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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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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: 142] [Impact Index Per Article: 47.3] [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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Nelson B, Barrord M, Wang K, Wages NA, Sudhoff M, Kharofa J. Relationship of dose to vascular target volumes and local failure in pancreatic cancer patients undergoing neoadjuvant chemoradiation. Front Oncol 2022; 12:906484. [PMID: 36119519 PMCID: PMC9470914 DOI: 10.3389/fonc.2022.906484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 08/09/2022] [Indexed: 11/13/2022] Open
Abstract
ObjectiveThe objectives of this study were to evaluate whether dose to the vasculature is associated with local control after surgery in patients with borderline resectable (BLR) and resectable pancreatic cancer (PCA) receiving neoadjuvant radiation therapy (RT) and to identify a dose threshold for clinical use.MethodsPatients with BLR and resectable PCA treated with neoadjuvant RT were retrospectively reviewed. During this period, the institutional paradigm shifted from standard fractionation to hypofractionation/stereotactic body radiation therapy (SBRT). A vasculature clinical target volume (Vasc CTV) was contoured for each patient and defined as a 5-mm margin around the superior mesenteric artery (SMA) from its origin to the pancreatic head, the celiac artery from its origin to the level of the trifurcation and any involved vein. The Vasc CTV D95 was normalized to a 2-Gy equivalent dose to determine the optimal dose associated with optimal local failure-free survival (LFFS).ResultsForty-seven patients were included in the analysis. A Vasc CTV D95 of 32.7 Gy was the optimal cutoff for LFFS. Patients with Vasc CTV D95 Equivalent dose in 2 Gy per fraction (EQD2) >32.7 Gy had significantly longer LFFS compared to patients with Vasc CTV D95 EQD2 ≤32.7 Gy at 12 months (91% vs. 51%, respectively) and 24 months (86% vs. 12%, respectively). The median disease-free survival (DFS) for patients with EQD2 >32.7 Gy was 30.4 months compared to 14.0 months in patients with EQD2 ≤32.7 Gy (p = 0.01). There was no significant difference in overall survival (OS) between the two groups.ConclusionsDuring neoadjuvant treatment, dose to the Vasc CTV is associated with durability of local control (LC) after resection and should be intentionally included in the treatment volume with an EQD2 goal of 31–33 Gy.
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Affiliation(s)
- Bailey Nelson
- Department of Radiation Oncology, University of Cincinnati, Cincinnati, OH, United States
- *Correspondence: Bailey Nelson,
| | - Michelle Barrord
- Department of Radiation Oncology, University of Cincinnati, Cincinnati, OH, United States
| | - Kyle Wang
- Department of Radiation Oncology, University of Cincinnati, Cincinnati, OH, United States
| | - Nolan A. Wages
- Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, United States
- Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, United States
| | - Mickaela Sudhoff
- Department of Radiation Oncology, University of Cincinnati, Cincinnati, OH, United States
| | - Jordan Kharofa
- Department of Radiation Oncology, University of Cincinnati, Cincinnati, OH, United States
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Davis CH, Beane JD, Gazivoda VP, Grandhi MS, Greenbaum AA, Kennedy TJ, Langan RC, August DA, Alexander HR, Pitt HA. Neoadjuvant Therapy for Pancreatic Cancer: Increased Use and Improved Optimal Outcomes. J Am Coll Surg 2022; 234:436-443. [PMID: 35290262 DOI: 10.1097/xcs.0000000000000095] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND The introduction of more effective chemotherapy a decade ago has led to increased use of neoadjuvant therapy (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to assess the evolving use of NAT in individuals with PDAC undergoing pancreatoduodenectomy (PD) and to compare their outcomes with patients undergoing upfront operation. STUDY DESIGN The American College of Surgeons NSQIP Procedure Targeted Pancreatectomy database was queried from 2014 to 2019. Patients undergoing pancreatoduodenectomy were evaluated based on the use of NAT versus upfront operation. Multivariable analysis was performed to determine the effect of NAT on postoperative outcomes, including the composite measure optimal pancreatic surgery (OPS). Mann-Kendall trend tests were performed to assess the use of NAT and associated outcomes over time. RESULTS A total of 13,257 patients were identified who underwent PD for PDAC between 2014 and 2019. Overall, 33.6% of patients received NAT. The use of NAT increased steadily from 24.2% in 2014 to 42.7% in 2019 (p < 0.0001). On multivariable analysis, NAT was associated with reduced serious morbidity (odds ratio [OR] 0.83, p < 0.001), clinically relevant pancreatic fistulas (OR 0.52, p < 0.001), organ space infections (OR 0.74, p < 0.001), percutaneous drainage (OR 0.73, p < 0.001), reoperation (OR 0.76, p = 0.005), and prolonged length of stay (OR 0.63, p < 0.001). OPS was achieved more frequently in patients undergoing NAT (OR 1.433, p < 0.001) and improved over time in patients receiving NAT (50.7% to 56.6%, p < 0.001). CONCLUSION NAT before pancreatoduodenectomy increased more than 3-fold over the past decade and was associated with improved optimal operative outcomes.
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Affiliation(s)
- Catherine H Davis
- From the Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
| | - Joal D Beane
- Division of Surgical Oncology, The Ohio State University, Columbus, OH (Beane)
| | - Victor P Gazivoda
- From the Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
| | - Miral S Grandhi
- From the Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
| | - Alissa A Greenbaum
- From the Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
| | - Timothy J Kennedy
- From the Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
| | - Russell C Langan
- From the Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
- the Department of Surgery, Saint Barnabas Medical Center, RWJ Barnabas Health, Livingston, NJ (Langan)
| | - David A August
- From the Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
| | - H Richard Alexander
- From the Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
| | - Henry A Pitt
- From the Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
- Department of Surgery, Rutgers Robert Wood Johnson University Medical School, New Brunswick, NJ (Davis, Gazivoda, Grandhi, Greenbaum, Kennedy, Langan, August, Alexander, Pitt)
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Zhang E, Wang L, Shaikh T, Handorf E, Karen Wong J, Hoffman JP, Reddy S, Cooper HS, Cohen SJ, Dotan E, Meyer JE. Neoadjuvant Chemoradiation Impacts the Prognostic Effect of Surgical Margin Status in Pancreatic Adenocarcinoma. Ann Surg Oncol 2022; 29:354-363. [PMID: 34114181 PMCID: PMC8660918 DOI: 10.1245/s10434-021-10219-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 04/19/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND Many studies show significantly improved survival after R0 resection compared with R1 resection in pancreatic adenocarcinoma (PAC); however, the effect of neoadjuvant chemoradiation (NACRT) on this association is unknown. OBJECTIVE The aim of this study was to evaluate the prognostic significance of positive surgical margins (SMs) after NACRT compared with upfront surgery + adjuvant therapy in PAC. METHODS All cases of surgically resected PAC at a single institution were reviewed from 1996 to 2014; patients treated with palliative intent, metastatic disease, and biliary/ampullary tumors were excluded. The primary endpoint was overall survival (OS). RESULTS Overall, 300 patients were included; 134 patients received NACRT with concurrent 5-fluorouracil or gemcitabine followed by surgery, and 166 patients received upfront surgery (+ adjuvant chemotherapy in 72% of patients and RT in 65%); 31% of both groups had a positive SM (+SM). The median OS for patients with a +SM or negative SM (-SM) was 26.6 and 31.6 months, respectively for NACRT, and 12.0 and 24.5 months, respectively, for upfront surgery. OS was significantly improved with -SM compared with +SM in both groups (p = 0.006). When resection yielded +SM, NACRT patients had improved OS compared with upfront surgery patients (p < 0.001). On multivariable analysis, +SM in the upfront surgery group (hazard ratio [HR] 2.94, 95% confidence interval [CI] 2.04-4.24; p < 0.001) and older age (HR 1.01, 95% CI 1.00-1.03, per year; p = 0.007) predicted worse OS. +SM in the NACRT group was not associated with worse OS (HR 1.09, 95% CI 0.72-1.65; p = 0.70). CONCLUSION Patients with a positive margin after NACRT and surgery had longer survival compared with patients with a positive margin after upfront surgery. NACRT should be strongly considered for patients at high risk of R1 resections.
