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Intraocular vascular endothelial growth factor (VEGF) levels play an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Here, we aimed to develop a paper-based enzyme-linked immunosorbent assay (P-ELISA) to analyze the suppression of aqueous VEGF concentrations following intravitreal injection (IVI) of anti-VEGF antibody (bevacizumab or ranibizumab). A total of 25 eyes with wet AMD, one with myopic neovascularization, and one with polypoidal choroidal vasculopathy were enrolled in this study. The limit of detection using P-ELISA was 0.03 pg/mL. Forty-six consecutive samples of aqueous humor were acquired. From all samples, 66.67% (10/15) achieved complete VEGF suppression (below the detection limit) within 5 weeks of receiving IVI of anti-VEGF antibody. Only 13.33% of samples (2/15) achieved complete VEGF suppression 5 weeks after receiving treatment. In some patients, elevated VEGF was still detected 5 weeks after receipt of anti-VEGF antibody, and all samples (10/10) were found to have elevated VEGF levels 49 days after treatment. Thus, we suggest that monthly IVI of anti-VEGF antibody may be required to ensure durable VEGF inhibition. Ultrasensitive P-ELISA can detect elevated VEGF at an earlier time point and may facilitate decision-making regarding appropriate treatment strategies., Competing Interests: M.-Y.H., K.H.L., and C.M.C. are inventors of a patent (patent no.: TW 201428105) owned by National Tsing Hua University based on the work reported in this paper. M.-Y.H. and C.M.C. have a patent pending in the USA based on the work reported in this paper (patent no:US20140315224 A1). Y.-C.H., D.-K.H., S.-C.L., K.-H.L., C.-Y.W., Y.-P.W. and H.-Y.C. have no potential conflicts of interest to declare.

It is now 12 years since the first article on medication-related osteonecrosis of the jaw (MRONJ) was reported in 2003. The recognition of MRONJ is still inconsistent between physicians and dentists but it is without doubt a severe disease with impairment of oral health-related quality of life. This position paper was developed by three Austrian societies for dentists, oral surgeons and osteologists involved in this topic. This update contains amendments on the incidence, pathophysiology, diagnosis, staging and treatment and provides recommendations for management based on a multidisciplinary international consensus. The MRONJ can be a medication-related side effect of treatment of malignant and benign bone diseases with bisphosphonates (Bp), bevacizumab and denosumab (Dmab) as antiresorptive therapy. The incidence of MRONJ is highest in the oncology patient population (range 1-15 %), where high doses of these medications are used at frequent intervals. In the osteoporosis patient population, the incidence of MRONJ is estimated to be 0.001-0.01 %, marginally higher than the incidence in the general population (< 0.001 %). Other risk factors for MRONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, ill-fitting dentures as well as other drugs, including antiangiogenic agents. Prevention strategies for MRONJ include elimination or stabilization of oral disease prior to initiation of antiresorptive agents, as well as maintenance of good oral hygiene. In those patients at high risk for the development of MRONJ, including cancer patients receiving high-dose BP or Dmab therapy, consideration should be given to withholding antiresorptive therapy following extensive oral surgery until the surgical site heals with mature mucosal coverage. Management of MRONJ is based on the stage of the disease, extent of the lesions and the presence of contributing drug therapy and comorbidity. Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic therapy. Early data have suggested enhanced osseous wound healing with teriparatide in those patients without contraindications for its use. The MRONJ related to denosumab may resolve more quickly with a drug holiday than MRONJ related to bisphosphonates. Localized surgical debridement is indicated in advanced nonresponsive disease and has proven successful. More invasive surgical techniques are becoming increasingly more important. Prevention is the key for the management of MRONJ. This requires a close teamwork for the treating physician and the dentist. It is necessary that this information is disseminated to other relevant health care professionals and organizations.

Purpose: Atezolizumab/bevacizumab (atezo-bev) is the first-line chemotherapy for patients with unresectable hepatocellular carcinoma (HCC). However, hepatic artery infusion chemotherapy (HAIC) can be used as an alternative. Our aim was to compare the prognosis of HAIC treatment between newly diagnosed patients and patients treated after failure of atezo-bev., Methods: We retrospectively assessed 73 patients with HCC treated with HAIC between January 2022 and September 2023. Fifty-seven patients were treated with HAIC at initial diagnosis, while 16 were treated with HAIC after first-line atezo-bev combination chemotherapy. We evaluated tumor responses, such as overall survival (OS), progression-free survival (PFS), and objective response rate (ORR)., Results: No significant difference was observed in either OS or PFS between patients with HCC treated with HAIC at the initial diagnosis and those treated after atezo-bev treatment failure. However, the ORR of the initial HAIC group was 19.6% and that of the HAIC group after atezo-bev therapy failure was 43.6%, which was a statistically significantly difference., Conclusion: Although no significant difference was observed for OS and PFS, the ORR of patients in the HAIC group after the failure of atezo-bev therapy was superior to that of newly diagnosed patients. HAIC may prolong survival in patients with HCC after atezo-bev treatment failure., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Byline: Mazda. Turel, Manjul. Tripathi, Ashish. Aggarwal, Navneet. Singla, Chirag. Ahuja, Aastha. Takkar, Sahil. Mehta, Kanwaljeet. Garg, Ravi. Yadav, Anant. Mehrotra, Kuntal. Das Vleggeert-Lankamp CLA, et al. The NECK trial: [...]

