Addition Of Bevacizumab Research Articles

Vascular endothelial growth factor facilitates the effects of telocytes on tumor cell proliferation and migration

BackgroundTelocytes, recently recognized as interstitial cells with a diverse range of potential functions, have attracted considerable attention for their involvement in tumorigenesis. Nevertheless, owing to certain challenges in the isolation and cultivation of telocytes, the research on telocytes has advanced rather slowly. Therefore, it is imperative to study the role and mechanisms of telocytes in tumors.MethodsWe improved the separation method and successfully isolated telocytes by exploiting the combination of cell adhesion and magnetic bead sorting. Telocytes conditioned medium was collected to culture tumor cells and explore the role and mechanisms of telocytes in tumors.ResultsMTT and colony formation assays demonstrated that telocytes promoted tumor cell proliferation. Wound healing experiments and transwell assays indicated that telocytes enhanced tumor cell migration. Real-time reverse transcriptase PCR analysis showed that the expression of E-cadherin was decreased, and that of Vimentin was notably increased. ELISA results revealed that telocytes secreted high levels of vascular endothelial growth factor (VEGF). And the promoting effects were alleviated by the VEGF inhibitor bevacizumab.ConclusionOur findings revealed that telocytes promoted tumor cell proliferation, migration, and angiogenesis through VEGF. Notably, these effects were inhibited by the addition of bevacizumab. In conclusion, our findings illuminated the role of telocytes in promoting tumor progression, and confirmed their crucial regulatory role in the growth of tumor cells.

Neoadjuvant Chemotherapy With the Angiogenesis Inhibitor Bevacizumab for Locally Advanced Cervical Cancer.

We hypothesized that adding bevacizumab to platinum-based neoadjuvant chemotherapy - whose efficacy for patients with recurrent or metastatic cervical cancer has already been proven - could optimize the therapy regimen, leading to improved response rates and survival outcomes. Forty patients with histologically confirmed cervical cancer with FIGO stage IB3-IVA who received platinum-based neoadjuvant treatment between March 2008 and January 2019 in the Department of Obstetrics and Gynecology of University Hospital Cologne were analyzed. Twenty patients were treated with additional bevacizumab. The comparative cohort consisted of 18 patients treated with neoadjuvant chemotherapy alone. The response rates and clinical outcomes, including progression-free survival and overall survival, were evaluated. Neoadjuvant chemotherapy combined with bevacizumab significantly improved the response rate (p=0.046). The survival analysis showed that patients treated without bevacizumab had better progression-free survival up to FIGO stage IVA than patients treated with bevacizumab. However, overall survival was similar for both cohorts. For patients with advanced tumor stage, including FIGO IVB, progression-free survival and overall survival improved with the addition of bevacizumab. Pathological complete remission was a statistically significant prognostic factor for progression-free survival (p=0.039) but did not significantly affect overall survival (p=0.098). While bevacizumab did not demonstrate a significant improvement in overall survival rates, it was associated with a notable reduction in tumor size and showed a trend towards improved clinical response rates. These findings suggest that bevacizumab may have potential in optimizing the neoadjuvant treatment approach.

First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis

This systematic review and network meta-analysis evaluates first-line treatment options for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases. We analyzed 24 randomized controlled trials (RCTs) involving 2,682 patients, comparing various EGFR tyrosine kinase inhibitors (TKIs) and combination therapies. Direct comparisons showed that the addition of bevacizumab or chemotherapy to first-generation (1G) EGFR-TKIs improved overall survival (OS) compared to 1G TKIs alone, with HRs of 0.704 (95% CI: 0.433–0.973) and 0.682 (95% CI: 0.464–0.899), respectively. However, third-generation (3G) TKI monotherapy did not significantly improve OS compared with 1G TKIs, with an HR of 0.855 (95% CI: 0.511–1.198). Indirect comparisons suggested that the combination of 3G TKIs with chemotherapy provided the most significant improvements in OS and progression-free survival (PFS), significantly outperforming 3G TKIs, with HRs of OS 1.69 (95% CI: 1.14–3.4) and PFS 2.13 (95% CI: 1.28–3.54). Intracranial PFS was best with 1G TKIs plus bevacizumab. Our findings suggest that 3G EGFR-TKIs in combination with chemotherapy may be the most effective strategy for patients with EGFR-mutant NSCLC and brain metastases, though further head-to-head trials are needed for validation.

