MRSI-Guided Dose Escalation of Radiotherapy Does Not Improve PFS, OS in Glioblastoma

Image-guided dose escalation of radiotherapy is well tolerated but does not improve outcomes in patients with glioblastoma receiving concomitant temozolomide, according to research published in Neuro-Oncology.

Researchers found that magnetic resonance spectroscopic imaging (MRSI)-guided dose escalation did not improve progression-free survival (PFS) or overall survival (OS) in these patients.

This phase 3 trial (ClinicalTrials.gov Identifier: NCT01507506) included 180 patients with glioblastoma who had a median age of 61 (range, 26-84) years. Most patients (85.0%) had undergone surgical resection, and 50.6% had unmethylated MGMT. Of 113 evaluable patients, 95.5% had wild-type IDH.

The patients were randomly assigned to receive standard-dose radiotherapy (n=90) or high-dose radiotherapy (n=90). Baseline characteristics were well balanced between the arms.

Patients in the standard arm received 60 Gy of radiation. Patients in the high-dose arm received 60 Gy as well as a simultaneous MRSI-guided boost, totaling 72 Gy. All patients received temozolomide during radiation and for 6 months after.

With a median follow-up of 43.9 months, the median OS was 22.6 months in the standard arm and 22.2 months in the high-dose arm. There was no significant difference in OS between the arms in an unadjusted analysis (hazard ratio [HR], 0.90; 95% CI, 0.64-1.27; P =.5526) or in a multivariate analysis (adjusted HR, 0.91; 95% CI, 0.64-1.29; P =.594).

The median PFS was 8.6 months in the standard arm and 7.8 months in the high-dose arm. There was no significant difference in PFS between the arms in an unadjusted analysis (HR, 1.0; 95% CI, 0.80-1.48; P =.6027) or a multivariate analysis (adjusted HR, 1.10; 95% CI, 0.80-1.50; P =.567).

Adverse events (AEs) were reported in all patients. General AEs, neurologic AEs, and hematologic AEs were generally comparable between the arms.

However, headaches were more common in the standard-dose arm than in the high-dose arm (59.1% and 44%, respectively; P =.0484). Neurologic deficits were more common in the high-dose arm than in the standard-dose arm (67.5% and 51.1%, respectively; P =.0299).

“Given the high radioresistance of GBM [glioblastoma], it may be surmised that the boost dose needs to be much higher than the one we administered,” the researchers wrote. “By extrapolation, the definition of boost volume may also need to be multimodal and include several metabolic and functional imaging modalities.”

This article originally appeared on Cancer Therapy Advisor