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The integration of bevacizumab improves tumor response and survival in patients with refractory cervical cancer treated with radical chemoradiotherapy.

ABSTRACT:

Background

Management of refractory cervical cancers (CC) is a debated question and rises dilemma in clinical practice. This study aimed to assess the safety and effectiveness of bevacizumab combined with concurrent chemoradiotherapy in the treatment of refractory CC.

Methods

A total of 129 patients with refractory CC who received radical concurrent chemoradiotherapy (CCRT) were included in this study. Among the patients, 64 received combination treatment with bevacizumab, while the 65 remaining patients did not receive bevacizumab. Treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumorsversion1.1. The Cox proportional-hazards model was applied to determine prognostic factors associated with overall survival and the tumor response during treatment was analyzed for patients treated with bevacizumab.

Results

Bevacizumab was an independent prognostic factor (P=0.017). Therefore, we only analyzed 64 patients who received combination treatment with bevacizumab. In the 64 patients treated with bevacizumab, the 3-year OS, locoregional relapse-free survival, and distant metastasis-free survival rates were 87.2%, 98.1%, and 81%, respectively. Complete clinical response rates were 37.8% (17/45) for patients with neoadjuvant chemotherapy and chemoradiotherapy after neoadjuvant chemotherapy (NACT), complete clinical response rates were 62.5% (40/64), 73.3% (33/45) and 52.6% (10/19) before brachytherapy (BT), respectively for the entire cohort, patients with NACT and chemoradiotherapy and patients with chemoradiotherapy only. The 2-year OS rate was higher for patients who achieved a complete clinical response BT than for patients who did not, 94.6% vs. 73.2%, P=0.03. Among the 64 patients who received it, 28 (43.8%) experienced hematological toxicities of grade 3 or 4, and 3 (4.7%) experienced grade 3 gastrointestinal toxicities.

Conclusions

Bevacizumab combined with radical chemoradiotherapy is a safe and tolerable treatment option for refractory CC, with quicker tumor regression and high OS, locoregional relapse-free survival, and distant metastasis-free survival rates.

SUBMITTER: Yang H

PROVIDER: S-EPMC8350679 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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The integration of bevacizumab improves tumor response and survival in patients with refractory cervical cancer treated with radical chemoradiotherapy.

Yang Hua H Zhang Ying Y Liu Changhao C Feng Bin B Zhang Jianjun J Zhou Yan Y Yin Yutian Y Li Jianping J Li Weiwei W Balaya Vincent V Shi Mei M Zhao Lina L Wei Lichun L

Annals of translational medicine 20210701 14

<h4>Background</h4>Management of refractory cervical cancers (CC) is a debated question and rises dilemma in clinical practice. This study aimed to assess the safety and effectiveness of bevacizumab combined with concurrent chemoradiotherapy in the treatment of refractory CC.<h4>Methods</h4>A total of 129 patients with refractory CC who received radical concurrent chemoradiotherapy (CCRT) were included in this study. Among the patients, 64 received combination treatment with bevacizumab, while t ...[more]

PMID: 34430625

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Project description:IntroductionAnemia has long been associated with poor prognosis in patients with cervical cancer. Recently, additional hematologic parameters have emerged as potential indicators of worse outcome in this patient group. In a cohort of cervical cancer patients treated with chemoradiotherapy (CRT) and brachytherapy, we report on the prognostic significance of hematologic parameters including anemia, leukocytosis, neutrophil to lymphocyte ratio (NLR), and thrombocytosis, the effect of combining anemia with other hematologic parameters, and the effect of changes in hemoglobin levels during treatment.Materials and methodsTwo-hundred fifty-seven cervical cancer patients were retrospectively identified from a single cancer institution's database. Hematologic parameters were categorized as: anemia (hemoglobin ≤115 g/L), leukocytosis (white blood cell count >10 × 109/L), thrombocytosis (platelets >400 × 109/L), and NLR (ratio >5). The association between clinical factors and hematologic parameters on progression-free survival (PFS) and overall survival (OS) were assessed at 5 years.ResultsAt 5 years, both pre-treatment anemia (PFS: 60% vs 34%, p < 0.0001; OS: 68% vs 41%, p < 0.0001) and on-treatment anemia (PFS: 62% vs 40%, p < 0.0001; OS: 70% vs 48%, p < 0.0001) were significantly associated with worse survival. This adverse effect on 5-year PFS and OS was increased in patients with both pre-treatment anemia and leukocytosis (PFS: 72% vs 42%, p < 0.0001; OS: 68% vs 37%, p < 0.0001) and pre-treatment anemia and elevated NLR (PFS: 61% vs 30%, p < 0.0001; OS: 68% vs 37%, p < 0.0001). Five-year PFS (50% vs 31%) and OS (60% vs 36%) was better in patients whose pre-treatment anemia improved to normal hemoglobin levels on treatment vs those patients who were anemic both pre- and on-treatment.ConclusionPre-treatment and on-treatment anemia were significant, independent predictors of worse PFS and OS. Anemia and other hematologic parameters remain prognostic markers for cervical cancer patients. Improvement in PFS and OS was seen in patients with normalization of hemoglobin.

