ArticleNeuro-oncology advances
Challenges in diagnostics and treatment of infant-type hemispheric gliomas.
Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Infant-type hemispheric gliomas (IHG) represent a novel entity, first codified in the WHO CNS 5 classification. Due to their rarity, as well as their neuroimaging and histopathologic heterogeneity, definitive diagnosis can be challenging. In the majority of cases, the tumors are large, and difficult to fully resect. The efficacy of standard cytotoxic chemotherapy remains unclear. IHGs frequently contain receptor tyrosine-kinase (RTK) gene fusions, denoting a potential vulnerability to targeted therapy by small-molecule RTK inhibitors. Methods: We report 15 patients with IHG receiving treatment during a 5-year period. Integrated diagnosis was achieved combining histopathology, DNA methylation profiling and RNA sequencing. Ten out of 15 patients received chemotherapy. Targeted therapy with entrectinib or lorlatinib was prescribed in 5 patients after progression and in 1 as first-line treatment. Results: The median follow-up was 1.5 years (range, 0.1-5.1 years). Six patients were asymptomatic despite large volumes and diagnosed during routine ultrasound screening. Neuroimaging revealed 2 general radiographic presentation, either cystic-solid or purely solid masses. These radiologic subtypes were not associated with differences in histology or clinical behavior, but demonstrated differential gene expression profiles. Standard cytotoxic chemotherapy was administered in 10 patients, in 6 of them disease progression was observed (all with residual tumor). RTK gene fusions were revealed in all cases. Six patients were treated with targeted therapies. All patients had an initial tumor response; following which 2 had disease progression. One-year event-free survival for the entire cohort was 47% (CI 27%-80%), 2-year overall survival was 61% (CI 39%-95%). Conclusions: IHGs are comprised of 2 radiologically and molecularly distinct groups. Huge cystic tumors are frequently associated with life-threating complications. The limited efficacy of the standard cytotoxic chemotherapy and presence of kinase fusion in nearly all cases render patients with IHG candidates for targeted therapies.
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