Administration Of Bevacizumab Research Articles

Incidence of port site complications in relation to timing of bevacizumab infusion.

Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor, with a serious complication of wound healing complications. The package insert currently does not have recommendations on the management of bevacizumab administration around minor procedures, including port placements. Currently, there are only two trials that have examined the optimal timing of bevacizumab after port placement. This is a single-center retrospective trial aiming to evaluate the rate of wound dehiscence and other port site complications depending on the time between port placement and bevacizumab infusion. Eligible patients who have had at least one port place and have received bevacizumab for an oncologic indication were identified in a study period of 1/1/2016-3/31/2021. The primary outcome of this study was the incidence of wound dehiscence in relation to the timing of bevacizumab infusion. A total of 243 patients met the inclusion criteria, and 116 port placements had a port site complication. For wound dehiscence, 6% was observed 0 days from port placement, 10% was observed 1 day from port placement, 0% was observed 2 days from port placement, 0% was observed 3-7 days from port placement, 3% was observed 8-14 days from port placement, and 3% was observed 15-30 days from port placement. The results of this study show an inverse relationship between the risk of wound dehiscence and port site complication and the timing of bevacizumab infusion to port placement, with an increase in absolute risk of wound dehiscence when bevacizumab is given within 2 days of port placement.

A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-containing therapy

Predictive markers and prognostic models are useful for the individualization of cancer treatment. In this study, we sought to identify clinical and molecular factors to predict overall survival in recurrent glioma patients receiving bevacizumab-containing regimens. A cohort of 102 patients was retrospectively collected from June 2011 to January 2022 at our institution. A nomogram was generated by Cox regression and feature selection algorithms based on 19 clinicopathological and 60 molecular variables. The model's performance was internally evaluated by bootstrapping in terms of discrimination and calibration. The median overall survival from the initiation of bevacizumab administration to death or last follow-up was 11.6 months (95% CI: 9.2–13.8 months) for all 102 patients, 10.2 months (95% CI: 6.4–13.3 months) for 66 patients with grade 4 tumors, and 13.8 months (lower limit of 95% CI: 11.5 months) for 36 patients with tumors of grade lower or not available. In the final model, a lower WHO 2021 grade (Grade lower or not available vs. Grade 4, HR: 0.398, 95% CI: 0.223–0.708, p = 0.00172), having received adjuvant radiochemotherapy (Yes vs. No, HR: 0.488, 95% CI: 0.268–0.888, p = 0.0189), and wildtype EGFR (Wildtype vs. Altered, HR: 0.193, 95% CI: 0.0506–0.733, p = 0.0157; Not available vs. Altered, HR: 0.386, 95% CI: 0.184–0.810, p = 0.0118) were significantly associated with longer overall survival in multivariate Cox regression. The overall concordance index was 0.652 (95% CI: 0.566–0.714), and the areas under the time-dependent curves for 6-, 12-, and 18-month overall survival were 0.677 (95% CI: 0.516–0.816), 0.654 (95% CI: 0.470–0.823), and 0.675 (95% CI: 0.491–0.860), respectively. A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-based therapy was established and internally validated. It could serve as a reference tool for clinicians to assess the extent the patients may benefit from bevacizumab and stratify their treatment response.

Re-irradiation combined with bevacizumab in the treatment of glioblastoma recurrence

Background. Glioblastoma (GB) remains an aggressive disease with a poor prognosis. despite a comprehensive approach to the treatment of the primary disease, recurrence is almost inevitable. There is still no standard of care for GB recurrence, and many guidelines recommend treating these patients within clinical trials. There are various treatment options available. They include surgery, radiation therapy, systemic or regional chemotherapy or targeted therapy, various immunotherapy strategies, low- and medium-frequency electric fields, and their combinations. The combination of two non-invasive techniques: re-irradiation and systemic targeted therapy remains the most commonly used approach in this group of patients, the potential of which has not been fully realized. The aim of the study was to analyze the literature data on the use of the combination of re-irradiation with bevacizumab as a therapeutic option in patients with GB. Material and Methods. Literature search was performed using Medline, Cochrane Library, E-library, Scopus, PubMed and Google Scholar databases. Results. The current state of the problem was determined, the data available to date on the use of repeated radiotherapy with competitive and/or adjuvant bevacizumab in the treatment of GB recurrence were summarized and analyzed, different regimens of this approach were compared, and the prospects and possible ways of solving the existing problems of this therapeutic option were described. Conclusion. Re-irradiation with concomitant administration of bevacizumab may provide safer treatment of GB recurrence, including large-volume glioblastoma, with acceptable toxicity, in particular radiation necrosis, especially when an appropriate fractionation schedule is used.

