Suggestions for Escaping the Dark Ages for Pediatric Diffuse Intrinsic Pontine Glioma Treated with Radiotherapy: Analysis of Prognostic Factors from the National Multicenter Study

Abstract

This multicenter retrospective study aimed to investigate clinical, radiologic, and treatmentrelated factors affecting survival in patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) treated with radiotherapy. Materials and MethodsPatients aged <30 years who underwent radiotherapy as an initial treatment for DIPG between 2000 and 2018 were included; patients who did not undergo magnetic resonance imaging at diagnosis and those with pathologically diagnosed grade I glioma were excluded. We examined medical records of 162 patients collected from 10 participating centers in Korea. The patients' clinical, radiological, molecular, and histopathologic characteristics, and treatment responses were evaluated to identify the prognosticators for DIPG and estimate survival outcomes. ResultsThe median follow-up period was 10.8 (interquartile range, 7.5-18.1) months. The 1-and 2year overall survival (OS) rates were 53.5 % and 19.0%, respectively, with a median OS of 13.1 months. Long term survival rate (≥2 years) was 16.7%, and median OS was 43.6 months. Age (<10 years), poor performance status, treatment before 2010, and post-radiotherapy necrosis were independently associated with poor OS in multivariate analysis. In patients with increased post-radiotherapy necrosis, the median OS estimates were 13.3 months and 11.4 months with and without bevacizumab, respectively (p=0.138). ConclusionTherapeutic strategy for DIPG has remained unchanged over time, and the associated prognosis remains poor. Our findings suggest that appropriate efforts are needed to reduce the occurrence of post-radiotherapy necrosis. Further well-designed clinical trials are recommended to improve the poor prognosis observed in DIPG patients.

The relationship between imaging features, therapeutic response, and overall survival in pediatric diffuse intrinsic pontine glioma

“…In this 10-year single-center study, we evaluated the survival outcomes, as well as the clinical, radiological, and therapeutic response-related factors that affect prognosis, in children with DIPG who received radiation therapy. Our findings confirmed some previously reported survival-related factors in DIPG patients [ 11 , 12 , 14 , 17 , 21 ], such as extrapontine lesion extension, necrosis, ring enhancement, Karnofsky, therapeutic response, and increased ring enhancement post-radiotherapy. Our results showed that 39% of patients exhibited ring enhancement, which is generally the same as previously reported results, and the proportion of patients with ring enhancement was approximately 35–37% [ 11 , 12 , 17 ].…”

Radiotherapy for Diffuse Intrinsic Pontine Glioma: Insufficient but Indispensable

“…Age ≤3 or >10 years and longer symptom duration at presentation are prognostic factors associated with a favorable survival outcome [ 8 15 ]. A Korean study [ 10 ] also confirmed these significant prognostic factors.…”

“…Similar to the current recommendation, the Children’s Cancer Study Group study performed in 1977 recommended radiotherapy to be administered 5 times a week at 8–9 Gy/week up to 50–60 Gy [ 9 ]. A Korean Radiation Oncology Group (KROG) study reported that the radiotherapy dose did not change over the last 20 years in clinical practice in Korea, and most patients received 54 Gy of radiation with conventional fractionation [ 10 ].…”

“…A systematic review of 61 studies involving 1,620 patients treated with upfront conventional radiotherapy with or without systemic therapy showed a median OS of 11.4 months [ 14 ]. Similarly, a multicenter study involving 162 patients treated with radiotherapy in Korea for 20 years showed a median OS of 13.1 months and a 2-year OS rate of 19% [ 10 ]. OS improved significantly over time, even after adjusting for other prognostic factors, to median OS of 11.4, 13.5, and 17.6 months for patients treated before 2010, during 2010–2015, and after 2015, respectively.…”

“…These findings suggested that an extended margin over 1 cm is not recommended, considering no apparent benefit in tumor control and the high risk of organ damage from the large target volume. Similarly, a multicenter KROG study showed that the infield failure rate was comparable among different CTV margin groups, since most failures represented infield progression (78.6% for no margin, 75.9% for <1 cm of margin, and 86% for 1–2 cm of margin; p =0.160) [ 10 ].…”