Abstract
Leptomeningeal dissemination of a primary brain tumor is a condition which is challenging to treat, as it often occurs in rather late disease stages in highly pretreated patients. Its prognosis is dismal and there is still no accepted standard of care. We report here a good clinical effect with a partial response in three out of nine patients and a stable disease with improvement on symptoms in two more patients following systemic anti-angiogenic treatment with bevacizumab (BEV) alone or in combination with chemo- and/or radiotherapy in a series of patients with leptomeningeal dissemination from primary brain tumors (diffuse astrocytoma WHO°II, anaplastic astrocytoma WHO°III, anaplastic oligodendroglioma WHO°III, primitive neuroectodermal tumor and glioblastoma, both WHO°IV). This translated into effective symptom control in five out of nine patients, but only moderate progression-free and overall survival times were reached. Partial responses as assessed by RANO criteria were observed in three patients (each one with anaplastic oligodendroglioma, primitive neuroectodermal tumor and glioblastoma). In these patients progression-free survival (PFS) intervals of 17, 10 and 20 weeks were achieved. In three patients (each one with diffuse astrocytoma, anaplastic astrocytoma and primitive neuroectodermal tumor) stable disease was observed with PFS of 13, 30 and 8 weeks. Another three patients (all with glioblastoma) were primary non-responders and deteriorated rapidly with PFS of 3 to 4 weeks. No severe adverse events were seen. These experiences suggest that the combination of BEV with more conventional therapy schemes with chemo- and/or radiotherapy may be a palliative treatment option for patients with leptomeningeal dissemination of brain tumors.
Highlights
Leptomeningeal dissemination (LMD) of primary brain tumors such as low-grade and anaplastic gliomas, glioblastomas, medulloblastomas (MB) and primitive neuroectodermal tumors (PNET) is a condition which considerably worsens the prognosis of the underlying disease [1,2]
Established therapy regimes include involved-field radiotherapy (IFXRT) of symptomatic lesions with a total dose of 25–40 Gy. This may result in some palliation, in particular of meningeal signs and cauda equina syndromes but its effect is rather vague with a median overall survival between 2.8 and 16.8 months and no effect on median progression-free survival [5,7,8]
Patients with a Karnofsky patient score of 50% were usually given a recommendation for best supportive care (BSC), and patients with limited alkylator pretreatment were usually treated with a chemotherapy based exclusively on temozolomide or lomustine (CCNU)
Summary
Leptomeningeal dissemination (LMD) of primary brain tumors such as low-grade and anaplastic gliomas, glioblastomas, medulloblastomas (MB) and primitive neuroectodermal tumors (PNET) is a condition which considerably worsens the prognosis of the underlying disease [1,2]. Published series report median progression-free survival (mPFS) intervals between 3.0 and 4.9 months and median overall-survival (mOS) intervals between 3.5 and 11.3 months for patients with LMD from malignant gliomas [1,7,12] These diverging reports could be explained by varying timepoints of diagnosis of LMD, pretreatment and histology of the underlying primary brain tumor as well as the different therapy schemes used. The rationale for combining anti-angiogenic therapies, e.g. bevacizumab (BEV) with these established therapy regimes in leptomeningeal gliomatosis is unclear, since often a significant portion of the malignant cells is dispersed in the cerebrospinal fluid (CSF). For this reason, anti-angiogenic strategies at first look do not seem to be purposeful. BEV may alleviate edema and compression of cranial nerves, the spinal cord and nerve roots, by normalizing leaky blood-brain-barrier function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
