SummaryBackgroundIncomplete surgical resection of medulloblastoma is controversially considered a marker of high-risk disease; driving aggressive surgical resections, “second-look” surgeries, and/or intensified chemoradiotherapy. All prior publications evaluating the clinical importance of extent of resection (EOR) failed to account for molecular subgroup. We analysed the prognostic value of EOR across 787 medulloblastoma samples in a subgroup-specific manner.MethodsWe retrospectively identified patients from Medulloblastoma Advanced Genomics International Consortium (MAGIC) centres with a histological diagnosis of medulloblastoma and complete extent of resection and survival data. Specimens were collected from 35 international institutions. Medulloblastoma subgroup affiliation was determined using nanoString gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. Extent of resection (EOR) based on post-operative imaging was classified as gross total (GTR), near total (NTR, <1·5cm2), or subtotal (STR, ≥ 1·5cm2). Overall survival (OS) and progression-free survival (PFS) multivariable analyses including subgroup, age, metastatic status, geographical location of therapy (North America/Australia vs world), and adjuvant therapy regimen were performed. The primary endpoint was the impact of surgical EOR by molecular subgroup and other clinical variables on OS and PFS.Findings787 medulloblastoma patients (86 WNT, 242 SHH, 163 Group 3, and 296 Group 4) were included in a multivariable Cox model of PFS and OS. The marked benefit of EOR in the overall cohort was greatly attenuated after including molecular subgroup in the multivariable analysis. There was an observed PFS benefit of GTR over STR (hazard ration [HR] 1·45, 95% CI; 1·07–1·96, p=0·02) but there was no observed PFS or OS benefit of GTR over NTR (HR 1·05, 0·71–1·53, p=0·82 and HR 1·14, 0·75–1·72, p=0.55). There was no statistically significant survival benefit to greater EOR for patients with WNT, SHH, or Group 3 patients (HR 1·03, 0·67–1·58, p=0·9 for STR vs. GTR). There was a PFS benefit for GTR over STR in patients with Group 4 medulloblastoma (HR1·97, 1·22–3·17, p=0·01), particularly those with metastatic disease (HR 2·22, 1–4·93, p=0·05). A nomogram based on this multivariable cox proportional hazards model shows the comparably smaller impact of EOR on relative risk for PFS and OS than subgroup affiliation, metastatic status, radiation dose, and adjuvant chemotherapy.InterpretationThe prognostic benefit of EOR for patients with medulloblastoma is attenuated after accounting for molecular subgroup affiliation. Although maximal safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high as there is no definitive benefit to GTR over NTR. Our results suggest a re-evaluation of the long-term implications of intensified craniospinal irradiation (36 Gy) in children with small residual portions of medullobla...

The use of the Dextroscope for pre-operative surgical planning allows for appreciation of complex anatomical relationships in 3D. This appreciation is further translated for use during surgical navigation utilizing the DEX-Ray platform that provided us with the superior advantage of allowing fast and accurate surgical resection confidently.

Epileptogenic triggers are multifactorial and not well understood. Here we aimed to address the hypothesis that inappropriate pro-inflammatory mechanisms contribute to the pathogenesis of refractory epilepsy (non-responsiveness to antiepileptic drugs) in human patients. We used single-cell cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to reveal the immunotranscriptome of surgically resected epileptic lesion tissues. Our approach uncovered a pro-inflammatory microenvironment, including extensive activation of microglia and infiltration of other pro-inflammatory immune cells. These findings were supported by ligand–receptor (LR) interactome analysis, which demonstrated potential mechanisms of infiltration and evidence of direct physical interactions between microglia and T cells. Together, these data provide insight into the immune microenvironment in epileptic tissue, which may aid the development of new therapeutics.