect of Neo-CRT in BRPC with IVVI may be multifactorial, providing proper patient selection, complete adjuvant chemotherapy, and potential therapeutic (downstaging) effect.
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Affiliation(s)
- Jin Ho Lee
- From the Division of Pancreaticobiliary Cancer Clinic, Department of Surgery, Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea (JHL, CMK, HKH, WJL); Division of Gastroenterology, Department of Internal Medicine and Yonsei Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea (SMB); Department of Radiology, Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea (JYC); Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea (JSS); and Division of Hepatobiliary and Pancreas, Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Korea (SHC)
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Schwarz L, Katz MHG. Diagnosis and Management of Borderline Resectable Pancreatic Adenocarcinoma. Hematol Oncol Clin North Am 2015; 29:727-40. [PMID: 26226907 DOI: 10.1016/j.hoc.2015.04.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Borderline resectable pancreatic cancer represents a subcategory of advanced cancer that is typically defined by limited involvement of the major mesenteric vasculature. Such involvement is associated with a high likelihood of microscopically incomplete resection if surgery is used as the primary therapeutic modality. Increasing data support the role of neoadjuvant therapy as part of multimodality management but there is no uniformly accepted standard of care. This review discusses, based on recent literature and the experience of the Pancreatic Tumor Study Group at The University of Texas MD Anderson Cancer Center, the classification, definition, diagnosis, and management of borderline resectable pancreatic cancer.
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Affiliation(s)
- Lilian Schwarz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, 17th Floor, Houston, TX 77030, USA
| | - Matthew Harold G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, 17th Floor, Houston, TX 77030, USA.
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Sirohi B, Singh A, Dawood S, Shrikhande SV. Advances in chemotherapy for pancreatic cancer. Indian J Surg Oncol 2015; 6:47-56. [PMID: 25937764 PMCID: PMC4412866 DOI: 10.1007/s13193-014-0371-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 12/17/2014] [Indexed: 12/26/2022] Open
Abstract
Pancreatic cancer remains challenging to treat. Over the past decade, there have been some major improvements in systemic therapy. Gemcitabine remains the key drug for both early and advanced cancer but combination chemotherapy is emerging as a new paradigm for patients with good performance status. This review focuses on current chemotherapy status for patients with pancreatic cancer.
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Affiliation(s)
- Bhawna Sirohi
- />Department of Medical Oncology, Mazumdar Shaw Cancer Centre, Narayana Health, Bangalore, India
| | - Ashish Singh
- />Department of Medical Oncology, CMC, Vellore, India
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Verbeke C, Löhr M, Karlsson JS, Del Chiaro M. Pathology reporting of pancreatic cancer following neoadjuvant therapy: challenges and uncertainties. Cancer Treat Rev 2015; 41:17-26. [PMID: 25434282 DOI: 10.1016/j.ctrv.2014.11.002] [Citation(s) in RCA: 84] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 11/07/2014] [Accepted: 11/08/2014] [Indexed: 12/22/2022]
Abstract
An increasing number of studies investigate the use of neoadjuvant treatment for ductal adenocarcinoma of the pancreas. While a strong rationale supports this approach, study results are difficult to interpret and compare due to marked variance in multiple aspects of study design and performance. Divergence in pathology examination and reporting as a cause for heterogeneity and incomparability of study results has not been brought into this discussion yet, despite the fact that several key outcome measures for neoadjuvant treatment are pathology-based. This article discusses areas of controversy and difficulty regarding the evaluation of the extent of residual tumour tissue, grading of tumour regression and assessment of the margins, and explains the important clinical implications of the present uncertainty and divergence in pathology practice.
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Affiliation(s)
- C Verbeke
- Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Hälsovägen, 141 86 Stockholm, Sweden; Department of Pathology & Cytology, Karolinska University Hospital, Hälsovägen, 141 86 Stockholm, Sweden.
| | - M Löhr
- Gastrocentrum, Karolinska Institute, Hälsovägen, 141 86 Stockholm, Sweden.
| | - J Severin Karlsson
- Department of Pathology & Cytology, Karolinska University Hospital, Hälsovägen, 141 86 Stockholm, Sweden.
| | - M Del Chiaro
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Hälsovägen, 141 86 Stockholm, Sweden.
