tbuckley/cabot-search huggingface dataset:
GCT-28. THE IMPACT OF RESIDUAL TUMOR ON THE OUTCOMES OF CENTRAL NERVOUS SYSTEM GERMINOMA
Authors: Lorena V Baroni, Daniel Alderete, Mohamed S Abdelbaki
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The inclusion of chemotherapy in the treatment backbone of central nervous system germinoma has helped reduce the field and dose of radiotherapy. Typically, patients wirh residual disease after chemotherapy are treated with higher doses of radiotherapy, which may not be necessary. Hence, we aimed to assess the impact of residual disease at different points during therapy on the outcomes of germinoma patients. METHODS We performed an extensive review of all germinoma patients diagnosed at Hospital Garrahan in Argentina over the last 20 years. We evaluated the chemotherapy response after 2 cycles and 4 cycles of chemotherapy and after radiotherapy. RESULTS Thirty nine germinoma were included (localized 34; disseminated 5). All patients were treated as per the SIOP-CNS-GCT-96 strategy. At the end of 2 cycles of chemotherapy, 21 patients achieved a complete response (CR), 10 had a partial response (PR), and 8 patients didn’t have MRI evaluation. At the end of 4 chemotherapy cycles, 10 additional patients achieved a CR, 7 still had a PR, while one patient didn’t have MRI evaluation. Only 3 patients had residual tumour after radiotherapy; one had a second-look surgery that didn’t show any evidence of viable tumour. None of the patients with residual tumour at the end of chemotherapy or radiotherapy relapsed with a median follow up of 6.3 years. CONCLUSION Residual tumor at the end of both chemotherapy and radiotherapy does not have an impact on the outcomes. Clinical trials in germinomas may need to investigate administering the same dose of radiotherapy for patients regardless of the presence of residual disease at the end of chemotherapy. Furthermore, patients with no residual disease at the end of two cycles of chemotherapy may benefit from moving directly to radiotherapy without the need to receive two additional cycles of chemotherapy.
MDB-98. HISTOPATHOLOGY IS A ROBUST TOOL TO DIFFERENTIATE BETWEEN SHH AND WNT MEDULLOBLASTOMA VERSUS NON-SHH/NON-WNT MEDULLOBLASTOMA: COMPARATIVE ANALYSIS OF HISTOPATHOLOGY, CHROMOSOMAL MICROARRAY, NANOSTRING BASED 22-GENE ASSAY, AND DNA METHYLATION FOR MEDULLOBLASTOMA SUBGROUP ASSIGNMENT ON “HEAD START” 4 CLINICAL TRIAL
Authors: Mary Elizabeth Littrell, Parth Patel, Megan Blue, Jaclyn Biegel, Isabel Almira-Suarez, Eugene Hwang, Katherine Miller, Diana Thomas, Christopher Pierson, Daniel Boue, Elaine Mardis, Jonathan Finlay, Girish Dhall
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND “Head Start-4” (HS-4) is a prospective, randomized clinic trial that tailors treatment based on medulloblastoma molecular subgroups (WNT, SHH, Group 3, and Group 4) and response to induction chemotherapy, and compares the efficacy of one versus three (tandem) cycles of myeloablative therapy. Here we compare different methodologies used to distinguish between WNT/SHH medulloblastoma (low-risk arm) and non-SHH/non-WNT medulloblastoma (high-risk arm) during the course of the trial. METHODS When HS-4 trial began enrolling patients in 2015, in the absence of a CAP-CLIA certified test for methylation and gene expression profile, we utilized histopathology/immunochemistry (HP/IHC) and chromosomal microarray (CMA) via OncoScanTM (Thermo Fisher) to classify medulloblastoma samples into either WNT, SHH, or non-WNT/non-SHH (Subgroups 3 and 4) at the time of diagnosis. Retrospectively, we performed both NanoString based 22-gene assay and DNA methylation profiling on all patient samples. RESULTS We have HP/IHC, CMA, NanoString and methylation profiling for 54 infants and young children with medulloblastoma enrolled on HS-4. While indeterminate result occurred with CMA in three cases and NanoString in two cases, HP/IHC successfully assigned samples to SHH/WNT and non-SHH/non-WNT arms of the study in all 54 cases. We have HP/IHC, CMA and DNA methylation profiling for additional 33 patients. While pathology/IHC was indeterminate in two cases (one WNT and one group 3 MB), remaining cases accurately categorized medulloblastoma methylation subtype as WNT/SHH and non-WNT/non-SHH. CONCLUSION Due to the long turnaround time, waiting for medulloblastoma molecular subtype confirmation by DNA methylation array may delay treatment initiation. HS-4 data displays robust prediction of WNT/SHH versus non-WNT/non-SHH molecular subtypes by HP/IHC in comparison to DNA methylation profiling and provides a platform to initiate treatment based on HP/IHC while awaiting molecular information. In addition, these data support relying on histopathology for medulloblastoma subtypes in resource poor countries where methylation profiling is not readily available.