Cumulative incidence and risk factors of brain metastases in metastatic non-small cell lung cancer without baseline brain metastasis: Pooled analysis of individualized patient data from IMpower130, IMpower131, and IMpower150.

The objective of this study was to explore the abilities of atezolizumab plus chemotherapy in preventing brain metastases (BMs) among metastatic non-small cell lung cancer (NSCLC) without initial BMs, as well as the risk factors of BMs. Individual patient data from three trials involving first-line atezolizumab for metastatic NSCLC (IMpower130, IMpower131, and IMpower150) were pooled. Among patients without baseline BMs and without epidermal growth factor receptor(EGFR) and/or anaplastic lymphoma kinase (ALK) mutations, those receiving atezolizumab+chemotherapy±bevacizumab were classified as the atezolizumabplus chemotherapy group and those receiving placebo+chemotherapy±bevacizumab were classified as the chemotherapy group. The cumulative incidences of BM (CI-BMs) between the two groups were compared. Other factors associated with the CI-BM were analyzed by Cox regression analyses. With a median follow-up of 17.6 months (range, 0.03-33.64 months), 74 (3.1%) of the 2380 enrolled patients developed BMs, including 50 (3.1%) and 24 (3.0%) in the atezolizumab plus chemotherapy group (n=1589) and the chemotherapy group (n=791), respectively. The CI-BMs at 6, 12, and 24months were 1.7%, 2.8%, and 3.3%, respectively. After taking competing risk events into account, there was no significant difference in the CI-BMs between the two groups (p=.888). Nevertheless, the use of bevacizumab and the histology of nonsquamous NSCLC were found to be independently associated with the risk of BMs. In patients with metastatic EGFR/ALK wild-type NSCLC without baseline BMs, adding atezolizumab in the first-line treatment might not reduce the CI-BM. However, the administration of bevacizumab may reduce the risk of BMs.

Five years of safety profile of bevacizumab: an analysis of real-world pharmacovigilance and randomized clinical trials

ObjectiveBevacizumab is a monoclonal antibody against vascular endothelial growth factor. It has a wide range of clinical applications in various cancers and retinal diseases. The drugs entered the Chinese market by a large margin in 2017, and the user population changed to some extent. This study reevaluated the safety of bevacizumab through an analysis of the World Pharmacovigilance database (Food and Drug Administration Open Vigil 2.1) in conjunction with a comprehensive meta-analysis of RCTs.MethodsReal-world pharmacovigilance data originating from case reports were mined using Open Vigil and coded at the preferred term (PT) level using the Standardized MedDRA Query. Proportional reporting ratios (PRR) and reporting odds ratios (ROR) were used to detect safety signals. Eligible items were screened by searching PubMed, Wanfang, and Web of Science, and data were extracted for systematic review and meta-analysis using RevMan 5.4 software.ResultsAnalysis of the drug pharmacovigilance database revealed that the most significant PRRs were limb decortication syndrome (PRR = 2926), stomal varices (PRR = 549), anastomotic (PRR = 457) and ureteral fistula (PRR = 406). Most safety signals at the PT level emerged as various types of injuries, toxicities, operational complications, systemic diseases, various reactions at the administration site, hematological and lymphatic disorders, and gastrointestinal disorders. Adverse reactions such as nasal septal perforation (PRR = 47.502), necrotizing fasciitis (PRR = 20.261), and hypertensive encephalopathy (PRR = 18.288) listed as rare in drug specifications should not be ignored with a high signal in the real world. A total of 8 randomized controlled trials (RCTs) were included in the meta-analysis, and the overall risk of adverse reactions following bevacizumab administration was relatively low, indicating a good safety profile (HR = 1.19, 95% CI:0.85 ~ 1.65, p = 0.32).ConclusionThe frequent adverse reactions of bevacizumab occurring in the real world are consistent with the data provided in RCTs and drug specifications. However, adverse reactions such as nasal septum perforation, necrotizing fasciitis, hypertensive encephalopathy and so on, listed as rare in drug specifications, may have a high signal of correlation in the real world, which all requires active monitoring and timely adjustment of bevacizumab posology during its clinical use.

