Stereotactic radiosurgery in patients with small cell lung cancer and 1-10 brain metastases: A multi-institutional, phase II, prospective clinical trial.
Authors: Aizer Ayal , Bi Wenya Linda , Catalano Paul J. , Chipidza Fallon , Haas-Kogan Daphne A. , Hertan Lauren , Kozono David E. , Krishnan Monica , Mak Raymond H. , Pashtan Itai , Peng Luke , Qian Jack , Rahman Rifaquat , Ricca Ivy , Sands Jacob , Shiloh Ron Y. , Shin Kee-Young , Tanguturi Shyam Kumar 
Published: June 2024

2020

Background: Stereotactic radiosurgery (SRS) as opposed to whole brain radiation (WBRT) represents the standard of care for patients with a limited number of brain metastases. Brain metastases from small cell lung cancer (SCLC), however, represent an exception to this dogma, given that prior trials evaluating SRS in lieu of WBRT excluded patients with SCLC due to the historical role of prophylactic cranial irradiation (PCI) and concerns relating to neurologic decline and death when WBRT is omitted from upfront management. We conducted a prospective, multi-center, phase II trial of SRS in patients with SCLC and 1-10 brain metastases to determine how rates of neurologic death compared to historical controls managed with WBRT. Methods: Following approval from the Dana-Farber/Harvard Cancer Center IRB, we opened a single-arm, multi-center, phase II trial to investigate SRS in patients with SCLC and 1-10 brain metastases naïve to prior brain-directed radiation including PCI (NCT03391362). Prior resection of a brain metastasis was permitted. Patients with leptomeningeal disease were excluded. Metastases <2cm in maximal size were generally managed with SRS to 20 Gy; larger tumors, or those near sensitive structures, were dose reduced to 16-19 Gy or managed with fractioned SRS (SRT) to 30 Gy in 5 fractions. Gross totally resected brain metastases received SRT to 25 Gy in 5 fractions. We sought to determine, as the primary endpoint, whether or not use of SRS in lieu of WBRT would lead to meaningfully higher rates of neurologic death (HR 1.61, corresponding to a 1-year event rate of 26.7% relative to a historical 1-year rate of 17.5% in patients previously managed with WBRT at our center), with 90% power and a one-sided alpha error of 5%. Neurologic death was defined as marked, progressive, radiographic brain progression accompanied by corresponding neurologic symptomatology without systemic disease progression / systemic symptoms of a life-threatening nature and was assessed by a panel of 2-3 neuro-radiation oncologists. Results: Between 3/2018 – 4/2023, 100 patients were enrolled across 4 centers. The median age was 68 years (IQR 63 – 74 years). The median number of brain metastases was 2 (IQR 1 – 3); 16 (16%) of patients underwent prior neurosurgical resection. On study, 66 (66%) patients were treated with SRS alone while 32 (32%) were treated with SRT to at least 1 site; 2 patients died of systemic disease progression before study treatment. The median overall survival was 10.3 months. In total, 19 neurologic deaths were observed, relative to 62 systemic deaths. The neurologic death rate at 1 year was 11.0% (95% CI 4.8% – 17.2%). Conclusions: Our prospective, multi-institutional study demonstrated modest rates of neurologic death when SRS as opposed to WBRT is used in patients with SCLC and 1-10 brain metastases and represents the largest prospective experience to date. Clinical trial information: NCT03391362 .