Leptomeningeal dissemination in glioblastoma; an inspection of risk factors, treatment, and outcomes at a single institution

Abstract

There are few studies reporting the incidence of leptomeningeal dissemination (LMD) in patients with glioblastoma; only small case series have been published. Consequently, there are no established standards of care for these patients. Therefore, we undertook this retrospective review to evaluate a large series of patients with glioblastoma treated at MD Anderson Cancer Center to estimate the incidence of LMD and assess the impact of a variety of treatment modalities. Analysis was performed on 595 patients with glioblastoma treated on clinical trials from 2006 to 2012. The diagnosis of LMD was made by imaging or positive cerebrospinal fluid cytology in 24 patients. An additional 12 patients with known LMD diagnosed during this same period were included to evaluate the impact of treatment on outcome for a total of 36 patients. LMD developed in 4.0 % (24/595 patients) of the clinical trial cohort. Median survival from glioblastoma diagnosis was 16.0 months. Estimated median time of glioblastoma diagnosis to LMD was 11.9 months. Median overall survival from the time of LMD diagnosis was 3.5 months. Patients treated for LMD with chemotherapy/targeted therapy and radiation had a significantly prolonged survival (7.7 months) compared to chemotherapy/targeted therapy alone, radiation alone or palliative care. LMD remains an uncommon event in patients with glioblastoma. Patients treated aggressively with chemotherapy/targeted therapy and radiation had the longest median survival following diagnosis of LMD. However, patients receiving chemotherapy/targeted therapy and radiation were younger and this may have influenced survival. Given the overall poor outcomes, improved therapeutic approaches are needed for glioblastoma patients with LMD.

Prognostic analysis of patients who underwent gross total resection of newly diagnosed glioblastoma

“…In the present study, ventricular opening during surgery was not correlated with leptomeningeal dissemination at recurrence or poor survival, consistent with previous reports [15,19,20]. Our results suggested that surgical difficulty based on close proximity to subcortical fibers and critical neurological tissue, as well as surgical intervention including ventricular opening along with tumor involvement of the SVZ, were less likely to contribute to poor survival than the biological nature of tumor cells and the anatomical environment of the SVZ.…”

Therapy of leptomeningeal metastasis in solid tumors

“…glioblastoma) evidence of LM is not rare: Autopsy series suggest an incidence of approximately 20-25% [11,12]. A symptomatic dissemination is reported only in about 2% [13] and an overall diagnosis made by imaging or positive cerebrosinal fluid cytology in about 4% of patients [14,15]. However, breast cancer (27-50%), lung cancer (22-36%) and melanoma (12%) account for most cases in large series of this disorder [16].…”

Combining therapy with recombinant human endostatin and cytotoxic agents for recurrent disseminated glioblastoma: a retrospective study

“…However, for recurrent patients, re-radiation was always not recommended due to the dose restriction. In addition, this study did not focus on one chemotherapy regimen and fail to provide an effective therapeutic approach [17]. Most of the other published studies were case reports [18][19][20].…”