Prise en charge diagnostique et thérapeutique du mésothéliome pleural en 2024

Pleural mesothelioma (PM) is a quite rare tumor, usually due to previous asbestos exposure. Its global prognosis is poor, without validated curative treatment to date. Diagnosis relies ideally on thoracoscopy with pleural biopsies, ± combined with (immediate) talc pleurodesis. Surgery with curative intent, included with multimodal treatment and restrained to highly selected patients, was recently rechallenged. As frontline treatment, standard pemetrexed/platinum-based chemotherapy was lightly improved by addition of bevacizumab. It is currently challenged by the immunotherapy combination of Nivolumab + Ipilimumab, and perhaps soon by combinations of chemotherapy + immunotherapy. No standard treatment is firmly validated beyond first line treatment, even if anti-PD-1/PD-L1 ± anti-CTLA-4 checkpoint inhibitors also exhibited some interesting results in this setting, in phase II and III clinical trials. Therefore, the search of new treatments, strategies and biomarkers is a crucial goal, and recruitment of patients in clinical trials strongly encouraged. Other immunotherapies alone or combined with standard treatments and/or targeted therapies, multimodal strategies are currently assessed. In France, the national network of expert centers for PM management, “NETMESO” (labelled by INCa), aims at proposing an optimal management to all patients systematically discussed in regional (± national) MTB dedicated to PM, and at stimulating clinical and translational research in collaboration with its partners including patients advocating associations.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Health-related quality of life in patients with progressive glioblastoma treated with combined bevacizumab and lomustine versus lomustine only: Secondary outcome of the randomized phase III EORTC 26101 study

Abstract Background Progression-free survival, but not overall survival, was prolonged with bevacizumab and lomustine compared to lomustine only in the randomized phase 3 European Organization for Research and Treatment of Cancer (EORTC) 26101 study. Objective To evaluate the impact of treatment on health-related quality of life (HRQoL) in progressive glioblastoma patients participating in the EORTC 26101 study. Methods Patients with progressive glioblastoma, after standard radio-chemotherapy, were 2:1 randomized to either BEV/LOM or LOM. HRQoL was a secondary trial outcome and assessed using the EORTC QLQ-C30 and QLQ-BN20 questionnaires at baseline, and subsequently every 12 weeks. Predefined scales for analysis were global health status (GH), physical functioning, social functioning (SF), motor dysfunction, and communication deficit. The primary endpoint was HRQoL during the last assessment up to week 36. Moreover, time to HRQoL deterioration (TTD) and HRQoL deterioration-free survival (DFS) were calculated. Results Out of 437 patients, 402 (92%) patients had a baseline HRQoL assessment, which dropped to 66% at week 36. During the last assessment up to week 36, no differences were observed for predefined scales, apart from SF being clinically relevant lower in the combination arm (mean 66.0 versus 81.0, p = .001). Of note, the baseline SF score was 66.4 for patients in the combination arm, showing stable SF. Median DFS was significantly longer in the combination arm (12.4 weeks) compared to lomustine alone (6.7 weeks), reflecting the difference in time to progression between arms. TTD, not including progression as an event, was not different between treatment arms (median 13.0 versus 12.9 weeks). Conclusion The addition of bevacizumab to lomustine did not negatively affect HRQoL during the progression-free period.

132P The potential of VEGF-A in the peripheral blood serum as a biomarker of response in the addition of bevacizumab with chemotherapy-combined immunotherapy for metastatic nonsquamous non-small cell lung cancer

132P The potential of VEGF-A in the peripheral blood serum as a biomarker of response in the addition of bevacizumab with chemotherapy-combined immunotherapy for metastatic nonsquamous non-small cell lung cancer

Bevacizumab-Based Therapies in Malignant Tumors-Real-World Data on Effectiveness, Safety, and Cost.

