NTOX-06. INCREASE OF PSEUDOPROGRESSION AND TREATMENT RELATED EFFECTS IN LOW-GRADE GLIOMA PATIENTS TREATED WITH PROTON RADIATION AND TEMOZOLOMIDE

Abstract

INTRODUCTION

Chemoradiation with temozolomide (TMZ) can be associated with pseudoprogression (PsP) in glioblastoma. The occurrence of early or delayed treatment effects and pseudoprogression is less well understood in low-grade gliomas (LGG). We hypothesized that adding TMZ to radiotherapy might increase the incidence of treatment related effects or pseudoprogression.

METHODS

Chart review and volumetric MRI-analysis was performed on 109 chemotherapy-naïve patients with grade I-II or IDH1-mutant grade III glioma treated with proton-radiotherapy (RT) between 2005-2015. Progression was defined by tissue-diagnosis or new chemotherapy-initiation. Post-treatment related effects (PTRE) were defined as increase in T2/FLAIR or new/increase in abnormal enhancement without evidence of tumor progression or growth 6-12 months later. PsP was defined if a lesion meeting PTRE-criteria was suspicious for progression or volumetrically increased at least 40% from baseline. Late-PsP was defined as PTRE occurring more than 12 months after RT. Pearson’s chi-squared test was used for statistical analysis.

RESULTS

Median RT-dose was 54 Gy (RBE) (range: 45-60). There were 70, 27, and 12 patients who respectively received RT alone, RT with concurrent-TMZ, and RT with adjuvant (sequential)-TMZ. PsP was not more common with concurrent-TMZ versus adjuvant-TMZ (PsP: 67% versus 83%; p=0.29; enhancing-PsP: 52% versus 58%; p=0.710). However, PsP was significantly more frequent with TMZ+RT versus RT alone (PsP: 72% versus 39%; p<0.001; enhancing-PsP: 54% versus 34%; p=0.047). There were no significant inter-group-differences in mean-change from pre-RT-baseline in KPS, MMSE, or seizures during the year following RT-initiation. PsP was significantly more common in presence of p53-mutation (PsP: 62% versus 38%; p=0.048; enhancing-PsP: 48% versus 29%; p=0.124), but unrelated to IDH1-mutant status (PsP: 59% versus 38%; p=0.101; enhancing-PsP: 43% versus 43%; p=1.0) and MGMT promoter methylation (PsP: 66% versus 47%; p=0.296; enhancing-PsP: 50% versus 47%; p=0.876).

CONCLUSIONS

Treatment with TMZ and p53-mutation status were associated with increased PsP in LGGs treated with proton-radiotherapy.