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Franke AJ, Rosati LM, Pawlik TM, Kumar R, Herman JM. The role of radiation therapy in pancreatic ductal adenocarcinoma in the neoadjuvant and adjuvant settings. Semin Oncol 2014; 42:144-62. [PMID: 25726059 DOI: 10.1053/j.seminoncol.2014.12.013] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Pancreatic adenocarcinoma (PCA) is associated with high rates of cancer-related morbidity and mortality. Yet despite modern treatment advances, the only curative therapy remains surgical resection. The adjuvant therapeutic standard of care for PCA in the United States includes both chemotherapy and chemoradiation; however, an optimal regimen has not been established. For patients with resectable and borderline resectable PCA, recent investigation has focused efforts on evaluating the feasibility and efficacy of neoadjuvant therapy. Neoadjuvant therapy allows for early initiation of systemic therapy and identification of patients who harbor micrometastatic disease, thus sparing patients the potential morbidities associated with unnecessary radiation or surgery. This article critically reviews the data supporting or refuting the role of radiation therapy in the neoadjuvant and adjuvant settings of PCA management, with a particular focus on determining which patients may be more likely to benefit from radiation therapy.
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Affiliation(s)
- Aaron J Franke
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Lauren M Rosati
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Timothy M Pawlik
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Rachit Kumar
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Joseph M Herman
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.
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Epelboym I, DiNorcia J, Winner M, Lee MK, Lee JA, Schrope BA, Chabot JA, Allendorf JD. Neoadjuvant therapy and vascular resection during pancreaticoduodenectomy: shifting the survival curve for patients with locally advanced pancreatic cancer. World J Surg 2014; 38:1184-95. [PMID: 24305935 DOI: 10.1007/s00268-013-2384-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Neoadjuvant therapy and vascular resection may offer patients with locally advanced pancreatic cancer potential cure. METHODS We reviewed medical records of patients with ductal adenocarcinoma who underwent pancreaticoduodenectomy (PD) from 1992 through 2011. We identified patients who received neoadjuvant therapy (NA+) or required vascular resection (VR+) for locally advanced disease and compared outcomes to those who did not. RESULTS Of the 643 patients who were initially explored, 506 (143 NA+ and 363 NA- patients) ultimately underwent PD. There were no significant differences in R0 resection or morbidity. Mortality was higher in the NA+ versus NA- group (7.0 vs 3.0 %, p = 0.04). More NA+ patients underwent PD VR+ (p < 0.001). Among VR+ patients, neoadjuvant therapy resulted in significantly lower R1 resection. Among resected patients, survival of NA+ patients was significantly longer than both NA- patients (27.3 vs 19.7 months, p < 0.05) and patients abandoned because of locally advanced disease. Age, tumor grade, lymph node ratio, and R1 resection were independent predictors of poor survival. CONCLUSIONS Neoadjuvant therapy and vascular resection offer patients with locally advanced pancreatic cancer the chance for cure with acceptable morbidity and mortality. These patients have improved survival over patients deemed locally inoperable by traditional criteria.
