Adjuvant Chemotherapy With Gemcitabine vs Observation in Patients Undergoing Curative-Intent Resection of Pancreatic Cancer

Oettle, Helmut; Post, Stefan; Neuhaus, P.; Gellert, Klaus; Langrehr, Jan M.; Ridwelski, K.; Schramm, H; Fahlke, J.; Zuelke, Carl; Burkart, Christoph; Gutberlet, Klaus; Kettner, E.; Schmalenberg, Harald; Weigang-Koehler, Karin; Bechstein, Wolf O.; Niedergethmann, Marco; Schmidt‐Wolf, Ingo G.H.; Roll, L.; Doerken, Bernd; Riess, Hanno

doi:10.1001/jama.297.3.267

Cited by 2,168 publications

(1,403 citation statements)

References 30 publications

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“…From 1988 to 2014, the number of patients receiving adjuvant chemotherapy increased, reflecting the results of major clinical trials, with the practice changing CONKO-001 trial first presented in 2007. 25 To account for the temporal treatment bias in our historical cohort, we excluded patients before 2003 in our analysis showing that mismatch repair status continued to predict the response to chemotherapy in this more contemporary subgroup.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…Rates of recurrence can be high, ranging from 50 % to 87 % of patients, even after resection with curative intent [31][32][33]. Adjuvant chemotherapy with gemcitabine has been shown to significantly increase overall survival and disease-specific survival in pancreatic cancer patients after resection compared to observation alone, although this increase in overall survival is seen to be only 2 months [34]. The care of patients with pancreatic cancer will continue to be multi-disciplinary in the future; however surgery remains the cornerstone in improving outcomes for patients, and by pushing the boundaries of resection in appropriatelyselected patients we may see improved outcomes and survival in the future.…”

Section: Resultsmentioning

confidence: 99%

Beyond the Whipple Operation: Radical Resections for Cancers of the Head of the Pancreas

Schoellhammer

Goldner

Kim

et al. 2013

Indian J Surg Oncol

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Pancreatic adenocarcinoma is the most common pancreatic malignancy, and it occurs most commonly in the pancreatic head. It has a relatively low incidence; however it is a deadly disease and is the fourth most common cause of cancer deaths for males and females in the United States. Surgical resection in the form of pancreaticoduodenectomy is the mainstay of treatment and can lead to improved overall survival as well as the possibility of a cure, although only 10 % of patients are resectable at presentation. In an attempt to improve outcomes and survival, surgeons over the decades have employed various aggressive resectional strategies to combat this disease. In this paper we review the development of pancreaticoduodenectomy and touch on the role played by the American surgeon Allan Whipple in this development. We review modern data regarding radical pancreaticoduodenectomy and extended lymphadenectomy for pancreatic head cancers, as well as data and controversies regarding arterial and venous resection performed during the course of pancreaticoduodenectomy. The role of extended and vascular resections in the treatment of pancreatic neuroendocrine tumors in contrast to adenocarcinomas is also examined. We summarize the current state of data regarding radical pancreaticoduodenectomy and discuss pushing the boundaries of surgical resection to help improve outcomes for select groups of patients.

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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%

“…A statistically significant difference in survival could be demonstrated in two trials and nearly achieved in a third trial. CONKO-001 trial [11] evaluated the impact of gemcitabine in adjuvant setting. Gemcitabine almost doubled median disease-free survival and 5-year overall survival.…”

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%

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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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Adjuvant Chemotherapy With Gemcitabine vs Observation in Patients Undergoing Curative-Intent Resection of Pancreatic Cancer

Cited by 2,168 publications

References 30 publications

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

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

Beyond the Whipple Operation: Radical Resections for Cancers of the Head of the Pancreas

Improving Survival of Pancreatic Cancer. What Have We Learnt?

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