Brain metastases in the elderly - Impact of residual tumor volume on overall survival.

Abstract

Due to demographic changes and an increased incidence of cancer with age, the number of patients with brain metastases (BMs) constantly increases, especially among the elderly. Novel systemic therapies, such as immunotherapy, have led to improved survival in recent years, but intracranial tumor progression may occur independently of a systemically effective therapy. Despite the growing number of geriatric patients, they are often overlooked in clinical trials, and there is no consensus on the impact of BM resection on survival. The aim of this study was to analyze the impact of resection and residual tumor volume on clinical outcome and overall survival (OS) in elderly patients suffering from BM. Patients ≥ 75 years who had surgery for BM between April 2007 and January 2020 were retrospectively included. Residual tumor burden (RTB) was determined by segmentation of early postoperative brain MRI (72h). Contrast-enhancing tumor subvolumes were segmented manually. "Postoperative tumor volume" refers to the targeted BMs. Impact of preoperative Karnofsky performance status scale (KPSS), age, sex and RTB on OS was analyzed. Survival analyses were performed using Kaplan-Meier estimates for the univariate analysis and the Cox regression proportional hazards model for the multivariate analysis. One hundred and one patients were included. Median age at surgery was 78 years (IQR 76-81). Sixty-two patients (61%) had a single BM; 16 patients (16%) had two BMs; 13 patients (13%) had three BMs; and 10 patients (10%) had more than three BMs. Median preoperative tumor burden was 10.3 cm3 (IQR 5-25 cm3), and postoperative tumor burden was 0 cm3 (IQR 0-1.1 cm3). Complete cytoreduction (RTB = 0) was achieved in 52 patients (52%). Complete resection of the targeted metastases was achieved in 78 patients (78%). Median OS was 7 months (IQR 2-11). In univariate analysis, high preoperative KPSS (HR 0.986, 95% CI 0.973-0.998, p = 0.026) and small postoperative tumor burden (HR 1.025, 95% CI 1.002-1.047, p = 0.029) were significantly associated with prolonged OS. Patients with RTB = 0 survived significantly longer than those with residual tumor did (12 [IQR 5-19] vs. 5 [IQR 3-7] months, p = 0.007). Furthermore, prolongation of survival was significantly associated with surgery in patients with favorable KPSS, with an adjusted HR of 0.986 (p = 0.026). However, there were no significances regarding age. RTB is a strong predictor for prolonged OS, regardless of age or cancer type. Postoperative MRI should confirm the extent of resection, as intraoperative estimates do not warrant a complete resection. It is crucial to aim for maximal cytoreduction to achieve the best long-term outcomes for these patients, despite the fact the patients are advanced in age.