tbuckley/cabot-search huggingface dataset:
QOLP-24. ENGAGING PATIENTS AND CAREGIVERS TO IMPROVE THE IMPORTANCE AND QUALITY OF SUPPORTIVE CARE RESEARCH IN NEURO-ONCOLOGY
Authors: Katherine Peters, Dina Randazzo, Margaret Johnson, Jung-Young Kim, Mallika Patel, Mary Affronti
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND From the time of diagnosis to end of life, patients with primary brain tumors experience challenges to maintain quality of life. While traditional research focuses on clinical trials that involve directly treating cancer, we have designed a specific research committee at our institution that promotes supportive care research to improve patients’ and caregivers’ quality of life. Past research has shown that issues key to patients and caregivers often differ from what researchers and providers might appreciate as important. Incorporating input from brain tumor patients and caregivers is vital to direct the most relevant and necessary supportive care research. METHODS As part of an IRB-approved quality improvement project, we sought the opinions of our supportive care research committee about what are the essential quality of life issues for brain tumor patients and caregivers. We polled our committee before and after a session with patients and caregivers discussing factors relevant to their quality of life. After this patient/caregiver intervention, we used a group discussion and note comparison technique to distill down key elements to advance supportive care research for this population. RESULTS Engagement of the committee included members that were neuro-oncology providers, biostatisticians, and data/regulatory/clinical trial staff. Before the intervention, common themes about key issues for patients and caregivers were comfort, pain management, counteracting side effects, cognitive issues, and financial toxicity. While similar themes emerged after the patient/caregiver intervention, the committee gleaned that aspects of communicating outcomes and support of caregivers were consistently mentioned from the discussion session with patients and caregivers. CONCLUSIONS Opinions of brain tumor patients and caregivers are crucial in driving future direction and relevance of supportive care research in neuro-oncology. Our supportive care research committee will continue to engage patients and caregivers and are planning interventions to improve communication and support for caregivers.
Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial
Authors: Renu R Bahadoer, Esmée A Dijkstra, Boudewijn van Etten, Corrie A M Marijnen, Hein Putter, Elma Meershoek-Klein Kranenbarg, Annet G H Roodvoets, Iris D Nagtegaal, Regina G H Beets-Tan, Lennart K Blomqvist, Tone Fokstuen, Albert J ten Tije, Jaume Capdevila, Mathijs P Hendriks, Ibrahim Edhemovic, Andrés Cervantes, Per J Nilsson, Bengt Glimelius, Cornelis J H van de Velde, Geke A P Hospers, L. Østergaard, F. Svendsen Jensen, P. Pfeiffer, K.E.J. Jensen, M.P. Hendriks, W.H. Schreurs, H.P. Knol, J.J. van der Vliet, J.B. Tuynman, A.M.E. Bruynzeel, E.D. Kerver, S. Festen, M.E. van Leerdam, G.L. Beets, L.G.H. Dewit, C.J.A. Punt, P.J. Tanis, E.D. Geijsen, P. Nieboer, W.A. Bleeker, A.J. Ten Tije, R.M.P.H. Crolla, A.C.M. van de Luijtgaarden, J.W.T. Dekker, J.M. Immink, F.J.F. Jeurissen, A.W.K.S. Marinelli, H.M. Ceha, T.C. Stam, P. Quarles an Ufford, W.H. Steup, A.L.T. Imholz, R.J.I. Bosker, J.H.M. Bekker, G.J. Creemers, G.A.P. Nieuwenhuijzen, H. van