Pseudoprogression in patients with malignant gliomas treated with concurrent temozolomide and radiotherapy: potential role of p53

Abstract

We investigated pseudoprogression (psPD) in patients with malignant gliomas treated with radiotherapy (RT) and maintenance temozolomide (TMZ) in terms of incidence, outcomes, and predictive and prognostic factors. We evaluated p53 overexpression by immunohistochemical analysis of thirty-five tumor samples as a predictor for psPD. The time to progression and overall survival were compared between subgroups, psPD versus early progression (ePD) versus nonprogression (nonPD). Eight patients developed psPD among eighteen patients with lesion enlargement at the first MRI scan, and the others were classified as ePD. The remaining stable or improved patients were classified as nonPD. All patients with psPD were alive at last follow-up (median follow-up period was 12 months; range 5.8-58.5 months). Overall survival of psPD patients was significantly higher than ePD patients (P < 0.01). There was no significant survival difference between the psPD group and nonPD group (P = 0.25). Seven (87.5%) of eight tumors with psPD showed p53 overexpression, as compared to 3 (30%) of the ten tumors with ePD (P = 0.03). Our study indicates that psPD following chemoradiotherapy with TMZ is associated with significantly better overall survival compared to that of ePD, and is comparable to nonPD group. Overexpression of p53 was identified as a potential biomarker for predicting the development of psPD.