An Australian Three-Centre Feasibility Study of Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer with Collection of Baseline Circulating Tumor Cells

Abstract

Stereotactic body radiotherapy (SBRT) has an increasing role for treatment of locally advanced pancreatic adenocarcinoma (LAPC). Selection of appropriate cases may be improved with identification of useful prognostic and predictive clinical biomarkers. This study aimed to establish the feasibility and safety of neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) chemotherapy followed by SBRT for patients with LAPC (including borderline resectable), and to identify a role for circulating tumor cells (CTCs) in prognostication. Eligible patients were enrolled to a three-center prospective pilot study (MASTERPLAN Pilot ACTRN12617001642370). Eligibility criteria included age > 18 years, histological confirmation of PA, ECOG 0-1, with confirmation of borderline resectable (BRPC) or unresectable LAPC according to NCCN guidelines. The initial patient cohort was enrolled in a sub-study, to collect peripheral blood CTCs at baseline (bCTCs) which was correlated with overall survival (OS), progression free survival (PFS) and locoregional relapse free survival (LRFS). Patients received 4 cycles of mFOLFIRINOX (oxaliplatin, irinotecan, 5-fluorouracil), followed by insertion of pancreatic fiducials and 5 fractions of SBRT to a dose of 30Gy with a simultaneous integrated boost to 45Gy, determined by proximity to organs at risk. Acute toxicity was collected to 3 months post-SBRT. Between April 2018 and October 2019, 12 patients were enrolled (initial 10 to the bCTC sub-study). The median follow-up from diagnosis was 10 months (range 4-18). Three patients did not commence treatment after enrollment, and 2 patients did not proceed to SBRT after mFOLFIRINOX. Seven patients with a median age of 62 years completed trial therapy. The median CA19.9 at baseline was 225kU/L (range 1-2558), 72% had BRPC and 57% were lymph node positive. One patient with BRPC proceeded to resection with positive surgical margins. At the time of evaluation, two further patients with BRPC were awaiting re-evaluation prior to surgery. Of those alive at 6 and 12 months follow up, local control was achieved in 83.3% and 66.7% of patients respectively. The first patient experienced acute Grade 3 neutropenia. Thereafter, G-CSF was administered with mFOLFIRINOX and no further Grade 3 toxicities were seen. Six patients experienced Grade 2 acute toxicity, and no patients developed Grade 4 toxicity. Nine patients had bCTCs collected, and of these, 6 completed trial therapy. The median number of CTCs was 11 per 8mls blood (range 1-12), and in this study bCTCs did not significantly correlate with OS, PFS or LRFS, however due to small numbers interpretation of this data is limited. Neoadjuvant mFOLFIRINOX with G-CSF and SBRT to 30-45Gy is feasible and safe. A role of bCTCs in prognostication was not identified in this small study.