den Berg, W.M. van der Deure, R.F. Schmitz, J.M. van Rooijen, A.F.T. Olieman, A.C.M. van den Bergh, D.J.A. de Groot, K. Havenga, J.C. Beukema, J. de Boer, P.H.J.M. Veldman, E.J.M. Siemerink, J.W.P. Vanstiphout, B. de Valk, Q.A.J. Eijsbouts, M.B. Polée, C. Hoff, A. Slot, H.W. Kapiteijn, K.C.M.J. Peeters, F.P. Peters, P.A. Nijenhuis, S.A. Radema, H. de Wilt, P. Braam, G.J. Veldhuis, D. Hess, T. Rozema, O. Reerink, D. Ten Bokkel Huinink, A. Pronk, J. Vos, M. Tascilar, G.A. Patijn, C. Kersten, O. Mjåland, M. Grønlie Guren, A.N. Nesbakken, J. Benedik, I. Edhemovic, V. Velenik, J. Capdevila, E. Espin, R. Salazar, S. Biondo, V. Pachón, J. die Trill, J. Aparicio, E. Garcia Granero, M.J. Safont, J.C. Bernal, A. Cervantes, A. Espí Macías, L. Malmberg, G. Svaninger, H. Hörberg, G. Dafnis, A. Berglund, L. Österlund, K. Kovacs, J. Hol, S. Ottosson, G. Carlsson, C. Bratthäll, J. Assarsson, B.L. Lödén, P. Hede, I. Verbiené, O. Hallböök, A. Johnsson, M.L. Lydrup, K. Villmann, P. Matthiessen, J.H. Svensson, J. Haux, S. Skullman, T. Fokstuen, T. Holm, P. Flygare, M. Walldén, B. Lindh, O. Lundberg, C. Radu, L. Påhlman, A. Piwowar, K. Smedh, U. Palenius, S. Jangmalm, P. Parinkh, H. Kim, M.L. Silviera
Journal: The Lancet Oncology (2020)
Alcohol associated liver cirrhotics have higher mortality after index hospitalization: Long-term data of 5,138 patients
Authors: Priyanka Jain, Saggere Muralikrishna Shasthry, Ashok Kumar Choudhury, Rakhi Maiwall, Guresh Kumar, Ankit Bharadwaj, Vinod Arora, Rajan Vijayaraghavan, Ankur Jindal, Manoj Kumar Sharma, Vikram Bhatia, Shiv Kumar Sarin
Journal: Clinical and Molecular Hepatology (2020)

Background/Aims: Liver cirrhosis is an important cause of morbidity and mortality globally. Every episode of decompensation and hospitalization reduces survival. We studied the clinical profile and long-term outcomes comparing alcohol-related cirrhosis (ALC) and non-ALC.&lt;br/&gt;Methods: Cirrhosis patients at index hospitalisation (from January 2010 to June 2017), with ≥1 year follow-up were included.&lt;br/&gt;Results: Five thousand and one hundred thirty-eight cirrhosis patients (age, 49.8±14.6 years; male, 79.5%; alcohol, 39.5%; Child-A:B:C, 11.7%:41.6%:46.8%) from their index hospitalization were analysed. The median time from diagnosis of cirrhosis to index hospitalization was 2 years (0.2–10). One thousand and seven hundred seven patients (33.2%) died within a year; 1,248 (24.3%) during index hospitalization. 59.5% (2,316/3,890) of the survivors, required at least one readmission, with additional mortality of 19.8% (459/2,316). ALC compared to non-ALC were more often (P&lt;0.001) male (97.7% vs. 67.7%), younger (40–50 group, 36.2% vs. 20.2%; P&lt;0.001) with higher liver related complications at baseline, (P&lt;0.001 for each), sepsis: 20.3% vs. 14.9%; ascites: 82.2% vs. 65.9%; spontaneous bacterial peritonitis: 21.8% vs. 15.7%; hepatic encephalopathy: 41.0% vs. 25.0%; acute variceal bleeding: 32.0% vs. 23.7%; and acute kidney injury 30.5% vs. 19.6%. ALC patients had higher Child-Pugh (10.6±2.0 vs. 9.0±2.3), model for end-stage liver-disease scores (21.49±8.47 vs. 16.85±7.79), and higher mortality (42.3% vs. 27.3%, P&lt;0.001) compared to non-ALC.&lt;br/&gt;Conclusions: One-third of cirrhosis patients die in index hospitalization. 60% of the survivors require at least one rehospitalization within a year. ALC patients present with higher morbidity and mortality and at a younger age.
