Abstract Radiation-induced high-grade gliomas (RIG) are rare, aggressive secondary malignancies arising after cranial or spinal irradiation for pediatric CNS tumors, typically associated with poor prognosis and limited therapeutic response. Here we describe a patient who achieved prolonged progression-free survival (PFS) after nivolumab therapy for recurrent RIG. A female patient, initially treated for WNT-activated medulloblastoma at 6 years of age with gross-total resection, craniospinal irradiation (23.4 Gy with a 30.6 Gy posterior fossa boost), and adjuvant chemotherapy, developed a left brachium pontis IDH-wildtype, TP53-mutant, CDKN2A-homozygous deleted RIG with complex intrachromosomal copy number alterations, 66 months after completing radiation. Following resection, she received 60 Gy focal irradiation in 30 fractions with concurrent temozolomide. A small residual nodule was identified on her post-radiation scan. She continued chemotherapy with adjuvant temozolomide ± CCNU complicated by prolonged, recurrent thrombocytopenia. The decision was made for further tumor resection, resulting in a 1-2mm residual nodule. A single dose of neo-adjuvant nivolumab (3 mg/kg) was administered prior to surgery and then followed by adjuvant nivolumab (3mg/kg) continued every two weeks. Treatment was briefly paused for cutaneous toxicity and successfully resumed with antihistamine premedication. At 36 months after nivolumab initiation, the patient remains radiographically stable with no evidence of progression or new neurological deficits. Her baseline left-sided weakness and ataxia remain unchanged. No immune-related adverse events have recurred since premedication was introduced. This case demonstrates an exceptional, durable response to neo-adjuvant followed by adjuvant PD-1 blockade in radiation-induced HGG, a setting typically refractory to immunotherapy. Prolonged PFS in this molecularly characterized tumor suggests potential immunogenic vulnerability in radiation-induced gliomas, possibly due to an altered tumor microenvironment. Further studies are warranted to identify biomarkers predictive of durable response in this rare and challenging entity.
Goldberg et al. (Tue,) studied this question.