Compared with intravenous (i.v.) chemotherapy, oral administration is convenient, requires fewer healthcare resources, is generally preferred by patients, and may be appropriate in older people with breast, colorectal and lung cancers. The effects of organ dysfunction on drug metabolism and drug interactions in patients with multiple comorbidities must be considered but are not specific to oral chemotherapy. Single-agent oral chemotherapy with capecitabine or vinorelbine is active in older patients with advanced or metastatic breast cancer. Choice of treatment is based mainly on different safety profiles. In the adjuvant treatment of colorectal cancer (CRC), single-agent oral capecitabine is an effective alternative to i.v. fluorouracil (5-FU) regimens. In metastatic CRC, oral, single-agent capecitabine has recently shown encouraging median overall survival in combination with bevacizumab. In non-small cell lung cancer, fit older patients, like their younger counterparts, benefit from platinum-based doublets, with carboplatin preferred to cisplatin. Single agent vinorelbine is an option for those less suited to combination chemotherapy, and oral may be an alternative to i.v. administration. For elderly cancer patients in general, metronomic chemotherapy combines good tolerability with acceptable activity. [ABSTRACT FROM AUTHOR]

Abstract: Treatments currently recommended for metastatic renal cell cancer (mRCC) have not been evaluated specifically in elderly patients. Here we consider what may be learned by analysing according to age the efficacy and toxicity data from key phase III trials of the targeted agents sorafenib (Nexavar), sunitinib (Sutent), temsirolimus (Torisel), and bevacizumab (Avastin), and from a study of expanded access to sunitinib and sorafenib. This paper represents the first systematic review of the role of targeted agents specifically in the elderly population. Retrospective subgroup analyses of clinical trial data cannot be considered definitive. However, they suggest in general that the progression-free and overall survival benefits seen in mRCC patients aged 65 years and over are similar to those in the younger age group. The frequency of major toxicities in elderly patients treated with targeted agents is no greater than in younger patients, although such toxicities may have greater impact on the quality of life. That said, no meaningful data are available for patients over 85 years. To confirm and extend these conclusions, prospective studies should be undertaken in the elderly to determine whether recommendations made for the wider mRCC population apply equally to this group of patients in whom comorbidities, comedication and the greater impact of low-grade toxicity may influence the efficacy and tolerability of treatment. Such studies are increasingly needed, given the growing number of elderly people and their rising life expectancy. Meanwhile, when considering the most appropriate drug to use in a particular patient, the toxicity profiles of the individual targeted agents – and any implications for specific comorbid conditions – should be taken into account. [Copyright &y& Elsevier]

Colorectal cancer (CRC), as a fatal cancer, is one of the most common cancers worldwide. Although the standard treatment for colorectal cancer is well researched and established, long-term patient survival remains poor, and mortality remains high. Therefore, more and more effective treatment options are needed. To evaluate the efficacy of bevacizumab, the histone demethylase inhibitor IOX1, or their combination for the treatment of colorectal cancer, we examined the effects of IOX1, bevacizumab, and IOX1 combined with bevacizumab on cell activity, proliferation, and migration of colorectal cancer cell lines HCT116, RKO, and CT26 by CCK8, colony formation assay, wound healing assay, and transwell assay. The effects of the drugs alone as well as in combination on apoptosis in colorectal cancer cell lines were examined by flow cytometry and further validated by Western blotting for apoptosis-related proteins. The antitumor effects of treatment alone or in combination on colorectal cancer cells were examined in animal models. Mice were injected subcutaneously with CT26 cells and the growth and immune infiltration in tumor tissues were detected by IHC after drug treatment. We found that IOX1 could effectively inhibit the activity of CRC cells and had a significant inhibitory effect on the proliferation and migration of CRC cells. The apoptosis rate increased in a dose-dependent manner after IOX1 treatment on colorectal cancer cells, and the expression of apoptosis-related proteins changed accordingly. Further combination with bevacizumab revealed that the combination had a more significant effect on the proliferation, migration, and apoptosis of CRC cells than either IOX1 or bevacizumab alone. In vivo experiments have found that both alone and combination drugs can inhibit the growth of mouse tumors, but the effect of combination inhibition is the most obvious. Combination therapy significantly inhibited the expression of proliferative marker (Ki67) in tumor xenograft models, and increased content of antigen-specific CD4 + , CD8 + T