Overcoming the challenge of a thin skull in a 2-year-old patient undergoing laser interstitial thermal therapy using an individualized stereotactic platform: illustrative case.

BACKGROUND: Ependymoma is the third most common pediatric brain tumor that can present with headaches, cranial nerve deficits, nausea, vomiting, and ataxia. Current treatment is maximal safe resection followed by radiation therapy. More recently, laser interstitial thermal therapy (LITT) has become an alternative to traditional resection. In this report, the authors describe the utilization of a single-use, patient-specific stereotactic platform for the treatment of supratentorial ependymoma with LITT. OBSERVATIONS: A 2-year-old female had a complex history of supratentorial ependymoma after multiple craniotomies for repeated tumor progression and ventriculoperitoneal shunt placement. Imaging demonstrated an enlarging, complex, enhancing mass in the right occipital region. LITT was decided on for treatment. Given the thinness of the patient's skull, which precluded traditional means of stereotaxy, the authors elected to use a personalized stereotactic platform. Immediate postoperative imaging captured complete laser ablation of the tumor, with long-term imaging demonstrating a decreased tumor size. LESSONS: Individualized stereotactic platforms are increasingly used in adult populations, but pediatric use continues to be infrequent. In this report, the authors present the youngest reported case using a personalized stereotactic platform and show the effectiveness of this system for performing LITT in the youngest of populations with very thin skulls.

TERT Promoter Mutation Analysis for Blood-Based Diagnosis and Monitoring of Gliomas.

PURPOSE: Liquid biopsy offers a minimally invasive tool to diagnose and monitor the heterogeneous molecular landscape of tumors over time and therapy. Detection of TERT promoter mutations (C228T, C250T) in cfDNA has been successful for some systemic cancers but has yet to be demonstrated in gliomas, despite the high prevalence of these mutations in glioma tissue (>60% of all tumors). EXPERIMENTAL DESIGN: Here, we developed a novel digital droplet PCR (ddPCR) assay that incorporates features to improve sensitivity and allows for the simultaneous detection and longitudinal monitoring of two TERT promoter mutations (C228T and C250T) in cfDNA from the plasma of patients with glioma. RESULTS: In baseline performance in tumor tissue, the assay had perfect concordance with an independently performed clinical pathology laboratory assessment of TERT promoter mutations in the same tumor samples [95% confidence interval (CI), 94%-100%]. Extending to matched plasma samples, we detected TERT mutations in both discovery and blinded multi-institution validation cohorts with an overall sensitivity of 62.5% (95% CI, 52%-73%) and a specificity of 90% (95% CI, 80%-96%) compared with the gold-standard tumor tissue-based detection of TERT mutations. Upon longitudinal monitoring in 5 patients, we report that peripheral TERT-mutant allele frequency reflects the clinical course of the disease, with levels decreasing after surgical intervention and therapy and increasing with tumor progression. CONCLUSIONS: Our results demonstrate the feasibility of detecting circulating cfDNA TERT promoter mutations in patients with glioma with clinically relevant sensitivity and specificity.