Pseudoprogression as an adverse event of glioblastoma therapy

• Published in: Cancer medicine (Malden, MA) Vol. 6; no. 12; pp. 2858 - 2866
• Main Authors: Balaña, Carmen, Capellades, Jaume, Pineda, Estela, Estival, Anna, Puig, Josep, Domenech, Sira, Verger, Eugenia, Pujol, Teresa, Martinez‐García, Maria, Oleaga, Laura, Velarde, JoseMaria, Mesia, Carlos, Fuentes, Rafael, Marruecos, Jordi, Del Barco, Sonia, Villà, Salvador, Carrato, Cristina, Gallego, Oscar, Gil‐Gil, Miguel, Craven‐Bartle, Jordi, Alameda, Francesc
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.12.2017; John Wiley and Sons Inc
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Brain cancer; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - genetics; Brain Neoplasms - mortality; Brain Neoplasms - therapy; Chi-Square Distribution; Clinical Cancer Research; Disease Progression; Disease-Free Survival; DNA Methylation; DNA Modification Methylases - genetics; DNA Repair Enzymes - genetics; Female; Glioblastoma; Glioblastoma - diagnostic imaging; Glioblastoma - genetics; Glioblastoma - mortality; Glioblastoma - therapy; Humans; IDH1 mutation; imaging; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Medical prognosis; Methylation; MGMT; Middle Aged; Odds Ratio; Original Research; Polymerase Chain Reaction; Predictive Value of Tests; Proportional Hazards Models; pseudoprogression; radionecrosis; Retrospective Studies; Risk Factors; Spain; Survival; Time Factors; Treatment Outcome; Tumor Suppressor Proteins - genetics; Young Adult; pseudoprogression; IDH1 mutation; radionecrosis; MGMT; imaging; Glioblastoma
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.1242

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. We explored clinical, molecular and imaging (MRI) predictive factors of pseudoprogression (PsP) in 256 glioblastoma patients. MGMT methylation was the only factor associated with PsP and PsP did not improve OS over nP (neither PsP nor early progression), suggesting that it should be considered an adverse event of therapy and should be reported as such in clinical trials.