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Clinical Trial
. 2025 Aug 1;11(8):890-899.
doi: 10.1001/jamaoncol.2025.1770.

Therapy, Safety, and Logistics of Preoperative vs Postoperative Stereotactic Radiation Therapy: A Preliminary Analysis of a Randomized Clinical Trial

Debra Nana Yeboa  1 , Jing Li  1 , Ruitao Lin  1 , Sujit S Prabhu  1 , Thomas H Beckham  1 , Kristina Woodhouse  2 , Todd Allen Swanson  1 , Jeffrey S Weinberg  1 , Xuemei Wang  1 , Xiaohan Chi  1 , Chinenye Lynette Ejezie  3 , Dima Suki  1 , Chenyang Wang  1 , Chibawanye Ene  1 , Ian E McCutcheon  1 , Susan McGovern  1 , Mary Frances McAleer  1 , Martin Tom  1 , Amol Ghia  1 , Subha Perni  1 , Wen Jiang  1 , Brian De  1 , Caroline Chung  1 , Betty Y S Kim  1 , Barbara J O'Brien  1 , Jason T Huse  1 , Jeffrey S Wefel  1 , Laurence Court  1 , Hussein Tawbi  1 , Filip Janku  4 , Nandita Guha-Thakurta  1 , J Matthew Debnam  1 , Jason Johnson  5 , Ceylan Altintas Taslicay  1 , Christopher Alvarez-Breckenridge  1 , Shaan M Raza  1 , Amy B Heimberger  6 , Franco DeMonte  1 , Robert North  1 , Tina M Briere  1 , John F de Groot  7 , Raymond Sawaya  8 , David Grosshans  1 , Frederick F Lang  1 , Ganesh Rao  9 , Sherise D Ferguson  1
Affiliations
Clinical Trial

Therapy, Safety, and Logistics of Preoperative vs Postoperative Stereotactic Radiation Therapy: A Preliminary Analysis of a Randomized Clinical Trial

Debra Nana Yeboa et al. JAMA Oncol. .

Abstract

Importance: Preoperative stereotactic radiation therapy (SRT) vs postoperative SRT logistics and toxic effects provides clinically significant data on management outcomes.

Objective: To determine preoperative SRT logistics and safety profile compared with postoperative in patients with brain metastases.

Design, setting, and participants: This single-institution phase 3 randomized clinical trial included patients 18 years and older and undergoing a planned surgical resection. Patients were required to have an Eastern Cooperative Oncology Group Performance Status score of 2 or greater and be candidates for SRT within 30 days of surgical resection. Patients with radiosensitive histologies (eg, small cell lung cancer and lymphoma), brain metastasis of unknown primary, and/or radiographic evidence of leptomeningeal disease were excluded. Data were collected from December 2018 to August 2023, and data were analyzed from September 2023 to December 2024.

Interventions: Patients were randomized 1:1. Patients randomized to the preoperative SRT cohort underwent SRT (in 1 to 5 fractions) followed by surgical resection within 1 month of radiation therapy. Patients randomized to the postoperative SRT cohort underwent resection followed by postoperative SRT within 1 month of surgery.

Main outcomes and measures: Outcomes reported focus on nonprimary end point analysis of the trial, including comparative toxic effect outcomes of preoperative vs postoperative SRT postprocedural events, feasibility of preoperative SRT, and radiation therapy management.

Results: Of 103 patients, 56 (54.4%) were male, and the median (range) age was 59 (26-83) years. Of 103 patients, 83 (80.6%) completed both radiation and surgery for brain metastases while in the study. Of these, 70 patients (84%) had 1 to 4 brain metastases at enrollment, 11 (13%) had 5 to 10 lesions, and 2 (2%) had more than 10 lesions. In the preoperative stereotactic radiosurgery (SRS)/SRT cohort, 45 (88%) completed both treatments compared with 38 (73%) in the postoperative SRS/SRT arm. There were no statistically significant differences between treatment groups in 30-day postoperative morbidity or postprocedural events. The median (range) time between surgery and SRT was significantly shorter in the preoperative arm (6 [0-24] days) compared with the postoperative arm (22 [12-42] days; P < .001). The median (range) time from randomization to receiving both brain-directed therapies was 10 (4-31) days in the preoperative arm compared with 32.5 (19-55) days for the postoperative arm (P < .001).

Conclusions and relevance: In this randomized clinical trial, preoperative SRT had comparable safety to postoperative SRT and resulted in shorter time to treatment completion, potentially facilitating expedited care.

Trial registration: ClinicalTrials.gov Identifier: NCT03741673.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Yeboa reported institutional grants from Robert Wood Johnson Foundation, Brockman Foundation, and MD Anderson Cancer Center during the conduct of the study as well as institutional grants from MD Anderson Cancer Center and Novartis outside the submitted work. Dr Lin reported personal fees from Eli Lilly and Merck Sharp & Dohme outside the submitted work. Dr Suki reported grants from Brockman Foundation during the conduct of the study. Dr C. Wang reported grants from Elekta outside the submitted work. Dr McGovern reported serving on the advisory board for Chimerix outside the submitted work. Dr O’Brien reported serving on the data safety monitoring board for Plus Therapeutics outside the submitted work. Dr Wefel reported grants from MD Anderson Cancer Center and Brockman Foundation during the conduct of the study; grants from GT Medical Technologies and Novocure; and personal fees from Astellas, Bayer, and Intra-Cellular Therapies outside the submitted work. Dr Court reported grants from Varian Medical Systems outside the submitted work. Dr Tawbi reported grants from Dragonfly Therapeutics, Eisai, Genentech, GlaxoSmithKline, Merck, Novartis, Regeneron, and Syntrix as well as personal fees from Bristol Myers Squibb, Corcept Therapeutics, Eisai, IO Biotech, Immunocore, Iovance, Krystal Biotech, Medicenna, Merck, Novartis, Pfizer, Regeneron, Strand Therapeutics, and T-Knife Therapeutics outside the submitted work. Dr Janku reported owning stock or stock options in Monte Rosa Therapeutics outside the submitted work. Dr Debnam reported royalties from Springer Nature outside the submitted work. Dr North reported research support from Stryker Corporation outside the submitted work. Dr Lang reported grants from Brockman Foundation during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. CONSORT Diagram of Brain Metastases Patients Enrolled
LMD indicates leptomeningeal disease; MRI, magnetic resonance imaging; SRT, stereotactic radiation therapy; WBRT, whole-brain radiation therapy.
See this image and copyright information in PMC

References

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