Background. To analyze the effect of treatment on neurocognitive functioning and the association of neurocognition with radiological abnormalities in primary central nervous system lymphoma (PCNSL)... Show moreBackground. To analyze the effect of treatment on neurocognitive functioning and the association of neurocognition with radiological abnormalities in primary central nervous system lymphoma (PCNSL).Methods. One hundred and ninety-nine patients from a phase Ill trial (HOVON 105/ALLG NHL 24), randomized to standard chemotherapy with or without rituximab, followed in patients <= 60 years old by 30-Gy whole-brain radiotherapy (WBRT), were asked to participate in a neuropsychological evaluation before and during treatment, and up to 2 years posttreatment. Scores were transformed into a standardized z-score; clinically relevant changes were defined as a change in z-score of >= SD.The effect of WBRT was analyzed in irradiated patients. All M Rls were centrally assessed for white matter abnormalities and cerebral atrophy, and their relation with neurocognitive scores over time in each domain was calculated.Results. 125/199 patients consented to neurocognitive evaluation. Statistically significant improvements in neurocognition were seen in all domains. A clinically relevant improvement was seen only in the motor speed domain, without differences between the arms. In the follow-up of irradiated patients (n = 43), no change was observed in any domain score, compared to after WBRT. Small but significant inverse correlations were found between neurocognitive scores over time and changes in white matter abnormalities (regression coefficients: -0.048 to -0.347) and cerebral atrophy (-0.212 to -1.774).Conclusions. Addition of rituximab to standard treatment in PCNSL patients did not impact neurocognitive functioning up to 2 years posttreatment, nor did treatment with 30-Gy WBRT in patients <= 60 years old. Increased white matter abnormalities and brain atrophy showed weak associations with neurocognition. Show less
Introduction A meningeal solitary fibrous tumor (SFT), also called hemangiopericytoma, is a rare mesenchymal malignancy. Due to anatomic constrains, even after macroscopic complete surgery with... Show moreIntroduction A meningeal solitary fibrous tumor (SFT), also called hemangiopericytoma, is a rare mesenchymal malignancy. Due to anatomic constrains, even after macroscopic complete surgery with curative intent, the local relapse risk is still relatively high, thus increasing the risk of dedifferentiation and metastatic spread. This study aims to better define the role of postoperative radiotherapy (RT) in meningeal SFTs. Patients and methods A retrospective study was performed across seven sarcoma centers. Clinical information was retrieved from all adult patients with meningeal primary localized SFT treated between 1990 and 2018 with surgery alone (S) compared to those that also received postoperative RT (S + RT). Differences in treatment characteristics between subgroups were tested using independent samplest-test for continuous variables and chi-square tests for proportions. Local control (LC) and overall survival (OS) rates were calculated as time from start of treatment until progression or death from any cause. LC and OS in groups receiving S or S + RT were compared using Kaplan-Meier survival curves. Results Among a total of 48 patients, 7 (15%) underwent S and 41 (85%) underwent S + RT. Median FU was 65 months. LC was significantly associated with treatment. LC after S at 60 months was 60% versus 90% after S + RT (p = 0.052). Furthermore, R1 resection status was significantly associated with worse LC (HR 4.08,p = 0.038). OS was predominantly associated with the mitotic count (HR 3.10,p = 0.011). Conclusion This retrospective study, investigating postoperative RT in primary localized meningeal SFT patients, suggests that combining RT to surgery in the management of this patient population may reduce the risk for local failures. Show less
Rhun, E. le; Weller, M.; Niclou, S.P.; Short, S.; Piil, K.; Boele, F.; ... ; EANO Women Neuro-Oncology Comm 2020
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... Show moreBackground. 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. Show less