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Affiliation(s)
- Irene Epelboym
- Department of Surgery, Columbia University, College of Physicians and Surgeons, New York, NY, 10032, USA,
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Hirono S, Yamaue H. Tips and tricks of the surgical technique for borderline resectable pancreatic cancer: mesenteric approach and modified distal pancreatectomy with en-bloc celiac axis resection. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2014; 22:E4-7. [PMID: 25366360 DOI: 10.1002/jhbp.184] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Borderline resectable (BR) pancreatic cancer involves the portal vein and/or superior mesenteric vein (PV/SMV), major arteries including the superior mesenteric artery (SMA) or common hepatic artery (CHA), and sometimes includes the involvement of the celiac axis. We herein describe tips and tricks for a surgical technique with video assistance, which may increase the R0 rates and decrease the mortality and morbidity for BR pancreatic cancer patients. First, we describe the techniques used for the "artery-first" approach for BR pancreatic cancer with involvement of the PV/SMV and/or SMA. Next, we describe the techniques used for distal pancreatectomy with en-bloc celiac axis resection (DP-CAR) and tips for decreasing the delayed gastric emptying (DGE) rates for advanced pancreatic body cancer. The mesenteric approach, followed by the dissection of posterior tissues of the SMV and SMA, is a feasible procedure to obtain R0 rates and decrease the mortality and morbidity, and the combination of this aggressive procedure and adjuvant chemo(radiation) therapy may improve the survival of BR pancreatic cancer patients. The DP-CAR procedure may increase the R0 rates for pancreatic cancer patients with involvement within 10 mm from the root of the splenic artery, as well as the CHA or celiac axis, and preserving the left gastric artery may lead to a decrease in the DGE rates in cases where there is more than 10 mm between the tumor edge and the root of the left gastric artery. The development of safer surgical procedures is necessary to improve the survival of BR pancreatic cancer patients.
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Affiliation(s)
- Seiko Hirono
- Second Department of Surgery, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, 641-8510, Japan
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Lee SH, Kang CM, Hwang HK, Choi SH, Lee WJ, Chi HS. Minimally invasive RAMPS in well-selected left-sided pancreatic cancer within Yonsei criteria: long-term (>median 3 years) oncologic outcomes. Surg Endosc 2014; 28:2848-2855. [PMID: 24853839 DOI: 10.1007/s00464-014-3537-3] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Accepted: 03/10/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND Although minimally invasive techniques for distal pancreatectomy with or without splenectomy have been regarded as a feasible and safe treatment option for benign and borderline malignant lesions of the pancreas, the management of left-sided pancreatic cancer remains controversial. METHODS From June 2007 to November 2010, 12 patients underwent laparoscopic or robotic radical antegrade modular pancreatosplenectomy (RAMPS) for well-selected left-sided pancreatic cancer. The Yonsei criteria for patient selection included the following conditions: (1) tumor confined to the pancreas, (2) intact fascial layer between the distal pancreas and the left adrenal gland and kidney, and (3) tumor located more than 1-2 cm from the celiac axis. We compared the clinicopathologic factors and oncologic outcomes of the minimally invasive surgery (MIS) and the conventional open surgery groups for treating left-sided pancreatic cancer. RESULTS In the MIS group, the mean tumor size was 2.75 ± 1.32 cm, and the mean number of retrieved lymph nodes was 10.5 ± 7.14. The resection margins were confirmed to be negative for malignancy in all patients. The MIS group and open group (n = 78) were statistically different in terms of tumor size (2.8 ± 1.3 vs. 3.5 ± 1.9 cm, p = 0.05) and length of hospital stay (12.3 ± 6.8 vs. 22.4 ± 21.6 days, p = 0.002). On survival analysis, the MIS group had longer disease-free survival (DFS) and overall survival (OS) than the open group (DFS: 47.6 vs. 24.7 months, p = 0.027; OS: 60.0 vs. 30.7 months, p = 0.046). In order to overcome the heterogeneity of subjects between the MIS and the open group, we performed statically matched comparisons using the propensity score analysis and then divided the open group into two subgroups according to the Yonsei criteria. There were no significant differences in median overall survival between the MIS group and the open group that met the Yonsei criteria (60.00 vs. 60.72 months, p = 0.616). CONCLUSIONS Minimally invasive RAMPS is not only technically feasible but also oncologically safe in cases of well-selected left-sided pancreatic cancer. Our selection criteria for minimally invasive RAMPS needs to be further validated based on additional large-volume studies.