Administration of Bevacizumab and the Risk of Chronic Kidney Disease Development in Taiwan Residents: A Population-Based Retrospective Cohort Study.

Vascular endothelial growth factor (VEGF) plays a significant role as a pro-angiogenic and pro-permeability factor within the kidney. Bevacizumab is a pharmaceutical monoclonal anti-VEGF antibody that inhibits the growth of new blood vessels, which blocks blood supply and thereby restricts tumor growth. Thus, we conducted a nationwide study to explore the risk of chronic kidney disease (CKD) development in Taiwan residents after bevacizumab therapy. We drew data from the extensive National Health Insurance Research Database (NHIRD), which encompasses data from >99% of Taiwan's population from 1995 onwards. Individuals who received bevacizumab between 2012-2018 were identified as the bevacizumab cohort, with the index date set at the first usage. We randomly selected dates within the study period for the control group to serve as index dates. We excluded patients with a history of CKD prior to the index date or those <20 years old. In both cohorts, patients' propensity scores matched in a 1:1 ratio based on sex, age, index year, income, urbanization level, comorbidities, and medications. We found patients treated with bevacizumab had a significantly higher risk of contracting CKD than patients without bevacizumab (adjusted hazard ratio = 1.35, 95% confidence interval = 1.35-1.73). The risk of CKD was 1.35-fold higher in participants with bevacizumab treatment than those in the control group. These findings suggest that close monitoring of CKD development after bevacizumab administration is needed.

Hydrogel Crosslinked with Nanoparticles for Prevention of Surgical Hemorrhage and Recurrence of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is acknowledged as an immunosuppressive neoplasm, whereby the inactive microenvironment facilitates immune tolerance and evasion of HCC. Post-surgical resected liver cancer exhibits a proclivity for relapse, rendering prevention of recurrence challenging as it may transpire at any point subsequent to surgery. Among the various anti-recurrence interventions, the primary clinical approach involving the administration of regimens atezolizumab and bevacizumab (A+T) is deemed the most efficacious in reversing the tumor microenvironment, albeit still lacking in complete satisfaction. Therefore, the objective is to utilize a recently developed block copolymer as a protective carrier for two specific monoclonal antibody drugs. Subsequently, a modified hemostatic hydrogel will be synthesized for application during hepatic surgery. The immunotherapy impact of this approach is significantly prolonged and intensified due to the combined hemostasis properties and controlled release of the constituents within the synthesized nanocomposite hydrogel. Furthermore, these nanocomposite hydrogels exhibit remarkable efficacy in preventing postoperative wound bleeding and substantially enhancing the safety of liver cancer resection. This research on the anti-recurrence hydrogel system presents a novel therapeutic approach for addressing local recurrence of liver cancer, potentially offering a substantial contribution to the field of surgical treatment for liver cancer in the future.

Effect of Bevacizumab on traumatic penumbra brain edema in rats at different time points

ABSTRACT Traumatic penumbra (TP) is a secondary injury area located around the core area of traumatic brain injury after brain trauma, and is an important factor affecting the outcome of traumatic brain injury (TBI). The main pathological change caused by TP is brain edema, including (cellular brain edema and vascular brain edema). The formation and development of brain edema in the TP area are closely related to the blood-brain barrier (BBB) and vascular endothelial growth factor (VEGF). VEGF is a vascular permeability factor that can promote angiogenesis and increase BBB permeability, and there is a debate on the pros and cons of its role in early TBI. Therefore, in the early stage of TBI, when using the VEGF inhibitor bevacizumab to treat TP area brain edema, the timing of bevacizumab administration is particularly important, and there are currently no relevant literature reports. This article explores the treatment time window and optimal treatment time point of bevacizumab in the treatment of cerebral edema in the TP area by administering the same dose of bevacizumab at different time points after brain injury in rats. The results showed that there was traumatic brain edema in TP area, BBB structure and function were damaged, VEGF expression and angiogenesis were increased. Compared with TBI + NS Group, after Bevacizumab treatment, brain edema in TP area was alleviated, BBB structure and function were improved, VEGF expression and angiogenesis were decreased in each treatment group, and the effect of TBI + Bevacizumab 1 h group was the most significant. Bevacizumab can be used as a targeted therapy for traumatic brain edema. The therapeutic time window of bevacizumab for traumatic brain edema is within 12 hours after TBI, and 1 h is the optimal therapeutic time point.