Najafabadi, A.Z.; Mortel, J. van de; Lobatto, D.; Brandsma, D.; Peul, W.; Taphoorn, M.; ... ; Furth, W. van 2018
Patients with brain metastases (BM) from melanoma have an overall survival (OS) of 2-6 months after whole-brain radiotherapy. Targeted therapy (TT) is an effective treatment for BRAF-mutated... Show morePatients with brain metastases (BM) from melanoma have an overall survival (OS) of 2-6 months after whole-brain radiotherapy. Targeted therapy (TT) is an effective treatment for BRAF-mutated metastatic melanoma. Moreover, recent studies indicate intracranial responses of TT in patients with BM. We analyzed 146 patients with BM from BRAF-mutated melanoma treated with vemurafenib, dabrafenib, or dabrafenib+trametinib between 2010 and 2016. We determined clinical and radiological response, progression-free survival (PFS), and OS. Median OS of patients treated with dabrafenib+trametinib was 11.2 months [n=30; 95% confidence interval (CI): 6.8-15.7], 8.8 months for dabrafenib alone (n=31; 95% CI: 3.9-13.7), and 5.7 months for vemurafenib (n=85; 95% CI: 4.6-6.8). A significantly longer OS was observed in the dabrafenib+trametinib group than in the vemurafenib group (hazard ratio for death, 0.52; 95% CI: 0.30-0.89; P=0.02). Median intracranial PFS of all patients was 4.1 months. Median intracranial PFS for patients treated with dabrafenib+trametinib was 5.8 months (95% CI: 3.2-8.5), 5.7 months (95% CI: 3.0-8.4) for dabrafenib, and 3.6 months (95% CI: 3.5-3.8) for vemurafenib (P=0.54). A total of 63 (43%) patients had symptomatic BM. Intracranial disease control rate at 8 weeks in these patients was 65 versus 70% extracranially. Neurological symptoms improved in 46% of patients with symptomatic BM, whereas in 21%, they remained stable. Median OS in patients with BM from BRAF-mutated melanoma treated with dabrafenib+trametinib was significantly longer than for vemurafenib. Improvement of neurological symptoms was seen in almost half of the patients with symptomatic BM treated with TT. Show less
Background: Historically leptomeningeal metastases (LM) from melanoma have a poor prognosis, with a median survival of only 2 months despite treatment. Targeted therapy and immune checkpoint... Show moreBackground: Historically leptomeningeal metastases (LM) from melanoma have a poor prognosis, with a median survival of only 2 months despite treatment. Targeted therapy and immune checkpoint inhibitors are promising new treatment options in advanced melanoma. We sought to determine the impact of targeted therapy and immunotherapy on the outcome of melanoma patients with LM and to evaluate the influence of prognostic factors.We analyzed a series of 39 consecutive patients diagnosed with LM from melanoma between May 2010 and March 2015 treated at the Netherlands Cancer Institute. Thirty-four of these patients also had brain metastases (BM). Statistical analyses assessed the influence of clinical and biological characteristics on survival.Median overall survival of the entire cohort was 6.9 weeks (95% confidence interval 0.9-12.8). Due to a poor performance status or rapidly progressive disease, 14 patients received no treatment. Median overall survival of untreated patients after the diagnosis of LM was 2.9 versus 16.9 weeks for treated patients (P < 0.001). The median survival of 21 patients treated with systemic targeted therapy and/or immunotherapy, with or without RT was 21.7 weeks (range 2-235 weeks). Five patients had LM without BM. Three of these patients died within 3 weeks before any treatment was given, whereas 2 patients are in ongoing remission for 26 weeks (following dabrafenib) and 235 weeks (following WBRT and ipilimumab). Elevated serum lactate dehydrogenase and S100B at diagnosis of LM were associated with shorter survival.LM from melanoma still has an extremely poor prognosis. As observed in extracranial metastatic disease, new treatment modalities such as systemic targeted therapy and immune checkpoint inhibitors seem to increase overall survival in LM, and may result in long-term remission. These new treatment options should be considered in patients with LM. Show less
