Predictors of leptomeningeal disease following hypofractionated stereotactic radiotherapy for intact and resected brain metastases

Abstract

Background The objective was to evaluate the risk and predictors of developing leptomeningeal disease (LMD) in patients with brain metastases treated with 5-fraction hypofractionated stereotactic radiotherapy (HSRT). Methods Patients treated with HSRT for intact brain metastases and/or surgical cavities were reviewed from a prospectively maintained database. Radiographic patterns of LMD were classified as focal classical, diffuse classical, focal nodular, and diffuse nodular. Results HSRT was delivered, most commonly 30 Gy in 5 fractions, to 320 intracranial lesions (57% intact and 43% surgical cavities) in 235 patients. The median follow-up was 13.4 months (range, 0.8 to 60 mo). LMD developed in 19% of patients with a 1-year LMD rate of 12%. From the diagnosis of LMD, the median overall survival (OS) was 3.8 months (range, 2–20.8 mo). The most common LMD pattern was diffuse nodular (44%). No difference in OS was observed between LMD patterns (P = 0.203). Multivariable analysis identified surgical cavities at significantly higher risk of LMD compared with intact lesions (odds ratio [OR] = 2.30, 95% CI: 1.24, 4.29, P = 0.008). For cavities, radiosensitive tumors (OR = 2.35, 95% CI: 1.04, 5.35, P = 0.041) predicted for LMD, while, for intact metastases, patients receiving treatment with targeted agents or immunotherapy (TA/I) were at lower risk (OR = 0.178, 95% CI: 0.04, 0.79, P = 0.023). Conclusions Patients who had a brain metastasis resected were at an increased risk of LMD. OS was poor despite treatment of LMD, and no differences in OS based on the pattern of LMD was observed. Treatment with TA/I was observed to be protective against LMD and requires further study.

The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers

“…To this effect, patients with type 2A or 2C nodular LM lesions have been reported to exhibit a worse prognosis compared to patients with non-nodular disease [ 50 ]. However, it is well documented that nodular LM lesions are associated with a surgical resection of parenchymal brain metastases treated with adjuvant stereotactic radiosurgery and have been shown in other studies to confer improved prognosis when compared to diffuse LM [ 49 , 66 , 67 , 68 ]. Further efforts to better define the prognostic and predictive relevance of distinct LM imaging patterns is an active area of study that can lead to a refined clinical and biological understanding of distinct LM entities.…”

Stereotactic Radiosurgery and Stereotactic Body Radiotherapy in the Management of Oligometastatic Disease

“…It is increasingly recognised that surgery is independently increasing the risk of leptomeningeal dissemination [3,39,40]. This risk could be mitigated by using SRS alone [41] or, if surgery is unavoidable, by treating with preoperative SRS [42,43].…”

“…Surgery for extracranial oligometastatic disease is controversial, as there was a lack of definitive evidence showing a survival benefit, and many questioned the allocation of surgical resources for this patient population. Surgery must also be considered in terms of its invasiveness, the potential to significantly delay or interrupt systemic therapy and the potential to disseminate disease [3,4].…”

Classifying Leptomeningeal Disease: An Essential Element in Managing Advanced Metastatic Disease in the Central Nervous System

“…Nonetheless, 72% of patients undergoing salvage treatment exhibited neurologic death. A study by Nguyen et al 8 of hypofractionated SRS (typically 30 Gy in 5 fractions) to the resection cavity or intact brain metastases also identified surgical resection as an adverse predictor for the development of LMD (odds ratio, 2.30; P Z .008). Conversely, the use of targeted or immunotherapeutic agents conferred protection from LMD.…”