Hill CS, Rosati L, Wang H, Tsai HL, He J, Hacker-Prietz A, Laheru DA, Zheng L, Sehgal S, Bernard V, Le DT, Pawlik TM, Weiss MJ, Narang AK, Herman JM
PURPOSE : In a prospective multicenter study, gemcitabine monotherapy followed by stereotactic body radiation therapy (SBRT) was well tolerated with outcomes comparable to chemoradiation for locally advanced pancreatic cancer (LAPC). Recent trials have reported improved survival with multi-agent chemotherapy (MA-CTX) alone. This prospective trial explored whether SBRT could be safely delivered following MA-CTX. Herein, we report the long-term outcomes of adding SBRT after MA-CTX in LAPC patients and evaluate whether genetic profiles of specimens obtained prior to SBRT influence outcomes.
METHODS : This prospective non-randomized controlled phase II trial enrolled 44 LAPC and 4 locally recurrent patients after multidisciplinary evaluation between 2012-2015 at a high-volume pancreatic cancer center. For induction CTX, most received modified FOLFIRINOX (mFFX), or gemcitabine and nab-paclitaxel (GnP) followed by 5-fraction SBRT for all. During fiducial placement, biopsies were obtained with DNA extracted for targeted sequencing using the MSK-IMPACT platform.
RESULTS : Median induction CTX duration was ≥ 4 mos, and 31 patients received mFFX (65%). Among 44 LAPC patients, 17 (39%) were surgically explored, and 12/16 (75%) achieved a R0 resection. Median overall survival (mOS) was 20.2/14.6 mos from diagnosis/SBRT. 1 and 2-year OS from SBRT was 58%/28%. The mOS after resection was 28.6/22.4 mos from diagnosis/SBRT. Median local progression-free survival (LPFS) was 23.9/15.8 mos from diagnosis/SBRT. The mOS for pre-SBRT CA 19-9 ≤180 U/mL vs. >180 was 23.1/11.3 months respectively (HR = 0.53, p=0.04). Only one patient (2.1%) had late grade ≥2 gastrointestinal toxicity attributable to SBRT. Despite significant pre-treatment with chemotherapy, 88% of tumor specimens were effectively sequenced; survival outcomes were not significantly associated with specific mutational patterns. Quality of life was prospectively collected pre- and post-SBRT with the EORTC QLQ-C30/PAN26 questionnaire showing no significant change.
CONCLUSION : SBRT was safely administered with MA-CTX with minimal toxicity. A high proportion of LAPC patients underwent R0 resection with favorable survival outcomes.