Toxicity and efficacy of re-irradiation of high-grade glioma in a phase I dose- and volume escalation trial

TY - JOUR

T1 - Toxicity and efficacy of re-irradiation of high-grade glioma in a phase I dose- and volume escalation trial

AU - Møller, Søren

AU - Munck Af Rosenschöld, Per

AU - Costa, Junia

AU - Law, Ian

AU - Poulsen, Hans Skovgaard

AU - Engelholm, Svend Aage

AU - Engelholm, Silke

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2017/11

Y1 - 2017/11

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Brain Neoplasms/diagnostic imaging

KW - Disease-Free Survival

KW - Dose Fractionation

KW - Female

KW - Glioma/diagnostic imaging

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Neoplasm Grading

KW - Neoplasm Recurrence, Local/diagnostic imaging

KW - Positron-Emission Tomography

KW - Prospective Studies

KW - Radiopharmaceuticals

KW - Radiotherapy, Intensity-Modulated/methods

KW - Re-Irradiation/adverse effects

KW - Tyrosine/analogs & derivatives

U2 - 10.1016/j.radonc.2017.09.039

DO - 10.1016/j.radonc.2017.09.039

M3 - Journal article

C2 - 29054380

SN - 0167-8140

VL - 125

SP - 223

EP - 227

JO - Radiotherapy & Oncology

JF - Radiotherapy & Oncology

IS - 2

ER -