Favorable Response to Conventional Chemoradiotherapy in Radiation-induced Glioma Harboring Coamplification of PDGFRA, KIT, and KDR: A Case Report and Literature Review

Abstract

One of the most serious complications of cranial radiotherapy is the development of radiation-induced glioma, which is estimated to occur in 1%-4% of patients who have received cranial irradiation and has a worse prognosis than sporadic glioblastoma. Although comprehensive genetic analysis has recently uncovered the molecular characteristics of radiation-induced glioma, the full picture remains unclear due to its rarity. A 45-year-old man presented with generalized seizures caused by multiple brain tumors involving the right frontal lobe, thalamus, and brainstem. The patient had a history of whole-brain radiotherapy for recurrent Burkitt's lymphoma at the age of 12. He underwent craniotomy, and the histological diagnosis revealed a high-grade glioma with isocitrate dehydrogenase-wildtype, which was presumed to be a radiation-induced glioma that developed 33 years after whole-brain irradiation. Next-generation sequencing identified a CDKN2A/B deletion, as well as coamplification of several receptor tyrosine kinases-encoding genes, including PDGFRA, KIT, and KDR, all of which are located at 4q12. Amplification of this region is broadly observed across cancers and is associated with poor prognosis in sporadic glioblastoma. Nevertheless, the patient received chemoradiotherapy with temozolomide, followed by temozolomide maintenance therapy, resulting in a complete response of all lesions. Although radiation-induced gliomas are generally difficult to treat, our patient unexpectedly responded well to conventional chemoradiotherapy despite the coamplification of multiple receptor tyrosine kinases-encoding genes, which is typically suggestive of an aggressive phenotype. Our case indicates that some radiation-induced gliomas may have distinct molecular characteristics influencing the therapeutic response, which differ from those of sporadic glioblastomas.