Plasma ctDNA Monitoring of a PTCH1-Mutant Metastatic Adult Medulloblastoma Showing a Durable Benefit With Vismodegib

Adult medulloblastoma (MB) is a rare disease affecting 0.6 persons per million adults over 19 years of age. The SHH-activated/TP53-wild type is the most common subtype, accounting for 60% of adult MBs, being characterized by mutations in PTCH1, SMO, or the TERT promoter. Several small studies demons...

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Published in:The oncologist (Dayton, Ohio) Ohio), 2024-05, Vol.29 (5), p.377-383
Main Authors: Cabezas-Camarero, Santiago, Garcia-Barberan, Vanesa, Perez-Alfayate, Rebeca, del Pulgar, Maria Elena Gomez, Cabrera-Martin, Maria Nieves, Casado-Farinas, Isabel, Perez-Segura, Pedro
Format: Article
Language:English
Subjects:
Adult
Anilides - therapeutic use
Cerebellar Neoplasms - blood
Cerebellar Neoplasms - drug therapy
Cerebellar Neoplasms - genetics
Cerebellar Neoplasms - pathology
Circulating Tumor DNA - blood
Circulating Tumor DNA - genetics
Dosage and administration
Drug therapy
Female
Gene mutations
Genetic aspects
Health aspects
Humans
Identification and classification
Male
Medulloblastoma
Medulloblastoma - blood
Medulloblastoma - drug therapy
Medulloblastoma - genetics
Medulloblastoma - pathology
Mutation
Patched-1 Receptor - genetics
Patient outcomes
Pyridines - therapeutic use
Vismodegib
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Summary:Adult medulloblastoma (MB) is a rare disease affecting 0.6 persons per million adults over 19 years of age. The SHH-activated/TP53-wild type is the most common subtype, accounting for 60% of adult MBs, being characterized by mutations in PTCH1, SMO, or the TERT promoter. Several small studies demonstrate objective but short-lived responses to SMO inhibitors such as vismodegib or sonidegib. Like other oncogene-addicted solid tumors, detection of the corresponding drivers through liquid biopsy could aid in the molecular diagnosis and monitoring of the disease through less invasive procedures. However, most studies have only evaluated cerebrospinal fluid as the ctDNA reservoir, and very limited evidence exists on the role of liquid biopsy in plasma in patients with primary central nervous system tumors, including MB. We present the case of a 26-year-old patient with a recurrent MB, in which next-generation sequencing (FoundationOne CDx) revealed a mutation in PTCH1, allowing the patient to be treated with vismodegib in second line, resulting in a durable benefit lasting for 1 year. Using an in-house digital PCR probe, the PTCH1 mutation could be tracked in ctDNA during treatment with first-line chemotherapy and while on treatment with vismodegib, demonstrating a precise correlation with the radiological and clinical behavior of the disease.
ISSN:1083-7159
1549-490X
DOI:10.1093/oncolo/oyae026