cell growth, and granzymeB (GZMB), which is associated with T cell cytotoxicity, was detected in combination therapy. Immunoassays suppressed the expression of relevant PD-1 and decreased. The anticancer drug bevacizumab and the histone demethylase inhibitor IOX1 may inhibit colon cancer cell growth by regulating apoptosis. The inhibitory effect of combination therapy on tumor growth may be achieved, in part, through upregulation of infiltration-mediated tumor immunity by T lymphocytes. The combination of IOX1 and bevacizumab produced significant synergistic effects. This study aims to provide a new direction for CRC combination therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This study introduces a novel approach utilizing a temporary drug-eluting hydrogel corneal patch to prevent neovascularization, alongside a numerical predictive tool for assessing the release and transport kinetics of bevacizumab (BVZ) after the keratoplasty. A key focus was investigating the impact of tear film clearance on the release kinetics and drug transport from the designed corneal patch. The proposed tear drug clearance model incorporates the physiological mechanism of lacrimal flow (tear turnover), distinguishing itself from previous models. Validation against experimental data confirms the model's robustness, despite limitations such as a 2D axisymmetrical framework and omission of blink frequency and saccadic eye movements potential effects. Analysis highlights the significant influence of lacrimal flow on ocular drug transport, with the corneal patch extending BVZ residence time compared to topical administration. This research sets the stage for exploring multi-layer drug-eluting corneal patches as a promising therapeutic strategy in ocular health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Re-irradiation (reRT) is an effective treatment modality for patients with recurrent glioma. Data on dose escalation, the use of simulated integrated boost and concomitant therapy to reRT are still scarce. In this monocentric cohort of n = 223 patients we investigated the influence of reRT dose escalation as well as the concomitant use of bevacizumab (BEV) with regard to post-recurrence survival (PRS) and risk of radionecrosis (RN)., Patients and Methods: Patients with recurrent glioma treated between July 2008 and August 2022 with reRT with BEV, reRT with temozolomide (TMZ) and reRT without concomitant systemic therapy were retrospectively analyzed. PRS and RN-free survival (RNFS) were calculated for all patients using the Kaplan-Meier estimator. Univariable and multivariable cox regression was performed for PRS and for RNFS. The reRT Risk Score (RRRS) was calculated for all patients., Results: Good, intermediate and poor risk of the RRRS translated into 11 months, 9 months and 7 months of median PRS (univariable: p = 0.008, multivariable: p = 0.013). ReRT was applied with a dose of ≤36 Gy (n = 140) or >36 Gy (n = 83). Concomitant bevacizumab (BEV) therapy was performed in n = 122 and concomitant temozolomide (TMZ) therapy in n = 32 patients. Median PRS was 10 months in patients treated with >36 Gy and 8 months in patients treated with ≤36 Gy (univariable: p = 0.032, multivariable: p = 0.576). Regarding concomitant TMZ therapy, median PRS was 14 months vs. 9 months for patients treated with or without TMZ (univariable: p = 0.041, multivariable: p = 0.019). No statistically significant influence on PRS was seen for concomitant BEV therapy in this series. RN was less frequent for reRT with concomitant BEV, (17/122; 13.9 %) than for reRT without BEV (30/101; 29.7 %). Regarding RNFS, the hazard ratio for reRT with BEV was 0.436 (univariable; p = 0.006) and 0.479 (multivariable; p = 0.023), respectively. ReRT dose did not show statistical significance in regards to RN (univariable: p = 0.073, multivariable: p = 0.404). RNFS was longer for patients receiving concomitant BEV to reRT than for patients treated with reRT only (mean 31.7 vs. 30.9 months, p = 0.004)., Conclusion: In this cohort, in patients treated with concomitant BEV therapy RN was less frequently detected and in patients treated with concomitant TMZ longer PRS was observed. Based on these results, the best concomitant therapy and the optimal dose should be decided on a patient-by-patient basis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maximilian Niyazi has received speaker honoraria from Astra Zeneca und Brainlab. Raphael Bodensohn has received honoraria from NovoCure for participating in invited meetings of specialized centers. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Though atezolizumab plus bevacizumab (A+B) offer promise for unresectable hepatocellular carcinoma (uHCC) treatment, the response rate remains suboptimal. Our previous studies highlighted the potential of transarterial chemoembolization (TACE) when combined with FOLFOX-based hepatic arterial infusion chemotherapy (HAIC) in HCC treatment. This study aims to evaluate the safety and efficacy of A+B plus TACE-HAIC for high tumor burden uHCC (HTB-uHCC)., Methods: This three-center retrospective study involved 82 HTB-uHCC patients administered with TACE-HAIC followed by A+B. We characterized HTB-uHCC patients as those surpassing the up-to-11 criteria, exhibiting VP 3-4, or presenting extrahepatic metastases. The primary outcomes were the objective response rate (ORR) and progression-free survival (PFS). Secondary outcomes encompassed the incidence of treatment-related adverse events (TRAEs) and overall survival (OS)., Results: Employing the mRECIST criteria, the ORR was 62.2 %, wherein 18 (22.0 %) patients achieved complete response, 33 (40.2 %) demonstrated partial response, 21 (25.6 %) maintained stable disease, and 10 (12.2 %) exhibited disease progression. Impressively, 11 (13.4 %) patients were converted to resectable HCC and underwent curative hepatectomy. The median PFS was 10.1 months (95 % CI, 8.4 to NA), and the median OS was still pending. At the one-year mark, the OS and PFS rates were 92.8 % (95 % CI, 86.1 to 100.0) and 42.9 % (95 % CI, 31.3 to 58.7), respectively. 79 (96.3 %) experienced TRAEs, and 39 (47.6 %) had grade 3-4 TRAEs, though no treatment-related death was recorded., Conclusions: The findings underscore the potential of the A+B and TACE-HAIC combined treatment for HTB-uHCC patients, marking it as a viable therapeutic option, given its potent efficacy and tolerable safety profile., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Angiogenesis is critical for tumor growth and metastasis. Bevacizumab is an antiangiogenic drug used to treat various adult and childhood solid tumors. Its potential efficacy in Wilms tumor (WT) with poor prognosis is not established., Areas Covered: The response to bevacizumab-containing regimens in relapsed or refractory WT was reviewed in available literature. Searches were conducted using PubMed, Scopus, and ClinicalTrials.gov databases. Eight papers were identified, published between 2007 and 2020, including six treatment regimens, predominantly vincristine, irinotecan, and bevacizumab (VIB) ± temozolomide (VITB). Among 16 evaluable patients, there were two complete responses, seven partial responses, five patients achieved stable disease (SD), and two patients had progressive disease. Objective responses (OR) were observed in 56% of all cases. OR or SD was observed in 89% (8/9) patients who received VIB/VITB. Bevacizumab was generally well tolerated. Related toxicities included hypertension, proteinuria, and delayed wound healing., Expert Opinion: This review suggests potential effectiveness and good tolerability of bevacizumab in the setting of relapsed/refractory WT when used in combination with other drugs. Such combination therapies may serve as a bridging treatment option to other interventions and more personalized treatment options in the future; however, focused trials are needed to obtain additional evidence.

We developed an aptamer-based fluorescence resonance energy transfer (FRET) assay capable of recognizing therapeutic monoclonal antibody bevacizumab and rapidly quantifying its concentration with just one mixing step. In this assay, two fluorescent dyes (fluorescein and tetramethylrhodamine) labeled aptamers bind to two Fab regions on bevacizumab, and FRET fluorescence is observed when both dyes come into close proximity. We optimized this assay in three different formats, catering to a wide range of analytical needs. When applied to hybridoma culture samples in practical settings, this assay exhibited a signal response that was concentration-dependent, falling within the range of 50-2000 μg/mL. The coefficients of determination (r 2 ) ranged from 0.998 to 0.999, and bias and precision results were within ±24.0 % and 20.3 %, respectively. Additionally, during thermal and UV stress testing, this assay demonstrated the ability to detect denatured samples in a manner comparable to conventional Size Exclusion Chromatography. Notably, it offers the added advantage of detecting decreases in binding activity without changes in molecular weight. In contrast to many existing process analytical technology tools, this assay not only identifies bevacizumab but also directly measures the quality attributes related to mAb efficacy, such as the binding activity. As a result, this assay holds great potential as a valuable platform for providing highly reliable quality attribute information in real-time. We consider this will make a significant contribution to the worldwide distribution of high-quality therapeutic mAbs in various aspects of antibody manufacturing, including production monitoring, quality control, commercial lot release, and stability testing., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Kenichiro Todoroki reports financial support was provided by Daiichi Sankyo Co. Ltd., Tokyo. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Portal hypertension (PHT) often complicates hepatocellular carcinoma (HCC) treatment and prognosis. We aimed to assess PHT's impact on AtezoBev outcomes and identify predictors of acute variceal bleeding (AVB) and clinical ascites occurrence., Methods: A prospective cohort of 200 HCC patients treated with AtezoBev was studied alongside a retrospective cohort of 123 patients treated with Sorafenib. We assessed factors influencing progression-free survival (PFS), overall survival (OS), AVB and clinical ascites development, focusing on PHT parameters, and comparing outcomes within and between the two cohorts (time-dependent Cox model and adjusted survival curves)., Results: Among the AtezoBev cohort, 10% experienced AVB, 24% had high-risk esophageal varices (EV) and 46% vascular invasion. Median PFS and OS in the AtezoBev cohort was 5.13 and 12.2 months. AVB (HR=1.81;[95%CI:1.03-3.17]) and clinical ascites occurrence (HR=2.29;[95%CI:1.52-3.45]) were independently associated with mortality. AVB incidence was 12% at 12 months in AtezoBev patients and EV, history of AVB<6months and vascular invasion were independently associated with AVB. The Sorafenib cohort had shorter median PFS and OS, with similar AVB incidence and only EV were associated with AVB., Conclusions: PHT-related events significantly affect not only liver decompensation but also OS in AtezoBev-treated patients. We suggest a more widespread use of NSBB to prevent liver decompensation, with intensified prophylaxis for high-risk patients., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Central nervous system (CNS) tumors are among the most common malignancies in various age ranges. Low-grade glioma (LGG) can account for nearly 30% of pediatric CNS malignancies. Progression or recurrence after the first-line treatments is common among these patients. Therefore, more treatments are required. Bevacizumab as an anti-VEGF antibody has come into the spotlight recently and is especially used in relapse or recurrence settings. This review aims to study the safety and efficacy of bevacizumab for patients with recurrent LGG., Methods: This study was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Scopus, Web of Science, and Embase were comprehensively searched using the relevant key terms until 24th August 2023 to retrieve the studies that investigated clinical outcomes of bevacizumab in patients with recurrent LGG. All statistical analysis was performed by STATA v.17., Results: A total of 1306 papers were gathered, out of which 13 were incorporated in the meta-analysis. The pooled incidence rate of treatment according to the RANO scale was 70% (95% CI = 43-98%) for objective response rate, 26% (95% CI = 58-96%) for partial response, 21% (95% CI = 15-28%) for minor response, 14% (95% CI = 3-24%) for complete response, 48% (95% CI = 37-59%) for stable disease, and 8% (95% CI = 4-11%) for progressive disease. Furthermore, according to progressive survival after treatment, it was 4% (95% CI = -1 to 9%) for 6-month PFS, 41% (95% CI = 32-50%) for 2-year PFS, and 29% (95% CI = 22-35%) for 3-year PFS., Conclusion: According to the RANO scale and PFS, clinicians should be aware that Bevacizumab could be a favorable alternative therapy for recurrent LGG. Furthermore, bevacizumab exhibits minimal toxicity and high tolerability in recurrent LGG., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: When treating Lung Cancer, it is necessary to identify early treatment failure to enable timely therapeutic adjustments. The Aim of this study was to investigate whether changes in tumor diffusion during treatment with chemotherapy and bevacizumab could serve as a predictor of treatment failure., Material and Methods: A prospective single-arm, open-label, clinical trial was conducted between September 2014 and December 2020, enrolling patients with stage IV non-small cell lung cancer (NSCLC). The patients were treated with chemotherapy-antiangiogenic combination. Diffusion weighted magnetic resonance imaging (DW-MRI) was performed at baseline, two, four, and sixteen weeks after initiating treatment. The differences in apparent diffusion coefficient (ADC) values between pre- and post-treatment MRIs were recorded as Delta values (ΔADC). We assessed whether ΔADC could serve as a prognostic biomarker for overall survival (OS), with a five year follow up., Results: 18 patients were included in the final analysis. Patients with a ΔADC value ≥ -3 demonstrated a significantly longer OS with an HR of 0.12 (95 % CI; 0.03- 0.61; p = 0.003) The median OS in patients with a ΔADC value ≥ -3 was 18 months, (95 % C.I; 7-46) compared to 7 months (95 % C.I; 5-9) in those with a ΔADC value < -3., Conclusion: Our findings suggest that early changes in tumor ADC values, may be indicative of a longer OS. Therefore, DW-MRI could serve as an early biomarker for assessing treatment response in patients receiving chemotherapy combined with antiangiogenic therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Atezolizumab/bevacizumab combination therapy became the first-line therapy for advanced hepatocellular carcinoma (HCC). Gastroesophageal varices should be monitored and managed before treatment. The progression of portal hypertension during bevacizumab-containing therapy is unclear., Method: A case of new development of esophageal varices, ascites, and hepatic hydrothorax during atezolizumab/bevacizumab therapy at National Taiwan University Hospital was reported, and relevant literature was reviewed., Results: We presented an 83-year-old male with resolved hepatitis B without cirrhosis. He had BCLC stage C HCC and received tri-weekly atezolizumab/bevacizumab therapy for 34 cycles with sustained partial response. Progressive ascites, esophageal varices, and