Project description:BackgroundVascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab, a humanized anti-VEGF monoclonal antibody, has single-agent activity in previously treated, recurrent disease. Most patients in whom recurrent cervical cancer develops have previously received cisplatin with radiation therapy, which reduces the effectiveness of cisplatin at the time of recurrence. We evaluated the effectiveness of bevacizumab and nonplatinum combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer.MethodsUsing a 2-by-2 factorial design, we randomly assigned 452 patients to chemotherapy with or without bevacizumab at a dose of 15 mg per kilogram of body weight. Chemotherapy consisted of cisplatin at a dose of 50 mg per square meter of body-surface area, plus paclitaxel at a dose of 135 or 175 mg per square meter or topotecan at a dose of 0.75 mg per square meter on days 1 to 3, plus paclitaxel at a dose of 175 mg per square meter on day 1. Cycles were repeated every 21 days until disease progression, the development of unacceptable toxic effects, or a complete response was documented. The primary end point was overall survival; a reduction of 30% in the hazard ratio for death was considered clinically important.ResultsGroups were well balanced with respect to age, histologic findings, performance status, previous use or nonuse of a radiosensitizing platinum agent, and disease status. Topotecan-paclitaxel was not superior to cisplatin-paclitaxel (hazard ratio for death, 1.20). With the data for the two chemotherapy regimens combined, the addition of bevacizumab to chemotherapy was associated with increased overall survival (17.0 months vs. 13.3 months; hazard ratio for death, 0.71; 98% confidence interval, 0.54 to 0.95; P=0.004 in a one-sided test) and higher response rates (48% vs. 36%, P=0.008). Bevacizumab, as compared with chemotherapy alone, was associated with an increased incidence of hypertension of grade 2 or higher (25% vs. 2%), thromboembolic events of grade 3 or higher (8% vs. 1%), and gastrointestinal fistulas of grade 3 or higher (3% vs. 0%).ConclusionsThe addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer was associated with an improvement of 3.7 months in median overall survival. (Funded by the National Cancer Institute; GOG 240 ClinicalTrials.gov number, NCT00803062.).

Project description:ObjectiveTo evaluate the association of number of radical hysterectomies performed per year in each center with disease-free survival and overall survival.MethodsWe conducted an international, multicenter, retrospective study of patients previously included in the Surveillance in Cervical Cancer collaborative studies. Individuals with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB1-IIA1 cervical cancer who underwent radical hysterectomy and had negative lymph nodes at final histology were included. Patients were treated at referral centers for gynecologic oncology according to updated national and international guidelines. Optimal cutoffs for surgical volume were identified using an unadjusted Cox proportional hazard model, with disease-free survival as the outcome and defined as the value that minimizes the P-value of the split in groups in terms of disease-free survival. Propensity score matching was used to create statistically similar cohorts at baseline.ResultsA total of 2,157 patients were initially included. The two most significant cutoffs for surgical volume were identified at seven and 17 surgical procedures, dividing the entire cohort into low-volume, middle-volume, and high-volume centers. After propensity score matching, 1,238 patients were analyzed-619 (50.0%) in the high-volume group, 523 (42.2%) in the middle-volume group, and 96 (7.8%) in the low-volume group. Patients who underwent surgery in higher-volume institutions had progressively better 5-year disease-free survival than those who underwent surgery in lower-volume centers (92.3% vs 88.9% vs 83.8%, P=.029). No difference was noted in 5-year overall survival (95.9% vs 97.2% vs 95.2%, P=.70). Cox multivariable regression analysis showed that FIGO stage greater than IB1, presence of lymphovascular space invasion, grade greater than 1, tumor diameter greater than 20 mm, minimally invasive surgical approach, nonsquamous cell carcinoma histology, and lower-volume centers represented independent risk factors for recurrence.ConclusionSurgical volume of centers represented an independent prognostic factor affecting disease-free survival. Increasing number of radical hysterectomies performed in each center every year was associated with improved disease-free survival.