Efficacy and toxicity of bimodal radiotherapy in WHO grade 2 meningiomas following subtotal resection with carbon ion boost: Prospective phase 2 MARCIE trial.

Novel radiotherapeutic modalities using carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, delivering a higher biological dose while reducing radiation exposure for adjacent organs. This prospective phase 2 trial investigated bimodal radiotherapy using photons with carbon-ion (C12)-boost in patients with WHO grade 2 meningiomas following subtotal resection (Simpson grade 4 or 5). A total of 33 patients were enrolled from July 2012 until July 2020. The study treatment comprised a C12-boost (18 Gy [RBE] in 6 fractions) applied to the macroscopic tumor in combination with photon radiotherapy (50 Gy in 25 fractions). The primary endpoint was the 3-year progression-free survival (PFS), and the secondary endpoints included overall survival, safety and treatment toxicities. With a median follow-up of 42 months, the 3-year estimates of PFS, local PFS and overall survival were 80.3%, 86.7%, and 89.8%, respectively. Radiation-induced contrast enhancement (RICE) was encountered in 45%, particularly in patients with periventricularly located meningiomas. Patients exhibiting RICE were mostly either asymptomatic (40%) or presented immediate neurological and radiological improvement (47%) after the administration of corticosteroids or bevacizumab in case of radiation necrosis (3/33). Treatment-associated complications occurred in 1 patient with radiation necrosis who died due to postoperative complications after resection of radiation necrosis. The study was prematurely terminated after recruiting 33 of the planned 40 patients. Our study demonstrates a bimodal approach utilizing photons with C12-boost may achieve a superior local PFS to conventional photon RT, but must be balanced against the potential risks of toxicities.

10018-COT-4 COMPARATIVE VOLUMETRIC ANALYSES FOLLOWING BEVACIZUMAB THERAPY FOR A PATIENT WITH CO- INCIDENCE OF GLIOBLASTOMA, MENINGIOM

Abstract BACKGROUND Given that glioblastoma, meningioma and dural arteriovenous fistura (dAVF) represent angiogenic disease mainly caused by high expression of vascular endothelial growth factor (VEGF), bevacizumab is expected to be effective for these diseases. We experienced a patient with co-incidence of these 3 diseases was given neoadjuvant bevacizumab which provided a volume reduction of glioblastoma with improvement of clinical symptoms. CASE REPORT An eighty five year-old man has suffered from aphasia and dementia. Brain MRI showed a ring enhanced intraaxial tumor with perifocal edema in left temporal lobe, a dural-attached extraaxial tumor in the left sphenoid ridge and dAVF at left transverse-sigmoid sinus. Due to elderly with poor general condition, he was treated by administrate bevacizumab rather than the resection to confirm histological diagnosis. Three days after the administration, he began to walk and speech. RESULTS For comparison of the reactivity to bevacizumab among these three diseases, we calculated the volumetric quantitative assessment of glioblastoma and meningioma by the contrast-enhanced MRI and made a qualitative assesment for the dAVF by digital subtraction angiography (DSA) and MRA with comparison between before and afterbevacizumab administration. The volume reduction rates 1 and 5 months later after bevacizumab administration in glioblastoma and in meningioma were 0.34% and 94.5%, 13.7%, 6.8%, respectively. The volume reduction rate of glioblastoma was significantly larger than of Mg. The DSA showed the dAVF did not change even though bevacizumab therapy. DISCUSSION As previously reported, the VEGF concentration in the glioblastoma was significantly higher than that in other types of tumors including meningioma. In dAVF, other angiogenic factors would be produced in addition to VEGF. CONCLUSIONS Based on these evidences and the current rare case with co-incidence of glioblastoma, meningioma, and dAVF, it suggested that the effectiveness of bevacizumab therapy would be depend on the expression level of the VEGF concentration.

Isolated adrenocorticotropic hormone deficiency associated with atezolizumab and bevacizumab administration for treating hepatocellular carcinoma: a case series.