hepatic hydrothorax developed, though his portal vein was patent and the tumor was under control. Five similar cases of HCC (BCLC B/C: n = 3/2) had been reported previously. Among them, three had cirrhosis with pre-existing small esophageal varices before treatment. After the administration of 1-15 cycles of atezolizumab/bevacizumab therapy, one patient had a progression of varices, and the other four developed variceal bleeding. The association between atezolizumab/bevacizumab and portal hypertension was possible, which might relate to the VEGF pathway and immune-related adverse events with progressive hepatic fibrosis., Conclusion: Atezolizumab/bevacizumab treatment might exacerbate portal hypertension. Careful monitoring and management should be considered during treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. none declared, (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This study aimed to carry out the preclinical studies of [ 89 Zr]Zr-DFO-Bevacizumab. The radiolabeled compound was prepared with radiochemical purity >99% (ITLC), and a specific activity of 74 GBq/g. Cellular studies indicated the great capability of [ 89 Zr]Zr-DFO-Bevacizumab for binding to SKOV3 cell lines. High accumulation was observed in the tumor. The liver and spleen received the highest absorbed dose with 1.12 and 0.72 mGy/MBq, respectively. This radiopharmaceutical can be considered as a suitable PET agent for VEGF-expressing ovarian cancer imaging., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Hassan Yousefnia reports financial support was provided by International Atomic Energy Agency. The authors would like to acknowledge the invaluable scientific and financial support of the International Atomic Energy Agency (IAEA) for this research under the Coordinated Research Project (Project Code; F22071, IAEA Research Contract No: 23763) If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Laser photocoagulation (LPC) and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections constitute the current standard treatment for retinopathy of prematurity (ROP). This network meta-analysis focus on whether a ranking of interventions may be established for different dose levels of intravitreal injection of anti-VEGF agents (aflibercept, bevacizumab, conbercept, ranibizumab) as primary treatments for ROP versus laser in terms of retreatment rate as primary outcome, and time to retreatment and refractive error as secondary endpoints, since best anti-VEGF dosage remains under debate. Sixty-eight studies (15 randomized control trials and 53 nonrandomized studies) of 12,356 eyes of 6445 infants were retrieved from databases (2005 Jan. - 2023 June). Studies were evaluated for model fit, risk of bias and confidence of evidence in Network Meta-Analysis (CINeMA). Bayesian NMA showed that anti-VEGF drugs were not inferior to laser in terms of retreatment rate. For intravitreal bevacizumab (IVB), doses half of the conventional infant dose showed a low risk of retreatment rate (risk ratio (RR) of 1.43; 95% credible interval (CrI): 0.508, 4.03). On probability ranking as surface under the cumulative ranking curve (SUCRA) plot, half dose of bevacizumab had a better position than conventional and augmented (1.2-2 times the regular dose) doses. A similar probability trend was observed for half vs. conventional doses of aflibercept and ranibizumab. Conventional infant dose of conbercept showed the lowest risk for retreatment (RR 0.846; 95% CrI: 0.245, 2.91). For secondary endpoints, lower doses of anti-VEGF agents were associated with shorter times to retreatment. The largest changes were noted for the augmented doses of bevacizumab and ranibizumab (0.3 mg) with means of 14.1 weeks (95% CrI: 6.65, 21.6) and 12.8 weeks (95% CrI: 3.19, 20.9), respectively. Finally, NMA demonstrated better refractive profile for anti-VEGF than laser therapy, especially for the conventional infant doses of bevacizumab and ranibizumab which exhibited a significantly better refractive profile than LPC, with mean differences of 1.67 (spherical equivalent - diopters) (95% CrI: 0.705, 2.67) and 2.19 (95% CrI: 0.782, 3.59), respectively. In the SUCRA plots, LPC had a markedly different position with a higher probability for myopia. Further clinical trials comparing different intravitreal doses of anti-VEGF agents are needed, but our findings suggest that low doses of these drugs retain efficacy and may reduce ocular and systemic undesired events., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Peritoneal metastases (PM) commonly occur in colorectal cancer patients. Systemic chemotherapy yields poor outcomes for these patients. It is hypothesised that traditional systemic chemotherapy is not very effective for this patient population. This study investigates to what extent systemic anti-cancer therapy crosses the peritoneal barrier., Methods: In a Phase I study, eighteen patients received systemic oxaliplatin, 5-FU, and bevacizumab. Plasma and peritoneal fluid samples were collected to measure drug concentrations. A non-compartmental analysis determined the Area Under the Curve (AUC) for oxaliplatin and 5-FU in both matrices. Intraperitoneal (IP) and intravenous (IV) exposure