Research Article: Hypofractionated radiation therapy and temozolomide in patients with glioblastoma and poor prognostic factors. A prospective, single-institution experience

Date Published: June 6, 2019

Publisher: Public Library of Science

Author(s): Paola Anna Jablonska, Ricardo Diez-Valle, Jaime Gállego Pérez-Larraya, Marta Moreno-Jiménez, Miguel Ángel Idoate, Leire Arbea, Sonia Tejada, Maria Reyes Garcia de Eulate, Luis Ramos, Javier Arbizu, Pablo Domínguez, José Javier Aristu, Aamir Ahmad.


Hypofractionated radiation therapy is a feasible and safe treatment option in elderly and frail patients with glioblastoma. The aim of this study was to evaluate the effectiveness of hypofractionated radiation therapy with concurrent temozolomide in terms of feasibility and disease control in primary glioblastoma patients with poor prognostic factors other than advanced age, such as post-surgical neurological complications, high tumor burden, unresectable or multifocal lesions, and potential low treatment compliance due to social factors or rapidly progressive disease.

GTV included the surgical cavity plus disease visible in T1WI-MRI, FLAIR-MRI and in the MET-uptake. The CTV was defined as the GTV plus 1.5–2 cm margin; the PTV was the CTV+0.3 cm margin. Forty, fourty-five, and fifty grays in 15 fractions were prescribed to 95% of PTV, CTV, and GTV, respectively. Treatment was delivered using IMRT or the VMAT technique. Simultaneously, 75 mg/m2/day of temozolomide were administered.

Between January 2010 and November 2017, we treated a total of 17 patients. The median age at diagnosis was 68-years; median KPS was 50–70%. MGMT-methylation status was negative in 5 patients, and 8 patients were IDH-wildtype. Eight of 18 patients were younger than 65-years. Median tumor volume was 26.95cc; median PTV volume was 322cc. Four lesions were unresectable; 6 patients underwent complete surgical resection. Median residual volume was 1.14cc. Progression-free survival was 60% at 6 months, 33% at 1-year and 13% at 2-years (median OS = 7 months). No acute grade 3–5 toxicities were documented. Symptomatic grade 3 radiation necrosis was observed in one patient.

Patients with poor clinical factors other than advanced age can be selected for hypofractionated radiotherapy. The OS and PFS rates obtained in our series are similar to those in patients treated with standard fractionation, assuring good treatment adherence, low rates of toxicity and probable improved cost-effectiveness.

Partial Text

Glioblastoma multiforme (GB) is the most common primary brain tumor. It usually develops in the sixth decade of life, with the median age at diagnosis of 64 years [1]. The standard of care consists of surgical resection, followed by conventional fractionated radiation therapy (CFRT) with concurrent and adjuvant temozolomide (TMZ). This approach shows a median overall survival (OS) time of 14.6 months (13.2–16.8 months) and a 5-year overall survival (OS) rate of 9.8% (6.4–14.0%) [2]. The impact of hypofractionated radiation therapy (HFRT) has recently been investigated. Results of initial research aimed at reducing the overall treatment time in frail and elderly GB patients suggest using both TMZ and HFRT as standard treatment option in this subgroup of patients [3].

All patients provided a written informed consent to the treatment and the use of their data for scientific purposes. The University of Navarra’s Ethics Committee approved the study. Patients with primary GB, 18 years of age or older, meeting any of the inclusion criteria (Table 1) were enrolled to receive HFRT and concomitant TMZ.

To our knowledge, there is no data available on HFRT/TMZ in GB patients with poor prognostic factors other than advanced age or fragility. Our study shows that short course RT of 40 Gy in 15 fractions with concurrent TMZ is a feasible and safe treatment option for GB patients with unfavorable general conditions.

Our results show that HFRT with concurrent TMZ is a feasible therapeutic approach in patients with primary GB and other poor prognostic factors, assuring high treatment compliance and low toxicity rates. Dose escalation and reduction in overall treatment time are clear advantages of HFRT, while at least the same survival rates as a longer course of RT are maintained. However, our results are preliminary and non-comparative. More solid research is needed to define more robust selection criteria for HFRT beyond the indication for elderly and fragile patients before HFRT can be established as the new standard of care in newly diagnosed GB.