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Affiliation(s)
- Sung Hwan Lee
- Department of Surgery, Yonsei University College of Medicine, Ludlow Faculty Research Building #204, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea
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Lopez NE, Prendergast C, Lowy AM. Borderline resectable pancreatic cancer: Definitions and management. World J Gastroenterol 2014; 20:10740-10751. [PMID: 25152577 PMCID: PMC4138454 DOI: 10.3748/wjg.v20.i31.10740] [Citation(s) in RCA: 112] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Revised: 01/06/2014] [Accepted: 03/19/2014] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is the fourth leading cause of cancer death in the United States. While surgical resection remains the only curative option, more than 80% of patients present with unresectable disease. Unfortunately, even among those who undergo resection, the reported median survival is 15-23 mo, with a 5-year survival of approximately 20%. Disappointingly, over the past several decades, despite improvements in diagnostic imaging, surgical technique and chemotherapeutic options, only modest improvements in survival have been realized. Nevertheless, it remains clear that surgical resection is a prerequisite for achieving long-term survival and cure. There is now emerging consensus that a subgroup of patients, previously considered poor candidates for resection because of the relationship of their primary tumor to surrounding vasculature, may benefit from resection, particularly when preceded by neoadjuvant therapy. This stage of disease, termed borderline resectable pancreatic cancer, has become of increasing interest and is now the focus of a multi-institutional clinical trial. Here we outline the history, progress, current treatment recommendations, and future directions for research in borderline resectable pancreatic cancer.
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Abstract
Pancreatic cancer is the fourth leading cause of cancer deaths in the USA. Although some patients will present with premalignant pancreatic lesions (i.e., intraductal papillary mucinous neoplasms) or localized tumors amenable to curative resection, the majority of patients will unfortunately present with technically unresectable or metastatic disease. This review of the recent medical literature will discuss the optimal work-up and management of premalignant pancreatic lesions and the surgical management of localized, borderline resectable, and locally advanced (i.e., unresectable) pancreatic tumors. It will focus on new criteria used to define surgical "resectability," the significance and clinical impact of surgical margins, the role of multimodality therapy in the management of patients with borderline resectable or locally advanced tumors, the role of surgery for local or distant recurrence, and minimally invasive surgical approaches.
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Affiliation(s)
- Andreas Karachristos
- Division of Surgical Oncology, Department of Surgery, Temple University School of Medicine, 3401 N. Broad Street, Suite 330 (NFE) and 640 (AK), Philadelphia, PA, 19140, USA,
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Abstract
OPINION STATEMENT Borderline resectable pancreatic adenocarcinoma represents a subset of localized cancers that are at high risk for a margin-positive resection and early treatment failure when resected de novo. Although several different anatomic definitions for this disease stage exist, there is agreement that some degree of reconstructible mesenteric vessel involvement by the tumor is the critical anatomic feature that positions borderline resectable between anatomically resectable and unresectable (locally advanced) tumors in the spectrum of localized disease. Consensus also exists that such cancers should be treated with neoadjuvant chemotherapy and/or chemoradiation before resection; although the optimal algorithm is unknown, systemic chemotherapy followed by chemoradiation is a rational approach. Although gemcitabine-based systemic chemotherapy with either 5-FU or gemcitabine-based chemoradiation regimens has been used to date, newer regimens, including FOLFIRINOX, should be evaluated on protocol. Delivery of neoadjuvant therapy necessitates durable biliary decompression for as many as 6 months in many patients with cancers of the pancreatic head. Patients with no evidence of metastatic disease following neoadjuvant therapy should be brought to the operating room for pancreatectomy, at which time resection of the superior mesenteric/portal vein and/or hepatic artery should be performed when necessary to achieve a margin-negative resection. Following completion of multimodality therapy, patients with borderline resectable pancreatic cancer can expect a duration of survival as favorable as that of patients who initially present with resectable tumors. Coordination among a multidisciplinary team of physicians is necessary to maximize these complex patients' short- and long-term oncologic outcomes.