SURG-03. IMMERSIVE VIRTUAL REALITY APPLICATIONS IN NEUROSURGICAL ONCOLOGY
Authors: Andrea Carai, Angela Mastronuzzi, Giovanna Stefania Colafati, Paul Voicu, Nicola Onorini, Alessia Carboni, Giada Del Baldo, Aalap Jamadagni Herur-Raman, Alessandro De Benedictis, Carlo Efisio Marras
Journal: Neuro-Oncology (2020)

Abstract Tridimensional (3D) rendering of volumetric neuroimaging is increasingly been used to assist surgical management of brain tumors. New technologies allowing immersive virtual reality (VR) visualization of obtained models offer the opportunity to appreciate neuroanatomical details and spatial relationship between the tumor and normal neuroanatomical structures to a level never seen before. We present our preliminary experience with the Surgical Theatre, a commercially available 3D VR system, in 60 consecutive neurosurgical oncology cases. 3D models were developed from volumetric CT scans and MR standard and advanced sequences. The system allows the loading of 6 different layers at the same time, with the possibility to modulate opacity and threshold in real time. Use of the 3D VR was used during preoperative planning allowing a better definition of surgical strategy. A tailored craniotomy and brain dissection can be simulated in advanced and precisely performed in the OR, connecting the system to intraoperative neuronavigation. Smaller blood vessels are generally not included in the 3D rendering, however, real-time intraoperative threshold modulation of the 3D model assisted in their identification improving surgical confidence and safety during the procedure. VR was also used offline, both before and after surgery, in the setting of case discussion within the neurosurgical team and during MDT discussion. Finally, 3D VR was used during informed consent, improving communication with families and young patients. 3D VR allows to tailor surgical strategies to the single patient, contributing to procedural safety and efficacy and to the global improvement of neurosurgical oncology care.
IMG-16. WHOLE TUMOR DIFFUSION KURTOSIS IMAGING ANALYSIS FOR DISCRIMINATING PEDIATRIC POSTERIOR FOSSA TUMORS: ACCURACY AND REPEATABILITY
Authors: Ioan Paul Voicu, Antonio Napolitano, Alessia Carboni, Massimo Caulo, Andrea Carai, Maria Vinci, Evelina Miele, Sabrina Rossi, Antonella Cacchione, Sabina Vennarini, Elisabetta Ferretti, Angela Mastronuzzi, Paolo Tomà, Giovanna Stefania Colafati
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Diffusion kurtosis imaging (DKI) has not yet been tested for pediatric brain tumors. Estimating diffusion values from whole-tumor based (VOI) segmentations may improve diffusion measurement repeatability compared to conventional region-of-interest (ROI) approaches. Our purpose was to compare repeatability between ROI and VOI DKI-derived diffusion measurements and to assess VOI-based DKI accuracy in discriminating among pediatric posterior fossa tumors. MATERIALS AND METHODS We retrospectively analyzed 34 children (19 M, 15F, mean age 7.48 years) with posterior fossa tumors who underwent preoperative 3T MRI including DKI. For each patient, two neuroradiologists independently segmented the whole solid tumor (VOI), the area of maximum tumor diameter and a smallROI.Inter-observer variability was assessed with coefficient of variation (COV) and Bland-Altman plots. VOI-based DKI metrics accuracy in discriminating among tumor histology and for tumor grading were assessed with MANOVA and ROC analyses respectively. Correlation between grading accuracy and inter-observer variability was assessed with Spearman’s rho. RESULTS Tumor histology included medulloblastoma (15), pilocytic astrocytoma (14) and ependymoma (5). VOI-based measurements presented lower variability than ROI-based measurements across all DKI metrics. DKI-derived metrics could accurately discriminate between tumor subtypes (Pillai’s trace: p&amp;lt;0.001) and were accurate for tumor grading (AUCs of 0.919, 0.986, 0.996, 0.842 and 0.926 for RK, MK, AK, FA and MD respectively). VOI-based COV was significantly correlated to AUC values (R=-0.900, p&amp;lt;0.037). CONCLUSIONS DKI-derived metrics are useful for pediatric posterior fossa tumor discrimination and grading. VOI-based diffusion measurements present improved repeatability compared to ROI-based measurements and are significantly correlated to diagnostic accuracy.
