Maximal Ablative Irradiation Because of Encasement for Patients With Locally Advanced Pancreatic Cancer: A Nonrandomized Clinical Trial.

Authors

Marsha Reyngold, Alice C Wei, Eileen M O'Reilly, Michael I D'Angelica, T Peter Kingham, Kevin C Soares, Anna M Varghese, Charlie White, Melissa Zinovoy, Paul B Romesser, Abraham Wu, Carla Hajj, John J Cuaron, Danny N Khalil, Fiyinfolu Balogun, Wungki Park, Kenneth H Yu, Vinod P Balachandran, Jeffrey A Drebin, Maria Lagratta, Zhigang Zhang, William R Jarnagin, Christopher H Crane

Published in

JAMA surgery. Jul 29, 2026. Epub Jul 29, 2026.

Abstract

The best local therapy approach for patients with locally advanced pancreatic cancer (LAPC) remains undefined.
To evaluate hypofractionated ablative radiation therapy (A-RT) followed by evaluation for surgery in patients with LAPC whose cancer remained unresectable after induction chemotherapy.
This was a phase 2 single-arm nonrandomized clinical trial conducted at the Memorial Sloan Kettering Cancer Center, New York, New York, from June 2018 to April 2024. Participants with histologically confirmed pancreatic adenocarcinoma unresectable by multidisciplinary review after 3 or more months of modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) or gemcitabine plus nab-paclitaxel were eligible.
Hypofractionated A-RT (67.5 Gy in 15 fractions or 75 Gy in 25 fractions) with capecitabine followed by evaluation for resection.
Coprimary end points included resectability and 2-year overall survival. Secondary end points included 90-day surgical adverse events (AEs) and 2-year locoregional and distant metastasis rates.
Forty-eight participants underwent A-RT (25 [52.1%] male; median [range] age, 67 [50-80] years; median [range] tumor size 4.1 [2.4-8.3] cm; 47 (98%) with arterial and venous involvement; median [range] carbohydrate antigen 19-9, 88 [<1-1601] U/mL). Forty-five patients (94%) received mFOLFIRINOX. Seventeen participants (34%) underwent a laparoscopy, with resection performed in 13 (27%). Resections included 11 pancreaticoduodenectomies (84.6%) and 2 distal pancreatectomies (15.4%). At median follow-up of 3 years, 2-year overall survival from A-RT for the cohort was 38% (95% CI, 26%-54%) overall and 31% (95% CI, 19%-51%) and 54% (95% CI, 33%-89%) in participants with unresected and resected disease, 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 groups, respectively. Two-year rate of distant metastasis was 73% (95% CI, 57%-84%). There were no deaths within 90 days of surgery. Eleven surgical AEs (including 4 Clavien-Dindo grade III) occurred in 12 evaluable participants. Acute and late RT-related grade III or higher AEs occurred in 6 (12.5%) and 12 (26.1%) participants, respectively. The most common late AE was ascites in 7 (15.2%; 3 postsurgery).
For patients with LAPC with extensive vascular encasement after induction chemotherapy, hypofractionated A-RT prior to possible surgery was associated with promising overall survival for both ultimately resected and unresected groups. A-RT was not associated with an increase in postsurgical morbidity when surgery was performed and was an effective destination therapy when it was not. Further evaluation of this strategy to maximize outcomes regardless of resection is warranted.
ClinicalTrials.gov Identifier: NCT03523312.

PMID:
42525419
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.

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