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Affiliation(s)
- Eddie Zhang
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Lora Wang
- Department of Radiation Oncology, University of Miami, Miami, Florida
| | - Talha Shaikh
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Elizabeth Handorf
- Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - J. Karen Wong
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - John P. Hoffman
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennyslvania
| | - Sanjay Reddy
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennyslvania
| | - Harry S. Cooper
- Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Steven J. Cohen
- Department of Medical Oncology, Abington Hospital/Jefferson Health, Abington, Pennsylvania
| | - Efrat Dotan
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Joshua E. Meyer
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
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Affiliation(s)
- Kristin N Kelly
- Division of Surgical Oncology, Dewitt-Daughtry Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, CRB, 4th Floor, Miami, FL 33136, USA
| | - Francisco I Macedo
- Department of Surgery, North Florida Regional Medical Center, University of Central Florida College of Medicine, Gainesville, FL, USA
| | - Nipun B Merchant
- Division of Surgical Oncology, Dewitt-Daughtry Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, CRB, 4th Floor, Miami, FL 33136, USA.
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Patterns of Failure After Neoadjuvant Stereotactic Body Radiation Therapy or Fractionated Chemoradiation in Resectable and Borderline Resectable Pancreatic Cancer. Pancreas 2020; 49:941-946. [PMID: 32658077 DOI: 10.1097/mpa.0000000000001602] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVES The goal of this study was to compare outcomes of patients with borderline and resectable pancreatic cancer treated with neoadjuvant stereotactic body radiation therapy (SBRT) versus fractionated chemoradiation. METHODS Patients with borderline or resectable pancreatic cancer treated with neoadjuvant intent between November 2011 and December 2017 were reviewed. The SBRT volume/dose was 33 Gy in 5 fractions to gross tumor plus abutting vessel with or without 25 Gy in 5 fractions to pancreatic head/body and celiac/superior mesenteric artery. Fractionated chemoradiation volume/dose was 50.4 Gy in 28 fractions to gross tumor, superior mesenteric/celiac arteries, and enlarged lymph nodes with concurrent bolus 5-FU, leucovorin, oxaliplatin, irinotecan or gemcitabine/nab-paclitaxel. Failure patterns, local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival were assessed. RESULTS Forty-three patients were reviewed (18 SBRTs and 25 fractionated). Among patients who underwent resection, patients treated with fractionated chemoradiation had improved LRFS (12-month LRFS, 86% vs 62%, P = 0.003) and PFS (median PFS, 23 months vs 11 months, P = 0.006) compared with SBRT. There was no difference in overall survival. CONCLUSIONS Stereotactic body radiation therapy may result in inferior LRFS and PFS compared with fractionated chemoradiation, likely because of under coverage of high-risk vascular targets.
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Azab B, Macedo FI, Chang D, Ripat C, Franceschi D, Livingstone AS, Yakoub D. The Impact of Prolonged Chemotherapy to Surgery Interval and Neoadjuvant Radiotherapy on Pathological Complete Response and Overall Survival in Pancreatic Cancer Patients. CLINICAL MEDICINE INSIGHTS-ONCOLOGY 2020; 14:1179554920919402. [PMID: 32669884 PMCID: PMC7336830 DOI: 10.1177/1179554920919402] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 03/04/2020] [Indexed: 01/15/2023]
Abstract
Background: We aimed to study the impact of neoadjuvant chemotherapy to surgery (NCT-S)
interval and neoadjuvant radiotherapy (NRT) on pathological complete
response (pCR) and overall survival (OS) in pancreatic cancer (pancreatic
ductal adenocarcinoma [PDAC]). Methods: National Cancer Data Base (NCDB)–pancreatectomy patients who underwent
NCT/NRT were included. The NCT-S interval was divided into time quintiles in
weeks: 8 to 11, 12 to 14, 15 to 19, 20 to 29, and >29 weeks. Results: A total of 2093 patients with NCT were included with median follow-up of
74 months and 71% NRT. The pCR rate was 2.1% with higher median OS compared
with non-pCR (41 vs 19 months, P = .03). The pCR rate
increased with longer NCT-S interval (quintiles: 1%, 1.6%, 1.7%, 3%, and 6%,
P < .001, respectively). In logistic regression, NRT
(odds ratio [OR] = 2.5, 95% confidence interval [CI]: 1.1-6.1,
P = .03) and NCT-S >29 weeks (OR = 6.1, 95%
CI = 2.02-18.50, P < .001) were predictive of increased
pCR. The prolonged NCT-S interval and pCR were independent predictors of OS,
whereas NRT was not. Conclusions: Longer NCT-S interval and pCR were independent predictors of improved OS in
patients with PDAC. The NRT predicted increased pCR but not OS.
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Affiliation(s)
- Basem Azab
- Surgical Oncology, Sentara Healthcare, Sentara CarePlex Hospital, Hampton, VA, USA
| | - Francisco Igor Macedo
- Surgical Oncology, DeWitt Daughtry Family Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - David Chang
- Virginia Oncology Associate, Hampton, VA, USA
| | - Caroline Ripat
- Surgical Oncology, DeWitt Daughtry Family Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Dido Franceschi
- Surgical Oncology, DeWitt Daughtry Family Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Alan S Livingstone
- Surgical Oncology, DeWitt Daughtry Family Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Danny Yakoub
- Surgical Oncology, DeWitt Daughtry Family Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
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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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10
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Wang D, Liu C, Zhou Y, Yan T, Li C, Yang Q, Xu Y, Zhao L, Pei Q, Tan F, Güngör C, Li Y. Effect of neoadjuvant radiotherapy on survival of non-metastatic pancreatic ductal adenocarcinoma: a SEER database analysis. Radiat Oncol 2020; 15:107. [PMID: 32404114 PMCID: PMC7222314 DOI: 10.1186/s13014-020-01561-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Accepted: 05/04/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Neoadjuvant radiotherapy has been shown to improve marginal negative resection and local control of Pancreatic Ductal Adenocarcinoma (PDAC). However, whether it improves overall survival (OS) in patients with non-metastatic PDAC remains controversial. Therefore, the purpose of this study was to analyze the benefits of only surgery, neoadjuvant radiotherapy, adjuvant radiotherapy, and surgery plus chemotherapy for OS in patients with non-metastatic PDAC. METHODS PDAC diagnosed by surgical histopathology in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016 was selected. Kaplan-Meier analysis was used to compare the prognosis of patients with different treatments. Cox proportional risk model was used to analyze independent predictors of OS. Propensity score matching (PSM) was used to analyze the tumor prognosis of different treatment methods. RESULTS Before PSM analysis, the OS of surgery plus chemotherapy (HRs = 0.896, 95%CIs, 0.827-0.970; P = 0.007) were significantly better than the other three treatments for stage T1-3N0M0 PDAC patients. For stage T1-3N + M0 patients, adjuvant radiotherapy (HRs = 0.613, 95% CIs, 0.579-0.649; P < 0.001) had significantly better OS than surgery plus chemotherapy and neoadjuvant radiotherapy. For stage T4N0M0 patients, neoadjuvant radiotherapy (HRs = 0.482, 95% CIs, 0.347-0.670; P < 0.001) had significantly better OS than surgery plus chemotherapy and adjuvant radiotherapy. For stage T4N + M0 patients, neoadjuvant radiotherapy (HRs = 0.338, 95% CIs, 0.215-0.532; P < 0.001) had significantly longer OS than adjuvant radiotherapy and surgery plus chemotherapy. Even after PSM, Chemotherapy plus surgery was still the best treatment for T1-3N0M0 patients. Postoperative adjuvant radiotherapy had the best prognosis among T1-3N + M0 patients, and neoadjuvant radiotherapy was the best treatment for T4 patients. CONCLUSIONS For patients with non-metastatic PDAC, neoadjuvant radiotherapy, adjuvant radiotherapy and surgery plus chemotherapy were superior to only surgery in OS. For patients with stage T4 non-metastatic PDAC, neoadjuvant radiotherapy had the potential to be strongly recommended over adjuvant radiotherapy and surgery plus chemotherapy. However, neoadjuvant radiotherapy failed to benefit the survival of T1-3N0M0 stage patients, and surgery plus chemotherapy was preferred. For T1-3N + M0, neoadjuvant radiotherapy had no obvious advantage over adjuvant radiotherapy or surgery plus chemotherapy in OS, and adjuvant radiotherapy was more recommended.
