R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial

Strahlenther Onkol. 2021 Jan;197(1):8-18. doi: 10.1007/s00066-020-01680-2. Epub 2020 Sep 10.

Abstract

Purpose: Chemotherapy with or without radiotherapy is the standard in patients with initially nonmetastatic unresectable pancreatic cancer. Additional surgery is in discussion. The CONKO-007 multicenter randomized trial examines the value of radiotherapy. Our interim analysis showed a significant effect of surgery, which may be relevant to clinical practice.

Methods: One hundred eighty patients received induction chemotherapy (gemcitabine or FOLFIRINOX). Patients without tumor progression were randomized to either chemotherapy alone or to concurrent chemoradiotherapy. At the end of therapy, a panel of five independent pancreatic surgeons judged the resectability of the tumor.

Results: Following induction chemotherapy, 126/180 patients (70.0%) were randomized to further treatment. Following study treatment, 36/126 patients (28.5%) underwent surgery; (R0: 25/126 [19.8%]; R1/R2/Rx [n = 11/126; 6.1%]). Disease-free survival (DFS) and overall survival (OS) were significantly better for patients with R0 resected tumors (median DFS and OS: 16.6 months and 26.5 months, respectively) than for nonoperated patients (median DFS and OS: 11.9 months and 16.5 months, respectively; p = 0.003). In the 25 patients with R0 resected tumors before treatment, only 6/113 (5.3%) of the recommendations of the panel surgeons recommended R0 resectability, compared with 17/48 (35.4%) after treatment (p < 0.001).

Conclusion: Tumor resectability of pancreatic cancer staged as unresectable at primary diagnosis should be reassessed after neoadjuvant treatment. The patient should undergo surgery if a resectability is reached, as this significantly improves their prognosis.

Keywords: Neoadjuvant chemoradiotherapy; Pancreatic adenocarcinoma; Prospective randomized multicenter trial; Surgery; Tumor resectability.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / surgery*
  • Carcinoma, Pancreatic Ductal / therapy
  • Chemoradiotherapy*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Fluorouracil / administration & dosage
  • Gemcitabine
  • Humans
  • Irinotecan / administration & dosage
  • Leucovorin / administration & dosage
  • Neoadjuvant Therapy
  • Oxaliplatin / administration & dosage
  • Pancreatectomy / methods*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / surgery*
  • Pancreatic Neoplasms / therapy
  • Postoperative Complications
  • Radiotherapy, Conformal
  • Radiotherapy, Intensity-Modulated
  • Survival Analysis

Substances

  • folfirinox
  • Oxaliplatin
  • Deoxycytidine
  • Irinotecan
  • Leucovorin
  • Fluorouracil
  • Gemcitabine