For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. The study consisted of 657 treatment episodes in 625 patients (F/B = 1.62/1, with a median age of 57.6 years) which were treated for malignant tumors (majority colorectal, non-small cell lung, ovarian, and breast cancer). First-line treatment was administered in 229 patients, and the rest received Bevacizumab as second or subsequent lines of treatment. The overall response rate to Bevacizumab-based therapies was around 60-65% across all indication except for subsequent treatment lines in colorectal and ovarian cancers, where lower values were recorded (27.1%, and 31.5% respectively). Median PFS for the entire cohort was 8.2 months (95% CI 6.8-9.6), and the median OS was 13.2 months (95% CI 11.5-14.9). Usual bevacizumab-related toxicities were observed, including bleeding, hypertension, wound-healing complications, gastrointestinal perforation, other types of fistulas, septic complications, and thromboembolic events. Although the clinical benefits are undeniable, the addition of Bevacizumab to standard chemotherapy increased the overall treatment cost by 213%. Bevacizumab remains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Off-label usage is encountered in clinical practice, and this aspect should be monitored given the potential adverse effects of the therapy.

A randomized phase III double-blind placebo-controlled trial of first-line chemotherapy and trastuzumab with or without bevacizumab for patients with HER2/neu-positive metastatic breast cancer: a trial of the ECOG-ACRIN Cancer Research Group (E1105)

BackgroundIn 2008, bevacizumab received accelerated Food and Drug Administration (FDA) approval for use in human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Based on the pre-clinical and preliminary clinical activity of the trastuzumab and bevacizumab combination, ECOG-ACRIN E1105 trial was developed to determine if the addition of bevacizumab to a chemotherapy and trastuzumab combination for first-line therapy would improve progression-free survival (PFS) in patients with HER2-positive MBC.Findings96 patients were randomized to receive standard first-line chemotherapy and trastuzumab with or without bevacizumab between November 2007 and October 2009, and 93 began protocol therapy. Induction therapy was given for 24 weeks, followed by maintenance trastuzumab with or without bevacizumab. 60% (56/93) began carboplatin and 74% (69/93) completed 6 cycles of induction therapy. Primary endpoint was PFS. Median PFS was 11.1 and 13.8 months for placebo and bevacizumab arms, respectively (hazard ratio [HR] 95%, Confidence Interval [Cl] for bevacizumab vs. placebo: 0.73 [0.43–1.23], p = 0.24), and at a median follow-up of 70.7 months, median survival was 49.1 and 63 months (HR [95% Cl] for OS: 1.09 [0.61–1.97], p = 0.75). The most common toxicities across both arms were neutropenia and hypertension, with left ventricular systolic dysfunction, fatigue, and sensory neuropathy reported more frequently with bevacizumab.ConclusionsIn this trial, the addition of bevacizumab did not improve outcomes in patients with metastatic HER2-positive breast cancer. Although the trial was underpowered due to smaller than anticipated sample size, these findings corroborated other clinical trials during this time.Clinical Trial Information: NCT00520975

VAMANA: A phase 2 study of low-dose bevacizumab plus CCNU in relapsed/recurrent glioblastoma.