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Affiliation(s)
- Dan Wang
- Department of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Chongshun Liu
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Yuan Zhou
- George Washington University Hospital, Washington, USA
| | - Tingyu Yan
- Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Chenglong Li
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Qionghui Yang
- Department of Pediatrics, Yueqing Third People's Hospital, Yueqing, China
| | - Yang Xu
- Department of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lilan Zhao
- Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Qian Pei
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Fengbo Tan
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Cenap Güngör
- Department of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Yuqiang Li
- Department of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China.
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11
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Araujo RLC, Silva RO, de Pádua Souza C, Milani JM, Huguet F, Rezende AC, Gaujoux S. Does neoadjuvant therapy for pancreatic head adenocarcinoma increase postoperative morbidity? A systematic review of the literature with meta-analysis. J Surg Oncol 2020; 121:881-892. [PMID: 31994193 DOI: 10.1002/jso.25851] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 01/09/2020] [Indexed: 12/11/2022]
Abstract
Neoadjuvant treatment (NT) for pancreatic head cancer may allow some patients to undergo curative resection, but its impact on postoperative complications remains unclear. A systematic review and meta-analysis were performed to compare overall postoperative morbidity, pancreatic fistula, and mortality between patients who underwent upfront surgery and those who underwent neoadjuvant therapy first. Forty-five studies with 3359 patients were included. No significant differences in morbidity and mortality rates associated with NT for pancreatic head cancer were detected in this study.
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Affiliation(s)
- Raphael L C Araujo
- Department of Digestive Surgery, Escola Paulista de Medicina (UNIFESP), São Paulo, São Paulo, Brazil.,Post-graduation Program, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.,Department of Oncology, Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil
| | - Raphael O Silva
- Department of Surgical Oncology, Hospital Santa Casa, Campo Mourão, Paraná, Brazil
| | | | - Jean M Milani
- Post-graduation Program, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
| | - Florence Huguet
- Department of Radiation Oncology, Hôpital Tenon AP-HP, Sorbonne University, Paris, France
| | - Ana C Rezende
- Department of Oncology, Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil
| | - Sebastien Gaujoux
- Department of Digestive, Pancreatic and Endocrine Surgery, Hôpital Cochin AP-HP, Paris, France
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12
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Klaiber U, Hackert T. Conversion Surgery for Pancreatic Cancer-The Impact of Neoadjuvant Treatment. Front Oncol 2020; 9:1501. [PMID: 31993372 PMCID: PMC6971165 DOI: 10.3389/fonc.2019.01501] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Accepted: 12/16/2019] [Indexed: 12/12/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis, mainly because only 15–20% of all patients present with resectable tumor stages at the time of diagnosis. Due to locally extended tumor growth or distant metastases upfront resection is not reasonable in the majority of patients. Considerably, PDAC will be the 2nd most frequent cause of cancer-related deaths within the next 10 years for both men and women. While there is currently no convincing evidence for the use of neoadjuvant therapy in resectable PDAC, there are controversial results from studies investigating neoadjuvant treatment concepts in borderline resectable PDAC (BR-PDAC). However, the definition of BR-PDAC is a topic of debate. While BR-PDAC has originally been defined on merely anatomical criteria, the International Association of Pancreatology (IAP) has recently suggested a broader definition based on a combination of anatomical (A) findings, biological (B) criteria (which reflect tumor aggressiveness), and conditional (C) aspects (which respect host-related condition). In case of BR-PDAC with venous invasion alone, upfront resection is generally recommended whenever technically possible in patients fit for surgery and without evidence for lymph node metastases. In contrast, in case of arterial invasion neoadjuvant therapy is regarded as the treatment of choice. The same accounts for high CA 19-9 levels, suspected or proven lymph node involvement and poor performance status. In locally advanced PDAC (LA-PDAC), neoadjuvant treatment represents the standard of care resulting in proportionally high rates of secondary resection. This “conversion” surgery offers the chance for improved survival times in an otherwise palliative situation. Herein, we summarize the current evidence of different treatment strategies for pancreatic cancer with a focus on conversion surgery and the impact of neoadjuvant treatment in this setting.
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Affiliation(s)
- Ulla Klaiber
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
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13
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Comparison of Tumor Regression Grading of Residual Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Chemotherapy Without Radiation: Would Fewer Tier-Stratification Be Favorable Toward Standardization? Am J Surg Pathol 2020; 43:334-340. [PMID: 30211728 DOI: 10.1097/pas.0000000000001152] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
To assess whether the College of American Pathologists (CAP) and the Evans grading systems for neoadjuvant chemotherapy without radiation-treated pancreatectomy specimens are prognostic, and if a 3-tier stratification scheme preserves data granularity. Conducted retrospective review of 32 patients with ordinary pancreatic ductal adenocarcinoma treated with neoadjuvant therapy without radiation followed by surgical resection. Final pathologic tumor category (AJCC eighth edition) was 46.9% ypT1, 34.4% ypT2, and 18.7% ypT3. Median follow-up time was 29.8 months, median disease-free survival (DFS) was 19.6 months, and median overall survival (OS) was 34.2 months. CAP score 1, 2, 3 were present in 5 (15.6%), 18 (56.3%), and 9 (28.1%) patients, respectively. Evans grade III, IIb, IIa, and I were present in 10 (31.2%), 8 (25.0%), 7 (21.9%), and 7 (21.9%) patients, respectively. OS (CAP: P=0.005; Evans: P=0.001) and DFS (CAP: P=0.003; Evans: P=0.04) were statistically significant for both CAP and Evans. Stratified CAP scores 1 and 2 versus CAP score 3 was statistically significant for both OS (P=0.002) and DFS (P=0.002). Stratified Evans grades I, IIa, and IIb versus Evans grade III was statistically significant for both OS (P=0.04) and DFS (P=0.02). CAP, Evans, and 3-tier stratification are prognostic of OS and DFS.
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14
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Pattern of Marginal Local Failure in a Phase II Trial of Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy for Resectable and Borderline Resectable Pancreas Cancer. Am J Clin Oncol 2019; 42:247-252. [PMID: 30724781 DOI: 10.1097/coc.0000000000000518] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES The main objectives of this study were to prospectively evaluate the safety and efficacy of stereotactic body radiation therapy (SBRT) in the neoadjuvant setting for resectable or borderline resectable pancreatic cancer. MATERIALS AND METHODS Eighteen patients were enrolled from November 2014 to June 2017. Following 3 cycles of chemotherapy, SBRT was delivered to the tumor and abutting vessel and a 3 mm planning target volume (PTV) margin to 33 Gy (6.6 Gy×5) with an optional elective PTV to 25 Gy (5 Gy×5) customized to the nodal space and mesenteric vessels. The primary endpoint is ≥grade 3 acute and late gastrointestinal toxicity. RESULTS Fifteen patients had borderline resectable tumors due to arterial abutment (n=7) or superior mesenteric vein encasement (n=8); 3 patients had resectable tumors. There were no ≥grade 3 acute or late gastrointestinal events. Following SBRT, surgery was performed in 12 patients (67%) with 11 (92%) R0 resections. The median overall survival and progression-free survival was 21 months (95% CI: 18-29) and 11 months (95% CI: 8.4-16). Progression occurred in 83% (10/12) of resected patients (distant [n=4, 40%], local-only [n=4, 40%], and local and distant [n=2, 20%]). The cumulative incidence of local failure (LF) at 12 months from resection was 50% (95% CI: 20-80). All LF were outside to the PTV33. CONCLUSIONS Neoadjuvant SBRT was well tolerated, however LFs were predominantly observed outside the PTV33 volume that would have been covered with conventional RT volumes. The durability of local control after SBRT in the neoadjuvant setting merits examination relative to chemoradiation before incorporation into routine practice.
