Sep 30

SS 33 - GI 2: Giving Radiation a Boost in Pancreatic Cancer and Responding to the Call for Esophageal Cancer

292 - Maximal Ablative Irradiation because of Encasement for Patients with Potentially Resectable Locally Advanced Pancreatic Cancer: Final Results of Phase II MAIBE Trial

08:30am - 08:40am PT

Room 156/158

Presenter(s)

Marsha Reyngold, MD, PhD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York

M. Reyngold¹, A. Wei², C. Hajj³, M. Zinovoy¹, W. Jarnagin², M. I. D'Angelica², T. P. Kingham², K. Soares², V. P. Balachandran², P. B. Romesser¹, A. M. Varghese⁴, A. J. Wu¹, J. Cuaron¹, Z. Zhang⁵, C. White⁵, W. Park⁴, J. A. Drebin², E. O'Reilly⁴, L. A. Diaz⁴, and C. H. Crane¹; ¹Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ²Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, ³Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates, ⁴Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ⁵Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): For patients with localized but not immediately resectable pancreatic adenocarcinoma (PDAC), best local therapy approach remains undefined. Ph2 MAIBE trial investigated hypofractionated ablative radiation (A-RT) followed by consideration of surgery for patients with locally advanced pancreatic cancer (LAPC) who remain unresectable after induction chemotherapy. Here we report final results for overall survival (OS).

Materials/Methods: Participants with histologically confirmed PDAC judged unresectable by multidisciplinary review using NCCN definition after completing 3 months of mFOLFIRINOX (FFX) or Gemcitabine/Nab-paclitaxel (GN) were eligible. They received hypofractionated A-RT (either 67.5Gy in 15 fractions or 75Gy in 25 fractions based on anatomy) with concurrent capecitabine followed by consideration of resection within 1-3 months. Primary endpoints included resectability (previously reported) and 2-year OS, which was estimated using the Kaplan-Meier method. Local and distant progression were estimated using the cumulative incidence function.

Results: Between 6/2018 and 4/2022, 48 eligible participants underwent A-RT. Median age was 67 (range, 50-80) years, 24 (51%) were male with a median tumor size of 3.95 (1.6 – 8.3) cm and CA19-9 of 92 (<1-1601) U/mL. Forty-four patients (94%) received at least 1 cycle of FFX with a median duration of chemotherapy (FFX or GN) of 3.5 months (1.0 – 9.4). Sixteen (34%) underwent a laparoscopy and 13 (28%) underwent a resection, including 2 at outside institutions (pancreaticoduodenectomy, n=11; distal pancreatectomy, n=2) at a median time of 3.2 months (1.9-16.9 months) from start of A-RT. With a median follow up of 3 years, 2-year OS from A-RT for the entire cohort was 38% (95%CI, 26-54%), including 31% (95% CI: 19%-51%) and 54% (95% CI: 33%-89%) in unresected and resected participants, respectively. Two-year rates of local progression were 11% (95% CI: 3.5-25%) and 15% (95% CI: 2.2-40%) in unresected and resected participants, respectively. Two-year rate of distant metastasis was 73% (95%CI, 57-84%). There were no deaths within 90 days of surgery and 9 surgical AEs were recorded in 6 of 12 evaluable participants, including 2 grade 3 AEs. Acute and late possibly RT-related grade =3 AEs were noted in 5 and 26 participants. Most common late AEs included ascites in 8 (17.4%, 4 of 8 in resected participants), gastric outlet obstruction in 7 (15.2%) and gastrointestinal hemorrhage in 5 (10.9%).

Conclusion: This is the first prospective confirmation of favorable OS rates in patients with LAPC treated with hypofractionated A-RT after 3-6 months of chemotherapy. Surgery after A-RT is feasible without excess surgical toxicity and warrants further evaluation.