Significant response to atezolizumab plus bevacizumab treatment in unresectable hepatocellular carcinoma with major portal vein tumor thrombus: a case report

Background Hepatocellular carcinoma (HCC) with major portal vein tumor thrombus (Vp4 PVTT) is an extremely advanced tumor with limited treatment options. Systemic chemotherapy is the only recommended treatment option, and atezolizumab plus bevacizumab has recently emerged as a first-line treatment option. Case presentation We describe the case of an 82-year-old man with unresectable advanced HCC with Vp4 PVTT who achieved a significant response to atezolizumab plus bevacizumab treatment. A single administration of atezolizumab plus bevacizumab ensured significant anti-tumor effects (regression in the tumor size and PVTT, portal vein recanalization, and serum alfa-fetoprotein levels decreased from 90,770 to 89 ng/mL). The patient continued with atezolizumab monotherapy, and after nine consecutive regimens, there was no apparent sign of residual tumor. Conclusions This case demonstrates the powerful anti-tumor effect of atezolizumab plus bevacizumab treatment for advanced HCC with Vp4 PVTT, suggesting that these agents can be a promising treatment option for such refractory tumors.

Inter-eye comparison of retinal vascular growth rate and angiographic findings following unilateral bevacizumab treatment

Purpose To compare retinal vascularization progression rate, final retinal vascularization, and fluorescein angiography (FA) findings in infants who received intravitreal bevacizumab (IVB) treatment in one eye and with spontaneous regression in the other eye. Methods Thirty eyes of 15 infants who underwent IVB in one eye due to asymmetric retinopathy of prematurity, and who had pre-treatment fundus photographs and fluorescein angiography images were included in the study. Horizontal disc diameter (DD), optic disc-to-fovea distance (FD), and the length of temporal retinal vascularization (LTRV) distance were measured by evaluating pre-treatment and FA images. Results The mean ages at the time of treatment and FA were 40.38 ± 3.35 and 68.72 ± 10.52 weeks postmenstrual age, respectively. The pre-treatment LTRV/FD ratio was 3.11 ± 0.41 in the treated eyes and 3.26 ± 0.43 in the non-treated eyes (p = 0.053). The final LTRV/FD ratio was 4.23 ± 0.38 in the treated group and 4.33 ± 0.37 in the non-treated group (p = 0.286). Staining of the vessels, hyperfluorescent focus, and irregular branching of the vessels were similar between the groups, respectively (p = 1.000; p = 0.250; p = 0.625). Conclusion The progression rate of retinal vascularization and angiographic findings were similar between the treated eyes and the non-treated eyes. Our study suggests that incomplete retinal vascularization in eyes treated with anti-vascular endothelial growth factor (VEGF) is due to the nature of the disease, and anti-VEGF treatment was not to cause cessation in vascular progression.

ACT-6 Clinical manifestations of the patients with relapsed glioblastoma after bevacizumab treatment

Introduction:The outcome of glioblastoma (GBM) is improving recently, but still only temozolomide and bevacizumab (BEV) are recognized as the effective agents that are reimbursed in Japan. On large clinical trials, BEV prolonged progression free survival (PFS) but the remaining survival period from the relapse after BEV is only 3–5 month. On this study, we retrospectively analyzed the data of GBM patients who were treated with BEV to explore the best usage of BEV.Methods:230 patients were diagnosed as GBM and received BEV from July 2013 to March 2021 in our institution. Among them, 104 patient, whose clinical courses were followed, were included in this study. (M:F=59:45, median age was 65.5) Results:The patients were divided into three groups by when they used BEV; upfront group at first line therapy, 1st relapse group at second line, and 2nd+ relapse group at more than third line. There were 42, 35, 27 patients in each group. The median overall survival (OS) was 17.6, 24.7, 46.1 month (p<0.0001), median PFS after BEV treatment (PFSpBEV) was 8.8, 5.1, 5.0 month (p=0.2532), and the median survival after BEV treatment (OSpBEV) was 15.0, 9.9, 9.2 month (p=0.4437), respectively. There were 64 patients (22, 25, 17 in each group) who reached progressive disease (PD) after BEV. The median survival after PD (OSpBEVpPD) was 4.5, 5.8, 4.3 month (p=0.1590), respectively.Discussion:At the first onset, we use BEV only when the patients have low PS. Our results showed that OS was significantly longer when BEV was used in the later stage, but there was no significant difference in OS or PFS after BEV treatment. Especially OSpBEVpPD was 4–6 month regardless of the timing of BEV. To improve the treatment outcome of GBM, breakthrough therapy is needed in addition to optimizing the usage of BEV.

