Background: High-dose methotrexate (HDMTX) is considered standard of care for

The transplantation of progenitor cells is a promising new approach for the treatment of gliomas. Marrow stromal cells (MSC) are possible candidates for such a cell-based therapy, since they are readily and autologously available and show an extensive tropism to gliomas in vitro and in vivo. However, the signals that guide the MSC are still poorly understood. In this study, we show that gliomas have the capacity to actively attract MSC by secreting a multitude of angiogenic cytokines. We demonstrate that interleukin-8 (IL-8), transforming growth factor-ss1 (TGF-ss1) and neurotrophin-3 (NT-3) contribute to this glioma-directed tropism of human MSC. Together with the finding that vascular endothelial growth factor (VEGF) is another MSC-attracting factor secreted by glioma cells, these data support the hypothesis that gliomas use their angiogenic pathways to recruit mesenchymal progenitor cells.

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Eighty-five brain tumour patients were examined for further characteristics of brain tumour-associated headache. The overall prevalence of headache in this population was 60%, but headache was the sole symptom in only 2%. Pain was generally dull, of moderate intensity, and not specifically localized. Nearly 40% met the criteria of tension-type headache. An alteration of the pain with the occurrence of the tumour was experienced by 82.5%, implying that the pre-existing and the brain tumour headaches were different. The classic characteristics mentioned in the International Classification of Headache Disorders (worsening in the morning or during coughing) were not found; this might be explained by the patients not having elevated intracranial pressure. Univariate analysis revealed that a positive family history of headache and the presence of meningiomas are risk factors for tumour-associated headache, and the use of beta-blockers is prophylactic. Pre-existing headache was the only risk factor according to logistic regression, suggesting that patients with pre-existing (primary) headache have a greater predisposition to develop secondary headache. Dull headache occurs significantly more often in patients with glioblastoma multiforme, and pulsating headache in patients with meningioma. In our study, only infratentorial tumours were associated with headache location, and predominantly with occipital but rarely frontal pain.

OBJECTIVE This is the final report of a phase III randomized study to evaluate whole-brain radiotherapy (WBRT) in primary therapy of primary CNS lymphoma (PCNSL) after a median followup of 81.2 months. METHODS Patients with newly diagnosed PCNSL were randomized to high-dose methotrexate (HDMTX)-based chemotherapy alone or followed by WBRT. We hypothesized that the omission of WBRT would not compromise overall survival (OS; primary endpoint), using a noninferiority design with a margin of 0.9. RESULTS In the per-protocol population (n = 320), WBRT nonsignificantly prolonged progression-free survival (PFS) (median 18.2 vs 11.9 months, hazard ratio [HR] . CONCLUSION Although the statistical proof of noninferiority regarding OS was not given, our results suggest no worsening of OS without WBRT in primary therapy of PCNSL. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that in PCNSL HDMTX-based chemotherapy followed by WBRT does not significantly increase survival compared to chemotherapy alone. The study lacked the precision to exclude an important survival benefit or harm from WBRT. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma ABSTRACTObjective: This is the final report of a phase III randomized study to evaluate whole-brain radiotherapy (WBRT) in primary therapy of primary CNS lymphoma (PCNSL) after a median follow-up of 81.2 months.Methods: Patients with newly diagnosed PCNSL were randomized to high-dose methotrexate (HDMTX)-based chemotherapy alone or followed by WBRT. We hypothesized that the omission of WBRT would not compromise overall survival (OS; primary endpoint), using a noninferiority design with a margin of 0.9.Results: In the per-protocol population (n 5 320), WBRT nonsignificantly prolonged progressionfree survival (PFS) (median 18.2 vs 11.9 months, hazard ratio Conclusion:Although the statistical proof of noninferiority regarding OS was not given, our results suggest no worsening of OS without WBRT in primary therapy of PCNSL. Classification of evidence:This study provides Class II evidence that in PCNSL HDMTX-based chemotherapy followed by WBRT does not significantly increase survival compared to chemotherapy alone. The study lacked the precision to exclude an important survival benefit or harm from WBRT. Neurology ® 2015;84:1242-1248 GLOSSARY CHT 5 chemotherapy; CI 5 confidence interval; CR 5 complete response; G-PCNSL-SG 5 German PCNSL Study Group; HD-Ara-C 5 high-dose cytarabine; HDMTX 5 high-dose methotrexate; HR 5 hazard ratio; ITT 5 intent-to-treat; KPS 5 Karnofsky Performance Score; OS 5 overall survival; PCNSL 5 primary CNS lymphoma; PFS 5 progression-free survival; PP 5 per protocol; PR 5 partial remission; WBRT 5 whole-brain radiotherapy.Standards of care have not been well-defined for primary CNS lymphoma (PCNSL). Highdose methotrexate (HDMTX) is the only undisputed standard of care, whereas the addition of whole-brain radiotherapy (WBRT) has been increasingly questioned because of the high frequency of late neurotoxicity ...