Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance

PURPOSE: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS: A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P \u3c .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P \u3c .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION: Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD

The Brain Tumor Segmentation (BraTS) Challenge 2023: Focus on Pediatrics (CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs)

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20\%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a landmark community benchmark event with a successful history of 12 years of resource creation for the segmentation and analysis of adult glioma. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which represents the first BraTS challenge focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on benchmarking the development of volumentric segmentation algorithms for pediatric brain glioma through standardized quantitative performance evaluation metrics utilized across the BraTS 2023 cluster of challenges. Models gaining knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training data will be evaluated on separate validation and unseen test mpMRI dataof high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors

Liquid Biopsy for Pediatric Central Nervous System Tumors.

Abstract Central nervous system (CNS) tumors are the most common solid tumors in children, and the leading cause of cancer-related death. Over the past decade, molecular profiling has been incorporated into treatment for pediatric CNS tumors, allowing for a more personalized approach to therapy. Through the identification of tumor-specific changes, it is now possible to diagnose, assign a prognostic subgroup, and develop targeted chemotherapeutic treatment plans for many cancer types. The successful incorporation of informative liquid biopsies, where the liquid biome is interrogated for tumor-associated molecular clues, has the potential to greatly complement the precision-based approach to treatment, and ultimately, to improve clinical outcomes for children with CNS tumors. In this article, the current application of liquid biopsy in cancer therapy will be reviewed, as will its potential for the diagnosis and therapeutic monitoring of pediatric CNS tumors

MEK Inhibitor Treatment Promotes Retinal Ganglion Cell Preservation without Preventing Retrobulbar Demyelination in Neurofibromatosis Mice

To better understand the disparity frequently seen between optic pathway glioma (OPG) characteristics and visual loss among young children with neurofibromatosis type 1 (NF1), we extend our previous findings of anatomic, physiologic, and behavioral abnormalities in an established animal model. We now report differential effects of treatment targeting the MAPK/ERK cellular pathway: 1) preserving retinal ganglion cell (RGC) number, and yet 2) failing to ameliorate demyelination of the retrobulbar optic nerve

MEK Inhibitor Treatment Promotes Retinal Ganglion Cell Preservation without Preventing Retrobulbar Demyelination in Neurofibromatosis Mice

To better understand the disparity frequently seen between optic pathway glioma (OPG) characteristics and visual loss among young children with neurofibromatosis type 1 (NF1), we extend our previous findings of anatomic, physiologic, and behavioral abnormalities in an established animal model. We now report differential effects of treatment targeting the MAPK/ERK cellular pathway: 1) preserving retinal ganglion cell (RGC) number, and yet 2) failing to ameliorate demyelination of the retrobulbar optic nerve

MEK Inhibitor Treatment Promotes Retinal Ganglion Cell Preservation without Preventing Retrobulbar Demyelination in Neurofibromatosis Mice

To better understand the disparity frequently seen between optic pathway glioma (OPG) characteristics and visual loss among young children with neurofibromatosis type 1 (NF1), we extend our previous findings of anatomic, physiologic, and behavioral abnormalities in an established animal model. We now report differential effects of treatment targeting the MAPK/ERK cellular pathway: 1) preserving retinal ganglion cell (RGC) number, and yet 2) failing to ameliorate demyelination of the retrobulbar optic nerve