Assessment of Therapeutic Outcome and Role of Reirradiation in Patients With Radiation-induced Glioma

Abstract

Background: We retrospectively reviewed the clinical characteristics and treatment outcomes to clarify the optimal therapeutic strategy, especially the role of reirradiation in patients with radiation-induced glioma (RIG). Methods: We identified patients with high-grade glioma who satisfied Cahan’s criteria for RIG in our database during 2001–2021 and analyzed the outcomes.Results: We identified 11 patients with RIG. The primary diseases included germinomas (n=2), acute lymphoblastic lymphomas (n=2), medulloblastomas (n=3), diffuse astrocytoma with isocitrate dehydrogenase (IDH) 2 mutant (n=1), pilocytic astrocytoma (n=1), pituitary adenoma (n=1), and a metastatic tumor from lung cancer (n=1). The median latency period was 17 years (range: 9–30 years). The RIGs included glioblastoma with IDH 1/2 wild-type (n=7), glioblastoma not otherwise specified (n=2), anaplastic astrocytoma with IDH1/2 wild-type (n=1), and anaplastic astrocytoma not otherwise specified (n=1). All patients underwent tumor removal or biopsy, 5 patients postoperatively received reirradiation combined with chemotherapy, and 6 patients were treated with chemotherapy alone. The median progression-free and overall survival times were 11.3 and 28.3 months, respectively. The median progression-free survival time of patients treated with reirradiation and chemotherapy (n=5) tended to be longer than that of patients that received chemotherapy alone (n=6) (17.0 vs 8.1 months; p=0.45); the median survival time was similar (29.6 vs 27.4 months; p=0.28). Local recurrences were observed less frequently in patients who received reirradiation combined with chemotherapy (50%) than in those who received chemotherapy alone (100%; p=0.046). None of the patients developed radiation necrosis. In one case, the different IDH2 mutational states between the primary and secondary tumors were useful for diagnosing the secondary tumor as RIG. Conclusions: RIG can occur more than 20 years after successful treatment of the primary disease using radiotherapy; thus, follow-up times should be extended to 30 years. Reirradiation combined with chemotherapy appears to be feasible and have favorable outcomes. Identifying the IDH1/2 mutational status can have a diagnostic effect on establishing RIG in recurrent gliomas.