Hypofractionated Stereotactic Radiation Therapy: An Effective Therapy for Recurrent High-Grade Gliomas

Abstract

Purpose Salvage options for recurrent high-grade gliomas (HGGs) are limited by cumulative toxicity and limited efficacy despite advances in chemotherapeutic and radiotherapeutic techniques. Previous studies have reported encouraging survival results and favorable toxicity with fractionated stereotactic radiotherapy, and small studies have shown similar benefit using a shortened course of hypofractionated stereotactic radiation therapy (H-SRT). We sought to determine the efficacy and toxicity profile of H-SRT alone or in addition to repeat craniotomy or concomitant chemotherapy. Patients and Methods Between 1994 and 2008, 147 patients with recurrent HGG were treated with H-SRT (median dose, 35 Gy in 3.5-Gy fractions). Cox regression models were used to analyze survival outcomes. Variables included age, surgery before H-SRT, time to first recurrence, reirradiation dose, inclusion of chemotherapy with H-SRT, and gross tumor volume (GTV). Results Younger age (P = .001), smaller GTV (P = .025), and shorter time between diagnosis and recurrence (P = .034) were associated with improvement in survival from H-SRT. Doses of radiation ≥ 35 Gy approached significance (P = .07). There was no significant benefit of surgical resection or chemotherapy in this population when analysis was controlled for other prognostic factors. Conclusion H-SRT was well tolerated and resulted in a median survival time of 11 months after H-SRT, independent of re-operation or concomitant chemotherapy. Patients who experienced recurrence within 6 months after initial treatment had an excellent response and should not be disqualified from H-SRT. This is the largest series to examine the efficacy and tolerability of H-SRT in recurrent HGG.

EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma

“…The role of re-irradiation is uncertain, including the role of amino acid positron emission tomography (PET) for target delineation, and multiple fractionation regimens have been proposed, e.g., from 6 x 5 Gy to 18 x 2 Gy. 44,45 The three strategies of medical treatment for glioblastoma recurring after TMZ/RT→TMZ most commonly used across Europe include nitrosourea-based regimens, alternative dosing regimens of TMZ, and bevacizumab. The activity of CCNU has been confirmed in the standard arms of randomized trials exploring the activity of the protein kinase C-β inhibitor, enzastaurin, 46 or the vascular endothelial growth factor (VEGF) receptor inhibitor, cediranib, 47 with progression-free survival rates at 6 months of 20%.…”

Therapeutic options in recurrent glioblastoma—An update

“…Radiosurgery is less frequently used in glioblastoma. As favorable variables for selecting patients likely to benefit from re-irradiation again general prognostic factors such as young age, high KPS or small tumor size have been proposed [32,[34][35][36][37]. Different reports exist regarding the preferred time interval to initial radiation for benefit from re-irradiation, favoring either an interval of less than 6 months [35] or more than 6 or even 12 months [37,38].…”

Innovative Hypofractionated Stereotactic Regimen Achieves Excellent Local Control With No Radiation Necrosis: Promising Results in the Management of Patients With Small Recurrent Inoperable GBM

“…However, different methods of documenting tumor status make comparisons across studies difficult. For instance, Fogh, et al [19] reported stable disease in 60% of patients based on the three-month follow-up MRI scan. The present study uses the last available follow-up MRI scan to determine disease state.…”

“…Of these, HFSRT has emerged as a noninvasive method to deliver a high dose of radiation to the tumor site. In the treatment of recurrent GBM, numerous studies have documented a survival advantage on the use of HFSRT [10][11][12][13][14][15][16][17][18] and HFSRT in combination with chemotherapy [19][20][21][22][23][24]. Specifically, Iuchi, et al [25] has shown that a single dose of more than 20 Gy is able to achieve durable local control in 72% of patients; however, radiation necrosis (RN) was observed in 43% of patients.…”