Stereotactic body radiotherapy in locally advanced pancreatic adenocarcinoma: A single institution experience

Abstract

Introduction: Locally advanced pancreatic adenocarcinomas (PANCAN) are treated using multi-agent systemic chemotherapy with variable rates of resectability. Stereotactic Body Radiotherapy (SBRT) is utilized to improve tumor resectability or for sustained local tumor control. However, the safety and tolerance of combining FOLFIRINOX or Gemcitabine-nabPaclitaxel (Gem-Abr) with SBRT is unknown. This study aimed to evaluate the safety and tolerability of pancreatic SBRT following FOLFIRINOX or Gemcitabine-nabPaclitaxel chemotherapy in unresectable PANCAN. Methods: Between 2015 and 2018, 30 patients with locally advanced PANCAN were treated with systemic chemotherapy and SBRT. Patients with borderline or unresectable tumors were eligible, as determined based on findings on pancreatic protocol-CT, by a multidisciplinary team including pancreatico-biliary surgeons. Patients with performance status ECOG 0-2 received FOLFIRINOX (n=19), GemcitabinenabPaclitaxel (n=10) or Gemcitabine alone (n=1) for at least two months prior to SBRT. All patients proceeded to SBRT regardless of operability status at the end of chemotherapy as long as there was no progression by RECIST 1.1 criteria. SBRT dose was 33 Gy in 5 fractions in 25 patients, while in 4 patients SBRT dose was allowed escalate up to 40 Gy in 5 fractions, while staying within the tolerance limits of normal structures. All patients received SBRT utilizing a dynamic arc technique, with kV image guidance and appropriate respiratory motion correction. Patients deemed operable on CT evaluation at 4 weeks from the end of SBRT proceeded to Whipple resection. Results: Seventeen males and 13 females with median age of 66 years (40 to 83) were treated. All patients completed planned chemotherapy with minimal interruptions. At the end of chemotherapy 9 patients (31%) were down-staged to operable status. SBRT was completed in all patients without interruptions. All SBRT toxicities were graded < 2, except one instance of Grade 3 nausea in a patient who received 33 Gy. Nine patients (31%) were taken for Whipple resection and 8 successfully underwent R0 resection. One patient died postoperatively due to sepsis. 20 patients (69%) who did not proceed to surgery received additional chemotherapy and were followed up until death. The median follow-up for the study cohort is 6.2 months. Nine patients (30%) have died, due to distant or loco-regional progression. Six patients showed disease progression at the primary site of tumor, of which 2 patients documented progression prior to SBRT. The overall loco-regional control rate was 79%. The median progression-free survival and overall survival of the study cohort were 9.43 and 11.7 months respectively. Conclusion: Neoadjuvant chemotherapy using FOLFIRINOX or Gem-Abr followed by SBRT is a safe approach to manage locally advanced PANCAN. SBRT doses up to 40 Gy in 5 fractions are associated with minimal toxicities provided tolerances of normal tissues are respected.