Pathology and Molecular Analysis of Vestibular Schwannomas that Progress after Gamma Knife Radiosurgery: A Single-Institution Retrospective Study

The rate of vestibular schwannomas that fail stereotactic radiosurgery is low (< 5%). Potential reasons include insufficient doses for specific tumors, but likely also differences in tumor biology. Characterizing the genetic alterations of these tumors is important to understanding the underlying mechanisms of failure. The Genome Profiling of Actionable Cancer Targets (PACT) test, which is an FDA-approved assay of mutations in 607 genes linked to the development of cancer, has been applied broadly to all solid tumors resected at our institution since 2021. We reviewed our registry of patients with vestibular schwannomas who underwent SRS between 2010 and 2022. Of 630 patients screened, 23 patients (mean age: 57.8 years, 9:14 male:female ratio) were identified as requiring surgery after SRS. Data was collected from a retrospective chart review. The median tumor volume was 1.65 cc, and the median margin dose was 12.5 Gy. The median time interval between SRS and the time of resection was 48.7 months. Translabyrinthine was the most common surgical approach taken in surgical resection. The pathology report from five cases commented on an abundance of inflammatory cells and six cases of nuclear atypia. The median Ki-67 index was 4% (range: 1–8%, N = 13). Eleven genome PACT analyses were available. NF2 mutations were always detected with mutational frequency ranging from 7 to 51%. Mutations in MHL1 (mismatch repair), RPTOR (RAS pathway), ERBB3 (EGFR), and MPL were identified in select cases. Finally, five samples were analyzed for genetic fusions, and none were detected. The next step is to complete the genome PACT analysis for the rest of the cohort and conduct a comparison analysis of samples of vestibular schwannomas that had a good response to stereotactic radiosurgery.

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Artikel online veröffentlicht:
07. Februar 2025