LBA2064 Background: There are limited systemic therapy options for recurrent glioblastomas (rGBM). CCNU and/or Bevacizumab are often used to treat rGBM not amenable to local therapy. The addition of Bevacizumab (10 mg/kg) to CCNU failed to improve overall survival in the EORTC 26101 study. The question is whether the failure was due to the high dose of Bevacizumab used in the study. High doses of Bevacizumab may lead to excessive pruning & destruction of blood vessels, hampering the delivery of CCNU. In vitro & in vivo studies showed that a lower dose of Bevacizumab (1-1.5 mg/kg) has the potential to normalize tumor vasculature leading to improved drug delivery & outcomes. To test this hypothesis, we conducted this study to evaluate the efficacy of low-dose Bevacizumab in combination with CCNU in rGBM. Methods: This was a phase 2 open-label, single-arm trial that included adults with rGBM with an ECOG PS 0-2 and adequate organ & marrow function. The participants received CCNU 110 mg/m2 PO once a day, on day 1 of a 42-day cycle (max. 8 cycles) with Bevacizumab 1.5 mg/kg intravenously every 3 weeks (max.16 cycles). Appropriate anti-emetic prophylaxis was given. Treatment continued until disease progression, clinical deterioration, or development of intolerable side effects. Response assessment was done with MRI Brain +/- spine at 2 monthly intervals till disease progression. The modified RANO criteria were used for response assessment. Safety assessments were done on day 8 of cycle 1, & days 21 & 42 of each cycle. The primary end-point of this study was overall survival (OS) and secondary end-points were progression-free survival (PFS) & safety. A 6-month OS ≥ 40% was the signal to explore this regimen further and if the 6-month OS <20% it would be considered futile. Descriptive statistics were performed and the Kaplan-Meier method was used for time-to-event analysis. Results: Forty-six patients were enrolled in this study. The median age was 42 years (IQR 33-52.75) and 78.3% (36/46) were males. Most patients (76.1%, 35/46) had an ECOG PS of 1. The median follow-up duration was 15.27 months (95% CI 13.47-17.06). The median number of doses of Bevacizumab and CCNU were 4 and 2 respectively. Three (6.5%) patients completed all planned doses of Bevacizumab and CCNU. The objective response rate (ORR) was 15.2 % (7/46). The median OS was 6.133 months (95% CI 5.474-6.793). The 6-month OS was 57.1%. The median PFS was 3.267 months (95% CI 0.850-5.684). The most frequent grade 3 or higher toxicities seen were neutropenia (7/46, 15.2%), thrombocytopenia (5/46,10.8%), elevated ALT levels (3/46, 6.5%), anemia (2/46, 4.3%) and hyponatremia (2/46, 4.3%). Conclusions: This study demonstrates the efficacy of low-dose Bevacizumab in combination with CCNU in rGBM (the median OS exceeded the preplanned cut-off of 40%) with an acceptable toxicity profile and no new safety signals. This combination should be explored further in a phase III randomized study. Clinical trial information: CTRI/2020/07/026696 .

Trifluridine–tipiracil plus bevacizumab versus trifluridine–tipiracil monotherapy for chemorefractory metastatic colorectal cancer: a systematic review and meta-analysis

Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included − 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42–0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52–0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51–6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28–2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19–1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44–0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR.Graphical

A phase II trial combining SHR-1316, bevacizumab, and cisplatin/carboplatin in patients with TNBC with active brain metastases.

