Local Therapy For A Systemic Disease: Indications And Impact Of Radiation Therapy To The Pancreatic Primary In Metastatic Pancreatic Cancer

Metastatic pancreatic ductal adenocarcinoma (mPDAC) carries a poor prognosis, with median survival (MS) of 6-11 months. However, with more effective multi-agent chemotherapy (CTX) regimens, there has been increasing debate regarding potential role of local therapy. We aim to report our experience of radiation therapy (RT) delivered to the primary in the setting of mPDAC, hypothesizing that in select patients, RT may offer improved survival and time off chemotherapy (TOC). An IRB-approved retrospective analysis of 44 patients with mPDAC who received pancreas RT between November 2007 and August 2018 was performed. Indications for RT were: “symptom palliation” (n=13, 30%), “consolidative RT” after response in metastases (n=29, 66%), or both (n=2, 5%). Of “consolidative RT” patients, 21 (48%) were treated after response of primary and metastases, and 10 (23%) for local progression. 38 patients (86%) received CTX prior to RT (median 1 line, 76% FOLFOX/FOLFIRINOX, 27% gemcitabine); 6 received upfront RT for symptom palliation. Median RT dose was 50.4 Gy (range: 25-58.8 Gy) with concurrent 5-FU/capecitabine; 2 patients received SBRT. Clinical and treatment characteristics were reviewed. Statistical analyses were performed using JMP 14.0 (SAS Institute Inc., Cary, NC). Kaplan-Meier calculations and univariate (UVA) and multivariate (MVA) Cox proportional hazards models were used to evaluate TOC and survival after RT. Median follow-up was 18 months (Range: 1-66). Median age was 61 (range: 40-81) with 55% male and 77% ECOG 0-1. 77% had 1 metastatic site; 57% had liver metastases, with liver as only site in 43%. Median time from diagnosis to RT start was 8.5 months (range: 0-49 months). 5 patients (11%) underwent surgical resection of primary after RT. MS from diagnosis was 20 (CI: 15-27) months; MS from RT completion was 7.6 (CI: 5.1–10.8) months. 68% had local control of primary. Median TOC was 3.9 (CI 2.1 – 10.4) months, with 27% off for 6 months. On UVA, better performance status, FOLFIRINOX, surgery, CTX-responsive metastases at RT start, CTX-responsive primary at RT start, normal CA 19-9 at RT start and consolidative RT indication were associated with improved survival from RT. On MVA, only CA19-9 elevation at RT start was predictive of survival (HR 5.13; CI 1.60-22.14, p=0.0062). On UVA for TOC, prior FOLFIRINOX, CTX-responsive primary at RT start, and consolidative RT indication were associated with TOC. On MVA, only CTX-responsive primary at RT start was associated with more TOC (HR 0.38; CI 0.15-0.96, p=0.0408). Despite the systemic nature of metastatic PDAC, RT to the pancreatic primary may offer benefit in highly selected patients with chemo-responsive disease and normal pretreatment CA 19-9. This work suggests a potential role of local RT in selected patients with metastatic PDAC, and warrants further study.