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15
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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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16
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Hackert T. Surgery for Pancreatic Cancer after neoadjuvant treatment. Ann Gastroenterol Surg 2018; 2:413-418. [PMID: 30460344 PMCID: PMC6236102 DOI: 10.1002/ags3.12203] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 07/06/2018] [Accepted: 07/29/2018] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains to be a therapeutic challenge as only 15%-20% of all patients present with resectable tumor stages by the time of diagnosis. In the remaining patients, either local tumor extension or systemic spread are obstacles for a surgical therapy as the only chance for long-term survival. With regard to local tumor extension, PDAC has been classified as resectable, borderline-resectable (BR) or locally advanced (LA). While there is currently no evidence for neoadjuvant therapy in resectable PDAC, this issue remains controversial in BR-PDAC. In the case of venous tumor involvement, guidelines mostly recommend upfront resection, when technically possible; whereas arterial involvement is regarded as an indication for chemotherapy or chemoradiotherapy first. Furthermore, in locally advanced PDAC, neoadjuvant treatment approaches have recently resulted in high rates of secondary resection, thus allowing "conversion" surgery in an otherwise palliative treatment situation. The present review gives an overview on the current literature of treatment concepts in these situations and additionally focuses of evaluation of resectability after neoadjuvant therapy as well as technical aspects in this specific situation.
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Affiliation(s)
- Thilo Hackert
- Department of General, Visceral and Transplantation SurgeryUniversity of HeidelbergHeidelbergGermany
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17
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Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer. Ann Surg 2018; 268:215-222. [PMID: 29462005 DOI: 10.1097/sla.0000000000002705] [Citation(s) in RCA: 491] [Impact Index Per Article: 70.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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18
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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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19
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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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20
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Can Neoadjuvant Therapy in Pancreatic Cancer Increase the Pool of Patients Eligible for Pancreaticoduodenectomy? Adv Surg 2017; 51:1-10. [PMID: 28797331 DOI: 10.1016/j.yasu.2017.03.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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21
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Nayır E, Ermis E. Chemoradiation of pancreatic carcinoma. JOURNAL OF ONCOLOGICAL SCIENCES 2016. [DOI: 10.1016/j.jons.2016.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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22
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Kim SS, Nakakura EK, Wang ZJ, Kim GE, Corvera CU, Harris HW, Kirkwood KS, Hirose R, Tempero MA, Ko AH. Preoperative FOLFIRINOX for borderline resectable pancreatic cancer: Is radiation necessary in the modern era of chemotherapy? J Surg Oncol 2016; 114:587-596. [PMID: 27444658 DOI: 10.1002/jso.24375] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Accepted: 07/01/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND No consensus exists regarding the optimal neoadjuvant treatment paradigm for patients with borderline resectable pancreatic cancer (BRPC), including the respective roles of chemotherapy and radiation. METHODS We performed a retrospective analysis, including detailed pathologic and radiologic review, of pancreatic cancer patients undergoing FOLFIRINOX, with or without radiation therapy (RT), prior to surgical resection at a high-volume academic center over a 4-year period. RESULTS Of 26 patients meeting inclusion criteria, 22 (84.6%) received FOLFIRINOX alone without RT (median number of treatment cycles = 9). The majority of patients met formal radiographic criteria for BRPC, with the superior mesenteric vein representing the most common vessel involved. R0 resection rate was 90.9%, with 12 patients (54.5%) requiring vascular reconstruction. Treatment response was classified as moderate or marked in 16 patients (72.7%) according to the College of American Pathologists grading system. Estimated median disease-free and overall survival rates are 22.6 months and not reached (NR), respectively. CONCLUSIONS This is one of the largest series to describe the use of neoadjuvant FOLFIRINOX, without radiation therapy, in patients with BRPC undergoing surgical resection. Given the high R0 resection rates and favorable clinical outcomes with chemotherapy alone, this strategy should be further assessed in prospective study design. J. Surg. Oncol. 2016;114:587-596. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Sunhee S Kim
- Division of Hematology/Oncology, University of California San Francisco, San Francisco, California
| | - Eric K Nakakura
- Department of Surgery, University of California San Francisco, San Francisco, California.
| | - Zhen J Wang
- Department of Radiology, University of California San Francisco, San Francisco, California
| | - Grace E Kim
- Department of Pathology, University of California San Francisco, San Francisco, California
| | - Carlos U Corvera
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - Hobart W Harris
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - Kimberly S Kirkwood
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - Ryutaro Hirose
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - Margaret A Tempero
- Division of Hematology/Oncology, University of California San Francisco, San Francisco, California
| | - Andrew H Ko
- Division of Hematology/Oncology, University of California San Francisco, San Francisco, California.
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23
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Triantopoulou C, Papaparaskeva K, Agalianos C, Dervenis C. Innovations in macroscopic evaluation of pancreatic specimens and radiologic correlation. Eur J Radiol Open 2016; 3:49-59. [PMID: 27069980 PMCID: PMC4811858 DOI: 10.1016/j.ejro.2016.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 02/23/2016] [Indexed: 02/07/2023] Open
Abstract
The axial slicing technique offers many advantages in accurate estimation of tumors extend and staging. Cross-sectional axial imaging is the best technique for accurate radiologic-pathologic correlation. Correlation may explain any discrepancies between radiological and histopathological findings. Pathology correlation may offer a better understanding of the missed findings by imaging or pitfalls The purpose of this study was to evaluate the feasibility of a novel dissection technique of surgical specimens in different cases of pancreatic tumors and provide a radiologic pathologic correlation. In our hospital, that is a referral center for pancreatic diseases, the macroscopic evaluation of the pancreatectomy specimens is performed by the pathologists using the axial slicing technique (instead of the traditional procedure with longitudinal opening of the main pancreatic and/or common bile duct and slicing along the plane defined by both ducts). The specimen is sliced in an axial plane that is perpendicular to the longitudinal axis of the descending duodenum. The procedure results in a large number of thin slices (3–4 mm). This plane is identical to that of CT or MRI and correlation between pathology and imaging is straightforward. We studied 70 cases of suspected different solid and cystic pancreatic tumors and we correlated the tumor size and location, the structure—consistency (areas of necrosis—hemorrhage—fibrosis—inflammation), the degree of vessels’ infiltration, the size of pancreatic and common bile duct and the distance from resection margins. Missed findings by imaging or pitfalls were recorded and we tried to explain all discrepancies between radiology evaluation and the histopathological findings. Radiologic-pathologic correlation is extremely important, adding crucial information on imaging limitations and enabling quality assessment of surgical specimens. The deep knowledge of different pancreatic tumors’ consistency and way of extension helps to improve radiologists’ diagnostic accuracy and minimize the radiological-surgical mismatching, preventing patients from unnecessary surgery.
