Impact of adjuvant anti-VEGF therapy on treatment-related pseudoprogression in patients with newly diagnosed glioblastoma receiving chemoradiation with or without anti-VEGF therapy.

Abstract

2025 Background: Chemoradiation (CRT) can significantly modify the appearance of glioblastoma (GBM) on MRI, especially within the 3-month window after CRT. Pseudoprogression (PsP) is an increasingly recognized phenomenon in this scenario, and is thought to be secondary to increased permeability of the tumor vessels from irradiation, possibly enhanced by temozolomide (TMZ). We sought to determine if the addition of a VEGF signaling inhibitor (cediranib) during and after CRT had an impact on the frequency of PsP, by comparing two groups of patients with newly diagnosed GBMs. Methods: Two groups of patients enrolled in IRB-approved trials underwent serial MRIs at baseline, weekly during CRT and monthly thereafter. The control group received radiation plus TMZ, while the other group (CED) also received cediranib until progression (which was defined by RANO criteria) or toxicity. Patients that progressed up to 3 months after CRT were considered to have apparent progression (AP) and kept on treatment. Lesions that subsequently stabilized/regressed were classified as PsP, while those that maintained growth despite treatment were classified as true early progression (EP). Results: Forty patients were enrolled in CED and 11 as controls. Ten patients from CED and three controls were excluded due to treatment discontinuation before 3 months (drug-related toxicity and enrollment in post-CRT trials respectively). Three patients in CED (6%) had AP (all confirmed as EP) and no patients fulfilled criteria for PsP. Six patients from control (54%) had AP; 3 (27%) were eventually classified as EP and 3 (27%) as PsP. The frequency of PsP was significantly higher in the control group (p=0.0086). Conclusions: The addition of a VEGF inhibitor as part of adjuvant treatment in this cohort of glioblastoma patients prevented the development of early treatment-related effects (PsP). Suppressing the edema and mass effect that accompanies PsP may improve the tolerability of treatment. Additionally, this effect may be exploited as a strategy to make chemoradiation feasible in patients with large, unresectable tumors and/or poor baseline performance status.