CTNI-13. UPDATES ON CLINICAL OUTCOMES AND TUMOR RECURRENCE PATTERNS OF A HUMAN PILOT STUDY ASSESSING EFFICACY OF BELINOSTAT (PXD-101) COMBINING WITH CHEMORADIATION IN TREATING GLIOBLASTOMA
Authors: Karen Xu, Vicki Huang, Karthik Ramesh, Saumya Gurbani, Eduard Schreibmann, Brent Weinberg, Soma Sengupta, Alfredo Voloschin, Matthias Holdhoff, Peter Barker, Lawrence Kleinberg, Jeffrey Olson, Hyunsuk Shim, Hui-Kuo Shu
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Glioblastoma (GBM) is highly aggressive with poor prognosis. Belinostat is a histone deacetylase inhibitor with blood–brain barrier permeability that has anti-GBM activity and may enhance effects of chemoradiation. Our institution conducted a clinical trial evaluating clinical efficacy of belinostat with standard-of-care therapy for GBMs. METHODS 13 and 14 patients were enrolled into cohort 1 (c1, control) or cohort 2 (c2, belinostat) with 12 in each group with sufficient follow-up MRIs for recurrence analysis. All patients received concurrent, adjuvant temozolomide and focal radiation therapy (RT). For c2 patients, the belinostat regimen (500-750mg/m2 1x/day x 5 days) was given over three cycles every 3 weeks (weeks -1, 2, and 5 of RT). RT margins of 5–10 mm and 3 mm were added to generate clinical tumor volumes and planning target volumes (PTVs). PTV1 (based on FLAIR MRI) and PTV2 (based on CE-T1w MRI) received 51 and 60 Gy, respectively, over 30 fractions. Volume at initial recurrence (rGTV) was contoured. RESULTS Mean age was 58.3 years for c1 and 51.1 years for c2. Patient/tumor characteristics were similar between cohorts. Median OS were 16.6 and 18.5 months for c1 and c2 (p=0.538), respectively. Average minimum, maximum and mean radiation dose to rGTV was 54.1 Gy, 64.2 Gy and 62 Gy, for c1, and 47.5 Gy, 57.6 Gy and 53.5 Gy, for c2 (p=0.322, 0.088 and 0.071), respectively. The mean overlap between rGTV and PTV1/PTV2 for c1 &amp; c2 were 99.2% &amp; 96.9%/99.8% &amp; 78.7% (p=0.489/0.133), respectively. CONCLUSION Median OS was slightly longer for c2 though not statistically significant. rGTV in c1 received higher radiation doses and had more overlap with PTV2 than in c2. Out-of-field recurrence appears more likely in c2 suggesting better infield control with belinostat. This study highlights the potential of belinostat as a synergistic therapeutic agent for GBM treatment.
Calcitriol effects on breast cancer tumorgrafts
Authors: Maria Lúcia Hirata Katayama, Victor Celso N. Fonseca-Filho, Eduardo Carneiro Lyra, Durvanei Augusto Maria, Ricardo Alves Basso, Suely Nonogaki, Juliana Mariotti Guerra, simone Maistro, João Carlos Sampaio Goes, Maria Aparecida A. Koike Folgueira
Journal: Cancer Research (2014)
Abstract 12059: The Absolute Risk of Death and Cardiovascular Diseases in Past Smokers With a 10-year Cessation is Identical to the Risk in Never Smokers
Authors: Masaki Ohsawa, Kozo Tanno, Kuniaki Ogasawara, Kazuyoshi Itai, Yuki Yonekura, Toru Kuribayashi, Yoshihiro Morino, Tomonori Itoh, Fumiaki Takahashi, Koichi Asahi, Yasushi Ishigaki, Shinichi Omama, Yasuhiro Ishibashi, Fumitaka Tanaka, Toshiyuki Onoda, Kiyomi Sakata, Makoto Koshiyama, Megumi Tsubota, Akira Okayama
Journal: Circulation (2019)

Introduction: A few studies indicated that long-term smoking cessation contributed to a decreased risk of cardiovascular incidence, however, to what extent of decreases in the absolute risk of deat...
