A more accurate identification of tumors by image-guided radiation therapy (IGRT) and improved radiation delivery by advanced technology have led to a wider use of hypofractionated radiation schedules for the treatment of locally advanced pancreatic cancer (LAPC). The aim of this prospective phase II study was to evaluate the effect of neoadjuvant GEMOX plus accelerated hypofractionated radiotherapy on the resectability of LAPC.
From April 2011 to August 2016, a total of 42 patients with non resectable LAPC were enrolled onto the study, of whom 40 were evaluable. Median age was 67 years (range 41-78). Patients were treated as the following: gemcitabine (GEM) 1000 mg/m2 on day 1, and oxaliplatin (OX) 100 mg/m2 on day 2, every two weeks (GEMOX regimen) for 4 cycles, 15 days off, hypofractionated radiotherapy, 15 days off, a further 4 cycles of GEMOX, restaging. Radiotherapy was delivered by helical tomotherapy at a dose of 35 Gy (with an inhomogeneous dose distribution inside the target volume of up to 30% of the prescription dose) in 7 fractions (one fraction per day) over 9 days on the gross tumor volume; 28 Gy-35 Gy was administered on the clinical target volume (CTV) 1-2 on the basis of nodal status.
Overall 5 patients (12.5%) obtained a partial tumor response and 20 (50%) a stable disease. Of these, 9 underwent surgical laparotomy (5 radical pancreatic resection 1 termoablation and 3 explorative laparotomy), 1 patient became operable but refused surgery. The overall resectability rate was 25%, while the R0 resection rate was 12.5%. Toxicity to GEMOX was similar to that reported elsewhere. Radiotherapy was well tolerated and the most frequently encountered adverse events were mild to moderate nausea and vomiting, abdominal pain and fatigue. At a median follow-up of 50 months, the median progression free survival and overall survival were 9.3 (95% CI 6.2-14.9) and 15.8 (95% CI 8.2-23.4) months, respectively.
Our results show the feasibility of using accelerated hypofractionated radiotherapy on tumor volume and locoregional lymph nodes in LAPC. Treatment was well tolerated and survival rates are promising.
Clinical trial identification
EudraCT / RSO2010-020379-22.
Legal entity responsible for the study
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS.
Has not received any funding.
All authors have declared no conflicts of interest.