Survival, neurocognitive function, and health-related quality of life outcomes after rituximab-methotrexate, BCNU, teniposide, and prednisolone for primary CNS lymphoma:Final results of the HOVON 105/ALLG NHL 24 study

Background. Studies on the efficacy of rituximab in primary CNS lymphoma (PCNSL) reported conflicting results. Our international randomized phase 3 study showed that the addition of rituximab to high-dose methotrexate, BCNU, teniposide, and prednisolone (MBVP) in PCNSL was not efficacious in the short term. Here we present long-term results after a median follow-up of 82.3 months. Methods. One hundred and ninety-nine eligible newly diagnosed, nonimmunocompromised patients with PCNSL aged 18–70 years with WHO performance status 0–3 was randomized between treatment with MBVP chemotherapy with or without rituximab, followed by high-dose cytarabine consolidation in responding patients, and reduced-dose WBRT in patients aged ≤ 60 years. Event-free survival was the primary endpoint. Overall survival rate, neurocognitive functioning (NCF), and health-related quality of life (HRQoL) were additionally assessed, with the IPCG test battery, EORTC QLQ-C30 and QLQ-BN20 questionnaires, respectively. Results. For event-free survival, the hazard ratio was 0.85, 95% CI 0.61–1.18, P = .33. Overall survival rate at 5 years for MBVP and R-MBVP was 49% (39–59) and 53% (43–63) respectively. In total, 64 patients died in the MBVP arm and 55 in the R-MBVP arm, of which 69% were due to PCNSL. At the group level, all domains of NCF and HRQoL improved to a clinically relevant extent after treatment initiation, and remained stable thereafter up to 60 months of follow-up, except for motor speed which deteriorated between 24 and 60 months. Although fatigue improved initially, high levels persisted in the long term. Conclusions. Long-term follow-up confirms the lack of added value of rituximab in addition to MBVP and HD-cytarabine for PCNSL.</p

Survival, neurocognitive function, and health-related quality of life outcomes after rituximab-methotrexate, BCNU, teniposide, and prednisolone for primary CNS lymphoma:Final results of the HOVON 105/ALLG NHL 24 study

Background. Studies on the efficacy of rituximab in primary CNS lymphoma (PCNSL) reported conflicting results. Our international randomized phase 3 study showed that the addition of rituximab to high-dose methotrexate, BCNU, teniposide, and prednisolone (MBVP) in PCNSL was not efficacious in the short term. Here we present long-term results after a median follow-up of 82.3 months. Methods. One hundred and ninety-nine eligible newly diagnosed, nonimmunocompromised patients with PCNSL aged 18–70 years with WHO performance status 0–3 was randomized between treatment with MBVP chemotherapy with or without rituximab, followed by high-dose cytarabine consolidation in responding patients, and reduced-dose WBRT in patients aged ≤ 60 years. Event-free survival was the primary endpoint. Overall survival rate, neurocognitive functioning (NCF), and health-related quality of life (HRQoL) were additionally assessed, with the IPCG test battery, EORTC QLQ-C30 and QLQ-BN20 questionnaires, respectively. Results. For event-free survival, the hazard ratio was 0.85, 95% CI 0.61–1.18, P = .33. Overall survival rate at 5 years for MBVP and R-MBVP was 49% (39–59) and 53% (43–63) respectively. In total, 64 patients died in the MBVP arm and 55 in the R-MBVP arm, of which 69% were due to PCNSL. At the group level, all domains of NCF and HRQoL improved to a clinically relevant extent after treatment initiation, and remained stable thereafter up to 60 months of follow-up, except for motor speed which deteriorated between 24 and 60 months. Although fatigue improved initially, high levels persisted in the long term. Conclusions. Long-term follow-up confirms the lack of added value of rituximab in addition to MBVP and HD-cytarabine for PCNSL.</p

Liquid biopsy in central nervous system metastases: a RANO review and proposals for clinical applications