ratios were calculated, along with the bevacizumab concentration IP/IV ratio. The relationship between tumour load and IP/IV ratios and the correlation between the IP/IV ratios of different treatments were assessed statistically., Results: A total of 438 5-FU samples and 578 oxaliplatin samples were analysed in plasma and peritoneal fluid. Bevacizumab was quantified with 17 measurements in plasma and 15 measurements IP. Median IP/IV ratios were 0.143, 0.352 and 0.085 for 5-FU, oxaliplatin and bevacizumab, respectively. Oxaliplatin exhibited a longer IP half-life than 5-FU. A correlation was found between oxaliplatin and bevacizumab IP/IV ratios (R=0.69, p=0.01). No statistical correlations were found between the other investigated drugs., Conclusions: Our findings indicate that only a small percentage of systemically administered anti-cancer treatment reaches the IP cavity, questioning their efficacy against PM. This strengthens the hypothesis for repeated intraperitoneal chemotherapy to reach adequate anti-cancer drug levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To assess the prognostic value of pre- and post-therapeutic changes in extracellular volume (ECV) fraction of liver metastases (LMs) for treatment response (TR) and survival outcomes in colorectal cancer liver metastases (CRLM)., Methods: 186 LMs were confirmed by pathology or follow-up (Training: 130; Test: 56). We analyzed the changes in ECV fraction of LMs before and after 2 cycles of chemotherapy combined with bevacizumab. After 12 cycles, we evaluated the TR on LMs based on the RECIST v1.1. Relative changes in ECV fraction and Hounsfield Units (HU), defined as ΔECV and ΔHU, were associated with progression-free survival (PFS), overall survival (OS), and TR. We identified TR predictors with multivariate logistic regression and PFS, OS risk factors with COX analysis., Results: 186 LMs were classified as TR lesions (TR+: 84) and non-TR lesions (TR-:102). ΔECV, ΔHU A-E , and texture could distinguish the TR of LMs in training and test set (P < 0.05). ΔECV [Odds ratio (OR): 1.03; 95% Confidence interval (CI): 1.02-1.05, P < 0.01] was an independent predictor of TR-. Area under the curve (AUC), sensitivity and specificity of TR model in training and test set were 0.87, 0.84, 90.14%, 90.32%, 72.88%, 64.00%, respectively. High CRD&#95;score indicates that patients have shorter PFS [Hazard ratio (HR): 2.01; 95%CI: 1.02-3.98, P = 0.045)] and OS (HR: 1.89, 95%CI: 1.04-3.42, P = 0.038)., Conclusion: ΔECV can be used as an independent predictor of TR of CRLM chemotherapy combined with bevacizumab., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aimed to develop and evaluate an anti-angiogenesis-based model for predicting the survival and the potential benefits of targeted therapy for patients with localized advanced cervical cancer., Methods: We collected clinical data from 163 patients with cervical cancer who received paclitaxel and cisplatin (TP) or TP plus bevacizumab during or after radiotherapy from June 2017 to February 2023. We analyzed the clinical measures of recent efficacy and overall survival (OS) using univariate and logistic multivariate and Cox regression methods, respectively. We constructed a nomogram model and evaluated its efficacy using the c-index, the area under the curve (AUC), a calibration curve, and the clinical decision curve (DCA)., Results: We found that targeted agents and hemoglobin were independent determinants of near-term efficacy (P < 0.05), while targeted agents and stage were independent factors of OS (P < 0.05). We developed a predictive model for an OS prognostic nomogram and performed internal validation 1000 times using the Bootstrap re-sampling method. The c-index was 0.81, and the AUC was 0.84 (P < 0.01).The calibration curves showed a good agreement between the projected and actual values. The DCA curve indicated that the model had a high positive predictive accuracy., Conclusion: We developed a novel anti-angiogenesis-based survival prediction model for patients with locally advanced cervical cancer. This model could estimate the benefit of targeted therapy before treatment, and it had good validation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Atezolizumab plus bevacizumab is a standard of care, first-line therapy for advanced hepatocellular carcinoma (HCC). Myeloid and T regulatory cells are key immunosuppressive cell types within the hepatic tumor microenvironment associated with clinical resistance to atezolizumab and bevacizumab therapy for HCC and overall poor prognosis. Therapeutic targeting of TIGIT, which is highly expressed in these cells, with tiragolumab may overcome the immunosuppressive environment and improve clinical benefit, a hypothesis supported by positive efficacy signals in the Phase Ib/II MORPHEUS-Liver study. This paper describes the rationale and design of IMbrave152/SKYSCRAPER-14, a randomized, double-blind, placebo-controlled Phase III study comparing atezolizumab and bevacizumab with tiragolumab or placebo in patients with HCC and no prior systemic treatment. Clinical Trial Registration: NCT05904886 (ClinicalTrials.gov) Plain Language Summary This research study is designed to test a new treatment