Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF)

Abstract

Background: Despite a high incidence of brain metastases in patients with small-cell lung cancer (SCLC), limited data exist on the use of stereotactic radiosurgery (SRS), specifically Gamma Knife™ radiosurgery (Elekta AB), for SCLC brain metastases.

Objective: To provide a detailed analysis of SCLC patients treated with SRS, focusing on local failure, distant brain failure, and overall survival (OS).

Methods: A multi-institutional retrospective review was performed on 293 patients undergoing SRS for SCLC brain metastases at 10 medical centers from 1991 to 2017. Data collection was performed according to individual institutional review boards, and analyses were performed using binary logistic regression, Cox-proportional hazard models, Kaplan-Meier survival analysis, and competing risks analysis.

Results: Two hundred thirty-two (79%) patients received SRS as salvage following prior whole-brain irradiation (WBRT) or prophylactic cranial irradiation, with a median marginal dose of 18 Gy. At median follow-up after SRS of 6.4 and 18.0 mo for surviving patients, the 1-yr local failure, distant brain failure, and OS were 31%, 49%, and 28%. The interval between WBRT and SRS was predictive of improved OS for patients receiving SRS more than 1 yr after initial treatment (21%, <1 yr vs 36%, >1 yr, P = .01). On multivariate analysis, older age was the only significant predictor for OS (hazard ratio 1.63, 95% CI 1.16-2.29, P = .005).

Conclusion: SRS plays an important role in the management of brain metastases from SCLC, especially in salvage therapy following WBRT. Ongoing prospective trials will better assess the value of radiosurgery in the primary management of SCLC brain metastases and potentially challenge the standard application of WBRT in SCLC patients.

Keywords: Gamma Knife; Small-cell lung cancer; Stereotactic radiosurgery; Whole-brain radiation.

Graphical Abstract

FIGURE 1.

Tumor control and survival following SRS for small-cell brain metastases: (top row) all patients, (middle row) SRS salvage following prior WBRT, and (bottom row) SRS alone (without prior WBRT). N below X-axis = number at risk; CIC = cumulative incidence curve; KM = Kaplan-Meier estimation.

FIGURE 2.

Overall survival for patients treated with salvage SRS following by time interval from prior WBRT. N = N at risk. Patients were analyzed for overall survival based on the salvage SRS being performed at greater than or less than 1 yr post WBRT.