SRS is a safe and effective management modality for the CNS metastases from NSCLC. Bowden et al. reported that the median survival of NSCLC patients with brain metastasis was 19.9 months, with 1-year survivals of 70% and 5-year survival rates of 16% [9]. The initial management of patients with both solitary and multiple management of metastatic NSCLC continues to evolve, despite past guidelines that only patients with 1–4 brain metastases are considered appropriate for initial treatment by SRS. In the current study, we sought to determine whether tumor number or total tumor volume can serve as a better predictive factor for patients’ survival after SRS.
Although high definition MRI can determine the number of brain metastases, simple tumor number is insufficient to determine the best strategy. At present neither medical oncologists, radiation oncologists, or neurosurgeons are able to provide accurate predictions of survival when confronted with a new patient with metastatic brain disease [12]. Routman et al. [13] found that the number of brain metastases was not a significant predictor of patient survival for patients who underwent SRS with or without prior WBRT and/or surgery. Chang et al. [14] reviewed 323 brain metastasis patients who underwent SRS and found no significant difference in survivals among patient groups that had 1–5, 6–10, 11–15, and ≥ 15 BMs.
Prior to the current analysis, we hypothesized that tumor volume was more prognostically important than the number of brain metastases. We found that the median survival in patients with ≥ 20 metastases were statistically no different than the survival of patients with single metastases (p = 0.3). Our experience compares favorably with other outcome reports in current management of NSCLC patients. In 2013, Rava et al. [15] reported a median survival of 6.5 months in 53 patients with ≥ 10 metastatic brain lesions. Chang and colleagues [14] reported that the median survival times for patients with 11–15 and ≥ 15 BMs was 13 months and 8 months, respectively. Karlsson et al. [16] analyzed 1921 metastatic patients who underwent SRS over the time span of 30 years and found no statistically significant survival differences among individuals with 2, 3–4, 5–8, or ≥ 8 metastases.
The model constructed by Ali et al. [17] found brain metastasis number as a continuous variable and only a 4% increase in the hazard of death for every increment of 6-7 metastases. This study showed that the number of brain metastases only serves as a modest prognostic factor in predicting patient survival and treatment recommendations should be evaluated using other factors when trying to decide between in the greater clinical context in the decision making between SRS and WBRT. While tumor number is often evaluated, cumulative tumor volume is rarely included in guidance documents [18].
In the context of active systemic cancer, some patients will experience new tumor development, progression of treated disease, or treatment related side effects. The present study showed a median onset of 8 months until the development of new tumors in patients with initially solitary tumors. In comparison, the interval between SRS and new tumor detection in the ≥ 20 cohort was slightly less at 8 months. Somewhat surprisingly we found that median survivals were slightly longer in the ≥ 20 cohort, although this finding was not statistically significant. In such patients additional salvage SRS can be considered along with the clinical symptoms, signs, Karnofsky performance status (KPS), prior WBRT treatment, extracranial disease status, absence of neurological symptoms, and patient’s preference, among others.
Even patients who present with ≥ 20 brain metastases can have survivals comparable to patients who have a single tumor of comparable cumulative volume. Active systemic disease status, neurological function in part measured by KPS scores remain important prognostic factors for both survival and new tumor development.