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Kang CM, Lee SH, Lee WJ. Minimally invasive radical pancreatectomy for left-sided pancreatic cancer: current status and future perspectives. World J Gastroenterol 2014; 20:2343-2351. [PMID: 24605031 PMCID: PMC3942837 DOI: 10.3748/wjg.v20.i9.2343] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2013] [Revised: 12/31/2013] [Accepted: 01/08/2014] [Indexed: 02/06/2023] Open
Abstract
Minimally invasive distal pancreatectomy with splenectomy has been regarded as a safe and effective treatment for benign and borderline malignant pancreatic lesions. However, its application for left-sided pancreatic cancer is still being debated. The clinical evidence for radical antegrade modular pancreatosplenectomy (RAMPS)-based minimally invasive approaches for left-sided pancreatic cancer was reviewed. Potential indications and surgical concepts for minimally invasive RAMPS were suggested. Despite the limited clinical evidence for minimally invasive distal pancreatectomy in left-sided pancreatic cancer, the currently available clinical evidence supports the use of laparoscopic distal pancreatectomy under oncologic principles in well-selected left sided pancreatic cancers. A pancreas-confined tumor with an intact fascia layer between the pancreas and left adrenal gland/kidney positioned more than 1 or 2 cm away from the celiac axis is thought to constitute a good condition for the use of margin-negative minimally invasive RAMPS. The use of minimally invasive (laparoscopic or robotic) anterior RAMPS is feasible and safe for margin-negative resection in well-selected left-sided pancreatic cancer. The oncologic feasibility of the procedure remains to be determined; however, the currently available interim results indicate that even oncologic outcomes will not be inferior to those of open radical distal pancreatosplenectomy.
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Oh TG, Chung MJ, Bang S, Park SW, Chung JB, Song SY, Seong J, Kang CM, Lee WJ, Park JY. Validation of group B borderline resectable pancreatic cancer: retrospective analysis. Gut Liver 2014; 8:557-62. [PMID: 25228978 PMCID: PMC4164249 DOI: 10.5009/gnl13264] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Revised: 10/17/2013] [Accepted: 10/17/2013] [Indexed: 12/18/2022] Open
Abstract
Background/Aims Among borderline resectable pancreatic cancer (BRPC), group B BRPC patients have findings that are suggestive but not diagnostic of metastasis. In this study, we attempted to validate whether group B could truly be categorized as a borderline resectable group. Methods We placed the BRPC patients into group A or group B. The survival outcomes were compared between the groups. Results A total of 53 patients with pancreatic adenocarcinoma was classified as either group A or B borderline resectable. In group A, 23 (60.5%) of 38 patients underwent pancreatectomy after concurrent chemoradiotherapy or chemotherapy, but in group B, only five (33.3%) of 15 patients underwent pancreatectomy, mainly because of the progression of suspected distant metastasis. There was a significant difference in overall survival (OS) between group A and B patients (median OS, 21.2 months vs 10.2 months, respectively; p=0.007). Of the patients who underwent pancreatectomy, group B had a higher recurrence rate compared to group A (recurrence rate: 11 of 23 patients [47.8%] vs five of five patients [100%], respectively; p=0.033). Conclusions This report is the first to validate the definition of BPRC. Group B had much worse outcomes, and whether group B BRPC can be categorized as BRPC together with group A is questionable.