Atezolizumab and bevacizumab are currently available as first-line treatments for unresectable hepatocellular carcinoma, but immune-related adverse events are a major concern. We herein report two cases of isolated adrenocorticotropic hormone (ACTH) deficiency. Both patients presented with general fatigue, appetite loss, eosinophilia, and hyponatremia after nine cycles in case 1 and three months after stopping treatment for inflammatory arthritis in case 2. Endocrinological investigations revealed unsatisfactory ACTH and cortisol responses despite the preservation of other anterior pituitary hormones, suggesting isolated ACTH deficiency. As it is rapidly improved by steroid replacement therapy, an early diagnosis and treatment make it possible to resume immunotherapy.

CTIM-26. IMPACT ON SURVIVAL OF INTERFERON-ALPHA DELIVERY IN GLIOBLASTOMA WITH UNMETHYLATED MGMT BY IMMUNO-GENE THERAPY WITH TEMFERON

Abstract Temferon is an ex vivo gene therapy consisting of autologous Hematopoietic Stem Progenitor Cells (HSPCs) genetically modified with a lentiviral vector to deliver IFN-α2 within the tumor microenvironment by Tie-2 expressing macrophages. TEM-GBM is an open-label, Phase I / IIa dose-escalation study evaluating safety and efficacy of Temferon in up to 27 newly diagnosed GBM patients with unmethylated MGMT (uMGMT). As of 30th April 2023, 19 GBM patients in 4 cohorts received incremental doses of Temferon and four are still alive after a median follow-up of 15 months. Six of the treated patients underwent a second surgical intervention at a median of 11 months after 1st surgery. For all patients, median overall survival (OS) and median progression free survival following first surgery reach 15 months and 9.8 months from diagnosis, respectively. The interim survival rate at 2 years in Temferon-treated patients is 28% (5 of 18 patients; 1 patient excluded as follow-up is below 1 year). OS and survival rate at 2 years of uMGMT patients treated as per the current standard of care (SOC) is 12.7 months and 14,8% respectively. One out of the surviving patients is alive 3 years after first surgery without second line therapy added up to 2 years. The other four patients with 2 year follow-up were treated with Gamma-Knife followed by bevacizumab (n = 1), regorafenib followed by bevacizumab (n = 1) and bevacizumab only (n = 2). Bevacizumab administration started 12 months after 1st surgery for one patient and 19 months for the other 2 patients at 5 mg/kg. These data corroborate the initial evidence on safety and tolerability of Temferon. They also suggest that Temferon has potential to counteract disease progression in patients affected by uMGMT GBM.

Bevacizumab promotes tenogenic differentiation and maturation of rat tendon-derived cells in vitro.

Previous work suggested that tenogenic differentiation of tendon stem/progenitor cells (TSPCs) was suppressed by upregulated expression of the angiogenic marker vascular endothelial growth factor (VEGF). The purpose of this study was to test the hypothesis that anti-VEGF antibody, bevacizumab, promotes in vitro tenogenic differentiation and maturation of two distinct types of TSPCs, tendon proper-derived cells (TDCs), and paratenon-derived cells (PDCs) originating from rat Achilles tendon. TDCs and PDCs were isolated from the tendon proper and the paratenon of rat Achilles tendons. TDCs and PDCs were cultured for 3 days on plates with or without VEGF. TDCs and PDCs were also cultured in collagen gel matrix, and the blocking effect of VEGF was examined by the addition of 100 ng/mL of bevacizumab. Effects of bevacizumab on tenogenic differentiation were assessed using real-time PCR, immunofluorescent staining, and western blotting. VEGF significantly attenuated expression of the Tnmd gene in both PDCs and TDCs (P<0.05). Expressions of the Scx, Tnmd, and Col1a1 genes were significantly upregulated by the addition of bevacizumab (P<0.05). Immunofluorescent staining showed that the percentage of tenomodulin-positive PDCs and TDCs was significantly higher with bevacizumab treatment than in control cultures (P<0.05). Western blotting showed that bevacizumab suppressed pVEGFR-2 protein expression in both PDCs and TDCs. Bevacizumab promoted the in vitro tenogenic differentiation and maturation of two distinct TSPCs derived from rat Achilles tendon. Since the previous studies demonstrated that TSPCs have a potential to contribute to tendon repair, attenuating VEGF levels in TSPCs by administration of bevacizumab is a novel candidate therapeutic option for promoting tendon repair.