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Affiliation(s)
| | - Kleo Papaparaskeva
- Histopathology Department, Konstantopouleio General Hospital, Athens, Greece
| | | | - Christos Dervenis
- Surgery Department, Konstantopouleio General Hospital, Athens, Greece
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24
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Versteijne E, van Eijck CHJ, Punt CJA, Suker M, Zwinderman AH, Dohmen MAC, Groothuis KBC, Busch ORC, Besselink MGH, de Hingh IHJT, Ten Tije AJ, Patijn GA, Bonsing BA, de Vos-Geelen J, Klaase JM, Festen S, Boerma D, Erdmann JI, Molenaar IQ, van der Harst E, van der Kolk MB, Rasch CRN, van Tienhoven G. Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): study protocol for a multicentre randomized controlled trial. Trials 2016; 17:127. [PMID: 26955809 PMCID: PMC4784417 DOI: 10.1186/s13063-016-1262-z] [Citation(s) in RCA: 125] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 02/26/2016] [Indexed: 12/20/2022] Open
Abstract
Background Pancreatic cancer is the fourth largest cause of cancer death in the United States and Europe with over 100,000 deaths per year in Europe alone. The overall 5-year survival ranges from 2–7 % and has hardly improved over the last two decades. Approximately 15 % of all patients have resectable disease at diagnosis, and of those, only a subgroup has a resectable tumour at surgical exploration. Data from cohort studies have suggested that outcome can be improved by preoperative radiochemotherapy, but data from well-designed randomized studies are lacking. Our PREOPANC phase III trial aims to test the hypothesis that median overall survival of patients with resectable or borderline resectable pancreatic cancer can be improved with preoperative radiochemotherapy. Methods/design The PREOPANC trial is a randomized, controlled, multicentric superiority trial, initiated by the Dutch Pancreatic Cancer Group. Patients with (borderline) resectable pancreatic cancer are randomized to A: direct explorative laparotomy or B: after negative diagnostic laparoscopy, preoperative radiochemotherapy, followed by explorative laparotomy. A hypofractionated radiation scheme of 15 fractions of 2.4 gray (Gy) is combined with a course of gemcitabine, 1,000 mg/m2/dose on days 1, 8 and 15, preceded and followed by a modified course of gemcitabine. The target volumes of radiation are delineated on a 4D CT scan, where at least 95 % of the prescribed dose of 36 Gy in 15 fractions should cover 98 % of the planning target volume. Standard adjuvant chemotherapy is administered in both treatment arms after resection (six cycles in arm A and four in arm B). In total, 244 patients will be randomized in 17 hospitals in the Netherlands. The primary endpoint is overall survival by intention to treat. Secondary endpoints are (R0) resection rate, disease-free survival, time to locoregional recurrence or distant metastases and perioperative complications. Secondary endpoints for the experimental arm are toxicity and radiologic and pathologic response. Discussion The PREOPANC trial is designed to investigate whether preoperative radiochemotherapy improves overall survival by means of increased (R0) resection rates in patients with resectable or borderline resectable pancreatic cancer. Trial registration Trial open for accrual: 3 April 2013 The Netherlands National Trial Register – NTR3709 (8 November 2012) EU Clinical Trials Register – 2012-003181-40 (11 December 2012)
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Affiliation(s)
- Eva Versteijne
- Department of Radiation Oncology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Casper H J van Eijck
- Department of Surgery, Erasmus Medical Center, Postbus 2040, 3000 CA, Rotterdam, The Netherlands.
| | - Cornelis J A Punt
- Department of Medical Oncology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Mustafa Suker
- Department of Surgery, Erasmus Medical Center, Postbus 2040, 3000 CA, Rotterdam, The Netherlands.
| | - Aeilko H Zwinderman
- Department of Clinical Epidemiologic Biostatics, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Miriam A C Dohmen
- Clinical Research Department, Comprehensive Cancer Organisation the Netherlands (IKNL), Postbus 1281, 6501 BG, Nijmegen, The Netherlands.
| | - Karin B C Groothuis
- Clinical Research Department, Comprehensive Cancer Organisation the Netherlands (IKNL), Postbus 1281, 6501 BG, Nijmegen, The Netherlands.
| | - Oliver R C Busch
- Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Marc G H Besselink
- Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Ignace H J T de Hingh
- Department of Surgery, Catharina Hospital, Postbus 1350, 5602 ZA, Eindhoven, The Netherlands.
| | - Albert J Ten Tije
- Department of Medical Oncology, Amphia Hospital, Postbus 90158, 4800 RK, Breda, The Netherlands.
| | - Gijs A Patijn
- Department of Surgery, Isala Clinics, Postbus 10400, 8000 GK, Zwolle, The Netherlands.
| | - Bert A Bonsing
- Department of Surgery, Leiden University Medical Center, Postbus 9600, 2300 RC, Leiden, The Netherlands.
| | - Judith de Vos-Geelen
- Department of Medical Oncology, Maastricht University Medical Center, Postbus 3035, 6202 NA, Maastricht, The Netherlands.
| | - Joost M Klaase
- Department of Surgery, Medical Spectrum Twente, Postbus 50 000, 7500 KA, Enschede, The Netherlands.
| | - Sebastiaan Festen
- Department of Surgery, Onze Lieve Vrouwe Gasthuis, Postbus 95500, 1090 HM, Amsterdam, The Netherlands.
| | - Djamila Boerma
- Department of Surgery, Sint Antonius Hospital, Postbus 2500, 3430 EM, Nieuwegein, The Netherlands.
| | - Joris I Erdmann
- Department of Surgery, University Medical Center Groningen, Postbus 30.001, 9700 RB, Groningen, The Netherlands.
| | - I Quintus Molenaar
- Department of Surgery, University Medical Center Utrecht, Postbus 85500, 3508 GA, Utrecht, The Netherlands.
| | - Erwin van der Harst
- Department of Surgery, Maasstad Hospital, Maasstadweg 21, 3079 DZ, Rotterdam, The Netherlands.
| | - Marion B van der Kolk
- Department of Surgery, Radboud University Medical Center, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, The Netherlands.
| | - Coen R N Rasch
- Department of Radiation Oncology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Geertjan van Tienhoven
- Department of Radiation Oncology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
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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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The effects of neoadjuvant chemoradiation on pancreaticoduodenectomy—the American College of Surgeon's National Surgical Quality Improvement Program analysis. J Surg Res 2015; 196:67-73. [DOI: 10.1016/j.jss.2015.01.045] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Revised: 01/20/2015] [Accepted: 01/23/2015] [Indexed: 02/06/2023]
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Desai NV, Sliesoraitis S, Hughes SJ, Trevino JG, Zlotecki RA, Ivey AM, George TJ. Multidisciplinary neoadjuvant management for potentially curable pancreatic cancer. Cancer Med 2015; 4:1224-39. [PMID: 25766842 PMCID: PMC4559034 DOI: 10.1002/cam4.444] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 02/12/2015] [Accepted: 02/14/2015] [Indexed: 12/24/2022] Open
Abstract
Pancreatic adenocarcinoma remains the fourth leading cause of cancer mortality in the U.S. Despite advances in surgical technique, radiotherapy technologies, and chemotherapeutics, the 5-year survival rate remains approximately 20% for the 15% of patients who are eligible for surgical resection. The majority of this group suffers metastatic recurrence. However, despite advances in therapies for patients with advanced pancreatic cancer, only surgery has consistently proven to improve long-term survival. Various combinations of chemotherapy, biologic-targeted therapy, and radiotherapy have been evaluated in different settings to improve outcomes. In this context, a neoadjuvant (preoperative) treatment strategy offers numerous potential benefits: (1) ensuring delivery of early, systemic therapy, (2) improving selection of patients for surgical therapy with truly localized disease, (3) potential downstaging of the neoplasm facilitating a negative margin resection in patients with locally advanced disease, and (4) providing a superior clinical trial mechanism capable of rapid assessment of the efficacy of novel therapeutics. This article reviews the recent trends in the management of pancreatic adenocarcinoma, with a particular emphasis on a multidisciplinary neoadjuvant approach to treatment.
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Affiliation(s)
- Neelam V Desai
- Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, Florida
| | - Sarunas Sliesoraitis
- Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, Florida
| | - Steven J Hughes
- Department of Surgery, University of Florida, Gainesville, Florida
| | - Jose G Trevino
- Department of Surgery, University of Florida, Gainesville, Florida
| | - Robert A Zlotecki
- Department of Radiation Oncology, University of Florida, Gainesville, Florida
| | - Alison M Ivey
- University of Florida Health Cancer Center, Gainesville, Florida
| | - Thomas J George
- Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, Florida
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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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Chao YJ, Sy ED, Hsu HP, Shan YS. Predictors for resectability and survival in locally advanced pancreatic cancer after gemcitabine-based neoadjuvant therapy. BMC Surg 2014; 14:72. [PMID: 25258022 PMCID: PMC4182443 DOI: 10.1186/1471-2482-14-72] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 09/10/2014] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND To evaluate the predictors for resectability and survival of patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based neoadjuvant therapy (GBNAT). METHODS Between May 2003 and Dec 2009, 41 tissue-proved LAPC were treated with GBNAT. The location of pancreatic cancer in the head, body and tail was 17, 18 and 6 patients respectively. The treatment response was evaluated by RECIST criteria. Surgical exploration was based on the response and the clear plan between tumor and celiac artery/superior mesentery artery. Kaplan-Meier analysis and Cox Model were used to calculate the resectability and survival rates. RESULTS Finally, 25 patients received chemotherapy (CT) and 16 patients received concurrent chemoradiation therapy (CRT). The response rate was 51% (21 patients), 2 CR (1 in CT and 1 in CRT) and 19 PR (10 in CT and 9 in CRT). 20 patients (48.8%) were assessed as surgically resectable, in which 17 (41.5%) underwent successful resection with a 17.6% positive-margin rate and 3 failed explorations were pancreatic head cancer for dense adhesion. Two pancreatic neck cancer turned fibrosis only. Patients with surgical intervention had significant actuarial overall survival. Tumor location and post-GBNAT CA199 < 152 were predictors for resectability. Post-GBNAT CA-199 < 152 and post-GBNAT CA-125 < 32.8 were predictors for longer disease progression-free survival. Pre-GBNAT CA-199 < 294, post-GBNAT CA-125 < 32.8, and post-op CEA < 6 were predictors for longer overall survival. CONCLUSION Tumor location and post-GBNAT CA199 < 152 are predictors for resectability while pre-GBNAT CA-199 < 294, post-GBNAT CA-125 < 32.8, post-GBNAT CA-199 < 152 and post-op CEA < 6 are survival predictors in LAPC patients with GBNAT.