Abstract Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a surrogate for tumor tissue in the management of both primary and secondary brain tumors. Herein we critically review available literature on spinal fluid and plasma circulating tumor cells (CTCs) and cell-free tumor (ctDNA) for diagnosis and monitoring of leptomeningeal and parenchymal brain metastases. We discuss technical issues and propose several potential applications of liquid biopsies in different clinical settings (ie, for initial diagnosis, for assessment during treatment, and for guidance of treatment decisions). Last, ongoing clinical studies on CNS metastases that include liquid biopsies are summarized, and recommendations for future clinical studies are provided

Leptomeningeal metastasis: a Response Assessment in Neuro-Oncology critical review of endpoints and response criteria of published randomized clinical trials

Purpose. To date, response criteria and optimal methods for assessment of outcome have not been standardized in patients with leptomeningeal metastasis (LM). Methods. A Response Assessment in Neuro-Oncology working group of experts in LM critically reviewed published literature regarding randomized clinical trials (RCTs) and trial design in patients with LM. Results. A literature review determined that 6 RCTs regarding the treatment of LM have been published, all of which assessed the response to intra-CSF based chemotherapy. Amongst these RCTs, only a single trial attempted to determine whether intra-CSF chemotherapy was of benefit compared with systemic therapy. Otherwise, this pragmatic question has not been formally addressed in patients with solid cancers and LM. The methodology of the 6 RCTs varied widely with respect to pretreatment evaluation, type of treatment, and response to treatment. Additionally there was little uniformity in reporting of treatment-related toxicity. One RCT suggests no advantage of combined versus single-agent intra-CSF chemotherapy in patients with LM. No specific intra-CSF regimen has shown superior efficacy in the treatment of LM, with the exception of liposomal cytarabine in patients with lymphomatous meningitis. Problematic with all RCTs is the lack of standardization with respect to response criteria. There was considerable variation in definitions of response by clinical examination, neuroimaging, and CSF analysis. Conclusion. Based upon a review of published RCTs in LM, there exists a significant unmet need for guidelines for evaluating patients with LM in clinical practice as well as for response assessment in clinical trials

EANO guidelines for the diagnosis and treatment of meningiomas

Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades

Gender issues from the perspective of health-care professionals in Neuro-oncology: An EANO and EORTC Brain Tumor Group survey

Background: Women represent an increasing proportion of the overall workforce in medicine but are underrepresented in leadership roles. Methods: To explore gender inequalities and challenges in career opportunities, a web-based survey was conducted among the membership of the European Association of Neuro-Oncology and the Brain Tumor Group of the European Organisation for Research and Treatment of Cancer. Results: A total of 228 colleagues responded to the survey: 129 women (median age 45 years; range, 25-66 years) and 99 men (median age 48 years; range, 24-81 years); 153 participants (67%) were married and 157 participants (69%) had at least 1 child. Women less often declared being married (60% vs 77%, P =. 007) or having a child (63% vs 77%, P =. 024). Men more frequently had a full-time position (88% vs 75%, P =. 036). Women and men both perceived an underrepresentation of women in leadership positions. Half of participants agreed that the most important challenges for women are leading a team and obtaining a faculty position. Fewer women than men would accept such a position (42% vs 56%). The main reasons were limited time for career and an inappropriate work and life balance. Women specifically cited negative discrimination, limited opportunities, and lack of self-confidence. Discrimination of women at work was perceived by 64% of women vs 47% of men (P =. 003). Conclusion: Women are perceived as experiencing more difficulties in acquiring a leadership position. Personal preferences may account for an underrepresentation of women in leadership positions, but perceived gender inequalities extend beyond disparities of access to leadership

Leptomeningeal metastases: A RANO proposal for response criteria

Leptomeningeal metastases (LM) currently lack standardization with respect to response assessment. A Response Assessment in Neuro-Oncology (RANO) working group with expertise in LM developed a consensus proposal for evaluating patients treated for this disease. Three basic elements in assessing response in LM are proposed: a standardized neurological examination, cerebral spinal fluid (CSF) cytology or flow cytometry, and radiographic evaluation. The group recommends that all patients enrolling in clinical trials undergo CSF analysis (cytology in all cancers; flow cyt