Pseudoprogression as an adverse event of glioblastoma therapy.

Carmen Balaña,Laura Oleaga,Anna Estival,Cristina Carrato,Estela Pineda,Francesc Alameda,Teresa Pujol,Josep Puig,Jaume Capellades,Sonia Del Barco,R Fuentes ,Jordi Craven–Bartle ,J Marruecos ,Carlos Mesía ,Salvador Villá ,J.m Velarde ,Miguel Gil-Gil ,E Verger ,Óscar Gallego ,Sira Domènech ,Maria Martinez-García

doi:10.1002/cam4.1242

Abstract

We explored predictive factors of pseudoprogression (PsP) and its impact on prognosis in a retrospective series of uniformly treated glioblastoma patients. Patients were classified as having PsP, early progression (eP) or neither (nP). We examined potential associations with clinical, molecular, and basal imaging characteristics and compared overall survival (OS), progression‐free survival (PFS), post‐progression survival (PPS) as well as the relationship between PFS and PPS in the three groups. Of the 256 patients studied, 56 (21.9%) were classified as PsP, 70 (27.3%) as eP, and 130 (50.8%) as nP. Only MGMT methylation status was associated to PsP. MGMT methylated patients had a 3.5‐fold greater possibility of having PsP than eP (OR: 3.48; 95% CI: 1.606–7.564; P = 0.002). OS was longer for PsP than eP patients (18.9 vs. 12.3 months; P = 0.0001) but was similar for PsP and nP patients (P = 0.91). OS was shorter–though not significantly so—for PsP than nP patients (OS: 19.5 vs. 27.9 months; P = 0.63) in methylated patients. PPS was similar for patients having PsP, eP or nP (PPS: 7.2 vs. 5.4 vs. 6.7; P = 0.43). Neurological deterioration occurred in 64.3% of cases at the time they were classified as PsP and in 72.8% of cases of eP (P = 0.14). PsP confounds the evaluation of disease and does not confer a survival advantage in glioblastoma.

Highlights

Standard first-line treatment for newly diagnosed glioblastoma is surgery followed by radiotherapy with concomitant and adjuvant temozolomide [1]
We have reviewed our series of patients in order to identify predictive factors for PsP and found that MGMT_MET patients had a 3.5-fold greater possibility of having PsP than early progression (eP)
In consistent with previous reports [4, 5, 16, 17], none of the isocitrate dehydrogenase 1 (IDH1)-m utated patients had eP and patients undergoing gross total resection showed a trend toward a lower probability of having either PsP or eP

Summary

Introduction

Standard first-line treatment for newly diagnosed glioblastoma is surgery followed by radiotherapy with concomitant and adjuvant temozolomide [1]. Patients were classified in three groups: PsP, eP, or nP Those who were diagnosed as having suspected progressive disease at their first evaluation but whose subsequent MRI evaluations (performed after the third and sixth cycle of adjuvant temozolomide) showed stable disease or partial or complete response were classified as PsP. Those whose first MRI evaluation showed a pattern indicating suspected progressive disease that was confirmed at subsequent evaluations were classified as eP. The date of progression was the date of the first progression if subsequent MRI evaluations showed no improvement

Methods

Literature search criteria

Results

Discussion