Bevacizumab confers significant improvements in survival for ovarian cancer patients with low miR-25 expression and high miR-142 expression

Background Lymphovascular space invasion (LVSI) is the first step of hematogenous metastasis. Exploration of the differential miRNA expression profiles between LVSI-positive and LVSI-negative ovarian cancer tissues may help to identify key miRNAs involved in the hematogenous metastasis of ovarian cancer. This study is aimed to identify microRNAs (miRNAs) that are differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tissues, followed by exploring their association with bevacizumab response in ovarian cancer patients. Methods The Cancer Genome Altas (TGGA) dataset was used to identify the differentially expressed miRNAs between LVSI-positive and LVSI-negative ovarian cancer tissues. The prognostic value of the differentially expressed miRNAs was determined using GSE140082 dataset. Results We showed that miR-25 and miR-142 were differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tumors. Kaplan-Meier analysis indicated that high miR-25 expression was associated with increased progression free survival (PFS) and extended overall survival (OS). Moreover, patients with low miR-25 expression benefited significantly from bevacizumab treatment in terms of PFS. A similar trend was observed in terms of OS though without reaching statistical significance. In contrast, no significant survival benefits from bevacizumab were observed in patients with high miR-25 expression in terms of PFS and OS. There was no significant correlation between miR-142 expression and PFS. In contrast, high miR-142 expression was associated with reduced OS. Moreover, patients with high miR-142 expression benefited significantly from bevacizumab treatment in terms of PFS and OS. However, bevacizumab treatment conferred no significant improvements in both PFS and OS in patients with low miR-142 expression. The nomogram for PFS indicated that miR-25 expression had a larger contribution to PFS than debulking status and bevacizumab treatment. And the nomogram for OS illustrated both miR-25 expression and miR-142 expression as sharing a larger contribution to OS than bevacizumab treatment and debulking status. Conclusion In conclusion, miR-25 expression correlates with a better PFS and OS in ovarian cancer. Patients with low miR-25 expression and high miR-142 expression could benefit from bevacizumab treatment significantly.

Correlation of response to intravitreal bevacizumab treatment between the first and second treated eyes in diabetic macular edema

Purpose To evaluate whether outcome of bevacizumab treatment in the first treated eye can guide the selection of compound for the second treated eye in patients with bilateral diabetic macular edema. Methods Demographic, clinical, and optical coherence tomography data were retrospectively collected from consecutive patients who underwent bevacizumab therapy for bilateral diabetic macular edema. Change in central subfield thickness and visual acuity were evaluated and compared between the first treated eye and second treated eye. Results A total of 66 eyes of 33 patients were included in the study. The mean ± SD follow-up time was 13 ± 5 months. The mean ± SD central subfield thickness at baseline was 464 ± 30 μm in the first treated eye and 461 ± 29 μm in the second treated eye ( p = 0.91). Final central subfield thickness was reduced to 392 ± 27 μm in the first treated eye ( p = 0.01 compared with baseline) and 416 ± 25 μm in the second treated eye ( p = 0.03 compared with baseline). Using ≥5% or ≥10% reduction of central subfield thickness as diagnostic criteria to predict similar magnitude of thickness reduction in the first treated eye yielded a positive and negative predictive value ranging from 46% to 81%, and sensitivity and specificity ranging from 54% to 84%. Regression models did not show correlation between central subfield thickness reduction in first treated eye and the second treated eye at the end of follow-up. Conclusions Bevacizumab therapy reduced macular thickness in both eyes in bilateral diabetic macular edema. Treatment outcome of the first treated eye could not predict the outcome of the second treated eye. Particularly, failure to reduce central subfield thickness in the first treated eye does not preclude a favorable response to bevacizumab therapy in the second eye.