Early Assessment of Radiation Treatment at Clinical Field Strength by D2O Administration and Deuterium MRI

An accurate and non-invasive assessment of tumor response following treatment is essential. Traditional anatomical imaging techniques are insufficient before a significant morphological change can be observed. Metabolic imaging of molecular processes in the living body is also used. In recent years, deuterium magnetic resonance spectroscopic (MRS) imaging has been demonstrated as an alternative for cancer metabolic imaging by high-field (4-11T) MRI using deuterium-labeled molecules as a contrast agent. The study aim was to evaluate the feasibility of using deuterium MRI 1.5T for tumor visualization and early assessment of the efficacy of three anticancer treatment strategies (radiation and anticancer drugs) in pancreatic cancer model mice given heavy water (D2O) to induce deuterium (2H)-tissue labeling. A MIA PaCa-2 pancreatic cancer model of six BALB/c-nu mice was prepared, and repeated deuterium MRI was performed during the first 10 days after starting free drinking of 30% D2O. We also evaluated 2H accumulation in the tumor after irradiation, bevacizumab administration, or gemcitabine administration of other 20 mice. Additional confirmatory proton MRI, ex vivo metabolic hyperpolarization 13C-MRS and histopathology were performed. The mouse's whole-body distribution of 2H was visible 1 day after drinking, and the signal intensity increased daily. Although the tumor size did not change 1 and 3 days after irradiation, the amount of 2H in the tumor decreased significantly. The 2H image intensity of the tumor also significantly decreased after the administration of bevacizumab or gemcitabine. Metabolic hyperpolarization 13C-MRS, proton MRI and 2H-NMR spectroscopy confirmed the efficacy of the anticancer treatments. Deuterium MRI at 1.5T proved feasibility to track 2H distribution throughout mouse tissues during D2O administration and revealed a higher 2H accumulation in the tumor xenografts. This research demonstrated a promising successful method for early assessment of radiotherapy and chemotherapy of pancreatic cancer.

Deuterium Magnetic Resonance Imaging Using Deuterated Water-Induced 2H-Tissue Labeling Allows Monitoring Cancer Treatment at Clinical Field Strength.

An accurate and noninvasive assessment of tumor response following treatment other than traditional anatomical imaging techniques is essential. Deuterium magnetic resonance spectroscopic (MRS) imaging has been demonstrated as an alternative for cancer metabolic imaging by high-field MRI using deuterium-labeled molecules. The study aim was to use 2H tissue labeling and deuterium MRI at clinical field strength for tumor visualization and assessment of three anticancer therapies in pancreatic cancer model mice. MIA PaCa-2 pancreatic carcinoma and C26 colorectal carcinoma models of BALB/c-nu mice was prepared, and repeated deuterium MRI was performed during the first 10 days of free drinking of 30% D2O to track 2H distribution in tissues. 2H accumulation in the tumor after irradiation, bevacizumab administration, or gemcitabine administration was also measured in MIA PaCa-2-bearing mice. Confirmatory proton MRI, ex vivo metabolic hyperpolarization 13C-MRS, and histopathology were performed. The mouse's whole-body distribution of 2H was visible 1 day after drinking, and the signal intensity increased daily. Although the tumor size did not change 1 and 3 days after irradiation, the amount of 2H decreased significantly. The 2H image intensity of the tumor also significantly decreased after the administration of bevacizumab or gemcitabine. Metabolic hyperpolarization 13C-MRS, proton MRI, and 2H-NMR spectroscopy confirmed the efficacy of the anticancer treatments. Deuterium MRI at 1.5T proved feasible to track 2H distribution throughout mouse tissues during D2O administration and revealed a higher 2H accumulation in the tumor xenografts. This research demonstrated a promising successful method for preliminary assessment of radiotherapy and chemotherapy of cancer.

Topical Administration of Bevacizumab to Facilitate the Functional Filtering Bleb After Trabeculectomy in the Rabbit.

