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Comparative Study
. 2025 Sep;174(3):645-652.
doi: 10.1007/s11060-025-05093-y. Epub 2025 Jun 3.

A comparison of outcomes after radiosurgery in non-small cell lung cancer patients with one versus more than twenty brain metastases: an international multi-center study

Chris Z Wei  1   2   3 , Regan Shanahan  1   2   3 , David Puccio  2   3 , Hansen Deng  2   3 , Cheng-Chia Lee  4 , Huai-Che Yang  4 , Christopher P Cifarelli  5 , Joshua D Hack  6 , Daniel T Cifarelli  5 , Selcuk Peker  7 , Yavuz Samanci  7 , David Mathieu  8 , Jocelyn Blanchard  8 , Haley K Perlow  9 , Joshua D Palmer  9 , Manjul Tripathi  10 , Nuria Martínez Moreno  11 , Roberto Martínez Álvarez  11 , Herwin Speckter  12 , Wenceslao Hernandez  12 , Roman Liščák  13 , Jaromir May  13 , Shahed Elhamdani  14 , Matthew J Shepard  14 , Rodney Wegner  15 , Constantinos G Hadjipanayis  2   3 , L Dade Lunsford  2   3 , Ajay Niranjan  16   17
Affiliations
Comparative Study

A comparison of outcomes after radiosurgery in non-small cell lung cancer patients with one versus more than twenty brain metastases: an international multi-center study

Chris Z Wei et al. J Neurooncol. 2025 Sep.

Abstract

Background: Whether the number or cumulative volume of brain metastases affects survival in patients with metastatic non-small cell lung cancer (NSCLC) remains controversial. We conducted a volume matched multi-center study to determine whether patients with a single metastasis had better outcomes than patients with > 20 brain metastases.

Methods: Between 2014 and 2022, 317 NSCLC patients (21.14% female; single tumor: 278 patients; >20 tumors, 39 patients) underwent stereotactic radiosurgery (SRS). The prescribed margin dose, cumulative tumor volume, 12 Gy volume, and concurrent systematic disease managements were recorded. The overall survival (OS), local tumor control (LTC), adverse radiation effect (ARE) risk, and new tumor development were compared.

Results: No difference in OS was found between patients with > 20 brain metastases and patients with a single metastasis (p = 0.61). Compared to the single tumor cohort, where 217 of 278 (78.06%) patients had no recorded local tumor progression, patients with > 20 brain metastases had a local tumor control rate of 76.92% (p = 0.25). Patients with > 20 tumors had a significantly higher rate of distant tumor development (69.2%) after SRS compared to patients with single tumors (35.3%; **p = 0.024). No significant difference of ARE rate was found.

Conclusion: In this volume matched multi-center study, patients with > 20 tumors showed comparable OS and LTC outcomes compared to patients with single tumors. The number of brain metastases should not be used as a criteria to exclude patients from receiving SRS.

Keywords: Adverse radiation effects; Non-small cell lung cancer; Stereotactic radiosurgery.

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Conflict of interest statement

Declarations. Competing interests: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Dr. L. Dade Lunsford is an AB Elekta stockholder and Insightec consultant. Dr. Constantinos G. Hadjipanayis is a consultant for Stryker Corp, Hemerion Therapeutics, NICO Corp, Integra, Synaptive Medical, and True Digital Surgery. Dr. Matthew Shepard is a consultant at GT Medical Technologies Inc. All other authors have no competing interests to declare that are relevant to the content of this article. Details of previous presentation: The material has not been previously presented. Details of previous publication: The material has not been previously published. Informed consent: This study was approved and patient consent was waived by the institutional review board (IRB).

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