Project description:BackgroundIn 2018, a revised staging system was released for cervical cancer, which defined pelvic and paraaortic lymph node metastasis as stages IIIC1 and IIIC2, respectively. In this study, we constructed and validated nomograms to predict the 3- and 5-year survival of patients with cervical cancer based on the revised International Federation of Gynecology and Obstetrics (FIGO) staging system.MethodsWe retrospectively examined patients with 2009 FIGO stage IB-IVA cervical cancer who were treated at our institute between 2011 and 2015. Patients were randomized into the model development and validation cohorts (2:1). Univariate and multivariate analyses were conducted for the model development cohort to identify prognostic factors. In the multivariate analysis, nomograms were built to predict overall survival (OS) and disease-free survival (DFS) using significant variables. The nomograms were assessed based on the discrimination and calibration in both cohorts. Discrimination was assessed using the concordance index. Calibration was performed by comparing the mean nomogram estimated survival and the mean observed survival.ResultsWe included 1,192 patients, with 795 and 397 patients in the model development and validation cohorts, respectively. In the model development cohort, the median follow-up period was 49.2 months. After multivariate analysis, age, histology, 2018 FIGO stage, and pelvic lymph node number were independent factors for OS. Histology, 2018 FIGO stage, squamous cell carcinoma antigen, and pelvic lymph node number were significant predictors of DFS. The nomograms constructed to predict OS and DFS were based on these factors. In both model cohorts, the concordance index for the nomogram-predicted OS and DFS was 0.78 and 0.75 and 0.74 and 0.67, respectively. The calibration curve revealed good agreement between the nomogram predictions and actual values.ConclusionWe constructed robust nomograms to predict the OS and DFS of patients with cervical cancer undergoing treatment with concurrent chemoradiotherapy based on the 2018 FIGO staging system.

Project description:Background To investigate the magnetic resonance imaging (MRI)-based radiomics value in predicting the survival of patients with locally advanced cervical squamous cell cancer (LACSC) treated with concurrent chemoradiotherapy (CCRT). Methods A total of 185 patients (training group: n = 128; testing group: n = 57) with LACSC treated with CCRT between January 2014 and December 2018 were retrospectively enrolled in this study. A total of 400 radiomics features were extracted from T2-weighted imaging, apparent diffusion coefficient map, arterial- and delayed-phase contrast-enhanced MRI. Univariate Cox regression and least absolute shrinkage and selection operator Cox regression was applied to select radiomics features and clinical characteristics that could independently predict progression-free survival (PFS) and overall survival (OS). The predictive capability of the prediction model was evaluated using Harrell’s C-index. Nomograms and calibration curves were then generated. Survival curves were generated using the Kaplan-Meier method, and the log-rank test was used for comparison. Results The radiomics score achieved significantly better predictive performance for the estimation of PFS (C-index, 0.764 for training and 0.762 for testing) and OS (C-index, 0.793 for training and 0.750 for testing), compared with the 2018 FIGO staging system (C-index for PFS, 0.657 for training and 0.677 for testing; C-index for OS, 0.665 for training and 0.633 for testing) and clinical-predicting model (C-index for PFS, 0.731 for training and 0.725 for testing; C-index for OS, 0.708 for training and 0.693 for testing) (P < 0.05). The combined model constructed with T stage, lymph node metastasis position, and radiomics score achieved the best performance for the estimation of PFS (C-index, 0.792 for training and 0.809 for testing) and OS (C-index, 0.822 for training and 0.785 for testing), which were significantly higher than those of the radiomics score (P < 0.05). Conclusions The MRI-based radiomics score could provide effective information in predicting the PFS and OS in patients with LACSC treated with CCRT. The combined model (including MRI-based radiomics score and clinical characteristics) showed the best prediction performance. Supplementary Information The online version contains supplementary material available at 10.1186/s40644-022-00474-2.

Dataset Information

The integration of bevacizumab improves tumor response and survival in patients with refractory cervical cancer treated with radical chemoradiotherapy.

Background

Methods

Results

Conclusions

Publications

The integration of bevacizumab improves tumor response and survival in patients with refractory cervical cancer treated with radical chemoradiotherapy.

Similar Datasets

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