Craniospinal Irradiation in Patients Diagnosed with Glioblastoma with Primitive Neuronal Component Prevents Distant Intracranial and Leptomeningeal Recurrences

Abstract

Glioblastoma (GBM) is the most common primary central nervous system (CNS) malignancy. In recent years, molecular and histological analyses have identified GBM with primitive neuronal component (GBM-PNC) as a distinct entity with poor regional control and worse overall prognosis. GBM-PNCs are more prone to CNS dissemination and leptomeningeal (LM) metastasis, occurring in up to 40% of patients. Given the concern for distal CNS spread, we hypothesized that craniospinal irradiation (CSI) may be an effective treatment option for GBM-PNC. We performed a retrospective chart review of patients diagnosed with GBM-PNC treated at a large academic center with institutional review board approval. Clinical, histologic and treatment characteristics, as well as disease outcomes were obtained from the electronic medical record. Ten patients diagnosed with GBM-PNC were identified in the period of 2005-2019. Median follow-up was 17 months. Overall, 80% of patients were men, median age was 49 years (range 20-64) and ECOG 0-1. Fifty percent of patients received CSI as opposed to involved field radiation therapy (IFRT). Four of five patients receiving CSI were treated with proton therapy. All patients, but one received concurrent Temozolomide. Both IFRT and CSI were tolerated well with minimal grade 3-4 toxicities. Patients treated with CSI were more likely to experience transient grade 3-4 lymphopenia (60% vs 0%). Eighty percent of patients experienced a recurrence after treatment with median progression free survival (PFS) of 13 months (range 8-26). PFS did not differ between patients receiving IFRT and CSI (14 vs 12.5 months, p = 0.9). Median overall survival (OS) was 30 months for patients who received IFRT, and median OS was not reached in the CSI group. Of the patients who received CSI as part of their treatment, all recurrences were within the high dose radiation area. On the contrary, 75% of patients who received IFRT experienced multiple recurrences at new intracranial sites and later in the leptomeninges or the spine, requiring multiple treatment courses. This hypothesis generating study demonstrates that CSI may prevent distant intracranial metastasis and LM disease progression. CSI delivered with proton therapy was well tolerated with minimal additional toxicity. A larger study is needed to guide the optimal treatment of patients diagnosed with glioblastoma with primitive neuronal component.