The Role of Reirradiation in Childhood Progressive Diffuse Intrinsic Pontine Glioma (DIPG): An Ongoing Challenge beyond Radiobiology

Abstract

To investigate the clinical impact of multiple courses of irradiation on pediatric patients with progressive diffuse intrinsic pontine glioma (DIPG), we conducted a retrospective case series on three children treated at our institution from 2018 to 2022. All children were candidates to receive systemic therapy with vinorelbine and nimotuzumab. Radiotherapy was administered to a total dose of 54 Gy. At any disease progression, our local tumor board evaluated the possibility of offering a new course of radiotherapy. To determine feasibility and assess toxicity rates, all children underwent clinical and hematological evaluation both during and after the treatment. To assess efficacy, all children performed contrast-enhanced MRI almost quarterly after the end of the treatment. In all children, following any treatment course, neurological improvement (>80%) was associated with a radiological response (41.7-46%). The longest overall survival (24 months) was observed in the child who underwent three courses of radiotherapy, without experiencing significant side effects. Even though it goes beyond the understanding of conventional radiobiology, first and second reirradiation in pediatric patients with progressive DIPG may represent a feasible and safe approach, capable of increasing overall survival and disease-free survival in selected patients and improving their quality of life.

Keywords: DIPG; high-grade glioma; midline gliomas; nimotuzumab; pediatrics; radiobiology; reirradiation; vinorelbine.

Figure 1

First irradiation isodose distribution in axial (A), coronal (B), and sagittal (C): 20 Gy (dark blue), 32 Gy (light blue), 40 Gy (green), 45 Gy (yellow), 48 Gy (orange), and 54 Gy (red). Second irradiation isodose distribution in axial (D), coronal (E), and sagittal (F): 7.5 Gy (dark blue), 12 Gy (light blue), 15 Gy (green), 17.5 Gy (yellow), 19 Gy (orange), and 22 Gy (red). Third irradiation isodose distribution in axial (G), coronal (H), and sagittal (I): 4 Gy (dark blue), 8 Gy (light blue), 9 Gy (green), 10 Gy (yellow), 11 Gy (orange), and 12 Gy (red).

Figure 2

MRI images of a child treated with three courses of radiotherapy: at baseline, the mass located in the pons appeared to protrude and partially obliterate the prepontine cisterns, embrace the basilar artery, displace the cerebellar vermis and middle cerebellar peduncles, and compress the fourth ventricle and Sylvian aqueduct. It appeared to be (A) hyperintense in T2-weighted and FLAIR sequences and (B) hypointense in T1-weighted sequences. After the first radiotherapy course, the mass decreased, and it was neither obliterating prepontine cisterns nor compressing the fourth ventricle; furthermore, the basilar artery appeared to be free. The mass appeared to be (C) less hyperintense in T2-weighted and FLAIR sequences (almost isointense) and (D) less hypointense in T1-weighted sequences. At first recurrence (E,F), the mass was again obliterating prepontine cisterns and imprinting the fourth ventricle. After the second radiotherapy course (G,H), a considerable reduction in the lesion was seen with all ventricles appearing regular and symmetric. At the second recurrence (I,J), the lesion appeared to have increased again and extended to the midbrain and posterior cranial fossa, toward cerebellar tonsils. After the third radiotherapy course (K,L), a partial reduction in the mass was seen.