Stereotactic Radiosurgery in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases: A Multi-Institutional, Phase II, Prospective Clinical Trial

Author(s): Ayal A. Aizer, MD, MHS¹; Shyam K. Tanguturi, MD¹; Diana D. Shi, MD¹; Paul J. Catalano, ScD²; Kee-Young Shin, MS²; Ivy Ricca, BA¹; Marciana Johnson, MPH¹; Grant Benham¹; David E. Kozono, MD, PhD¹; Raymond H. Mak, MD¹; Lauren Hertan, MD³; Fallon Chipidza, MD^1,4,5; Monica Krishnan, MD^1,4; Itai Pashtan, MD^1,4,5; Luke Peng, MD^1,4; Jack M. Qian, MD^1,5; Ron Y. Shiloh, MD^1,4,5; Daniel N. Cagney, MD^6,7; Jacob Sands, MD⁸; Paul D. Brown, MD⁹; Patrick Y. Wen, MD¹⁰; Daphne A. Haas-Kogan, MD¹; Rifaquat Rahman, MD¹;

Source: doi.org/10.1200/JCO-25-00056

Dr. Anjan Patel's Thoughts

The Alliance phase II, multi-institutional trial evaluated SRS/SRT in small cell lung cancer (SCLC) patients with 1-10 brain metastases, showing a 1-year neurologic death rate of 11.0% vs 17.5% with historical whole brain radiation therapy (WBRT) controls, and a median OS of 10.2 months. Notably, only 22% required salvage WBRT, and 78% avoided WBRT entirely, with high rates of local control and manageable toxicity. The incidence of new brain mets was high (1-year: 59%), but most were managed with salvage SRS/SRT rather than WBRT. In short, for SCLC patients with limited brain mets, SRS/SRT with close MRI surveillance looks like a real alternative to upfront WBRT, potentially preserving neurocognition without compromising intracranial control.

PURPOSE

Stereotactic radiation (SRS/SRT) as opposed to whole-brain radiation (WBRT) represents the standard of care for patients with a limited number of brain metastases given the relatively favorable toxicity profile associated with stereotactic treatment. However, in patients with small cell lung cancer (SCLC), WBRT remains standard because of a lack of prospective data supporting SRS/SRT and concerns related to intracranial progression and neurologic death when WBRT is omitted. We conducted a single-arm, multicenter, phase II trial of SRS/SRT in patients with SCLC and 1-10 brain metastases to assess neurologic death rates relative to historical controls managed with WBRT (ClinicalTrials.gov identifier: NCT03391362).

METHODS

Patients were eligible if they had SCLC or an extrathoracic small cell primary and 1-10 brain metastases. Previous brain-directed radiation including prophylactic cranial irradiation was not permitted. Neurologic death was defined as marked, progressive, radiographic brain progression accompanied by corresponding neurologic symptomatology without systemic disease progression or systemic symptoms of a life-threatening nature. Close imaging-based surveillance of the brain post-SRS/SRT was used.

RESULTS

Between February 2018 and April 2023, 100 patients were enrolled. The median number of brain metastases was 2 (IQR, 1-4; range, 1-10). The median overall survival was 10.2 months; only 22% of patients required salvage WBRT. In total, 20 neurologic deaths were observed, relative to 64 non-neurologic deaths. The neurologic death rate 1 year was 11.0% (95% CI, 5.8 to 18.1); the historical rate in patients managed with WBRT was 17.5%.

CONCLUSION

Our prospective, multi-institutional study demonstrated low rates of neurologic death when SRS/SRT as opposed to WBRT is used in patients with SCLC and 1-10 brain metastases who are surveilled closely post-treatment, supporting the utility of stereotactic approaches in this population.

Author Affiliations

¹Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA; ²Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA; ³Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA; ⁴Department of Radiation Oncology, Milford Regional Medical Center, Milford, MA; ⁵Department of Radiation Oncology, South Shore Health, Weymouth, MA; ⁶Department of Radiation Oncology, Mater Private Hospital, Dublin, Ireland; ⁷Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland; ⁸Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA; ⁹Department of Radiation Oncology, Mayo Clinic, Rochester, MN; ¹⁰Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA

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