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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