HGG-35. SIGNIFICANT RESPONSE TO LAROTRECTINIB AS FIRST LINE THERAPY IN INFANT WITH INFANT-TYPE HEMISPHERIC GLIOMA
Authors: Abbey Rocco, Nicole M Brossier, Margaret Shatara, Mohamed Abdelbaki, Jennifer Strahle, Andrew S Cluster
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Infant-type hemispheric gliomas represent a recent WHO classification of high grade pediatric brain tumors that are often characterized by NTRK, ROS1, MET or ALK fusions. Novel agents may target their driver mutations but are not yet considered front line therapy. METHODS Patient data was reviewed retrospectively through chart review. RESULTS A 7 day old male infant who presented with vomiting, shaking and a full fontanelle was found to have a 8.7 x 7.2 x 9.3 cm solid and cystic mass with internal hemorrhage in the right parietal and occipital lobes associated with significant mass effect and midline shift. He underwent VP shunt placement and tumor biopsy, but later developed seizures and declining mental status. Cyst decompression was used as stabilizing measure. Due to his very small size and tenuous clinical status full tumor resection was not feasible at that time. Pathology revealed an infant-type hemispheric glioma with ETV6-NTRK3 fusion. Although cytogenetic testing for NTRK alterations was negative, the fusion was confirmed by NGS. Given his age and the risks for electrolyte imbalances and cytopenias in a patient with recent hemorrhage, we elected to treat with Larotrectinib instead of traditional cytotoxic chemotherapy. He had notable disease response within 8 weeks and remains on drug 18 months later with continued response. His tumor now measures 2 x 1.5 x 1.6 cm. He has had one grade 3 toxicity with neutropenia, which was likely impacted by viral bone marrow suppression. He is currently meeting most developmental milestones but does have orthotics and sees speech therapy. CONCLUSIONS Targeted agents may represent a viable front line therapy to decrease tumor mass and temporize very young patients until they can undergo definitive resection and therapy. Future clinical trials will need to compare efficacy to current standards of care.
PATH-13. LEARNED RESIZING WITH EFFICIENT TRAINING (LRET) FACILITATES IMPROVED PERFORMANCE OF LARGE-SCALE BRAIN TUMOR HISTOLOGY IMAGE CLASSIFICATION MODELS
Authors: Brent A Orr, Zahangir Alom, Quyhn T Tran
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Histologic examination is vital in oncology research and diagnostics. The adoption of digital scanning of whole slide images (WSI) has created an opportunity to leverage deep learning-based image classification methods to enhance diagnosis and risk stratification. However, technical limitations prevent training and deployment of accurate comprehensive multiclass deep convolutional neural networks (DCNN) models for histopathology image classification. The input dimensions of DCNN architectures are small compared to the typical pathologist field of view, degrading performance by excluding important architectural features. Furthermore, data requirements for comprehensive models are sufficiently large to overwhelm the system memory during training. METHODS A method termed Learned Resizing with Efficient Training (LRET) was developed to address the main limitations of traditional histopathology classification model training. The LRET method couples efficient training techniques with image resizing to facilitate seamless integration of larger histology image patches into state-of-the-art classification models while preserving important structural information. The LRET method was coupled with two distinct resizing techniques to train three diverse histology image datasets using five different DCNN architectures. Performance metrics were compared on cross validation and hold out test sets. RESULTS LRET-trained models were flexible to multiple input patch dimensions and DCNN models. We demonstrated performance improvement across all datasets while significantly reducing the training time and resources over traditional methods. Using a large-scale, multiclass brain tumor classification dataset consisting of 74 distinct histopathologic classes, LRET-trained models outperformed existing methods by 15-28% in accuracy, yielding 94% accuracy for the best model. CONCLUSION The LRET method for DCNN training significantly enhances the performance of large-scale multiclass histopathology image classification. The implications of this work extend to broader applications within medical imaging and beyond, where efficient integration of high-resolution images into deep learning pipelines is paramount for driving advancements research and clinical practice.