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Affiliation(s)
- Tak Geun Oh
- Division of Gastroenterology, Department of Internal Medicine and Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Moon Jae Chung
- Division of Gastroenterology, Department of Internal Medicine and Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Seungmin Bang
- Division of Gastroenterology, Department of Internal Medicine and Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Woo Park
- Division of Gastroenterology, Department of Internal Medicine and Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Bok Chung
- Division of Gastroenterology, Department of Internal Medicine and Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Si Young Song
- Division of Gastroenterology, Department of Internal Medicine and Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea ; Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea
| | - Chang Moo Kang
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Woo Jung Lee
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jeong Youp Park
- Division of Gastroenterology, Department of Internal Medicine and Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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Christians KK, Pilgrim CHC, Tsai S, Ritch P, George B, Erickson B, Tolat P, Evans DB. Arterial resection at the time of pancreatectomy for cancer. Surgery 2014; 155:919-26. [PMID: 24787115 DOI: 10.1016/j.surg.2014.01.003] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Accepted: 01/16/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND Tumor-induced arterial abutment/encasement has been traditionally a contraindication to surgery in patients with localized pancreatic cancer (PC). One recent meta-analysis reported greater mortality rates in this setting. We report herein a series of planned arterial resections in carefully selected patients who responded favorably to combined modality therapy for localized PC. METHODS We reviewed all patients with PC and arterial encasement treated between May 2011 and September 2013; all patients received an extensive course of neoadjuvant therapy before surgery. RESULTS Of 15 patients taken to surgery, 2 had peritoneal disease at laparoscopy, and therefore, laparotomy was not performed. Pancreatectomy (pancreaticoduodenectomy, 3; distal, 8; central pancreatectomy, 1; total, 1) was performed in the remaining 13, 10 of whom required arterial resection. The most common operation was an Appleby procedure. Of 10 patients who underwent combined pancreatectomy and arterial resection, their median age was 62 years (range, 33-75), median operative time was 7.5 hours, and median blood loss was 725 mL. Complications occurred in 3 of 15 patients with no perioperative mortality. Median duration of hospital stay was 9 days (range, 5-19). An R0 resection was achieved in 11 (85%) of 13 patients. At a median follow-up of 21 months, 8 of these 13 resected patients (62%) are alive without disease. CONCLUSION Planned arterial resection at the time of pancreatectomy can be performed with acceptable morbidity and mortality; patient selection and induction therapy are likely critically important variables that seem to impact patient outcome. Those patients with stable or responding disease after induction therapy represent the subset of patients with potentially favorable tumor biology in whom extended resections may enhance survival duration.
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Affiliation(s)
- Kathleen K Christians
- Department of Surgery, Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI.
| | - Charles H C Pilgrim
- Department of Surgery, Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Susan Tsai
- Department of Surgery, Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Paul Ritch
- Department of Medicine, Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Ben George
- Department of Medicine, Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Beth Erickson
- Department of Radiation Oncology, Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Parag Tolat
- Department of Radiology, Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Douglas B Evans
- Department of Surgery, Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
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46
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Resectable, Borderline Resectable, and Locally Advanced Pancreatic Cancer: What Does It Matter? Curr Oncol Rep 2014; 16:366. [DOI: 10.1007/s11912-013-0366-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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48
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A safe technique for radical antegrade modular pancreatosplenectomy with venous resection for pancreatic cancer. J Am Coll Surg 2013; 217:e35-9. [PMID: 24045139 DOI: 10.1016/j.jamcollsurg.2013.08.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2013] [Revised: 08/09/2013] [Accepted: 08/09/2013] [Indexed: 01/25/2023]
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49
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Toomey P, Childs C, Luberice K, Ross S, Rosemurgy A. Nontherapeutic Celiotomy Incidence is not Affected by Volume of Pancreaticoduodenectomy for Pancreatic Adenocarcinoma. Am Surg 2013. [DOI: 10.1177/000313481307900818] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Nontherapeutic celiotomy for pancreatic adenocarcinoma is detrimental to patients by delaying medical treatment as a result of unnecessarily incurred postoperative recovery time. This study was undertaken to evaluate whether surgeon volume of pancreaticoduodenectomy for pancreatic adenocarcinoma impacted the incidence of nontherapeutic celiotomy. All patients undergoing an intended pancreaticoduodenectomy for pancreatic adenocarcinoma were evaluated from 2003 to 2012. Survival was calculated using Kaplan-Meier analysis. The association between surgeon volume of pancreaticoduodenectomy and occurrence of nontherapeutic celiotomy was assessed using Fisher's exact test. Median data are presented. Eight surgeons undertook 443 intended pancreaticoduodenectomies for patients with pancreatic adenocarcinoma; 329 (74%) patients underwent pancreaticoduodenectomy, whereas 114 (26%) patients underwent nontherapeutic celiotomies. Two surgeons undertook 85 per cent of operations. Surgeon volume did not impact the incidence of nontherapeutic celiotomies ( P = 0.26). Seventy-seven (68%) patients had metastatic disease at the time of the operation, whereas 37 (32%) patients had locally advanced unresectable disease. These patients had survivals of 5.0 and 6.0 months, respectively ( P = 0.77). A high proportion of patients—one in four—undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma will ultimately undergo a nontherapeutic celiotomy. Surgeon volume of pancreaticoduodenectomy for pancreatic adenocarcinoma does not lessen the incidence of non-therapeutic celiotomies. Preoperative prediction of patients with imaging-occult metastatic or locally advanced disease remains a challenge, even for high-volume surgeons. Attempts to create algorithms for patients with high risk of imaging-occult metastatic or locally advanced disease to undergo staging laparoscopy and/or positron emission tomography scanning may decrease the burden of patients undergoing nontherapeutic celiotomies.
