Nonoperative Management of Technically Resectable Pancreatic Cancer With Ablative Radiation Therapy
Authors: Marsha Reyngold, Joshua D. Schoenfeld, Eileen M. O’Reilly, Anna M. Varghese, Charlie White, Melissa Zinovoy, Paul B. Romesser, Abraham J. Wu, Carla Hajj, John J. Cuaron, Danny N. Khalil, Wungki Park, Wei Lu, Zhigang Zhang, Kenneth H. Yu, Luis A. Diaz, Christopher H. Crane
Journal: JAMA Oncology (2025)

Importance Surgical resection of pancreatic ductal adenocarcinoma (PDAC) modestly improves long-term survival due to the competing risk of metastatic disease. However, postoperative morbidity often interferes with administration of systemic therapy and may be unacceptable to some patients. Ablative radiation therapy (A-RT) has emerged as an effective noninvasive local treatment in many tumor types and may provide an alternative to surgery in select patients with resectable PDAC. Objective To estimate the efficacy of A-RT in technically resectable PDAC. Design, Setting, and Participants This cohort study of consecutive patients with histologically confirmed, radiographically resectable T1-2N0-1M0 PDAC treated with A-RT at Memorial Sloan Kettering Cancer Center between June 2016 and December 2022 were included from a prospectively maintained database. Patients were not eligible for surgery because of noncancer-related comorbidities. Data were frozen for analysis in December 2023, which took place between March and November 2024. Exposures All patients received A-RT exceeding 97.5-Gy biologically effective dose with daily computed tomography or magnetic resonance imaging guidance, motion management, and daily or selective adaptation of the dose distribution. Main Outcomes and Measures The primary outcome was overall survival (OS). Secondary outcomes included biochemical and radiographic objective response rate, cumulative incidence of local progression, progression-free survival, and distant metastasis–free survival. Results Of 25 patients with radiographically resectable PDAC who received A-RT, 13 (52%) were male, and the median (IQR) age at time of A-RT was 80 (74-87) years. A total of 20 patients (80%) had a Karnofsky Performance Status score of 80 or lower. A total of 15 tumors (60%) were T2, and 4 (16%) were node positive. A total of 17 patients (68%) received induction chemotherapy for a median (range) of 2.9 (1.0-6.1) months. Radiation therapy regimens delivered with conventional linear accelerators included 75 Gy in 25 fractions among 13 patients, 67.5 Gy in 15 fractions among 9 patients, 50 Gy in 5 fractions among 2 patients (magnetic resonance imaging-guided linear accelerator), and 60 Gy in 10 for 1 patient. OS, local progression, and distant metastasis–free survival at 2 years were 43.7% (95% CI, 27.4%-69.5%), 20.8% (95% CI, 7.3%-39.0%), and 20.0% (95% CI, 9.1%-43.8%), respectively. Grade 3 acute and late gastrointestinal tract toxic effects were noted in 3 and 1 patients, respectively, with no grade 4 or higher events. Conclusions and Relevance In this cohort study, A-RT in patients with technically resectable PDAC led to effective local tumor control and favorable OS despite advanced age, poor Karnofsky Performance Status score, and conservative use of chemotherapy in the cohort studied. These data support a prospective study of A-RT for the management of resectable PDAC.