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Comment
. 2025 Jun 1;11(6):609-616.
doi: 10.1001/jamaoncol.2025.0460.

Nonoperative Management of Technically Resectable Pancreatic Cancer With Ablative Radiation Therapy

Marsha Reyngold  1   2 , Joshua D Schoenfeld  3 , Eileen M O'Reilly  2   3 , Anna M Varghese  2   3 , Charlie White  4 , Melissa Zinovoy  1 , Paul B Romesser  1 , Abraham J Wu  1 , Carla Hajj  5 , John J Cuaron  1 , Danny N Khalil  3 , Wungki Park  2   3 , Wei Lu  6 , Zhigang Zhang  4 , Kenneth H Yu  2   3 , Luis A Diaz Jr  3 , Christopher H Crane  1   2
Affiliations
Comment

Nonoperative Management of Technically Resectable Pancreatic Cancer With Ablative Radiation Therapy

Marsha Reyngold et al. JAMA Oncol. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Reyngold reported speaker fees from Elekta during the conduct of the study and grants from Elekta outside the submitted work. Dr O’Reilly reported grants to her institution from Genentech-Roche, BioNTech, AstraZeneca, Arcus, Elicio Therapeutics, Parker Institute for Cancer Immunotherapy, the National Cancer Institute, Digestive Care, Break Through Cancer, Agenus, Amgen, and Revolution Medicines; personal fees from Arcus, AstraZeneca, Alligator Bioscience, BioNTech, Merck, Novartis, Leap Therapeutics, and BMS; and other support from Ability Pharmaceuticals, Agenus, Ipsen, Ikena Oncology, MOMA Therapeutics, Astellas, Revolution Medicines, Regeneron, and other from Tango Therapeutics, all during the conduct of the study. Dr Romesser reported grants from EMD Serono, as well as personal fees from EMD Serono, Faeth Therapeutics, XRad Therapeutics, and Natera outside the submitted work. Dr Khalil reported research support from and has had intellectual property rights associated with Merck; consulting fees from AbbVie, Akamis Bio, Celldex, and Sanofi; and is an inventor on patents related to CD40 and in situ vaccination. Dr Park reported grants to his institution from the National Cancer Institute, Merck, Astellas, Lepu Biopharma, Amgen, Revolution Medicines, Break Through Cancer, The Society of MSK, Parker Institute for Cancer Immunotherapy, and Society for Immunotherapy of Cancer, as well as personal fees from Astellas, EXACT Therapeutics, Revolution Medicines, Innovent Biologics, Regeneron, KeyQuest, American Physician Institute, Curio, Integrity, and Physicians’ Education Resource, all outside the submitted work. Dr Lu reported grants from the National Cancer Institute during the conduct of the study. Dr Diaz reported serving as a member of the board of directors of Quest Diagnostics and Epitope; consulting fees from Innovatus Capital Partners, SEER, Absci, GSK, Delfi, Blackstone, and Neophore; and is the inventor of multiple licensed patents related to technology for circulating tumor DNA analyses and mismatch repair deficiency for diagnosis and therapy, in which some of these licenses and relationships are associated with equity or royalty payments to the inventors; he holds equity in Quest Diagnostics, Epitope, Absci, SEER, Delfi, and Neophore and divested his equity in Personal Genome Diagnostics to LabCorp in February 2022 and his equity in Thrive Earlier Detection to Exact Biosciences in January 2021. Dr Crane reported personal fees from Elekta outside the submitted work. No other disclosures were reported.

Comment on

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