e13133 Background: Triple-negative breast cancer (TNBC) has a high risk of brain metastases (BM), leading to poor survival. Treatment options for BMs are limited, and the combination of chemotherapy and immune checkpoint inhibitor is the standard-of-care for PD-L1 positive metastatic TNBC. Platinum-based systematic therapy is the mainstay of TNBC treatment and the addition of bevacizumab has shown improvement in the progression-free survival (PFS) of patients with BM. Therefore, this study aims to investigate the efficacy and safety of SHR-1316 (anti-PD-L1) in combination with bevacizumab and cisplatin/carboplatin in TNBC patients with BMs. Methods: In this single-center phase II trial, TNBC patients with active BM received SHR-1316, bevacizumab, and cisplatin/carboplatin. Prior treatment with bevacizumab or anti-PD-1/PD-L1 were not allowed. Prior platinum was allowed only in cases of previous platinum-sensitive response. The primary endpoint was objective response rate (ORR) of central nervous system (CNS), as assessed according to the response assessment in neuro-oncology brain metastases. The secondary endpoint included clinical benefit rate (CBR) of CNS, PFS, overall survival (OS), first progression site and safety. Results: As of January 12th, 2024, a total of 23 female patients with ECOG PS≥1(100%) were enrolled. The median number of previous lines of therapy for metastatic disease was 1 (0-3). All patients had active BM, of which 87% (20/23) were BM treatment-naïve and 13% (3/23) had BM progression after previous local therapy, 26.1% (6/23) had received a prior platinum agent. Of the 23 evaluable patients, the confirmed CNS ORR was 65.2% (95%CI: 42.7%-83.6%), with 3 complete response (CR), 12 partial response (PR), 7 stable disease (SD), and 1 progressive disease (PD). The median CNS-PFS was 11.2 months (95%CI, 5.8 to not reached), median PFS was 7.6 months (95%CI, 5.7-11.9), and median OS was 13.2 months (95%CI, 9.5 to not reached). Treatment-related adverse events (TRAEs) were reported in all 23 patients, and the most common TRAEs were neutrophil count decreased (69.6%, 16/23), anemia (65.2%, 15/23), asthenia (60.9%, 14/23), Hypomagnesaemia (56.5%, 13/23), leukopenia (52.2%, 12/23) and electrocardiogram T wave abnormal (52.2%, 12/23). The incidence of grade ≥3 TRAEs was 43.5% (10/23), including neutropenia (13%, 3/23), platelet count decreased (8.7%, 2/23), and hypertension (8.7%, 2/23). Only one patient had a grade 4 TRAE (lymphocytopenia), and SHR-1316 related serious adverse event (facial nerve disorder) occurred in only one patient. No grade 5 AEs were noted. Conclusions: SHR-1316 plus bevacizumab and cisplatin/carboplatin achieves a significant improvement in CNS ORR and brings PFS and OS benefits in TNBC patients with active BMs. As an effective and safe treatment, this triple-combination warrants further investigation. Clinical trial information: NCT04303988 .

The efficacy of PARP inhibitors in the treatment of patients with synchronous breast cancer.

e13041 Background: Currently, the role of BRCA1/2 in the development of primary and multiple malignant breast tumors is under discussion, along with the effectiveness of targeted therapy for this oncopathology. At the same time, there is a lack of sufficient research dedicated to the treatment of patients with synchronous breast cancer (BC) concurrent with ovarian cancer (OC) and the outcomes of using PARP inhibitors in this patient population. Methods: A retrospective analysis of treatment outcomes based on long-term survival indicators was conducted for 23 patients with synchronous BC, where the second tumor was OC. These patients underwent evaluation and treatment between 2017 and 2022. The average age of the patients was 45.3±5.6 years, with a prevalence of patients in stages IIb-IIIa of BC and IIb-IIIc of OC. Germline mutations in the BRCA1/2 genes were detected in 8 patients, among whom 5 exhibited the triple-negative phenotype of BC. The 1st group included 11 (47.8%) patients without BRCA1/2 mutations, who received neoadjuvant chemotherapy with paclitaxel 175 mg/m2 + carboplatin AUC 6 once every 3 weeks. In the 2nd group, consisting of 12 (52.2%) patients, olaparib 800 mg was added to this chemotherapy regimen. This group also included 8 patients with BRCA1/2 mutations. Results: In the majority of patients in both groups, a significant elevation in CA125 levels in serum was observed, averaging 563 U/mL, with practically normal CA153 levels at 32 U/mL. Identified mutations included 5382insC and 4154delA mutations in the BRCA1 gene, as well as the 6174delT mutation in the BRCA2 gene. Patients underwent three courses of treatment, and four weeks after completing the last course, surgical intervention was performed in the form of radical mastectomy, hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Following surgical treatment, patients received adjuvant chemotherapy following the same regimens. In the 2nd group, patients continued to receive olaparib for one year, and no signs of unacceptable toxicity were reported. The median overall survival in the first group of patients was 34.2 months (95% CI: 28.6-37.5), while in the second group, it was 36.8 months (95% CI: 31.4-41.1). The addition of bevacizumab significantly increased the median time to progression from 13.8 months (95% CI: 11.8-14.5) to 15.2 months (95% CI: 12.4-15.8), p=0.042. Lethal outcomes primarily occurred due to the progression of ovarian cancer. Conclusions: Thus, the addition of the PARP inhibitor olaparib to a platinum-based chemotherapy regimen in patients with synchronous breast cancer, associated with germline mutations in BRCA1/2 genes and the presence of ovarian cancer as a second tumor, has a positive impact on treatment outcomes. This contributes to the resectability of patients and significantly increases the median time to progression.

