Factors influencing disease control in metastatic lung cancer with intracranial metastasis post gamma-knife radiotherapy

Background: Traditionally, disease control of brain metastases (BM) has dictated the prognosis of those with metastatic lung cancer. Immune check-point inhibitors (ICI) have shown intracranial response but data on the magnitude of such effect in combination with radiation is still evolving. We report the time to progression of intracranial and systemic disease post gamma-knife radiation (GK) and associations with the use of ICI in this cohort. Methods: Patients with metastatic lung cancer with BM treated with GK between 2015 and 2019 were retrospectively analysed in a single institution at the Princess Alexandra Hospital, Queensland. The primary endpoint was time from first GK to death. Results: 104 patients were eligible. Median age was 63 years. BM was seen in 46.7% at diagnosis (versus relapsed in brain). Solitary BM was seen in 37.1% patients. 7.7% had prior whole-brain radiation (WBRT) prior to GK. 45.7% received ICI either at the time of GK or as the next line of treatment immediately post GK. 56.2% received ICI at any time during the study period. Oncogenic driver mutations were seen in 13 cases [EGFR mutant (9.5%), ALK mutation (2.5%)]. 15.2% patients had a high-PDL1 (≥50%) level. Time from GK to death was: 14 (9.7-18.3) months for all patients. Incidence of progressive BM was 46.7%. Time to intracranial PD was 5 months. Systemic PD was seen post GK in 44.8% patients. Survival was improved in those patients with the presence of a driver mutation (p = 0.043) on univariate analysis. Factors which did not impact survival included: the number of BM (solitary vs multiple; p = 0.837), PD-L1 status (PD-L1 < 50% vs ≥50%; p = 0.186), use of ICI (used vs not used; p = 0.307) and previous WBRT (treated vs not treated; p = 0.251). Failure of BM requiring GK on ICI was not associated with a worse outcome (p = 0.707). Conclusions: The presence of driver mutations was associated with prolonged overall survival in select patients undergoing GK for BM. High PDL-1 expressivity and timing of ICI relative to GK do not appear to positively influence outcome in this retrospective study