Retrospective Analysis of Radiotherapy with or Without Concurrent and Adjuvant Temozolomide in Newly Diagnosed Paediatric Diffuse Intrinsic Pontine Glioma

Abstract

Intracranial germ cell tumors (IGCTs) are rare tumors of the central nervous system with peak incidence around puberty. Due to the developmental origins of IGCTs, we investigated the prevalence of neurodevelopmental disorders, including autism spectrum disorder (ASD), in our retrospective institutional cohort of patients diagnosed with IGCTs. Materials/Methods: A retrospective review of medical records was conducted for 92 patients who were diagnosed with IGCTs and treated at a single institution between 1998 and 2016. The hospital's Institutional Review Board approved this study. All patients with ASD had thorough neuropsychological assessment at the time of radiation treatment that confirmed their diagnoses. Results: Median age at diagnosis was 14.4 years (4.3-20.9) and 12.0 years (5.3-21.7) for patients diagnosed with pure germinomas and nongerminomatous germ cell tumors (NGGCTs), respectively. Median followup time from diagnosis was 5.5 years (0.4-15.8) and 4.5 years (0.7-12.2) for the pure germinoma and NGGCT cohorts, respectively. Fourteen patients with IGCTs were diagnosed with NDDs prior to their cancer diagnoses: one patient with sensory processing disorder, three patients with chromosomal abnormalities, including one patient with Down syndrome, three patients with autism spectrum disorder (ASD), including one patient who had both ASD and attention deficit hyperactivity disorder (ADHD), and seven additional patients with ADHD. Interestingly, the patients with ASD all developed pure germinomas, giving an ASD prevalence rate of 5.6% and 0% in the pure germinoma and NGGCT cohorts, respectively. All other patients had no known diagnoses of NDDs, and met developmental milestones or had minor delays in developmental milestones that did not meet criteria for NDD diagnoses. Conclusion: Our study found fourteen patients with IGCTs were diagnosed with NDDs prior to their cancer diagnoses. Three of these patients had ASD diagnoses, and all three patients developed pure germinomas. An ASD prevalence of 5.6% in the pure germinoma cohort is more than threefold greater than the national prevalence, suggesting there may be an association between ASD and pure germinomas. Future prospective studies with larger cohorts are still needed to examine associations between NDDs and ASD and IGCTs.

Developing H3K27M mutant selective radiosensitization strategies in diffuse intrinsic pontine glioma

“…This mark is a key predictor for benefit from the alkylating chemotherapeutic agent temozolomide (TMZ) in adult glioma. It is therefore not surprising that compared to RT alone, combined treatment with TMZ and RT affords limited survival benefit in patients with DIPG [16] . Targeting the DNA damage response instead of directly damaging DNA, however, may be a better strategy.…”