The purpose of this study is to create a biobank for patients diagnosed with Sonic Hedgehog Medulloblastoma at Baylor College of Medicine/Texas Children's Cancer Center. A biobank is a facility that stores and manages biological samples (such as blood, tissue, or DNA) from individuals, along with detailed health information, for use in medical research to study diseases and develop new treatments. The investigators are requesting participants' permission to add their information and samples to this biobank.
Being in this research study is voluntary; it is the participant's choice. If the participant joins this study, they can still stop at any time.
If the participant decides to participate, the investigators will review the participant's clinical medical records, demographics, treatment history, family history, and imaging. The investigators will also collect biological samples from the participant and the biological parents' buccal swabs (optional).
The participation in this biobank will last about 5 years from the decision to participate.
Why am I being asked to participate? The participant or their child is invited to participate in this study if the participant or their tumor may have a U1 mutation. U1 mutation is associated with an error in the gene that splices the tumor DNA, leading to random splicing that may increase the tumor mutation burden and generate novel tumor neoantigens (targets). Studying the U1 mutation will enable the investigator to design more effective therapies and guide future treatments for patients with relapsed or refractory sonic hedgehog medulloblastoma, thereby improving their outcomes and quality of life. Moreover, the investigators aim to determine whether germline mutations inherited from parents may increase the risk of medulloblastoma in their offspring. The participant will receive no direct benefit from their participation in this study. However, participation in this study may help the investigators better understand SHH Medulloblastomas and benefit other patients in the future.
Age Patients must be ≥ 3 and ≤ 50 years of age at the time of initial diagnosis.
Diagnosis Participants must have a diagnosis of SHH medulloblastoma by histologic or molecular criteria at the time of original diagnosis or relapse.
Disease status The disease must be recurrent, refractory, or progressive following therapy, including radiotherapy and chemotherapy.
Available tumor tissue sample for U1 testing Participants must have available tumor tissue samples to be tested for the U1 mutation.
None
Group 1 - Patients diagnosed/treated at Texas Children's Hospital (TCH) or one of the participating registry institutions. Group 2 - Patients diagnosed at non-registry institutions (an institution not participating in the registry as a site with IRB approval with BCM/TCH as the coordinating center). Group 3 - Biological parents of patients in Group 1 or 2.
Cohort
Other
Not listed
To describe the incidence of the U1 mutation in SHH medulloblastoma subtypes and verify the feasibility of U1 testing. The primary outcome will be detecting the U1 mutation by polymerase chain reaction (PCR) testing or RNA sequencing (RNAseq).
U1 mutation status, as determined by PCR, will be summarized in the overall sample and within each SHH medulloblastoma subtype with counts and percentages, along with the corresponding 95% confidence intervals. Feasibility Sensitivity, specificity, PPV, NPV, and accuracy of the new RNASeq diagnostic test will be estimated, utilizing PCR as the reference standard. Only complete cases will be utilized in the following estimations. Sensitivity will be estimated as the proportion of true positives out of all positive PCR tests while specificity will be estimated as the proportion of true negatives. Positive predictive value will be estimated as the proportion of true positives out of all positive RNASeq tests. NPV will be estimated as the proportion of true negatives out of all negative RNASeq tests. Finally, accuracy will be estimated as the proportion of true positives and true negatives out of all tests completed.
To collect and compare the outcomes of the different treatment regimens utilized for pediatric and adult patients with recurrent, refractory, or progressive SHH medulloblastoma with and without U1 mutation.
Overall survival (OS) and event-free survival (EFS) will be summarized descriptively by U1 mutation status and SHH MB subtype. Both OS and EFS will utilize the Kaplan-Meier method to estimate counts, time-specific rates, corresponding 95% confidence intervals, and survival curves. Early withdrawals and those remaining alive and event-free at the end of the study will be censored at the time of last know status. No interim analyses are planned, as this is an observational study not designed for hypothesis testing. Given that this is an observational cohort study, patient safety with respect to adverse events, will not be assessed.
To facilitate somatic and germline tissue testing to understand the unique biology of these rare tumors.
Whenever available, tumor tissue will be requested pre- and post-treatment with or without immune checkpoint inhibition to uncover alterations in tumor biology secondary to treatment. Correlative studies performed on tissue will include the following: Methylation Profiling Intron detection via whole genome sequencing Whole genome sequencing RNA sequencing Spatial genomics \& transcriptomics Proteomics Patient derived xenografts (PDX) and cell lines generation Tissue banking Biological parental buccal swabs for whole genome sequencing
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Mohammad H. Abu Arja
Lead sponsor
Baylor College of Medicine
Sponsor institution
Baylor College of Medicine
Collaborator
M.D. Anderson Cancer Center
Collaborator
