A Randomized Trial of Chemoradiotherapy and Chemotherapy after Resection of Pancreatic Cancer

Neoptolemos, John P.; Stocken, Deborah; Friess, Helmut; Bassi, Claudio; Dunn, Janet A.; Hickey, Helen; Beger, Hans G.; Fernández‐Cruz, Laureano; Dervenis, Christos; Lacaine, F; Falconi, Massimo; Pederzoli, Paolo; Pap, Ákos; Spooner, D.; Kerr, David; Büchler, Markus W.

doi:10.1056/nejmoa032295

Cited by 2,391 publications

(1,790 citation statements)

References 31 publications

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“…In the ESPAC‐1 trial, Neoptolemos and colleagues31 compared overall survival of patients with and without adjuvant chemotherapy after curative resection. Patients who received adjuvant chemotherapy had an increased median survival of 20·1 months, compared with 15·5 months in those who did not (hazard ratio (HR) 0·71, 95 per cent c.i.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma

et al. 2018

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BackgroundNeoadjuvant therapy may increase the rate of radical tumour resection in patients with pancreatic cancer. Its impact on tumour recurrence has not been investigated fully. This study aimed to assess the impact of neoadjuvant therapy on patterns of recurrence.MethodsA systematic review was performed of articles identified through the PubMed, Scopus, Embase, Ovid and Google Scholar databases that analysed the relationship between neoadjuvant therapy and recurrence published to January 2016. The main endpoint was overall tumour recurrence. Other endpoints included local recurrence, any kind of distant, hepatic, pulmonary or peritoneal metastasis.ResultsA total of 4257 citations were reviewed. Twelve observational studies comprising 1365 patients were analysed. Neoadjuvant therapy significantly reduced the risk of overall (risk ratio (RR) 0·82, 95 per cent c.i. 0·74 to 0·90; P < 0·001) and local (RR 0·42, 0·32 to 0·55; P < 0·001) recurrence. Neoadjuvant therapy did not reduce the risk of any kind of distant (RR 1·02, 0·91 to 1·14; P = 0·78), hepatic (RR 0·86, 0·68 to 1·10; P = 0·23), pulmonary (RR 0·99, 0·37 to 2·66; P = 0·98) or peritoneal (RR 0·88, 0·57 to 1·38; P = 0·58) metastasis.ConclusionNeoadjuvant therapy reduced the risk of local recurrence but not that of distant metastasis.

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Section: Discussionmentioning

confidence: 99%

Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma

et al. 2018

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“…Adjuvant chemotherapy is considered the standard of care for patients with resectable pancreatic ductal adenocarcinoma. 6,7 Pyrimidine analogs (gemcitabine or 5-fluorouracil (5-FU)) are the most commonly used agents, with gemcitabine demonstrating an improved survival compared with no treatment in CONKO-001, 7 and an improved toxicity profile compared with 5-FU in ESPAC-3. 8 Molecular studies have shown that pancreatic ductal adenocarcinomas contain a high number of gene deletions, mutations, amplifications and rearrangements, 9,10 yet the contribution of these genetic abnormalities to tumor behavior and response to systemic therapy is not well understood.…”

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confidence: 99%

Mismatch repair status may predict response to adjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma

et al. 2015

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Deficiencies in DNA mismatch repair have been associated with inferior response to 5-FU in colorectal cancer. Pancreatic ductal adenocarcinoma is similarly treated with pyrimidine analogs, yet the predictive value of mismatch repair status for response to these agents has not been examined in this malignancy. A tissue microarray with associated clinical outcome, comprising 254 resected pancreatic ductal adenocarcinoma patients was stained for four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). Mismatch repair deficiency and proficiency was determined by the absence or presence of uniform nuclear staining in tumor cells, respectively. Cases identified as mismatch repair deficient on the tissue microarray were confirmed by immunohistochemistry on whole slide sections. Of the 265 cases, 78 (29%) received adjuvant treatment with a pyrimidine analog and 41 (15%) showed a mismatch repair-deficient immunoprofile. Multivariable diseasespecific survival in the mismatch repair-proficient cohort demonstrated that adjuvant chemotherapy, regional lymph-node status, gender, and the presence of tumor budding were significant independent prognostic variables (P ≤ 0.04); however, none of the eight clinico-pathologic covariates examined in the mismatch repairdeficient cohort were of independent prognostic significance. Univariable assessment of disease-specific survival revealed an almost identical survival profile for both treated and untreated patients with a mismatch repair-deficient profile, while treatment in the mismatch repair-proficient cohort conferred a greater than 10-month median disease-specific survival advantage over their untreated counterparts (P = 0.0018). In this cohort, adjuvant chemotherapy with a pyrimidine analog conferred no survival advantage to mismatch repairdeficient pancreatic ductal adenocarcinoma patients. Mismatch repair immunoprofiling is a feasible predictive marker in pancreatic ductal adenocarcinoma patients, and further prospective evaluation of this finding is Pancreatic ductal adenocarcinoma is among the deadliest solid cancers, with little improvement in overall survival achieved in the past few decades. 1-3 Lack of effective screening modalities and late presentation with advanced stage disease result in fewer than 20% of patients being eligible for surgical resection. 4 Even in surgically-treated patients, the 5-year survival rate is lower than 20%, 5 highlighting the need for more effective and personalized systemic therapeutic approaches. Adjuvant chemotherapy is considered the standard of care for patients with resectable pancreatic ductal adenocarcinoma. 6,7 Pyrimidine analogs (gemcitabine or 5-fluorouracil (5-FU)) are the most commonly used agents, with gemcitabine demonstrating an improved survival compared with no treatment in 7 and an improved toxicity profile compared with 5-FU in ESPAC-3. 8 Molecular studies have shown that pancreatic ductal adenocarcinomas contain a high number of

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“…Multiple randomized trials [10,11,[40][41][42][43]] have compared surgery with adjuvant therapy to surgery alone. A statistically significant difference in survival could be demonstrated in two trials and nearly achieved in a third trial.…”

Section: Adjuvant Treatmentmentioning

confidence: 99%

“…Most of these studies have examined the role of adjuvant treatment which has been shown to improve survival of these patients [9][10][11]. Additionally, there are reports that suggest that progress in surgical technique and perioperative care, in conjunction with the emergence of high-volume centers of excellence, has reduced the early mortality and morbidity rates after pancreatic resection [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Improving Survival of Pancreatic Cancer. What Have We Learnt?

Singh

Chaudhary

2015

Indian J Surg

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Pancreatic adenocarcinoma still ranks high among cancer-related deaths worldwide. In spite of substantial strides in preoperative staging, surgery, perioperative care, and adjuvant treatment, the survival still remains dismal. A number of patient-, disease-, and surgeon-related factors play a role in deciding the eventual outcome of the patient. The aim of this commentary is to review the current knowledge of various factors and the recent advances that impact the survival of patients with pancreatic adenocarcinoma. A search of scientific literature using Embase and MEDLINE, for the years 1985-2015, was carried out for search terms Bpancreatic cancer^and Bsurvival.^Further search was based on the various specific prognostic factors that contribute towards survival of patients with pancreatic cancer found in the literature. Most of the studies used for this review include those that deal with pancreatic head cancers, some include patients with pancreatic cancers in all locations while very few included patients with tumors of body and tail only. In spite of significant developments in pre-and perioperative management, increased rates of margin-negative resections, and use of adjuvant treatment, the survival rates of pancreatic cancer patients remains poor. A paradigm shift with more effective adjuvant regimen and genetic interventions may help change the outcomes of patients with pancreatic cancer.

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A Randomized Trial of Chemoradiotherapy and Chemotherapy after Resection of Pancreatic Cancer

Abstract: Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.

Cited by 2,391 publications

References 31 publications

Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma

Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma

Mismatch repair status may predict response to adjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma

Improving Survival of Pancreatic Cancer. What Have We Learnt?

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