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Affiliation(s)
| | | | | | - Yan-Shen Shan
- Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan.
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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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Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg 2014; 258:1040-50. [PMID: 23799421 DOI: 10.1097/sla.0b013e31829b3ce4] [Citation(s) in RCA: 103] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To evaluate the outcome of preoperative gemcitabine-based chemoradiation therapy (CRT) for resectable and borderline resectable pancreatic cancer (PC), with a focus on the differences in surgical outcomes and patterns of recurrence between these 2 categories. BACKGROUND Various multimodal treatment strategies have been proposed to improve the surgical outcomes of PC. Preoperative CRT and subsequent surgery is one of the promising strategies for resectable (PC-R) and borderline resectable (PC-BR) PC. METHODS A total of 268 patients with PC-R and PC-BR received preoperative gemcitabine-based CRT. The numbers of PC-R and PC-BR cases were 188 and 80, respectively. We evaluated the following comparisons between patients with PC-R and those with PC-BR: (1) resection rate, (2) rate of margin-negative resection, (3) survival, and (4) pattern of the treatment failure, including local recurrence, peritoneal dissemination, and distant metastasis. RESULTS The resection rate of patients with PC-R (87%) was higher than that of patients with PC-BR (54%) (P < 0.001). Pathological margin-negative resection was achieved in 99% and 98% of the patients with PC-R and PC-BR, respectively. The 5-year survival rates of the PC-R and PC-BR cases were 57% and 34%, respectively (P = 0.029). Although the 5-year cumulative incidence of local recurrence was comparable in both groups (15% and 13%, respectively; P = 0.508), the 5-year cumulative incidence of peritoneal and distant recurrence was significantly higher in the patients with PC-BR (43 and 76%) than in the patients with PC-R (17% and 43%). CONCLUSIONS In the resected cases, the locoregional control was comparable between patients with PC-R and PC-BR after preoperative CRT. The survival rate for the patients with PC-BR was lower than the rate for those with PC-R due to a higher incidence of peritoneal and distant recurrence in the patients with PC-BR. (UMIN000001804).
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Ashman JB, Moss AA, Rule WG, Callister MG, Reddy KS, Mulligan DC, Collins JM, De Petris G, Gunderson LL, Borad M. Preoperative chemoradiation and IOERT for unresectable or borderline resectable pancreas cancer. J Gastrointest Oncol 2013; 4:352-60. [PMID: 24294506 DOI: 10.3978/j.issn.2078-6891.2013.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2012] [Accepted: 01/24/2013] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Pre-operative chemoradiation (preop CRT) plus intraoperative electron irradiation (IOERT) has been used in the multidisciplinary treatment for patients with locally advanced unresectable or borderline resectable pancreas cancer. This review was performed to evaluate survival, relapse patterns and prognostic factors in patients treated with curative intent. METHODS Between January 2002 and December 2010, 48 patients with locally advanced pancreatic ductal adenocarcinoma received preop CRT prior to an attempt at resection and IOERT. 31/48 (65%) patients proceeded to curative-intent surgical resection. Resection status prior to preop CRT was locally unresectable (20 patients) and borderline resectable (11 patients). Preop CRT (45-50.4 Gy/25-28 Fx in 27/31) was delivered with concurrent 5FU or gemcitabine-based regimens. Subsequent gross total resection was achieved in 16 patients (R0, 11; R1, 5). IOERT was delivered in 28 patients (dose, 10-20 Gy). 16 patients also received adjuvant post-operative systemic chemotherapy. Outcomes evaluated include survival, local failure in the EBRT field (LF), central failure in the IOERT field (CF), and distant metastases. RESULTS Resection status was predictive for survival and for patterns of relapse. For patients with at least a gross total resection after preop CRT (R0/R1; n=16) vs. no resection (n=15), both median and overall survival were improved (median 23 vs. 10 months; 2-year, 40% vs. 17%; 3-year, 40% vs. 0%; P=0.002). Liver or peritoneal relapse was documented in 22/31 patients (71%); LF/CF in 5/26 (16%). CONCLUSIONS Long term survival and disease control are achievable in select patients with borderline resectable or locally unresectable pancreas cancer when gross total surgical resection is achieved after preop CRT. Continued evaluation of curative-intent combined modality therapy is warranted in this high risk population, but additional strategies are needed to improve resectability and disease control.
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Affiliation(s)
- Jonathan B Ashman
- Department of Radiation Oncology, Mayo Clinic Cancer Center - Arizona (MCCC-A), Scottsdale/Phoenix, AZ, USA
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Preparing for Prospective Clinical Trials: A National Initiative of an Excellence Registry for Consecutive Pancreatic Cancer Resections. World J Surg 2013; 38:456-62. [DOI: 10.1007/s00268-013-2283-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Aggressive surgery for borderline resectable pancreatic cancer: evaluation of National Comprehensive Cancer Network guidelines. Pancreas 2013; 42:1004-10. [PMID: 23532000 DOI: 10.1097/mpa.0b013e31827b2d7c] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES The objective of this study was to evaluate the relevance of defining borderline resectable (BR) pancreatic cancer as a distinct entity in the treatment scheme of pancreatic cancer as proposed by the National Comprehensive Cancer Network. METHODS Among 375 patients with pancreatic cancer, 137 patients were deemed to have resectable disease (R) by preoperative imaging studies, whereas 96 were found to have an unresectable disease during surgery. The remaining 142 patients fulfilled the definition of BR and were further classified into 3 subgroups based on the National Comprehensive Cancer Network guidelines: portal vein invasion (PV[+]), common hepatic artery invasion (CHA[+]), and superior mesenteric artery invasion (SMA[+]). PV(+) was subdivided into types B, C, and D according to the degree of portal vein invasion. RESULTS Patients in the R group had significantly better survival than those in the PV(+) group (P = 0.0038), who in turn survived significantly longer than those classified as SMA(+) (P = 0.041). Type B patients survived significantly longer than did types C and D patients (P = 0.013 and P = 0.030, respectively). In PV(+) patients, compliance with postoperative chemotherapy at 3 and 6 months was 56.9% and 44.6%, respectively, substantially inferior to patients with resectable disease (72.6% and 54.7%, respectively). CONCLUSIONS The optimal treatment strategy may differ among various subgroups within the BR category.
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An evaluation of neoadjuvant chemoradiotherapy for patients with resectable pancreatic ductal adenocarcinoma. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2013; 2013:298726. [PMID: 23864756 PMCID: PMC3705743 DOI: 10.1155/2013/298726] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2013] [Revised: 05/25/2013] [Accepted: 06/02/2013] [Indexed: 01/13/2023]
Abstract
Aims. The aim of this study is to compare our results of preoperative chemotherapy followed by pancreaticoduodenectomy (PD) with those of surgery alone in patients with localized resectable pancreatic ductal adenocarcinoma (PDAC). Methods. Outcome data for 112 patients of resectable PDAC who received preoperative chemoradiotherapy followed by PD (group I) between January 2004 and April 2010 were retrospectively analyzed and were compared with selected 120 patients who underwent PD alone (group II) in the same period. Results. Patients in group I had an incidence of locoregional recurrence of 17.1% compared to 30.8% in group II (P = 0.03). There were no statistically significant differences in postoperative morbidity (27.7% versus 30.8%) and mortality (2.67% versus 3.33%). The 1-, 2-, and 3-year survival rates were estimated at 82.1%, 54%, and 28%, respectively, with NCRT and 65.8%, 29.1%, and 10% without (P = 0.006). Nevertheless, preoperative chemotherapy did not reduce the 1-, 3-, and 5-year disease-free survival rates, which were estimated at 58%, 36.6%, and 12.5% with NCRT and 51.7%, 18.3%, and 7.5% without (P = 0.058). Conclusions. The treatment of NCRT followed by PD in patients with PDAC has a significantly lower rate of locoregional recurrence and a longer overall survival than those with surgery alone.
