Hypofractionated stereotactic radiotherapy and continuous low-dose temozolomide in patients with recurrent or progressive malignant gliomas

Giuseppe Minniti • Claudia Scaringi • Vitaliana De Sanctis • Gaetano Lanzetta •
Teresa Falco • Domenica Di Stefano • Vincenzo esposito • Riccardo Maurizi Enrici
J Neurooncol Received: 23 August 2012 / Accepted: 31 October 2012

To evaluate the efficacy of reirradiation and systemic chemotherapy as salvage treatment in patients with recurrent malignant glioma. Between May 2006 and December 2011, 54 patients with recurrent malignant glioma received hypofractionated stereotactic radiotherapy (HSRT) plus systemic therapy at University of Rome Sapienza, Sant’ Andrea Hospital. All patients had Karnofsky performance score C60 and were previously treated with standard conformal RT (60 Gy) with concomitant and adjuvant temozolomide (TMZ) up to 12 cycles. Thirtyeight patients had a GBM and 16 patients had a grade 3 glioma. The median time interval between primary RT and reirradiation was 15.5 months. At the time of recurrence all patients received HSRT (30 Gy in 6-Gy fractions) plus concomitant TMZ (75 mg/m2/day) followed by continuous TMZ at 50 mg/m2 everyday up to 1 year or until progression. Median overall survival after HSRT was 12.4 months, and the 12- and 24-month survival rates were 53 and 16 %, respectively. The median progression-free survival (PFS) was 6 months, and the 12- and 24-month PFS rates were 24 and 10 %, respectively. KPS [70 (P = 0.04) and grade 3 glioma were independent favourable prognostic factors for survival. In general chemoradiation regimen was well tolerated with relatively low treatment-related toxicity. HSRT plus concomitant TMZ followed by continuous dose-intense TMZ is a feasible treatment option associated with survival benefits and low risk of complications in selected patients with recurrent malignant glioma. The potential advantages of combined chemoradiation schedules in patients with recurrent malignant gliomas need to be explored in future studies.

Postoperative radiotherapy and concomitant temozolomide for elderly patients with glioblastoma

Radiotherapy & Oncology
Volume 97, Issue 3 , Pages 382-386, December 2010
Johanna Gerstein, Kea Franz, Joachim P. Steinbach, Valker Seifert, Inge Fraunholz, Christian Weiss, Claus Rödel

Background
The addition of temozolomide (TMZ) to radiotherapy (RT) improves survival of patients with glioblastoma (GB) when compared to postoperative RT alone in patients up to 65years of age. In older patients, RT alone has remained the standard of care because there is concern that radiochemotherapy causes excess toxicity and is less efficacious in this population, but no randomized trials have been reported. We retrospectively assessed feasibility, toxicity and outcome in elderly patients treated at a single institution with RT and concomitant TMZ.
Patient and methods
Between 04/1999 and 9/2009, 51 patients65years (median age 70years, range 65–84) with GB were treated by RT (total dose 60Gy in 30 fractions) and concomitant TMZ (75mg/m2/day throughout RT). Biopsy only had been performed in 23 patients (45.1%), 15 patients (29.4%) had undergone partial resection, and 13 patients (25.5%) macroscopically complete resection. Adjuvant TMZ was applied in 10 of 51 patients.
Results
Median overall survival (OS) and progression-free survival (PFS) were 11.5 (95% CI, 6.7–16.3) and 5.5months (95% CI, 3.7–7.3months), respectively, in the total cohort. After complete resection, partial resection and biopsy, median OS was 27.4, 15.5 and 7.9months (p=0.002), respectively. In multivariate Cox proportional hazards regression models extent of resection (p<0.0001) and Karnofsky’s performance score (p=0.002) were significant independent prognostic factors for OS. RT with concomitant TMZ was well tolerated in the majority of patients and could be completed as scheduled in 30 patients (59%). Five patients (10%) discontinued RT because of disease progression (n=4) or toxicity (pneumonia, n=1). Another 16 patients interrupted concomitant chemotherapy (cytopenia: 9; pneumonia: 2; transaminase elevation: 2; rash: 3).
Conclusion
RT with concomitant TMZ is a feasible regimen with acceptable toxicity in elderly patients. The promising outcome in patients with good performance status and patients with gross total resections are notable.
Keywords: Glioblastoma, Radiotherapy and concomitant temozolomide, Elderly patients