combination for liver cancer, specifically for patients whose cancer cannot be removed with surgery or has spread. The treatment involves three medications: atezolizumab, bevacizumab and tiragolumab. Atezolizumab and bevacizumab are already used together as a standard treatment for liver cancer. Tiragolumab is designed to block the TIGIT receptor, which is normally involved in holding back the immune cells that would attack the tumor. Because tiragolumab may restore the immune response against the tumor, adding tiragolumab might make the treatment more effective. The study is being done worldwide and includes patients who have not received any previous systemic treatment for their advanced liver cancer. Patients participating in the study will be randomly placed into two groups. One group will receive the new combination of three medications, while the other group will receive the standard treatment of two medications plus a placebo (a treatment with no active ingredient). The main goal is to see if the new combination helps patients live longer and slows the cancer's growth compared with the standard treatment. Safety and how patients feel during the treatment are also important parts of the study. Tweetable Abstract IMbrave152/SKYSCRAPER-14: New Phase III trial tests atezolizumab, bevacizumab & tiragolumab in advanced HCC, aiming to revolutionize treatment outcomes. #HCCResearch #OncologyInnovation Article highlights Advanced hepatocellular carcinoma treatment Atezolizumab in combination with bevacizumab has become the standard first-line therapy for advanced hepatocellular carcinoma (HCC). The immunosuppressive hepatic tumor microenvironment may limit the clinical activity of this combination in patients with HCC. TIGIT, a protein often found at high levels within these immunosuppressive cells, is a potential therapeutic target to overcome this resistance. Tiragolumab is an agent that inhibits TIGIT, suggesting a possible improvement in clinical outcomes when combined with the existing therapy. IMbrave152/SKYSCRAPER-14 trial rationale The randomized Phase III trial (NCT05904886) is designed to compare the efficacy and safety of the addition of tiragolumab to the current atezolizumab and bevacizumab regimen for HCC. The trial is designed to confirm efficacy signals from the Phase Ib/II MORPHEUS-Liver study, testing the hypothesis that targeting TIGIT with tiragolumab can enhance treatment response. Study design & eligibility Approximately 650 participants with no prior systemic treatment will be assigned to receive either the triple combination of atezolizumab, bevacizumab and tiragolumab or the standard dual therapy plus placebo. Participants will be randomly divided into two groups with stratification based on geographic region, disease progression, α-fetoprotein levels and HCC etiology. Treatment & trial objectives Patients will be administered intravenous doses of the treatment every three weeks, with outcomes measured in terms of progression-free survival and overall survival. Secondary end points include safety, efficacy, pharmacokinetics, immunogenicity and quality-of-life assessments. Preliminary results & safety profile The MORPHEUS-Liver trial indicated improved outcomes with the addition of tiragolumab to the existing atezolizumab and bevacizumab treatment, suggesting a well-tolerated safety profile with manageable adverse events. Conclusions & implications for hepatocellular carcinoma treatment IMbrave152/SKYSCRAPER-14 aims to establish whether the addition of tiragolumab can redefine the standard of care for unresectable HCC. This trial's findings could significantly impact the therapeutic landscape for HCC, addressing a critical unmet medical need [ABSTRACT FROM AUTHOR]

BACKGROUND: Real-world safety of bevacizumab in cancer patients is limited. OBJECTIVE: To review the adverse drug reactions (ADRs) due to bevacizumab in cancer patients, in published case reports. METHODS: PubMed was searched; case reports of patients with any type of cancer, administered with bevacizumab (monotherapy/combination) and reported ADRs were included. Causality of ADRs was presented as reported in individual papers. ADRs were classified using the information in the USFDA-approved prescribing information (PI) of bevacizumab as 'Serious', 'Common', and 'Post-marketing surveillance' ADRs; ADRs not mentioned in the bevacizumab PI were termed as 'Non-label ADRs'. RESULTS: A total of 130 published papers comprising 154 cases from 22 different countries were included. Most papers (102/130; 78.46%) had moderate methodological quality. Age range of patients was 9-77 years. Off-label use of bevacizumab was found in 34/154 cases (22.08%). Ninety-six unique ADRs were found among 154 ADRs; most reported ADRs affected circulatory, digestive, and respiratory systems (33, 32, and 26 cases respectively). Most commonly reported ADRs were posterior leukoencephalopathy, fistulae, and gastrointestinal perforation (17, 17, and 16 cases respectively). Twenty-eight unique non-label ADRs (29.17%) were found. CONCLUSION: Bevacizumab is associated with more ADRs in the real world among cancer patients than those reported during clinical trials. [ABSTRACT FROM AUTHOR]