Purpose: To evaluate the effects of bevacizumab in 3 different application methods, subconjunctival injection (SCI), hyaluronic acid retardant (HAR), and eye drop (ED), on attenuating scar formation in the filtering bleb. Methods: Trabeculectomy (TRAB) was performed on New Zealand rabbits. TRAB rabbits were intervened with bevacizumab SCI, HAR, ED, or mitomycin C, respectively. Intraocular pressure (IOP) of 1, 7, 14, and 28 days after TRAB was recorded, and the bleb survival rate was analyzed. Bleb height, area, and vascularization were evaluated using anterior segment optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) at 7, 14 and 28 days after surgery. A histopathology examination of the bleb tissue was performed. The expression levels of vascular endothelial growth factor (VEGF)-A, interleukin (IL)-1α, tumor necrosis factor-alpha (TNF-α), transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin (α-SMA) were measured by Western blot. Results: Bevacizumab significantly reduced postoperative IOP and increased the survival of the filtering bleb, especially in the ED group. Less vascularization was shown in the SCI, HAR, and ED groups. Histopathological results showed the fewest levels of scarring and fibrosis in the ED group. The local VEGF-A, IL-1α, and TNF-α expression levels after bevacizumab ED were decreased, combined with suppression of TGF-β1 and α-SMA. Conclusions: Postoperative use of bevacizumab EDs was an effective application method for improving surgical outcomes after TRAB in rabbits. It might be effective in preventing scarring of the filtering bleb by antivascularization and anti-inflammation.

EFFECT OF TOPICAL SODIUM DICLOFENAC AS ADJUVANT TO INTRAVITREAL BEVACIZUMAB INJECTION THERAPY ON VISUAL ACUITY INTRAOCULAR PRESSURE CHANGES IN PATIENTS WITH DIABETIC MACULAR EDEMA

Introduction dan Aim: Diabetic Macular Edema (DME) in Diabetic Retinopathy (DR) patients might threaten the patient's visual acuity. Therefore, a robust DME treatment is needed to prevent sight threatening condition in DR patients. In this study, we intended to compare the effects of intravitreal administration of bevacizumab versus bevacizumab and topical natrium diclofenac in DR patients who developed DME. Methods: This was a randomized controlled trial study with double blinds. Data were taken from April 2020 to June 2021 from the Dr. Sardjito Central General Hospital and the Dr. Suhardi Hardjolukito Indonesian Air Force Central Hospital, Yogyakarta. Our patients were assigned to a control group (intravitreal bevacizumab therapy only) and an intervention group (intravitreal bevacizumab and topical natrium diclofenac). Then, we evaluated best corrected visual acuity (LogMar) and intraocular pressure (IOP, mmHg) were recorded in both groups before and after therapy. Results: A total of 38 eyes from 36 patients with naive DME were included in this study. Both treatment groups showed a statistically significant improvement in visual acuity after treatment bevacizumab (pre = 0.8±0.5; post = 0.6±0.5; p-value = 0.033) and bevacizumab and natrium diclofenac (pre = 0.9±0.5; post = 0.5±0.3; p-value = 0.004). In contrast to the above findings, the IOP in both groups did not show a significant change in IOP after therapy, bevacizumab (pre = 15.7±4.1; post = 15.6±4.2; p-value = 0.810) and bevacizumab and natrium diclofenac (pre = 16.0±4.5; post = 16.0±3.9; p-value = 0.868). Conclusion: Our study showed that visual acuity was improved significantly in DME patients treated with either bevacizumab or bevacizumab and natrium diclofenac. This might be a valuable information on the improvement of DME therapy, given that no increased post-therapy IOP in patients treated topical natrium diclofenac.

Bevacizumab-induced proteinuria and its association with antihypertensive drugs: A retrospective cohort study using a Japanese administrative database.

Proteinuria is a major side-effect of the anti-tumor drug bevacizumab, although its incidence and risk factors in the real world are still unclear. Although renin-angiotensin-aldosterone system inhibitors are used clinically to prevent proteinuria, their efficacy remains unclear. The aim of the present study was to reveal the incidence and risk factors of bevacizumab-induced proteinuria and examine the effectiveness of antihypertensive drugs in preventing proteinuria. We conducted a retrospective cohort study using the National Hospital Organization Clinical Data Archives and Medical Information Analysis Databank. Hospitalized patients who received bevacizumab between January 1, 2016, and June 30, 2019, were included. The study outcome was proteinuria within 12 months of bevacizumab administration. Patient characteristics, laboratory tests, and medications were compared between patients with and without proteinuria using multivariable logistic regression analysis. Among the 2,458 patients, 27% developed proteinuria after bevacizumab administration. Nursing dependence (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.89-3.05; P<0.001) and systolic blood pressure ≥140 mmHg (OR, 1.44; 95% CI, 1.17-1.79; P<0.001) were identified as risk factors. Patients with an estimated glomerular filtration rate (eGFR) of 60-89, 45-59, and <45 mL/min/1.73 m2 had 29.7%, 76.8%, and 66.0% higher odds of proteinuria, respectively, than those with an eGFR ≥90 mL/min/1.73 m2. No significant relationship was observed between antihypertensive drugs and the occurrence of proteinuria. More patients may suffer from proteinuria after bevacizumab administration than previously reported. Nursing dependence and systolic blood pressure are predictive risk factors for bevacizumab-induced proteinuria. Patients at risk of proteinuria should be closely monitored.

