Pseudoprogression in patients with glioblastoma multiforme after concurrent radiotherapy and temozolomide

Abstract

Background: To evaluate pathologically confirmed incidence of pseudoprogression and its impact on survival in glioblastoma multiforme (GBM) patients treated with radiotherapy and concurrent temozolomide (TMZ), followed by 6 months of TMZ maintenance therapy.

Materials and methods: Sixty-three patients with histologic proof of GBM underwent 60 Gy (2 Gy/fr, 30 fractions) of brain radiotherapy concurrent with continuous 75 mg/m/d TMZ, followed by 6 cycles of maintenance TMZ (200 mg/m/d for 5 d, every 28 d). Response assessment was performed by magnetic resonance imaging every 2 months. All patients with radiologic doubt of early tumor progression (≤6 mo) underwent salvage surgery.

Results: All patients underwent surgical resection. Gross total, subtotal resection, and biopsy were performed in 17 (27.0%), 32 (51.6%), and 14 (21.4%) patients, respectively. Lesion enlargement on first follow-up magnetic resonance imaging evidenced in 28 (44.4%) patients. Salvage pathologies revealed pseudoprogression in 12 of 28 (42.8%) patients corresponding to an overall pseudoprogression rate of 19%. Survival analysis revealed that patients with pseudoprogression had superior overall and progression-free survival rates at both 1 and 2 years (P<0.05 for each, respectively).

Conclusions: Current results indicates the urgency of need for novel imaging techniques and/or biochemical marker(s) that can better distinguish pseudoprogression from true progression to avoid unnecessary and potentially harmful surgical interventions in almost half of the radiologically progressive GBM patients. Our additional observation which suggests better survival for patients with pseudoprogression warrants to be studied in larger patient cohorts.