Intravitreal bevacizumab treatment for exudative choroidal neovascularisation in best vitelliform macular dystrophy

Purpose To describe results of intravitreal bevacizumab treatment of the secondary choroidal neovascularisation in Best vitelliform macular dystrophy in an adult and paediatric patient, and present the management of three asymptomatic patients with confirmed BEST1 gene mutation. Case series description Five patients from the same family with the Best vitelliform macular dystrophy are presented. In two patients (aged 63 and 4 years) secondary choroidal neovascularisation caused a rapid decline in visual acuity. In the adult patient with advanced Best vitelliform macular dystrophy, visual acuity did not improve despite eight intravitreal bevacizumab injections to the right eye. The formation of a central scar and rapid reoccurrence of choroidal neovascularisation three months after completing the initial treatment affected the outcome. As for the paediatric patient with bilateral choroidal neovascularisation in the vitelliform stage of Best vitelliform macular dystrophy, a complete recovery of visual acuity was observed after two (left eye) and three (right eye) bevacizumab injections, with adjunctive amblyopia treatment. The other three patients with an abnormal electrooculogram reported no visual problems during more than 10 years of follow-up. Minimal changes were seen on optical coherence tomography in the youngest patient. Conclusions Intravitreal bevacizumab seems to be an effective treatment for exudative choroidal neovascularisation in the vitelliform stage of Best vitelliform macular dystrophy; however, it may not be beneficial in the advanced stages of Best vitelliform macular dystrophy. It is important to regularly screen all family members with an abnormal electrooculogram and confirmed mutation for vitelliform changes and choroidal neovascularisation from an early age. The decision for anti-vascular endothelial growth factor treatment should be made on a case-to-case basis as complications may arise.

Early Changes in Alpha-Fetoprotein Are a Useful Predictor of Efficacy of Atezolizumab plus Bevacizumab Treatment in Patients with Advanced Hepatocellular Carcinoma

<b><i>Introduction:</i></b> The aim of this study was to investigate the early changes in alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) levels in patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab and to evaluate the relationship between changes in these tumor markers and treatment efficacy. <b><i>Methods:</i></b> Of 58 consecutive patients who started atezolizumab plus bevacizumab at our institution, 50 patients with information on antitumor response obtained at 6 weeks after therapy were enrolled in this study and their treatment outcomes were retrospectively evaluated. <b><i>Results:</i></b> According to the Response Evaluation Criteria in Solid Tumors at 6 weeks, the objective response (OR) rate was 22.0% and the disease control (DC) rate was 78.0%. In patients who achieved OR at 6 weeks, median AFP and DCP ratios at weeks 1, 2, 3, and 6 were significantly lower than those in patients who did not achieve OR. AFP ratios in patients who did not achieve DC at 6 weeks (Non-6W-DC group) were significantly higher than in those who achieved DC at week 6 (6W-DC group). Median overall survival in the Non-6W-DC group was significantly shorter than in the 6W-DC group (156 days vs. not reached, <i>p</i> = 0.0008). An AFP ratio of 1.4 or higher at 3 weeks had a specificity of 88.0% and a sensitivity of 88.9% for predicting Non-6W-DC. Median progression-free survival was significantly shorter in patients with an AFP ratio of 1.4 or higher at 3 weeks than in those with an AFP ratio of &#x3c;1.4 (42 days vs. 210 days, <i>p</i> = 0.0003). <b><i>Conclusion:</i></b> Early changes in AFP might be useful for predicting the antitumor efficacy of atezolizumab plus bevacizumab in patients with advanced HCC. An AFP ratio of 1.4 or higher at 3 weeks might be an early predictor of refractoriness to atezolizumab plus bevacizumab therapy.