Fractionated stereotactic reirradiation and concurrent temozolomide in patients with recurrent glioblastoma

Abstract

The aim of this paper is to evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) and concomitant temozolomide (TMZ) as a salvage treatment option in patients with recurrent glioblastoma (GBM). Between May 2006 and December 2009, 36 patients with recurrent GBM received FSRT plus concomitant TMZ at University of Rome La Sapienza, Sant' Andrea Hospital. All patients had Karnofsky performance score ≥60 and were previously treated with standard conformal radiotherapy (RT) (60 Gy) with concomitant and adjuvant TMZ for 6-12 cycles. The median time interval between primary RT and reirradiation was 14 months. At the time of recurrence, all patients received FSRT plus concomitant daily TMZ at the dose of 75 mg/m(2), given 7 days per week from the first day of RT. Radiation dose was 37.5 Gy delivered in 15 fractions over 3 weeks. Median overall survival after FSRT was 9.7 months, and the 6- and 12-month survival rates were 84 and 33%, respectively. The median progression-free survival (PFS) was 5 months, and 6- and 12-month PFS rates were 42 and 8%, respectively. In univariate analysis, KPS (P = 0.04), the interval between primary RT and reirradiation (P = 0.02), and O6-methylguanine-DNA-methyltransferase (MGMT) methylation status at the time of diagnosis (P = 0.009) had an effect on survival; however, in multivariate analysis, only MGMT methylation was statistically significant (P = 0.03). In general, FSRT was well tolerated and the treatment was completed in all patients. Neurological deterioration due to radiation-induced necrosis occurred in three patients (8%). FSRT plus concomitant TMZ is a feasible treatment option associated with survival benefits and low risk of complications in selected patients with recurrent GBM. The potential advantages of combined chemoradiation schedules in patients with recurrent GBM need to be explored in future studies.

Concurrent hyperthermia and re-irradiation for recurrent high-grade gliomas

“…Furthermore, the median OS was longer than that of patients receiving supportive care (8.4 vs. 2.5 months) [25]. However, in the previous study, the majority of patients had a KPS of over 60 [12,23,25,27], with 92% patients having a KPS of more than 70 [26]. By comparison, in our study, the median KPS was 60 (range, 30-90) and 8 patients (40%) had a KPS of more than 60.…”

“…In another study, patients received re-RT (37.5 Gy in 2.5-Gy fractions) with concomitant TMZ followed by adjuvant TMZ. The median OS was 9.7 months, and the 12-month survival rate was 33% [27]. BVZ sensitizes the tumor endothelium to RT by depleting vascular endothelial growth factor levels, and also lowers the RT dose required to control 50% of the tumor [28,29].…”

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

“…A higher incidence of toxicities is seen in the setting of HFSRT with concomitant chemotherapy. Minniti, et al reported RN-associated neurological deterioration in 8% [22] and 7% [23] of patients when treated with TMZ concurrent with 37.5 Gy/15 fractions and 30 Gy/5 fractions, respectively. In a prospective analysis, Lederman, et al [21] documented RN in 10% of patients treated with 24 Gy/8 fractions and paclitaxel.…”

“…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.…”

Salvage Radiosurgery for High Grade Glioma in the Era of Modern Systemic Therapy

“…Evaluating the common factors that can contribute to radionecrosis including the dose, fractionation and volume of re-irradiation, this study utilized a higher mean dose prescribed to the 50% isodose line of 17.5 Gy (range: 12 -24 Gy) in a single fraction compared with prior studies that range from 13 Gy in a single fraction up to 37.5 Gy in 15 fractions. 5,[16][17][18] However, this study generally treated smaller volume tumours with a mean tumour volume of 4.8 cm 3 (range: 1.3 -18.2 cm 3 ) compared to other studies that included tumour volumes up to 30 cm 3 . 5,10 In this retrospective series, the rate of adverse radiation effects (ARE) was high, occurring in 26 of 29 patients (89.7%).…”