Main Session
Sep
30
SS 33 - GI 2: Giving Radiation a Boost in Pancreatic Cancer and Responding to the Call for Esophageal Cancer
291 - A Safety Study of Intraoperative Radiation Therapy Following Stereotactic Body Radiation Therapy and Multi-Agent Chemotherapy in the Treatment of Localized Pancreatic Adenocarcinoma
Presenter(s)
Abhinav Reddy, MD - Northside Hospital, Atlanta, GA
A. V. Reddy1, S. Sehgal2, S. Mao3, C. Hill4, T. Lin5, G. Paparoidamis4, D. Roche4, D. Kaplin6, A. Hacker-Prietz4, M. B. Roumeliotis4, and A. Narang4; 1Northside Radiation Oncology Consultants, Canton, GA, 2Johns Hopkins Medical Institute, Department of Radiation Oncology, Baltimore, MD, 3Johns Hopkins Radiation Oncology Kimmel Cancer Center, Baltimore, MD, 4Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 5Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 6Johns Hopkins Hospital, Baltimore, MD
Purpose/Objective(s):
In patients with borderline resectable and locally advanced pancreatic cancer (BRPC/LAPC) who are candidates for surgical resection, pre-operative radiation has been associated with high rates of margin negative resection. However, when only gross disease and involved vasculature are targeted with pre-operative radiation, local recurrence rates are high, exceeding 40%. The majority of local failures occur in the “Triangle” volume (TV), defined by extrapancreatic neural tract anatomy at risk. Targeting the TV can reduce local failures to as low as 20%. We subsequently opened a prospective trial to explore a strategy for dose-escalation to the TV involving intraoperative radiation therapy (IORT) to the TV following pre-operative SBRT. We report safety outcomes from this pilot study, and early local control outcomes.Materials/Methods:
A total of 20 patients were enrolled on this study. Following multi-agent chemotherapy, patients were treated with pre-operative SBRT to 40 Gy in 5 fractions to gross disease, involved vasculature, and the TV. Following SBRT, patients were surgically explored. If gross total resection was achieved, patients were treated to the TV to 15 Gy in 1 fraction using Ir-192, prescribed to the surface of a Freiburg flap applicator. The total BED10 to the TV was 109.5 Gy. Primary endpoint was post-operative complication rate, defined by as the rate of Clavien Dindo Grade IIIA or higher complications within the first 90 days following surgery as compared to a historical rate of 25% without pre-operative radiation. Secondary endpoints included post-operative complications > 90 days following surgery, local progression-free survival (LPFS), overall survival, distant metastasis-free survival, and progression-free survival. We report on safety outcomes and early local control data.Results:
Of the 20 patients who were enrolled on the study, median age was 64 years (range: 43-79 years) and 14 (70%) were male. The median follow-up was 11.1 months. A total of 13 (65%) patients had BRPC, while 7 (35%) patients had LAPC. Chemotherapy regimens consisted of FOLFIRINOX and gemcitabine plus nab-paclitaxel for a median duration of 4.5 months (range, 2.5-6 months). The rate of Clavien Dindo Grade > IIIA toxicity was 15% (3/20). No patients experienced post-operative mortality. The 1 year LPFS was 95%. Only one patient has experienced a local failure in the TV, which occurred on the left of the superior mesenteric artery (SMA) in the region of radiation dose falloff.Conclusion:
Intra-operative radiation to the TV following pre-operative SBRT was feasible and safe, without increase in 90-day post-operative complication rate compared to historical data and without post-operative mortality events. Early local control rates in the TV appear excellent, with the exception of one failure in a region of dose falloff. Additional follow-up is needed to understand long term toxicity and other oncologic endpoints. This approach may warrant further investigation in a phase II setting.