Long-term effects of intraoperative topical bevacizumab in sutureless scleral tunnel trabeculectomy: a prospective clinical trial.

To investigate the long-term efficacy and safety of the novel method sutureless trabeculectomy with topical administration of bevacizumab. Primary open-angle glaucoma patients with intraocular pressure (IOP) > 21mmHg despite maximum tolerated medication were included in a single-blind prospective interventional clinical trial. Group 1 underwent sutureless scleral tunnel trabeculectomy with intraoperative topical administration of bevacizumab (1.25mg) applied on the scleral incision for 1min. Group 2 underwent sutureless trabeculectomy alone and group 3 (control group) underwent conventional trabeculectomy with mitomycin C (MMC). Outcome measures were surgical success, IOP, number of needed anti-glaucoma medications, and complications. Patients were followed for two years. Finally, 50 eyes from group 1, 46 from group 2, and 47 from group 3 were analyzed. At the end of 24months, 52% (n = 26) of group 1, 34.8% (n = 16) of group 2, and 57.4% (n = 27) of group 3 had complete success (IOP < 18mmHg without medication). The difference was only significant between groups 2 and 3 (p = 0.003). 94% (n = 47) of group 1, 89.1% (n = 41) of group 2, and 91.5% (n = 43) of group 3 had qualified success (IOP < 18mmHg with ≤ 2 anti-glaucoma medications) (p = 0.69). There was a significant difference in the overall IOP mean between the three groups (p < 0.0001). There was no significant difference between the three groups in complication rates and the number of needed anti-glaucoma medications for IOP control. Sutureless trabeculectomy with topical application of bevacizumab showed comparable surgical success rates with conventional trabeculectomy and MMC in long-term follow-up. Additionally, adjuvant use of topical bevacizumab had a significant positive impact on long-term IOP control.

NEIM-14 PET/MRI DETECTS A RAPID DECREASE IN CEREBRAL BLOOD FLOW IN GLIOBLASTOMA FOLLOWING BEVACIZUMAB INFUSION

Abstract BACKGROUND The impacts of bevacizumab on the vasculature and metabolism of glioblastoma have been understudied. Previous work has shown that perfusion measurements of lesions decrease weeks after infusion. Metabolic consequences, either direct or as sequelae of vascular changes, have also been proposed. The timing of both processes in humans, however, is unclear. We aimed to study changes to the vasculature and metabolism of glioblastoma after the administration of bevacizumab. METHODS Patients (n = 8) diagnosed with recurrent glioblastoma requiring bevacizumab were enrolled. Baseline scans were acquired with a GE Healthcare SIGNA PET/MRI scanner. Following the first infusion of bevacizumab (7.5 mg/kg), repeat scans were obtained within two days and two weeks. All scans were co-registered and analyzed using 3D Slicer. Cerebral blood flow (CBF) and standard uptake value (SUV) measures were normalized by taking the ratio of the mean tumor and contralateral region values, and the ratios at different time points were compared using Wilcoxon signed-rank tests. RESULTS A statistically significant decrease in tumor CBF was detected within two days of infusion (0.88 ± 0.36 vs. 0.79 ± 0.29, p = 0.01), but no significant decrease in SUV was detected within the same timeframe (0.89 ± 0.36 vs. 0.88 ± 0.39, p = 0.26). No statistically significant drop was detected at two weeks in our sample. CONCLUSIONS Our results provide evidence that bevacizumab decreases glioblastoma blood flow within two days of the infusion. The measure of tumor metabolism also trended downward, though not significantly. Taken together, these data support a model by which bevacizumab rapidly affects VEGF-mediated vascular changes within the tumor, withpotential effects on tumor metabolism over a longer timeframe. These findings enrich our understanding of the impacts on glioblastoma of bevacizumab, which has a continued high clinical utility that is underscored by its ubiquity in the neuro-oncology clinic.