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Affiliation(s)
- Paul Toomey
- From The Southeastern Center for Digestive Disorders & Pancreatic Cancer, Advanced Minimally Invasive & Robotic Surgery, Florida Hospital Tampa, Tampa, Florida
| | - Christopher Childs
- From The Southeastern Center for Digestive Disorders & Pancreatic Cancer, Advanced Minimally Invasive & Robotic Surgery, Florida Hospital Tampa, Tampa, Florida
| | - Kenneth Luberice
- From The Southeastern Center for Digestive Disorders & Pancreatic Cancer, Advanced Minimally Invasive & Robotic Surgery, Florida Hospital Tampa, Tampa, Florida
| | - Sharona Ross
- From The Southeastern Center for Digestive Disorders & Pancreatic Cancer, Advanced Minimally Invasive & Robotic Surgery, Florida Hospital Tampa, Tampa, Florida
| | - Alexander Rosemurgy
- From The Southeastern Center for Digestive Disorders & Pancreatic Cancer, Advanced Minimally Invasive & Robotic Surgery, Florida Hospital Tampa, Tampa, Florida
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50
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Cho IR, Chung MJ, Bang S, Park SW, Chung JB, Song SY, Seong J, Hwang HK, Kang CM, Lee WJ, Park JY. Gemcitabine based neoadjuvant chemoradiotherapy therapy in patients with borderline resectable pancreatic cancer. Pancreatology 2013; 13:539-43. [PMID: 24075521 DOI: 10.1016/j.pan.2013.07.064] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2013] [Revised: 07/09/2013] [Accepted: 07/10/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Surgical resection is the only curative treatment for pancreatic cancer, but surgical outcomes for borderline resectable pancreatic cancer (BRPC) are generally poor because of the complexity of the surgery and the advanced nature of the tumor. The aim of this study was to evaluate whether neoadjuvant concurrent chemoradiation therapy (CCRT) in BRPC patients could improve surgical outcome. METHODS Baseline characteristics and treatment outcomes for patients who underwent surgery for BRPC with (CCRT (+) group) and without neoadjuvant treatment (CCRT (-) group) were retrospectively compared. Treatment outcomes measured included overall survival, recurrence-free survival, and perioperative complications. RESULTS A total of 30 patients were included in the CCRT (+) group and 21 patients in the CCRT (-) group. Baseline characteristics were not different before CCRT, but pathological examination after resection revealed reduced tumor size and a lower neurovascular invasion rate in the CCRT (+) group. Overall median survival time was 45.0 months in the CCRT (+) group and 23.5 months in the CCRT (-) group (p = 0.045). The CCRT (+) group had a lower recurrence rate (50.0% vs. 81.0%; p = 0.024) and a longer median disease-free survival period (21.0 months vs. 10.6 months; p = 0.004) than the CCRT (-) group. Perioperative complication rates were not different between the two groups. CONCLUSIONS Neoadjuvant chemoradiation therapy combined with surgical resection yielded better treatment outcomes in patients with BRPC compared with surgery alone. Further larger prospective clinical trials with well defined enrollment criteria and treatment plan are needed.
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Affiliation(s)
- In Rae Cho
- Division of Gastroenterology, Department of Internal Medicine and Yonsei Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea
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