Appraisal of re-irradiation for the recurrent glioblastoma in the era of MGMT promotor methylation

Despite recent innovation in treatment techniques and subsequently improved outcomes, the majority of glioblastoma (GBL) have relapses, especially in locoregional areas. Local re-irradiation (re-RT) has been established as a feasible option for recurrent GBL of all ages with safety, tolerability, and effectiveness both in survival and quality of life regardless of fractionation schedule. To keep adverse effects under acceptable range, cumulative dose limit in equivalent dose at 2 Gy fractions by the linear- quadratic model at alpha/beta = 2 for normal brain tissue (EQD2) with narrow margin should be observed and single/hypofractionated re-RT should be undertaken very carefully to recurrent tumor with large volume or adjacent to the brainstem. Promising outcome of re-operation (re-Op) plus re-RT (re-Op/RT) need to be validated and result from re-RT with temozolomide/bevacizumab (TMZ/BV) or new strategy is expected. Development of new-concept prognostic scoring or risk group is required to select patients properly and make use of predictive biomarkers such as O(6)-methylguanine-DNA methyltransferase (MGMT) promotor methylation that influence outcomes of re-RT, re-Op/RT, or re-RT with TMZ/BV.