The BEV1L study: Do real-world outcomes associated with the addition of bevacizumab to first-line chemotherapy in patients with ovarian cancer reinforce clinical trial findings?

The BEV1L study: Do real-world outcomes associated with the addition of bevacizumab to first-line chemotherapy in patients with ovarian cancer reinforce clinical trial findings?

Does addition of intravitreal bevacizumab confer additional benefit in management of proliferative diabetic retinopathy?

To evaluate visual outcome and complications of PDR after treatment with Intravitreal Bevacizumab followed by Pan Retinal Photocoagulation A hospital based retrospective study was done in the Department of Ophthalmology, to evaluate visual outcome and complications of PDR after treatment with intravitreal Bevacizumab followed by Pan Retinal Photocoagulation. Visual Acuity, Dilated fundus examination, OCT macula were done on subsequent follow ups 135 eyes of 133 patients were included in the study.The mean pre procedure visual acuity is 0.639±0.5327 which improved to 0.451±0.4089 post procedure. P value is &amp;#60;0.001 which is statistically significant.i.e, 94 (69.62%) eyes had improved vision, 21(15.55%) had stable vision and 20(14.81%) eyes had decreased vision. After injection followed by PRP out of 135 eyes,4(2.96%) eyes developed vitreous hemorrhage which resolved with repeat intravitreal anti-VEGF injection, 6(4.44%) eyes developed diabetic macular edema,3(2.2%) eyes developed Neovascularisation of iris and 4(2.96%)eyes developed vitreous hemorrhage with traction retinal detachment.From our study it appears that addition of intravitreal anti VEGF to Pan Retinal Photocoagulation for PDR confers the additional benefit of less incidence of vitreous hemorrhage and less incidence of traction retinal detachment requiring surgery in the 1 one year of follow up. This amounts to more compliance by the patient for taking the treatment as well as better visual outcome

Dummy run for planning of isotoxic dose-escalated radiation therapy for glioblastoma used in the PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06)

BackgroundThe PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06; NCT05871021) is designed to determine whether a dose escalation with 75.0 Gy in 30 fractions can enhance the median overall survival (OS) in patients with methylguanine methyltransferase (MGMT) promotor unmethylated glioblastoma compared to historical median OS rates, while being isotoxic to historical cohorts through the addition of concurrent bevacizumab (BEV). To ensure protocol-compliant irradiation planning with all study centers, a dummy run was planned and the plan quality was evaluated. MethodsA suitable patient case was selected and the computed tomography (CT), magnetic resonance imaging (MRI) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) contours were made available. Participants at the various intended study sites performed radiation planning according to the PRIDE clinical trial protocol. The treatment plans and dose grids were uploaded as Digital Imaging and Communications in Medicine (DICOM) files to a cloud-based platform. Plan quality and protocol adherence were analyzed using a standardized checklist, scorecards and indices such as Dice Score (DSC) and Hausdorff Distance (HD). ResultsMedian DSC was 0.89, 0.90, 0.88 for PTV60, PTV60ex (planning target volume receiving 60.0 Gy for the standard and the experimental plan, respectively) and PTV75 (PTV receiving 75.0 Gy in the experimental plan), respectively. Median HD values were 17.0 mm, 13.9 mm and 12.1 mm, respectively. These differences were also evident in the volumes: The PTV60 had a volume range of 219.1–391.3 cc (median: 261.9 cc) for the standard plans, while the PTV75 volumes for the experimental plans ranged from 71.5–142.7 cc (median: 92.3 cc). The structures with the largest deviations in Dice score were the pituitary gland (median 0.37, range 0.00–0.69) and the right lacrimal gland (median 0.59, range 0.42–0.78). ConclusionsThe deviations revealed the necessity of systematic trainings with appropriate feedback before the start of clinical trials in radiation oncology and the constant monitoring of protocol compliance throw-out the study. Trial registrationNCT05871021

An integrated omics approach highlights how epigenetic events can explain and predict response to neoadjuvant chemotherapy and bevacizumab in breast cancer.