LMIC-04. BUILDING PEDIATRIC NEURO-ONCOLOGY CAPACITY IN LMICS THROUGH MULTIDISCIPLINARY EDUCATION AND COLLABORATION
Authors: Daniel Moreira, Allyson Andujar, Ibrahim Qaddoumi
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The St. Jude Global Academy Neuro-Oncology Training Seminar (NOTS) is a course in pediatric neuro-oncology (PNO) designed for physicians from low-income and middle-income countries. The curriculum was systematically designed and includes 9 weeks of online learning and a 5-day in-person workshop. The NOTS has been run 3 times: 2019, 2022, and 2023. We sought to evaluate the outcomes of these courses. METHODS After the initial course where institutions were invited, applying institutions were selected based on the size of the neuro-oncology program, multidisciplinary representation, and perceived impact of the course. Data on course participants have been prospectively collected. A survey evaluating course impact was completed by graduates. RESULTS For 2022, 51 institutions from 29 countries applied and 15 were selected. In 2023, 60 institutions from 31 countries applied and 18 were selected. Overall, 41 institutions from 29 countries have participated in NOTS. Furthermore, 191 individuals, including 68 pediatric oncologists, 37 neurosurgeons, 22 radiation oncologists, 19 radiologists, 18 pathologists, and 27 other specialists have participated. Survey responses (n=39) describe that 47% did not have multidisciplinary tumor boards (MDTB) before NOTS. 55% of those institutions now have MDTB, all claiming to be influenced by their participation in NOTS. 89% of participants claim that multidisciplinary communication improved after the course. The participants of NOTS have continued to be engaged beyond the course through the creation of the Global Alliance in Pediatric Neuro-Oncology (GAPNO). GAPNO workstreams have included monthly cases discussions, a multisite retrospective review of medulloblastoma outcomes collecting &amp;gt;300 patients in 8 countries, and the design of a comprehensive tool to evaluate PNO services. CONCLUSIONS A multidisciplinary course focused on pediatric CNS tumors care for resource-limited settings can help expand international engagement in PNO. Furthermore, through multidisciplinary collaboration, the PNO community can be galvanized to expand activities in capacity building.
Treatment of osteoarthritis by implantation of Mg- and WE43-cylinders - A preclinical study on bone and cartilage changes and their influence on pain sensation in rabbits
Authors: Nina Angrisani, Christin von der Ahe, Regine Willumeit-Römer, Henning Windhagen, Verena Scheper, Michael Schwarze, Björn Wiese, Heike Helmholz, Janin Reifenrath
Journal: Bioactive Materials (2024)
LGG-39. REAL-LIFE STUDY OF THE EFFICACY AND TOLERANCE OF TRAMETINIB IN THE TREATMENT OF LOW-GRADE GLIOMAS IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1
Authors: Amandine BIBOLLET, Celine KHOURI, Samuel ABBOU, Cécile FAURE-CONTER, Mona AMINI-ADLE, Sophie DARNIS, Michael PHILIPPE, Florent NEUMANN, Pierre LEBLOND
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Low grade gliomas (LGG) are the most common brain tumors in children. Targeted therapies such as the MEK-inhibitor trametinib have revolutionized the management of pediatric LGGs. NF1 mutations generate misregulations in the RAS/MAP kinase pathway, but data on trametinib in type 1 neurofibromatosis (NF1)-related LGG are scarce. Efficacy and safety of trametinib in NF1 patients with LGG need to be further investigated. METHODS This retrospective study included patients with NF1 &amp;lt;18 years from two French centers having received trametinib for a relapsing/progressive LGG between March 2020 and July 2022. Treatment efficacy was assessed according to RAPNO criteria, and toxicities and therapeutic exposure were assessed using real-life data collected retrospectively up to July 2023. RESULTS The study enrolled 11 patients, the median age at LGG diagnosis was 3 (1-9) years. All patients previously received a median number of 2 (1-4) lines of chemotherapy. Median age at treatment initiation was 9 (4-13) years. Median duration of trametinib treatment was 9.3 (5.8-24) months. Progression-free survival was 91% at 6 months and 61% at 2 years. Median time to best response was 2.7 (1.1-9) months, including 5 stable diseases, 4 minor responses, and 2 partial responses. Median duration of response was 8.6 (3.7-36.2) months. Adverse events (AEs) occurred in all patients, and 64% of the patient had grade 3 AEs. Skin toxicities and paronychia were the most frequent AEs. Treatment interruption occurred in 55% of the patients, and 3 patients permanently discontinued trametinib due to treatment-related toxicities. Real therapeutic exposure was significantly shorter than theoretically expected (19.6% treatment reduction). CONCLUSION Trametinib showed promising efficacy in NF1 children with relapsing/progressive LGG. Trametinib toxicity remains challenging. Further prospective clinical trials stratified according to molecular alterations are needed to support these preliminary results.