<i>STK11</i>/LKB1 Mutations in NSCLC Are Associated with KEAP1/NRF2-Dependent Radiotherapy Resistance Targetable by Glutaminase Inhibition
Authors: Piyada Sitthideatphaiboon, Ana Galan-Cobo, Marcelo V. Negrao, Xiao Qu, Alissa Poteete, Fahao Zhang, Diane D. Liu, Whitney E. Lewis, Haley N. Kemp, Jeff Lewis, Waree Rinsurongkawong, Uma Giri, J. Jack Lee, Jianjun Zhang, Jack A. Roth, Stephen Swisher, John V. Heymach
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Radiotherapy with or without chemotherapy is a mainstay of treatment for locally advanced non–small cell lung cancer (NSCLC), but no predictive markers are currently available to select patients who will benefit from these therapies. In this study, we investigated the association between alterations in STK11/LKB1, the second most common tumor suppressor in NSCLC, and response to radiotherapy as well as potential therapeutic approaches to improve outcomes. Experimental Design: We conducted a retrospective analysis of 194 patients with stage I–III NSCLC, including 164 stage III patients bearing mutant or wild-type STK11/LKB1 treated with radiotherapy, and assessed locoregional recurrence (LRR), distant metastasis rates, disease-free survival (DFS), and overall survival (OS), and we investigated the causal role of LKB1 in mediating radiotherapy resistance using isogenic pairs of NSCLC cell lines with LKB1 loss or gain. Results: In stage III patients, with 4 years median follow-up, STK11/LKB1 mutations were associated with higher LRR (P = 0.0108), and shorter DFS (HR 2.530, P = 0.0029) and OS (HR 2.198, P = 0.0263). LKB1 loss promoted relative resistance to radiotherapy, which was dependent on the KEAP1/NRF2 pathway for redox homeostasis. Suppression of the KEAP1/NRF2 pathway via KEAP1 expression, or pharmacologic blockade of glutaminase (GLS) 1 sensitized LKB1-deficient tumors to radiotherapy. Conclusions: These data provide evidence that LKB1 loss is associated with LRR and poor clinical outcomes in patients with NSCLC treated with radiotherapy and that targeting the KEAP1/NRF2 pathway or GLS inhibition are potential approaches to radiosensitize LKB1-deficient tumors.
DIPG-43. CAN WE REPROGRAM DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)? EXPLORING THE ROLE OF DISTALLESS/DLX HOMEOBOX GENE REGULATION OF OLIGODENDROGLIAL PROGENITOR CELLS (OPC) IN THE DEVELOPING VERTEBRATE NERVOUS SYSTEM
Authors: Mikaela Nevin, Janine Gallego, Xiaohua Song, Qiang Jiang, Alan Underhill, Roseline Godbout, Oren Becher, David Eisenstat
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The identification of H3.3/H3.1K27M in most DIPG has changed our understanding of this disease. H3K27M mutations usually demonstrate global loss of H3K27 trimethylation (me3) with gain of H3K27 acetylation (ac). Single cell RNAseq has identified the putative cell of origin as oligodendroglial progenitor cells (OPC). The distalless gene family is necessary for the differentiation and tangential migration of committed neural progenitors to become GABAergic interneurons. Dlx1/Dlx2 double knockout (DKO) cells from the ganglionic eminences (GE) transplanted into a wild-type environment become oligodendrocytes. RESULTS We identified DLX2 occupancy of early (Olig2, Nkx2.2) and late (Myt1, Plp1) genes required for OPC differentiation in vivo and confirmed direct DLX2 protein-promoter DNA binding in vitro. Co-expression of Dlx2 with target sequences reduced reporter gene expression in vitro. There was increased expression of OLIG2, NKX2.2 and PLP-1 expression in vivo, consistent with de-repression in the absence of Dlx1/Dlx2 function. Transient over-expression of a Dlx2-GFP construct into murine DIPG cells from a GEMM that develops DIPG resulted in significant increases in expression of Gad isoforms with concomitant decreases in Olig2 and Nkx2.2. Dlx2-transfected mDIPG cells also demonstrated reduced migration, invasion and colony formation in vitro. Of significance, there was global restoration of H3K27me3 with corresponding loss of H3K27ac expression in transfected cells compared to controls. CONCLUSIONS DLX2 promotes GABAergic differentiation and migration while concomitantly repressing OPC differentiation in vivo. Developmental reprogramming of mDIPG cells by DLX2 demonstrates the potential role for directed differentiation strategies towards improving patient outcomes for this devastating pediatric cancer.