Treatment with the anti-angiogenic drug bevacizumab in addition to chemotherapy has shown efficacy for breast cancer in some clinical trials, but better biomarkers are needed to optimally select patients for treatment. Here, we present an omics approach where DNA methylation profiles are integrated with gene expression and results from proteomic data in breast cancer patients to predict response to therapy and pinpoint response-related epigenetic events. Fresh-frozen tumor biopsies taken before, during, and after treatment from human epidermal growth factor receptor 2 negative non-metastatic patients receiving neoadjuvant chemotherapy with or without bevacizumab were subjected to molecular profiling. Here, we report that DNA methylation at enhancer CpGs related to cell cycle regulation can predict response to chemotherapy and bevacizumab for the estrogen receptor positive subset of patients (AUC = 0.874), and we validated this observation in an independent patient cohort with a similar treatment regimen (AUC = 0.762). Combining the DNA methylation scores with the scores from a previously published protein signature resulted in a slight increase in the prediction performance (AUC = 0.784). We also show that tumors receiving the combination treatment underwent more extensive epigenetic alterations. Finally, we performed an integrative expression-methylation quantitative trait loci analysis on alterations in DNA methylation and gene expression levels, showing that the epigenetic alterations that occur during treatment are different between responders and non-responders and that these differences may be explained by the proliferation-epithelial-to-mesenchymal transition axis through the activity of grainyhead like transcription factor 2. Using tumor purity computed from copy number data, we developed a method for estimating cancer cell-specific methylation to confirm that the association to response reflects DNA methylation in cancer cells. Taken together, these results support the potential for clinical benefit of the addition of bevacizumab to chemotherapy when administered to the correct patients.

Cost-effectiveness of bevacizumab therapy in the care of patients with hereditary hemorrhagic telangiectasia

AbstractNo US Food and Drug Administration- or European Medicines Agency-approved therapies exist for bleeding due to hereditary hemorrhagic telangiectasia (HHT), the second-most common inherited bleeding disorder worldwide. The current standard of care (SOC) includes iron and red cell supplementation, alongside the necessary hemostatic procedures, none of which target underlying disease pathogenesis. Recent evidence has demonstrated that bleeding pathophysiology is amenable to systemic antiangiogenic therapy with the anti-vascular endothelial growth factor bevacizumab. Despite its high cost, the addition of longitudinal bevacizumab to the current SOC may reduce overall health care resource use and improve patient quality of life. We conducted, to our knowledge, the first cost-effectiveness analysis of IV bevacizumab in patients with HHT with the moderate-to-severe phenotype, comparing bevacizumab added to SOC vs SOC alone. The primary outcome was the incremental net monetary benefit (iNMB) reported over a lifetime time horizon and across accepted willingness-to-pay thresholds, in US dollar per quality-adjusted life year (QALY). Bevacizumab therapy accrued 9.3 QALYs while generating $428 000 in costs, compared with 8.3 QALYs and $699 000 in costs accrued in the SOC strategy. The iNMB of bevacizumab therapy vs the SOC was $433 000. No parameter variation and no scenario analysis, including choice of iron supplementation product, changed the outcome of bevacizumab being a cost-saving strategy. Bevacizumab therapy also saved patients an average of 133 hours spent receiving HHT-specific care per year of life. In probabilistic sensitivity analysis, bevacizumab was favored in 100% of all 10 000 Monte Carlo iterations across base-case and all scenario analyses. Bevacizumab should be considered for more favorable formulary placement in the care of patients with moderate-to-severe HHT.