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Papavasiliou P, Chun YS, Hoffman JP. How to Define and Manage Borderline Resectable Pancreatic Cancer. Surg Clin North Am 2013; 93:663-74. [DOI: 10.1016/j.suc.2013.02.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Katz MHG, Marsh R, Herman JM, Shi Q, Collison E, Venook AP, Kindler HL, Alberts SR, Philip P, Lowy AM, Pisters PWT, Posner MC, Berlin JD, Ahmad SA. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol 2013; 20:2787-95. [PMID: 23435609 DOI: 10.1245/s10434-013-2886-9] [Citation(s) in RCA: 243] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2012] [Indexed: 12/15/2022]
Abstract
BACKGROUND Methodological limitations of prior studies have prevented progress in the treatment of patients with borderline resectable pancreatic adenocarcinoma. Shortcomings have included an absence of staging and treatment standards and pre-existing biases with regard to the use of neoadjuvant therapy and the role of vascular resection at pancreatectomy. METHODS In this manuscript, we review limitations of studies of borderline resectable PDAC reported to date, highlight important controversies related to this disease stage, emphasize the research infrastructure necessary for its future study, and present a recently-approved Intergroup pilot study (Alliance A021101) that will provide a foundation upon which subsequent well-designed clinical trials can be performed. RESULTS We identified twenty-three studies published since 2001 which report outcomes of patients with tumors labeled as borderline resectable and who were treated with neoadjuvant therapy prior to planned pancreatectomy. These studies were heterogeneous in terms of the populations studied, the metrics used to characterize therapeutic response, and the indications used to select patients for surgery. Mechanisms used to standardize these and other issues that are incorporated into Alliance A021101 are reviewed. CONCLUSIONS Rigorous standards of clinical trial design incorporated into trials of other disease stages must be adopted in all future studies of borderline resectable pancreatic cancer. The Intergroup trial should serve as a paradigm for such investigations.
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Affiliation(s)
- Matthew H G Katz
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Neoadjuvant chemoradiation therapy for borderline pancreatic adenocarcinoma: report of two cases. World J Surg Oncol 2013; 11:37. [PMID: 23379413 PMCID: PMC3608242 DOI: 10.1186/1477-7819-11-37] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2012] [Accepted: 01/25/2013] [Indexed: 12/18/2022] Open
Abstract
Pancreatic cancer remains as one of the most aggressive human neoplasms, with overall poor survival rates. Radical surgery of the primary lesion is the best option for treatment. Borderline resectable pancreatic tumors (BRPT), defined as partial involvement of peripancreatic vasculature, may benefit from neoadjuvant therapy. We report on the first two BRPT cases treated with neoadjuvant chemoradiation at our institution. Preoperative CT and MRI demonstrated pancreatic tumors encasing the porto-mesenteric confluence suggestive of BRPT. Patients received neoadjuvant chemotherapy (gemcitabine/cisplatin), followed by radiochemotherapy. After treatment, follow-up images demonstrated tumor downsize, allowing for the tumors to be considered then as resectable. They underwent partial pancreatoduodenectomies (Whipple procedure). In case 1, histopathology revealed a complete, margin-free resection, whereas in case 2 there was a complete pathological response, with no evidence of residual tumor. According to the literature, our initial experience using neoadjuvant chemoradiotherapy on BRPT allowed us to downsize the tumor and, subsequently, to perform a curative surgery.
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Calvo F, Guillen Ponce C, Muñoz Beltran M, Sanjuanbenito Dehesa A. Multidisciplinary management of locally advanced–borderline resectable adenocarcinoma of the head of the pancreas. Clin Transl Oncol 2012. [DOI: 10.1007/s12094-012-0962-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Varadhachary GR. Preoperative therapies for resectable and borderline resectable pancreatic cancer. J Gastrointest Oncol 2012; 2:136-42. [PMID: 22811843 DOI: 10.3978/j.issn.2078-6891.2011.030] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2011] [Accepted: 07/24/2011] [Indexed: 12/30/2022] Open
Abstract
In the era of multidetector high quality CT imaging, it is feasible and critical to use objective criteria to define resectable pancreatic cancer. This allows accurate pretreatment staging and the development of stage-specific therapy. Tumors of borderline resectability have emerged as a distinct subset and the definition has been expanded in the last few years. Borderline resectable tumors are defined as those with tumor abutment of <180degrees (< 50%) of the SMA or celiac axis, short segment abutment or encasement of the common hepatic artery typically at the gastroduodenal artery origin, SMV-PV abutment with impingement and narrowing or segmental venous occlusion with sufficient venous flow above and below the occlusion to allow an option for venous reconstruction. Most of the patients whose cancer meet these CT criteria are candidates for preoperative systemic chemotherapy followed by chemoradiation since they are at a high risk for margin positive resection with upfront surgery. Patients whose imaging studies show radiographic stability or regression proceed to pancreaticoduodenectomy (or pancreatectomy) and this may require vascular resection and reconstruction. Prospective biomarker and functional imaging enriched studies are warranted to determine the best overall treatment strategy for these patients.
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Affiliation(s)
- Gauri R Varadhachary
- Department of Gastrointestinal Medical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA
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Shinoto M, Yamada S, Yasuda S, Imada H, Shioyama Y, Honda H, Kamada T, Tsujii H, Saisho H. Phase 1 trial of preoperative, short-course carbon-ion radiotherapy for patients with resectable pancreatic cancer. Cancer 2012; 119:45-51. [PMID: 22744973 DOI: 10.1002/cncr.27723] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Revised: 05/23/2012] [Accepted: 05/31/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND The authors evaluated the tolerance and efficacy of carbon-ion radiotherapy (CIRT) as a short-course, preoperative treatment and determined the recommended dose needed to reduce the risk of postoperative local recurrence without excess injury to normal tissue. METHODS Patients radiographically defined with potentially resectable pancreatic cancer were eligible. A preoperative, short-course, dose-escalation study was performed with fixed 8 fractions in 2 weeks. The dose of irradiation was increased by 5% increments from 30 grays equivalents (GyE) to 36.8 GyE. Surgery was to be performed 2 to 4 weeks after the completion of CIRT. RESULTS The study enrolled 26 patients. At the time of restaging after CIRT, disease progression with distant metastasis or refusal ruled out 5 patients from surgery. Twenty-one of 26 patients (81%) patients underwent surgery. The pattern of initial disease progression was distant metastasis in 17 patients (65%) and regional recurrence in 2 patients (8%). No patients experienced local recurrence. The 5-year survival rates for all 26 patients and for those who underwent surgery were 42% and 52%, respectively. CONCLUSIONS Preoperative, short-course CIRT followed by surgery is feasible and tolerable without unacceptable morbidity.
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Affiliation(s)
- Makoto Shinoto
- Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences. Chiba, Japan.
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Chuong MD, Springett GM, Weber J, Klapman J, Vignesh S, Hodul PJ, Malafa MP, Leuthold S, Hoffe SE, Shridhar R. Induction gemcitabine-based chemotherapy and neoadjuvant stereotactic body radiation therapy achieve high margin-negative resection rates for borderline resectable pancreatic cancer. ACTA ACUST UNITED AC 2012. [DOI: 10.1007/s13566-012-0039-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Zakharova OP, Karmazanovsky GG, Egorov VI. Pancreatic adenocarcinoma: Outstanding problems. World J Gastrointest Surg 2012; 4:104-13. [PMID: 22655124 PMCID: PMC3364335 DOI: 10.4240/wjgs.v4.i5.104] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2011] [Revised: 05/10/2012] [Accepted: 05/18/2012] [Indexed: 02/06/2023] Open
Abstract
Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%. Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma. About 40% of patients have locally advanced nonresectable disease. In the past, determination of pancreatic cancer resectability was made at surgical exploration. The development of modern imaging techniques has allowed preoperative staging of patients. Institutions disagree about the criteria used to classify patients. Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition of borderline resectable pancreatic cancer is also lacking. Thus, there is much room for improvement in all aspects of treatment for pancreatic cancer. Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer. With improved surgical techniques and advanced perioperative management, vascular resection and reconstruction are performed more frequently; patients thought once to be unresectable are undergoing radical surgery. However, when attempting heroic surgery, a realistic approach concerning the patient’s age and health status, probability of recovery after surgery, perioperative morbidity and mortality and life quality after tumor resection is necessary.
