Response to 1-Year Fixed-Regimen Bevacizumab Therapy in Treatment-Naïve DME Patients: Assessment by OCT Angiography.

PURPOSE: To evaluate the effectiveness of intravitreal bevacizumab treatment in patients with diabetic macular edema (DME) by assessing retinal changes using optical coherence tomography angiography (OCT-A). METHODS: This prospective study was performed in patients with treatment-naïve DME. The eyes of patients were imaged using a swept-source OCT system with a scan area of 6 × 6 mm. The DME patients with a central macular thickness (CMT) of ≥300 µm received nine bevacizumab injections within 12 months. The demographic, systemic, and ocular parameters, including the best-corrected visual acuity (BCVA), CMT, microaneurysm (MA) count, and foveal avascular zone (FAZ) area in both superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as vessel density in SCP, were assessed in the patients. In addition, the response (good or poor) of the DME eyes to bevacizumab treatment and the final visual acuity (BCVA of 75 letters) were analyzed. RESULTS: Seventy-seven eyes of DME patients were subjected to the final analysis. Bevacizumab treatment reduced CMT from 425.06 µm (±77.15) to 350.25 µm (±82.04) and improved BCVA by about 8.61 letters (from 64.73 to 73.34) in the patients. The mean number of MAs in SCP decreased from 3.51 ± 2.07 to 2.31 ± 1.15 (p < 0.001) and in DCP from 17.12 ± 11.56 to 12.21 ± 6.99 (p < 0.001), whereas the area of FAZ increased in SCP from 328.22 ± 131.38 to 399.70 ± 156.98 (p < 0.001) and in DCP from 571.13 ± 396.01 to 665.89 ± 412.77 (p = 0.001). The final BCVA letter score and CMT were statistically significant in both poor and good responders, as well as in BCVA < 75 and BCVA ≥ 75 groups. CONCLUSION: The fixed-regimen intravitreal bevacizumab therapy was effective in treating DME. Apart from noninvasive visualization of microvascular damage, OCT-A showed limited usefulness in predicting treatment response. Although the study showed that the number of MAs was significantly reduced during treatment, which is an OCT-A predictor of a good response to bevacizumab treatment at a 12-month visit, commonly observed artifacts may reduce the usefulness of OCT-A.

Assessment of tumor hypoxia and perfusion in recurrent glioblastoma following bevacizumab failure using MRI and 18F-FMISO PET.

Tumoral hypoxia correlates with worse outcomes in glioblastoma (GBM). While bevacizumab is routinely used to treat recurrent GBM, it may exacerbate hypoxia. Evofosfamide is a hypoxia-targeting prodrug being tested for recurrent GBM. To characterize resistance to bevacizumab and identify those with recurrent GBM who may benefit from evofosfamide, we ascertained MRI features and hypoxia in patients with GBM progression receiving both agents. Thirty-three patients with recurrent GBM refractory to bevacizumab were enrolled. Patients underwent MR and 18F-FMISO PET imaging at baseline and 28 days. Tumor volumes were determined, MRI and 18F-FMISO PET-derived parameters calculated, and Spearman correlations between parameters assessed. Progression-free survival decreased significantly with hypoxic volume [hazard ratio (HR) = 1.67, 95% confidence interval (CI) 1.14 to 2.46, P = 0.009] and increased significantly with time to the maximum value of the residue (Tmax) (HR = 0.54, 95% CI 0.34 to 0.88, P = 0.01). Overall survival decreased significantly with hypoxic volume (HR = 1.71, 95% CI 1.12 to 12.61, p = 0.01), standardized relative cerebral blood volume (srCBV) (HR = 1.61, 95% CI 1.09 to 2.38, p = 0.02), and increased significantly with Tmax (HR = 0.31, 95% CI 0.15 to 0.62, p < 0.001). Decreases in hypoxic volume correlated with longer overall and progression-free survival, and increases correlated with shorter overall and progression-free survival. Hypoxic volume and volume ratio were positively correlated (rs = 0.77, P < 0.0001), as were hypoxia volume and T1 enhancing tumor volume (rs = 0.75, P < 0.0001). Hypoxia is a key biomarker in patients with bevacizumab-refractory GBM. Hypoxia and srCBV were inversely correlated with patient outcomes. These radiographic features may be useful in evaluating treatment and guiding treatment considerations.