Neoadjuvant phase II trial of chemo-radiotherapy (CRT) in patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDA)
Damarla V, Dobrosotskaya D, Siddiqui F, Wollner I, Raoufi M, Li J, Kwon D, and Khan G. Neoadjuvant phase II trial of chemo-radiotherapy (CRT) in patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDA). Eur J Cancer 2018;92(Suppl 2):S8-S9.
Eur J Cancer
Background: (PDA) is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10e30% of patients are long-term survivors. Micro-metastatic disease has been hypothesized as contributing to recurrence. Emerging data suggest a role for neoadjuvant therapy with (CRT) to target occult micro-metastatic disease.
Aim: The aim of the study is to report our institutional experience with a novel neoadjuvant CRT regimen in (R) and (BR) PDA.
Methods: Design - Prospective Phase II trial. Eligibility - Patients with (R) and (BR) PDA as defined by the NCCN criteria for resectability. Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with Gemcitabine and Intensity modulated Radiotherapy (IMRT). Gemcitabine was dosed at standard dosing at 1000 mg/m2on Days 1, 8, 22 and 29 of IMRT. All subjects then received 50.4 Gy to the Gross Tumor Volume. Serial Imaging was performed to determine tumor response and resectability.
Results: From April 2014 to June 2017, 24 patients were enrolled.Median age is 63.5 years (range 44 to 80). 23 patients had (BR) disease and 1 patient had (R) disease. 58% of patient had Stage 2 PDA, 29%had Stage I PDA and 12.5% had Stage III PDA. All patients received induction chemotherapy with FOLFOX. 13 patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R 1 resection (15.4%). For patients who underwent resection, the median PFS was31 m, 1 year PFS rate was 69.2% (95% CI: 0.48e0.99) and 2-yearPFS rate was 51.9 % (95% CI: 0.3e0.89). Median OS was 34.8 m(95% CI: 1.045 to infinity), 1 year OS rate was 91.7 % (95% CI:0.77e1.0) and 2 year OS rate was 75% (95% CI: 0.54e1.0). Median CA 19-9 at screening for patients who underwent surgery was 659(range 18e2154), which decreased to 146.9 (range 18e462) after CRT prior to resection.
Conclusions: Neoadjuvant therapy for (BR) and (R) PDA with CRT facilitated R0 resection in 84% patients who underwent surgery in a prospective phase II trial. These results warrant further investigation of neoadjuvant CRT in a larger cohort of patients.