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Affiliation(s)
- Olga P Zakharova
- Olga P Zakharova, Grigory G Karmazanovsky, Department of Radiology, Vishnevsky Institute of Surgery, 117997 Moscow, Russia
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van Tienhoven G, Gouma DJ, Richel DJ. Neoadjuvant chemoradiotherapy has a potential role in pancreatic carcinoma. Ther Adv Med Oncol 2011; 3:27-33. [PMID: 21789153 DOI: 10.1177/1758834010383150] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Pancreatic cancer has an extremely poor prognosis, only a small minority of patients undergo a resection with curative intent. Chemotherapy and/or radiochemotherapy may improve this by prolonging survival or disease-free interval and improving resectability and the proportion of microscopically complete (R0) resections. With regard to prolonging survival, both in the postoperative adjuvant setting and in locally advanced disease, chemotherapy has a positive but limited effect on survival and may be considered standard. The role of postoperative adjuvant radiochemotherapy remains debatable. For improving resectability/proportion of R0 resections, many studies suggest that the proportion of patients undergoing a resection during exploration and the proportion of R0 resections increase after neoadjuvant radiochemotherapy. This may improve the prognosis of patients with a resectable or borderline resectable pancreatic carcinoma. The effect of neoadjuvant radiochemotherapy, if any, is modest. The search for better combinations, including targeted therapy, must continue. The interpretation of single-arm studies is hampered by (selection) biases. The reporting of pathology and study endpoints should be internationally standardized. To avoid biases in studies of patients with (borderline) resectable tumours, prospective parallel registration of all patients referred for surgery would help. Ultimately, randomized controlled phase III trials should establish the role of neoadjuvant radiochemotherapy. Thus, neoadjuvant radiochemotherapy has a potential benefit in resectable and borderline resectable pancreatic cancer, but better combinations are warranted.
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Affiliation(s)
- Geertjan van Tienhoven
- Department of Radiation Oncology, Academisch Medisch Centrum, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
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Chua TC, Saxena A. Preoperative chemoradiation followed by surgical resection for resectable pancreatic cancer: a review of current results. Surg Oncol 2011; 20:e161-8. [PMID: 21704510 DOI: 10.1016/j.suronc.2011.05.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2010] [Revised: 05/19/2011] [Accepted: 05/19/2011] [Indexed: 01/12/2023]
Abstract
BACKGROUND There has been an interest in the interdisciplinary and multimodality approach that combines chemotherapy and radiation therapy as a preoperative treatment for patients with resectable pancreatic cancer. METHODS Literature search of databases (Medline and PubMed) to identify published studies of preoperative chemoradiation for resectable pancreatic cancer (potentially resectable and borderline resectable) was undertaken. Response to treatment and survival outcomes was examined as endpoints of this review. RESULTS Seventeen studies; eight phase II studies, and nine observational studies, comprising of 977 patients were reviewed. Gemcitabine-based chemotherapy with radiotherapy was the most common preoperative regimen. Following preoperative treatment, pancreatic surgical resection was performed in 35-100% (median=61%) of patients after a range of 6-32 weeks (median=7 weeks). Rate of pathological response was complete in 5-15% of patients, partial in 33-60% and minimal in 38-42%. The median overall survival ranged from 12 months to 40 months (median=25 months) with a 5-year overall survival rate ranging between 8% and 36% (median=28%). Patients who underwent chemoradiation but did not undergo surgery survived a median period of 7-11 months (median=9 months). CONCLUSION Preoperative gemcitabine-based chemoradiation followed by restaging and surgical evaluation for pancreatic resection may identify a sub-population of patients with resectable disease who would benefit the most from surgery. Investigation of this schema of preoperative therapy in a randomized setting of resectable pancreatic cancer is warranted.
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Affiliation(s)
- Terence C Chua
- Hepatobiliary and Surgical Oncology Unit, University of New South Wales, Department of Surgery, St George Hospital, Kogarah, NSW 2217, Sydney, Australia.
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Ottenhof NA, de Wilde RF, Maitra A, Hruban RH, Offerhaus GJA. Molecular characteristics of pancreatic ductal adenocarcinoma. PATHOLOGY RESEARCH INTERNATIONAL 2011; 2011:620601. [PMID: 21512581 PMCID: PMC3068308 DOI: 10.4061/2011/620601] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/01/2010] [Revised: 12/07/2010] [Accepted: 01/10/2011] [Indexed: 12/14/2022]
Abstract
Pancreatic cancer is an almost universally lethal disease and despite extensive research over the last decades, this has not changed significantly. Nevertheless, much progress has been made in understanding the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) suggesting that different therapeutic strategies based on these new insights are forthcoming. Increasing focus exists on designing the so-called targeted treatment strategies in which the genetic characteristics of a tumor guide therapy. In the past, the focus of research was on identifying the most frequently affected genes in PDAC, but with the complete sequencing of the pancreatic cancer genome the focus has shifted to defining the biological function that the altered genes play. In this paper we aimed to put the genetic alterations present in pancreatic cancer in the context of their role in signaling pathways. In addition, this paper provides an update of the recent advances made in the development of the targeted treatment approach in PDAC.
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Affiliation(s)
- Niki A. Ottenhof
- Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
| | - Roeland F. de Wilde
- Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
| | - Anirban Maitra
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
| | - Ralph H. Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
| | - G. Johan A. Offerhaus
- Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
- *G. Johan A. Offerhaus:
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Katz MHG, Pisters PWT, Lee JE, Fleming JB. Borderline resectable pancreatic cancer: what have we learned and where do we go from here? Ann Surg Oncol 2011; 18:608-10. [PMID: 21136179 DOI: 10.1245/s10434-010-1460-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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Karapanos K, Nomikos IN. Current surgical aspects of palliative treatment for unresectable pancreatic cancer. Cancers (Basel) 2011; 3:636-51. [PMID: 24212633 PMCID: PMC3756381 DOI: 10.3390/cancers3010636] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2010] [Revised: 01/19/2011] [Accepted: 02/05/2011] [Indexed: 02/06/2023] Open
Abstract
Despite all improvements in both surgical and other conservative therapies, pancreatic cancer is steadily associated with a poor overall prognosis and remains a major cause of cancer mortality. Radical surgical resection has been established as the best chance these patients have for long-term survival. However, in most cases the disease has reached an incurable state at the time of diagnosis, mainly due to the silent clinical course at its early stages. The role of palliative surgery in locally advanced pancreatic cancer mainly involves patients who are found unresectable during open surgical exploration and consists of combined biliary and duodenal bypass procedures. Chemical splanchnicectomy is another modality that should also be applied intraoperatively with good results. There are no randomized controlled trials evaluating the outcomes of palliative pancreatic resection. Nevertheless, data from retrospective reports suggest that this practice, compared with bypass procedures, may lead to improved survival without increasing perioperative morbidity and mortality. All efforts at developing a more effective treatment for unresectable pancreatic cancer have been directed towards neoadjuvant and targeted therapies. The scenario of downstaging tumors in anticipation of a future oncological surgical resection has been advocated by trials combining gemcitabine with radiation therapy or with the tyrosine kinase inhibitor erlotinib, with promising early results.
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Affiliation(s)
- Konstantinos Karapanos
- Department of Surgery (B′ Unit), “METAXA” Cancer Memorial Hospital, Piraeus, Greece; E-Mail:
| | - Iakovos N. Nomikos
- Department of Surgery (B′ Unit), “METAXA” Cancer Memorial Hospital, Piraeus, Greece; E-Mail:
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