The 5-factor modified frailty index as a prognostic factor following stereotactic radiosurgery for metastatic disease to the brain from non-small cell lung cancer: A multi-center cohort analysis

Background: Non-small cell lung cancer (NSCLC) patients often develop brain metastases (BMs), complicating management. We have shown that increasing frailty is associated with decreased overall survival (OS) and central nervous system progression free survival (PFS) for patients undergoing stereotactic radiosurgery (SRS) to BMs. Leveraging the International Radiosurgery Research Foundation, we sought to expand upon these findings, in NSCLC specifically.

Methods: Across four institutions, 193 patients with (≥1) NSCLC derived BMs with minimum 3 months of clinical/radiographic follow-up were analyzed. Primary outcomes included OS and PFS. Patients were stratified utilizing the mFI-5 into pre-frail (0-1), frail (2), and severely frail (3 + ).

Results: Increased frailty was associated with diminished OS (frail hazard ratio (HR) = 2.49, 95 % CI [1.61-3.85]; severely frail HR = 2.65, 95 % CI [1.57-4.45]). The 6-month post-SRS survival rate was 86.1 %, 69.5 % and 54.5 % for pre-frail, frail and severely frail patients, respectively (p < 0.001). Frailty was not significantly predictive of time to PFS on multivariate Cox Proportional Hazards analysis although there was a trend towards diminished PFS with increasing frailty (median PFS was 18.4, 8.0, and 7.4 months for pre-frail, frail, and severely frail, respectively (p = 0.11). As age > 65 was also predictive of shorter OS (HR = 1.78, 95 % CI [1.23-2.56]). We generated a novel scoring system incorporating age and frailty status. The median survival of patients that scored 0, 1, 2, and 3 points were 21.1, 18.3, 8.9, and 5.6 months, respectively (p < 0.001). The area under the curve of the validation cohort using a logistic regression model was 0.77.

Conclusions: Our results indicate that the MFI-5 is a promising metric with application at the point of care to provide decision support for patients with NSCLC derived BMs.