Assessment of therapeutic outcome and role of reirradiation in patients with radiation-induced glioma

Abstract

Background We sought to clarify the optimal follow-up, therapeutic strategy, especially the role of reirradiation, and the diagnostic impact of isocitrate dehydrogenase (IDH) 1 and 2 mutation status in patients with radiation-induced glioma (RIG). Methods We retrospectively reviewed the clinical characteristics and treatment outcomes of 11 patients with high-grade glioma who satisfied Cahan’s criteria for RIG in our database during 2001–2021. IDH 1/2 mutations were analyzed by Sanger sequencing and/or pyrosequencing. Results 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). The median period from primary disease and RIG diagnosis was 17 years (range: 9–30 years). 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 survival times were 11.3 and 28.3 months. 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). However, the median survival time was similar (29.6 vs 27.4 months). Local recurrence was observed in 5 patients treated with chemotherapy alone, whereas in 2 patients among 4 patients treated with reirradiation and chemotherapy. None of the patients developed radiation necrosis. In one case, the primary tumor was diffuse astrocytoma with IDH2 mutant, and the secondary tumor was glioblastoma with IDH 1/2 wild-type. Based on the difference of IDH2 mutation status, the secondary tumor with IDH 1/2 wild-type was diagnosed as a de novo tumor that was related to the previous radiation therapy. Conclusions RIG can occur beyond 20 years after successfully treating the primary disease using radiotherapy; thus, cancer survivors should be informed of the long-term risk of developing RIG and the need for timely neuroimaging evaluation. Reirradiation combined with chemotherapy appears to be feasible and has favorable outcomes. Determining the IDH1/2 mutational status is useful to establish RIG diagnosis when the primary tumor is glioma.

Clinical, imaging, and molecular features of radiation-induced glioblastomas developing more than 20 years after radiation therapy for intracranial germinomatous germ cell tumor: illustrative cases

“…However, there have been just a handful of reports about the fatality of radiation necrosis during the survival periods of patients after re-RT for RIMG. 23 Such radiation necrosis has been reported in patients with high-grade gliomas or other brain tumors, who survived for a longer period, 7 but not in patients with GCTs. In general, the tolerance to re-RT increased with an increasing time to re-RT and a decreasing initial radiation dose.…”

“…Previous reports recommended re-RT in addition to chemotherapy for RIMG. 7 , 23 A study regarding the role of RT in the treatment of patients with RIMG showed that 1-, 2-, and 5-year overall survival rates were 58.9%, 20.5%, and 6.8%, respectively, in the patients undergoing re-RT, which were higher than those in patients not undergoing re-RT (15.1%, 3%, and 0%, respectively). 7 Another article showed that the median progression-free survival time of patients treated with re-RT and chemotherapy tends to be longer than that of patients who received chemotherapy alone (17.0 versus 8.1 months).…”

Clinical and molecular study of radiation-induced gliomas

“…RT improves the outcome of pediatric patients but is also associated with long-term risks. These can be observed especially in children with long-term follow-up 1 . One of the most serious risks is the development of radiation-induced gliomas (RIGs), which have been described in patients primarily treated mainly for acute lymphoblastic leukemia (ALL) and central nervous system (CNS) malignancies by cranial RT 2 , 3 .…”

“…However, significant progress is now being made in their molecular biological characterization 6 , 7 . Unlike their primary counterparts, RIG do not usually carry the typical mutations in the Histon3, IDH1/2 or BRAF genes 1 , 8 , 9 . Based on methylation profiling, RIG mostly clustered within the GBM_pedRTK1 methylation group.…”

“…RIGs are characterized by an aggressive clinical course with a poor prognosis 1 , 3 , 10 . Treatment regimens are not defined and include modalities used to treat primary high-grade gliomas.…”