Introduction: Diffuse intrinsic pontine glioma (DIPG) are highly aggressive brain tumors with limited treatment options and dismal outcome. Brainstem biopsy to enable molecular characterization of the tumor is currently controversial due to unclear benefits. The INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) registry offers platform for comprehensive molecular profiling of DIPG biopsies to identify alterations as target for potential precise therapy approaches.
Methods: We aimed to assess feasibility for applying comprehensive next generation sequencing and high density array technologies on stereotactic biopsies and to perform a risk-benefit assessment on 19 newly diagnosed DIPG patients undergoing a brainstem biopsy from 10 German pediatric oncology centers registered in the INFORM registry within the last 2 years. Clinical data were acquired. For all tumors samples, molecular profiling was performed based on whole-genome, whole-exome sequencing and DNA methylation analysis complemented with RNA sequencing in some cases.
Results: The majority of patients (17/19) presented with neurological deficits at diagnosis. 7/19 patients suffered from newly arisen or worsening of preexisting neurological deficits. Symptoms were reversible in 4 cases and permanent in one. Tumor material obtained was sufficient for molecular analysis including next-generation sequencing and genome-wide DNA methylation analysis in all cases. RNA analysis (RNA-Seq and/or microarray based gene expression profiling) could be performed for 18/19 tumor samples. In 18/19 patients, potential targetable alterations could be identified, 7 cases harbored well known genetic alterations (like e.g. PDGFRA or FGFR alterations, NTRK or MET fusion) which were described to be promising targets for targeted therapy approaches.
Conclusions: This study illustrated that brainstem biopsy in patients with DIPG might be associated with postoperative complications, however, new deficits were reversible in all but one case. On the other hand, relevant molecular characteristics of the tumors could be obtained thereby providing a basis for potential individualized treatment options in about a third of cases.
Patient Care: Through discovering new targeted chemotherapy for management of diffuse intrinsic pontine glioma
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of stereotactic biopsy in cases of DIPG. 2) Discuss, in small groups, technique of stereotactic biopsy in brainstem lesions. 3) Identif new targets for treating DIPG.