Time-Dependent Effects of Oral Contraceptive Use on Breast, Ovarian, and Endometrial Cancers
Authors: Torgny Karlsson, Therese Johansson, Julia Höglund, Weronica E. Ek, Åsa Johansson
Journal: Cancer Research (2021)

Abstract Oral contraceptive use has been suggested to influence the risk of breast, ovarian, and endometrial cancer. The purpose of this study is to clarify the time-dependent effects between long-term oral contraceptive use and cancer risk. We performed an observational study in 256,661 women from UK Biobank, born between 1939 and 1970. Information on cancer diagnoses were collected from self-reported data and from national registers until March 2019. Cumulative risk of cancer over the timespan of the study, as measured by the OR, and instantaneous risk, as measured by the HR, were assessed using Logistic and Cox regression analyses, respectively. The odds were lower among ever users, compared with never users, for ovarian cancer [OR = 0.72; 95% confidence interval (CI), 0.65–0.81] and endometrial cancer (OR = 0.68; 95% CI, 0.62–0.75), an association that was stronger with longer use (P &amp;lt; 0.001). Increased odds were seen for breast cancer in women when limiting the follow-up to 55 years of age (OR = 1.10; 95% CI, 1.03–1.17), but not for the full timespan. We only found a higher HR for breast cancer in former users immediately (≤2 years) after discontinued oral contraceptive use (HR = 1.55; 95% CI, 1.06–2.28), whereas the protective association for ovarian and endometrial cancer remained significant up to 35 years after last use of oral contraceptives. Given the body of evidence presented in our study, we argue that oral contraceptives can dramatically reduce women's risk of ovarian and endometrial cancer, whereas their effect on lifetime risk of breast cancer is limited. Significance: These results enable women and physicians to make more informed decisions considering oral contraceptive use, thus constituting an important step toward personalized medicine.
Celastrol nanoemulsion induces immunogenicity and downregulates PD-L1 to boost abscopal effect in melanoma therapy
Authors: Nasha Qiu, Yun Liu, Qi Liu, Yanzuo Chen, Limei Shen, Mengying Hu, Xuefei Zhou, Youqing Shen, Jianqing Gao, Leaf Huang
Journal: Biomaterials (2020)
Personalizing Radiotherapy Prescription Dose Using Genomic Markers of Radiosensitivity and Normal Tissue Toxicity in NSCLC
Authors: Jacob G. Scott, Geoff Sedor, Jessica A. Scarborough, Michael W. Kattan, Jeffrey Peacock, G. Daniel Grass, Eric A. Mellon, Ram Thapa, Michael Schell, Anthony Waller, Sean Poppen, George Andl, Jamie K. Teer, Steven A. Eschrich, Thomas J. Dilling, William S. Dalton, Louis B. Harrison, Tim Fox, Javier F. Torres-Roca
Journal: Journal of Thoracic Oncology (2020)
ETMR-08. INTERNATIONAL CONSENSUS PROTOCOL FOR EMBRYONAL TUMOR WITH MULTILAYER ROSETTES
Authors: Derek Hanson, Nicolas Andre, Susan Chi, Mariella Filbin, Michael Fisher, Lindsey Hoffman, Ziad Khatib, Marcel Kool, Aru Narendran, Barry Pizer, Irene Slavc, Timothy Vogel, David Ziegler, Mark Kieran
Journal: Neuro-Oncology (2020)

Abstract Embryonal tumors with multilayer rosettes (ETMR) are rare and highly-aggressive central nervous system (CNS) neoplasms which occur primarily in young children and carry a dismal prognosis. To date, no large clinical investigations have been conducted to determine the optimal therapy for ETMR. Data from retrospective case series suggest that our most aggressive standard therapies are not sufficient for cure in the majority of cases. New treatment approaches incorporating pre-clinical data and the known biology of ETMR are therefore urgently needed. A German drug screen using the patient-derived ETMR BT183 cell line and its xenograft revealed anti-tumor activity of topotecan, doxorubicin, and actinomycin D; three agents used infrequently for treating infant CNS tumors. Additional results from a small series of ETMR patients suggest that optimization of induction chemotherapy using these active agents may improve response and survival outcomes. In 2019, an international panel of pediatric neuro-oncology experts convened to advance therapy for ETMR. A consensus protocol was developed incorporating maximal safe surgical resection, induction chemotherapy with active pre-clinical agents, intrathecal chemotherapy, radiotherapy, and high-dose chemotherapy. This international consensus protocol represents the first prospective clinical investigation specific to ETMR and will be available through a treatment registry globally and as a clinical trial at select centers. The study aims to improve survival by providing aggressive, optimized therapy for ETMR and will serve as a platform to explore new biologically-promising agents. The investigation will also provide valuable prospective outcome data and correlative biological studies to serve as baseline comparators for future clinical trials.