First Line Chemotherapy in Metastatic Colorectal Cancers: A Review

Colorectal cancer (CRC) is a common malignancy detected. Approximately, 22% of CRCs are metastatic at initial diagnosis, and about 70% of patients will eventually develop metastatic relapse. Metastatic colorectal cancer is a disease with poor prognosis whose treatment is always palliative chemotherapy. Today, thanks to the knowledge of molecular biology and the discoveries of new pathways, we have managed to increase survival to around 40 months which can increase thanks to the use of surgery and locoregional treatments. The choice of chemotherapy in these patients therefore depends on the characteristics of the molecular profile and includes, in fit patients, chemotherapy with the addition of targeted therapies. In this article, we examine the most recent data from randomized clinical trials supporting the use of chemotherapy triplets or doublets as well as the addition of bevacizumab or anti-epidermal growth factor receptor (EGFR) agents.

The Effects of Bevacizumab in Augmenting Trabeculectomy for Glaucoma : Systematic Review and Meta-Analysis

Introduction &amp; Objectives : Anti-vascular endothelial growth factor (VEGF) agents have been used to slow the healing response and postoperative scar tissue formation. To determine the effectiveness of adding Anti VEGF bevacizumab to the results of trabeculectomy in glaucoma.&#x0D; Methods : Searches were conducted in a structured way using keywords across several data sources, including Pubmed, Proquest and Cochrane library. The keywords used for searching were “Bevacizumab”, “Trabeculectomy” and “Glaucoma”. The reviewed articles are Randomized Control Trial in english, conducted on humans in the last 15 years. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.&#x0D; Results : From a total of 353 articles, there were 6 studies with 362 eyes of 352 patients been evaluated for the effectiveness of bevacizumab addition to trabeculectomy. The primary outcome of all articles was the assessment of Intra Ocular Pressure (IOP). No significant difference in IOP was found between the subconjunctival bevacizumab + Mytomycin-c group and mytomycin-c alone group (MD 0.11 ; 95% CI -0.10 to 0.33), as well as subconjunctival comparison with mytomycin-c (MD 0.11 ; 95% CI -0.29 to 0.50). Similar results were also found in the intracameral and placebo groups (MD 0.08 ; -0.22 to 0.38). However, 3 articles reported significant differences in peripheral vascularity of the bleb both by the Moorfields Bleb Grading System and by the Indiana Bleb Appearance System.&#x0D; Conclusion : The addition of bevacizumab to trabeculectomy did not show any benefit in reducing IOP when compared with MMC. But it gives better peripheral vascularity of the bleb.

Effect of high-dose polymeric nanoparticle micellar paclitaxel on improved progression-free survival in patients with optimally resected stage III or IV high-grade carcinoma of the ovary: a prospective cohort study with historical controls.

We evaluated the effect of high-dose polymeric nanoparticle micellar paclitaxel (PM-Pac) on survival in patients with stage III-IV high-grade serous ovarian cancer (HGSC) who underwent upfront surgery. We prospectively recruited the patients who received PM-Pac (280 mg/m2) and carboplatin at an area under the curve (AUC) of 5 (cohort 1) in two tertiary centers between October 2015 and June 2019. As historical controls, we retrospectively collected data on those who received paclitaxel (175 mg/m2) and carboplatin (AUC 5; cohort 2) or paclitaxel (175 mg/m2), carboplatin (AUC 5) and bevacizumab (15 mg/kg; cohort 3). A total of 128 patients were divided into cohorts 1 (n=49, 38.3%), 2 (n=53, 41.4%), and 3 (n=26, 20.3%). Cohort 1 showed better progression-free survival (PFS) than cohort 2 in all patients and those treated with optimal debulking surgery (ODS; median, 35.5 vs. 28.1 and 35.5 vs. 28.9 months; p ≤ 0.01) despite no difference in PFS between cohorts 1 and 3 and between cohorts 2 and 3. In particular, stage III disease was a favorable factor for PFS, whereas cohort 2 was related to worse PFS (adjusted hazard ratios, 0.456 and 1.834; 95% confidence interval, 0.263 - 0.790 and 1.061 - 3.171), showing no difference in PFS between cohorts 1 and 3 in those treated with ODS. High-dose PM-Pac improved PFS compared to conventional chemotherapy, and the change of paclitaxel to PM-Pac had as much effect on PFS as the addition of bevacizumab in patients with stage III-IV HGSC who underwent ODS.