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We updated our data set, please use thenew version(md5:ece00981be0f2616c1c0a57d10f3176e). All data supporting the findings of the publication "Single-cell spatial immune landscapeof primary and metastatic brain tumours", including masks of high-dimension tif images, single-cell segmentation, single-cell cell types, and patient data. The code used to produce the results of this study is available at https://github.com/walsh-quail-labs/IMC_Brain. Raw primary imaging data can be obtained from the authors directly upon reasonable request. Glioma channel index names: Channel Name Channel Index CD117 1 CD11c 2 CD14 3 CD163 4 CD16 5 CD20 6 CD31 7 CD3 8 CD4 9 CD68 10 CD8 11 CD94 12 DNA1 13 FoxP3 14 GFAP 15 HLA-DR 16 MPO 17 Olig2 18 P2PY12 19 Sox2 20 Sox9 21 BrM channel index names: Channel Name Channel Index CD117 1 CD11c 2 CD14 3 CD163 4 CD16 5 CD20 6 CD31 7 CD3 8 CD4 9 CD68 10 CD8a 11 CD94 12 DNA1 13 FoxP3 14 GFAP 15 HLA-DR 16 MPO 17 MeLanA 18 P2PY12 19 PMEL 20 PanCK 21

Purpose As survival of patients with central nervous system (CNS) metastases from breast cancer is poor and incidence rates are increasing, there is a growing need for better treatment strategies. In the current study, the efficacy of local and systemic therapies was analyzed in breast cancer patients with CNS metastases.Methods Medical records from patients with breast cancer and brain and/or leptomeningeal metastases treated at a tertiary referral center and a teaching hospital between 2010 and 2020 were retrospectively studied. Main outcomes of interest were overall survival and CNS progression free survival. Analyses were performed for the different systemic and local therapies for CNS metastases, and subgroups based on breast cancer subtypes and brain metastases vs leptomeningeal metastases were tested.Results We identified 155 patients, 44 HER2-positive, 68 hormone receptor positive/HER2-negative and 43 triple negative. Median overall survival was 5.9 months for all 155 analyzed patients. Survival differed significantly between breast cancer subtypes (HER2-positive 22.8 months, hormone receptor positive/HER2-negative 2.4 months, triple negative 4.2 months, PConclusion Breast cancer patients with CNS metastases show longest median overall survival when the subtype is HER2-positive and when they are treated with both local and systemic therapy.

BACKGROUND Validation of the 2016 LANO MRI scorecard for leptomeningeal metastasis failed for multiple reasons. The objective of this joint EORTC Brain Tumor Group and RANO effort was to validate the feasibility of the revised MRI scorecard for assessing response in leptomeningeal metastasis. METHODS Coded paired cerebrospinal MRI of 20 patients with leptomeningeal metastases from solid cancers at baseline and follow-up after treatment and instructions for assessment were provided via the EORTC imaging platform. The kappa coefficient (K) was used to evaluate inter-observer pairwise agreement. Statistical analyses were performed using SAS V9.4 software (Cary, NC). The sponsor of the study was the University Hospital Zurich (2018-00192). RESULTS Thirty-five raters participated, including 9 neuroradiologists, 17 neurologists, 4 radiation oncologists, 3 neurosurgeons and 2 medical oncologists. Among leptomeningeal metastases-related items at baseline, the best median concordance was noted for hydrocephalus (K=0.63), and the worst median for spinal linear enhancing disease (K=0.46). The median concordance for overall response was moderate (K=0.44). Notably, the interobserver agreement for the presence of parenchymal brain metastases at baseline was minimal (K=0.29). Significant differences were observed when considering the specialty of the raters. Only 394 of 700 ratings (56%) were fully completed. Among 394 fully completed ratings, perfect concordance was noted in 293 ratings (74%) when comparing the overall response according to the guidelines provided in the scorecard and the overall response provided by the raters. The main discordances were noted for partial response according to the rater versus stable disease according to the guidelines (n=44), followed by progression according to the raters versus stable disease according to the guidelines (n=23). CONCLUSION Electronic case report forms with "blocking solutions" are probably required to enforce completeness and quality of scoring. These results confirm the necessity of central review and the need for training of MRI assessment in clinical trials.

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.

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). Methods One hundred and ninety-nine patients from a phase III 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 ≥1 SD. The effect of WBRT was analyzed in irradiated patients. All MRIs 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.

International audience; We appreciate the interest of our colleagues Dankner and Maritan in our efforts to delineate prognostic disease patterns in leptomeningeal metastasis. In their communication, they specifically address the role of prior surgery for brain metastasis in this patient population. The authors perceive a discrepancy between our findings and those of previous studies. These previous studies had reported that patients, who had surgery for brain metastases and developed leptomeningeal metastases thereafter, fared better if they had nodular disease rather than linear disease.However, what we report is that only in the absence of tumor cells in the cerebrospinal fluid (CSF), nodular disease is an indicator of inferior outcome, which likely corresponds to tumor burden driving the disease course. The previous studies1,2 report on imaging defined leptomeningeal metastases and did not distinguish patients with or without positive CSF cytology.In our cohort, a history of brain metastases prior to the diagnosis of leptomeningeal metastases was noted in 32 type II patients (defined as patients without positive CSF cytology), of whom only 11 had surgery which was combined with radiotherapy in all cases: stereotactic radiosurgery (SRS) in 5, whole brain radiotherapy (WBRT) in 5, and SRS plus WBRT in 1 patient).We understand the interest in the history of prior surgery, but to analyze these data would have been beyond the scope of our study, especially considering the small number of patients in this subgroup. Further, MRI was not centrally collected and re-reviewed, further, data on the location and distance of leptomeningeal nodules to the site of surgically approached brain metastases and the extent of resection, and surgical technique used, including potential opening of the ventricle during surgery, were not collected.Accordingly, we fully agree with the authors that further efforts at better defining risk profiles for the development of leptomeningeal metastases are needed, but we also would like to caution against underestimating the complexity of such studies, notably in a multicenter retrospective design. Heterogeneity of patients and tumors included in such studies also need to be considered. Accordingly, ideally, well-planned prospective cohort studies could try to resolve some of the important issues raised by our colleagues.

Background In primary central nervous system lymphoma (PCNSL), small enhancing lesions can persist after treatment. It is unknown whether a difference in response category (complete response [CR], complete response unconfirmed [CRu], or partial response [PR]) reflects survival. We aimed to determine the value of a central radiology review on response assessment and whether the extent of response influenced progression-free and/or overall survival. Methods All patients in the HOVON 105/ALLG NHL 24 study with at least a baseline MRI and one MRI made for response evaluation available for central review were included. Tumor measurements were done by 2 independent central reviewers, disagreements were adjudicated by a third reviewer. Crude agreement and interobserver agreement (Cohen's kappa) were calculated. Differences in progression-free and overall survival between different categories of response at the end-of-protocol-treatment were assessed by the log-rank test in a landmark survival-analysis. Results Agreement between the central reviewers was 61.7% and between local and central response assessment was 63.0%. Cohen's kappa's, which corrects for expected agreement, were 0.44 and 0.46 (moderate), respectively. Progression agreement or not was 93.3% (kappa 0.87) between local and central response assessment. There were no significant differences in progression-free and overall survival between patients with CR, CRu, or PR at the end-of-protocol-treatment, according to both local and central response assessment. Conclusions Reliability of response assessment (CR/CRu/PR) is moderate even by central radiology review and these response categories do not reliably predict survival. Therefore, primary outcome in PCNSL studies should be survival rather than CR or CR/CRu-rate.