Toxicity and efficacy of re-irradiation of high-grade glioma in a phase I dose- and volume escalation trial.
INTRODUCTION
The purpose of this study was to evaluate the safety and efficacy of PET and MRI guided re-irradiation of recurrent high-grade glioma (HGG) and to assess the impact of radiotherapy dose, fractionation and irradiated volume.


MATERIAL AND METHODS
Patients with localized, recurrent HGG (grades III-IV) and no other treatment options were eligible for a prospective phase I trial. Gross tumor volumes for radiotherapy were defined using T1-contrast enhanced MRI and 18F-fluoro-ethyl tyrosine PET. Radiotherapy was delivered using volumetric modulated arc therapy with a 2-mm margin. The dose prescription of four consecutive groups was (1) 35 Gy/10fr., (2) 42 Gy/10fr., (3) 29.5 Gy/5fr. and (4) 35 Gy/10fr. to larger tumor volumes (100-300 cm3), respectively.


RESULTS
Thirty-one patients were treated of which 81% had glioblastoma. The median progression-free survival was 2.8 months (95%CI: 2.1-3.5) and the median overall survival was 7.0 months (95%CI: 3.5-10.5). Early side effects were mild and included headache and fatigue. Seven patients were progression-free beyond 10 weeks and were evaluable for late toxicity. Among these patients, three (43%) suffered late adverse events which included radionecrosis and irreversible white matter changes.


CONCLUSION
Re-irradiation showed limited efficacy and 43% of patients achieving disease control suffered late toxicity that was manageable but not negligible.
['Møller|Søren|S|', 'Munck Af Rosenschöld|Per|P|', 'Costa|Junia|J|', 'Law|Ian|I|', 'Poulsen|Hans Skovgaard|HS|', 'Engelholm|Svend Aage|SA|', 'Engelholm|Silke|S|']
D000328:Adult D000368:Aged D001932:Brain Neoplasms D018572:Disease-Free Survival D019583:Dose Fractionation, Radiation D005260:Female D005910:Glioma D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D008875:Middle Aged D060787:Neoplasm Grading D009364:Neoplasm Recurrence, Local D049268:Positron-Emission Tomography D011446:Prospective Studies D019275:Radiopharmaceuticals D050397:Radiotherapy, Intensity-Modulated D000069475:Re-Irradiation D014443:Tyrosine
Re-irradiation High-grade glioma phase I trial