LMIC-01. SURVIVAL AND PROGNOSTIC FACTORS IN CHILDHOOD MEDULLOBLASTOMA SINGLE TERTIARY CENTER EXPERIENCE FROM KING FAHAD MEDICAL CITY KFMC SAUDI ARABIA
Authors: Nahla Aly Mobarak, Ali Abdullah O Balbaid, Fahad Alotabi, Ayman Al Banyan, Abdulelah A Alluhaybi, Maqsood Ahmad, Amal S AlYahya, Basma Mahmoud AlYamany, Wafa Al Shakweer, Malak Abedalthagafi, Sadeq Al-Dandan, Wael Aljabarat, Zaid G AlNaqib, Mohammed Rayis, Musa Alharbi
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Medulloblastoma (MB) is the most common childhood malignant brain tumor treated with intensive multimodalities therapy including Surgery, Craniospinal Radiation, and chemotherapy. Our study aims to document the clinical courses, prognostic factors, and survival outcomes in Saudi children above three years with Medulloblastoma treated in King Fahad Medical City KFMC. METHODS Retrospective analysis of MB patients diagnosed between January 2009 to January 2022 All patients received Risk-adapted Radiation therapy followed by maintenance chemotherapy,3 patients progressed and died after surgery and were excluded from analysis. RESULTS We identified 145 MB patients 65.5 % were male. median age at Diagnosis 7.00 years (range3-14 years), Age less than 5 years did not have a worse outcome in our cohort. Classic histology was predominant (80%), 42.1% of patients had metastatic disease at presentation; the Median time to start radiation therapy after surgery was 35 days. 51.7% were treated as High-Risk HR MB and Average Risk AR MB 48.3%. 65 cases having molecular testing for MB molecular subgroups. 6 patients 4.1% developed a second malignancy with a median time of 6 years post diagnosis. Multivariate survival analysis showed that progression-free survival was significantly reduced by the extent of surgical resection (P=0.021) and Metastatic MB at diagnosis(P=0.014). At Median follow-up of 7 years, Progression-free survival PFS and overall survival OS for the whole cohort were 72.4% and 71.7% respectively. PFS for AR MB and HR MB was 81.4% and 64.0% respectively. PFS analysis based on molecular subgroup: WNT subgroup 92.3%, SHH 69.2%, Group 4:57.7%:and group 3: 46.2%. CONCLUSIONS Our study is the largest analysis of childhood MB treatment outcomes in Saudi Arabia Defining the poor prognostic factor for these patients and will form the baseline for future pediatric Neuro-Oncology studies in KFMC, which may help to improve the outcome of childhood MB in Saudi Arabia.
