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.

Center for Image Guided Neurosurgery University of Pittsburgh Medical Center Pennsylvania PA USA

Department of Neurological Surgery University of Pittsburgh Medical Center Pennsylvania PA USA

Department of Neurosurgery Allegheny Health Network Pennsylvania PA USA

Department of Neurosurgery and Gamma Knife Radiosurgery Ruber Internacional Hospital Madrid Spain

Department of Neurosurgery and Radiation Oncology West Virginia University Morgantown USA

Department of Neurosurgery Centre de recherche du CHUS Université de Sherbrooke Sherbrooke Canada

Department of Neurosurgery Koc University School of Medicine Istanbul Turkey

Department of Neurosurgery Neurological Institute Taipei Veteran General Hospital Taipei Taiwan

Department of Neurosurgery Postgraduate Institute of Medical Education and Research Chandigarh India

Department of Radiation Oncology Allegheny Health Network Pennsylvania PA USA

Department of Radiation Oncology The Ohio State University Wexner Medical Center Columbus USA

Department of Radiation Oncology West Virginia University Morgantown USA

Department of Stereotactic and Radiation Neurosurgery Na Homolce Hospital Prague Czech Republic

Dominican Gamma Knife Center and Radiology Department CEDIMAT Santo Domingo Dominican Republic

School of Medicine University of Pittsburgh Medical Center Pennsylvania PA USA

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Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249 PubMed DOI

Siegel RL, Miller KD, Fuchs HE, Jemal A, Cancer Statistics (2021) CA Cancer J Clin 2021;71:7–33

Linskey ME, Andrews DW, Asher AL et al (2010) The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 96:45–68 PubMed DOI

Chang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:1037–1044 PubMed DOI

van Grinsven EE, Nagtegaal SHJ, Verhoeff JJC, van Zandvoort MJE (2021) The impact of stereotactic or whole brain radiotherapy on neurocognitive functioning in adult patients with brain metastases: A systematic review and Meta-Analysis. Oncol Res Treat 44:622–636 PubMed DOI PMC

Bin-Alamer O, Abou-Al-Shaar H, Singh R et al (2024) Local control and patient survival after stereotactic radiosurgery for esophageal cancer brain metastases: an international multicenter analysis. J Neurosurg 142(5):1357–1365

Pikis S, Mantziaris G, Protopapa M et al (2024) Stereotactic radiosurgery for brain metastases from human epidermal receptor 2 positive breast cancer: an international, multi-center study. J Neurooncol 170:199–208 PubMed DOI PMC

Yamamoto M, Serizawa T, Shuto T et al (2014) Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 15:387–395 PubMed DOI

Brown PD, Jaeckle K, Ballman KV et al (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: A randomized clinical trial. JAMA 316:401–409 PubMed DOI PMC

Taori S, Wei Z, Deng H, Lunsford LD, Niranjan A (2024) The role of stereotactic radiosurgery in patients with brain metastases from colorectal cancers. Neurosurgery 94:828–837 PubMed DOI

Lin NU, Lee EQ, Aoyama H et al (2015) Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol 16:e270–278 PubMed DOI

Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC (1999) Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 45:427–434 PubMed DOI

Benjamin CG, Gurewitz J, Kavi A et al (2022) Survival and outcomes in patients with >/= 25 cumulative brain metastases treated with stereotactic radiosurgery. J Neurosurg 137:571–581 PubMed DOI

Wei Z, Luy DD, Jose S et al (2023) Single-Session Gamma Knife Radiosurgery for Patients With 20 or More Brain Metastases. Neurosurgery.;93:857–866

Lehrer EJ, Peterson JL, Zaorsky NG et al (2019) Single versus multifraction stereotactic radiosurgery for large brain metastases: an international Meta-analysis of 24 trials. Int J Radiat Oncol Biol Phys 103:618–630 PubMed DOI

Suzuki S, Omagari J, Nishio S, Nishiye E, Fukui M (2000) Gamma knife radiosurgery for simultaneous multiple metastatic brain tumors. J Neurosurg 93(Suppl 3):30–31 PubMed DOI

Chang WS, Kim HY, Chang JW, Park YG, Chang JH (2010) Analysis of radiosurgical results in patients with brain metastases according to the number of brain lesions: is stereotactic radiosurgery effective for multiple brain metastases? J Neurosurg 113:73–78 PubMed DOI

Wei Z, Niranjan A, Abou-Al-Shaar H, Deng H, Albano L, Lunsford LD (2022) A volume matched comparison of survival after radiosurgery in non-small cell lung cancer patients with one versus more than Twenty brain metastases. J Neurooncol 157(3):417–423

Soffietti R, Kocher M, Abacioglu UM et al (2013) A European organisation for research and treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol 31:65–72 PubMed DOI

Aoyama H, Shirato H, Tago M et al (2006) Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295:2483–2491 PubMed DOI

Hayashi M, Yamamoto M, Nishimura C, Satoh H (2007) Do recent advances in MR technologies contribute to better gamma knife radiosurgery treatment results for brain metastases?? Neuroradiol J 20:481–490 PubMed DOI

Mulvenna P, Nankivell M, Barton R et al (2016) Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet 388:2004–2014 PubMed DOI PMC