Chitosan/PLGA-based tissue engineered nerve grafts with SKP-SC-EVs enhance sciatic nerve regeneration in dogs through miR-30b-5p-mediated regulation of axon growth
Authors: Miaomei Yu, Mi Shen, Daiyue Chen, Yan Li, Qiang Zhou, Chunyan Deng, Xinyang Zhou, Qi Zhang, Qianru He, Hongkui Wang, Meng Cong, Haiyan Shi, Xiaosong Gu, Songlin Zhou, Fei Ding
Journal: Bioactive Materials (2024)
IMG-14. DIAGNOSTIC UTILITY OF THE T2-FLAIR MISMATCH SIGN FOR DNETS AND ITS ASSOCIATION WITH FGFR1 ALTERATIONS
Authors: Charles A Wheeler, Jia Liang, Yimei Li, Jason Chiang, Asim K Bag
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The T2-FLAIR mismatch sign, hyperintense T2-weighted signals with corresponding hypointensity on FLAIR sequence, has emerged as a potential diagnostic tool for identifying specific brain tumor subtypes. We tested the diagnostic utility of the sign in dysembryoplastic neuroepithelial tumors (DNETs) with and without FGFR1 alterations. METHODS We evaluated the T2-FLAIR mismatch sign in a cohort of 43 patients with definitive or probable DNET. Low-grade glioma patients with definite non-DNET diagnoses were chosen as control (n=43). Receiver operative curve analysis was performed, and the corresponding odds ratios were calculated. RESULTS Of the 43 DNET cases, 35 were definite, and 8 were probable DNETs. FGFR1 alterations were confirmed in 9 definitive DNETs. The area under the curve (AUC) for diagnosing DNET with the T2-FLAIR mismatch sign was 0.884 (DeLong CI: 0.2, 0.95) (Accuracy: 0.88, 95% CI: 0.80, 0.94; Sensitivity: 0.84; Specificity: 0.95); for definite DNET it was 0.891 (DeLong CI: 0.82, 0.96) (Accuracy: 0.90, 95% CI: 0.81, 0.95; Sensitivity: 0.87; Specificity: 0.94); for probable DNET it was 0.852 (DeLong CI: 0.69, 1;) (Accuracy 0.92, 95% CI: 0.81, 0.98; Sensitivity: 0.84; Specificity: 0.75), and for DNET with FGFR1 alterations was 0.977 (DeLong CI: 0.95, 1) (Accuracy 0.96, 95% CI: 0.87, 1; Sensitivity: 1; Specificity: 0.81). The odds of having DNET (definite +probable) if the T2-FLAIR mismatch sign was positive was 81.96 (CI: 16.25, 852.48, P&amp;lt;0.001), and DNET with FGFR1 is 315.4 (CI: 312.3, 318.5, P&amp;lt;0.001). CONCLUSION The T2-FLAIR mismatch sign is a reliable radiological biomarker for DNET and strongly predicts FGFR1 alterations in these tumors.
MDB-105. CONSTRUCTION OF AN INTERACTIVE MEDULLOBLASTOMA VISUALIZATION PORTAL FROM MOLECULAR AND CLINICAL DATA DERIVED FROM THREE MULTI-INSTITUTIONAL PROTOCOLS (ACNS0331, SJMB03, ACNS0332) TO COMPARE, CONTRAST, AND INVESTIGATE COHORTS AS A MEANS TO REFINE THERAPY
Authors: Giles W Robinson, Sandeep K Dhanda, Congyu Lu, Edgar Sioson, Karishma Gangwani, Airen Zaldivar Peraza, Qian Li, Kyle S Smith, Catherine Billups, Arzu Onar-Thomas, Paul A Northcott, Xin Zhou
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Medulloblastoma (MB) patients display a heterogeneous mix of molecular and clinical characteristics that influence tumor behavior and survival. We hypothesized that if these multiple characteristics could be incorporated into an organized, searchable, and interactive dataset, this would advance our understanding and improve treatment of this disease. Consequently, we organized multifaceted datasets into an interactive portal equipped with cutting-edge visualization tools. METHODS Clinical and molecular data from the ACNS0331, SJMB03, and ACNS0332 protocols were collated and harmonized. A data dictionary was built to capture demographics, treatment, histology, methylation classification, mutations, chromosomal copy number variations and outcomes. To display the data, a software framework was applied. Five visualization methods were implemented (summary plots, sample view, scatter plots, sample matrix, and survival plots) in an interconnected manner such that these “cross-talk” with each other. RESULTS Data from 898 patients with MB were incorporated: 131 WNT, 151 SHH, 220 G3, 396 G4. The portal features enabled the creation of custom cohorts that could be instantly queried by any of the dictionary terms. For example, cohorts could be customized to include only cases with a mutation of the user’s choice and analyzed by molecular group, gender, age at diagnosis, or treatment given. Survival of patients with SHH-MB harboring TP53 mutations could be compared to patients with WNT-MB harboring TP53 mutations. Moreover, the influence of MB subtype (e.g. G34_I-VIII), focal amplifications (MYC, MYCN) and whole chromosome aberration phenotype on survival could be queried across treatment regimens accounting for metastatic status and/or additional variables of the user’s choice. CONCLUSION The integration of molecular and clinical data from multiple trials into an interactive visualization data portal presents an unprecedented resource for research and clinical practice. This portal facilitates answering highly specific questions about mutational frequency and patient outcome by molecular and clinical risk factors.