Dataset Information

Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI.

ABSTRACT: The purpose of this study was to assess the impact of bevacizumab alone and in combination with cytotoxic therapy on tumour vasculature in osteosarcoma (OS) using DCE-MRI.Six DCE-MRI and three (18)F-FDG PET examinations were scheduled in 42 subjects with newly diagnosed OS to monitor the response to antiangiogenic therapy alone and in combination with cytotoxic therapy before definitive surgery (week 10). Serial DCE-MRI parameters (K(trans), v(p), and v(e)) were examined for correlation with FDG-PET (SUV(max)) and association with drug exposure, and evaluated with clinical outcome.K(trans) (P=0.041) and v(p) (P=0.001) significantly dropped from baseline at 24 h after the first dose of bevacizumab alone, but returned to baseline by 72?h. Greater exposure to bevacizumab was correlated with larger decreases in v(p) at day 5 (P=0.04) and week 10 (P=0.02). A lower K(trans) at week 10 was associated with greater percent necrosis (P=0.024) and longer event-free survival (P=0.034).This is the first study to demonstrate significant changes of the plasma volume fraction and vascular leakage in OS with bevacizumab alone. The combination of demonstrated associations between drug exposure and imaging metrics, and imaging metrics and patient survival during neoadjuvant therapy, provides a compelling rationale for larger studies using DCE-MRI to assess vascular effects of therapy in OS.

SUBMITTER: Guo J

PROVIDER: S-EPMC4815789 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI.

Guo J J Glass J O JO McCarville M B MB Shulkin B L BL Daryani V M VM Stewart C F CF Wu J J Mao S S Dwek J R JR Fayad L M LM Madewell J E JE Navid F F Daw N C NC Reddick W E WE

British journal of cancer 20151013 9

<h4>Background</h4>The purpose of this study was to assess the impact of bevacizumab alone and in combination with cytotoxic therapy on tumour vasculature in osteosarcoma (OS) using DCE-MRI.<h4>Methods</h4>Six DCE-MRI and three (18)F-FDG PET examinations were scheduled in 42 subjects with newly diagnosed OS to monitor the response to antiangiogenic therapy alone and in combination with cytotoxic therapy before definitive surgery (week 10). Serial DCE-MRI parameters (K(trans), v(p), and v(e)) wer ...[more]

PMID: 26461056

Similar Datasets

Project description:BackgroundBevacizumab and the antimetabolites capecitabine and gemcitabine have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer. The primary aims of this trial were to determine whether the addition of capecitabine or gemcitabine to neoadjuvant chemotherapy with docetaxel, followed by doxorubicin plus cyclophosphamide, would increase the rates of pathological complete response in the breast in women with operable, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and whether adding bevacizumab to these chemotherapy regimens would increase the rates of pathological complete response.MethodsWe randomly assigned 1206 patients to receive neoadjuvant therapy consisting of docetaxel (100 mg per square meter of body-surface area on day 1), docetaxel (75 mg per square meter on day 1) plus capecitabine (825 mg per square meter twice a day on days 1 to 14), or docetaxel (75 mg per square meter on day 1) plus gemcitabine (1000 mg per square meter on days 1 and 8) for four cycles, with all regimens followed by treatment with doxorubicin-cyclophosphamide for four cycles. Patients were also randomly assigned to receive or not to receive bevacizumab (15 mg per kilogram of body weight) for the first six cycles of chemotherapy.ResultsThe addition of capecitabine or gemcitabine to docetaxel therapy, as compared with docetaxel therapy alone, did not significantly increase the rate of pathological complete response (29.7% and 31.8%, respectively, vs. 32.7%; P=0.69). Both capecitabine and gemcitabine were associated with increased toxic effects--specifically, the hand-foot syndrome, mucositis, and neutropenia. The addition of bevacizumab significantly increased the rate of pathological complete response (28.2% without bevacizumab vs. 34.5% with bevacizumab, P=0.02). The effect of bevacizumab on the rate of pathological complete response was not the same in the hormone-receptor-positive and hormone-receptor-negative subgroups. The addition of bevacizumab increased the rates of hypertension, left ventricular systolic dysfunction, the hand-foot syndrome, and mucositis.ConclusionsThe addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response, which was the primary end point of this study. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00408408.).

Project description:Background This study sought to predict the early responses to neoadjuvant chemotherapy (NACT) of patients with primary conventional osteosarcoma (COS) using the apparent diffusion coefficient (ADC) and to evaluate the factors affecting the tumor necrosis rate (TNR). Methods The data of 41 patients who underwent magnetic resonance imaging (MRI) and diffusion-weighted imaging sequence scans before NACT, 5 days after the end of the first phase of NACT, after the end of the whole course of chemotherapy, were prospectively collected. ADC1 refers to the ADC before chemotherapy, ADC2 refers to the ADC after the first phase of chemotherapy, and ADC3 refers to the ADC before surgery. The change in values before and after the first phase of chemotherapy was calculated as follows: ADC2-1 = ADC2 − ADC1. The change in values before and after the last phase of chemotherapy was calculated as follows: ADC3-1 = ADC3 − ADC1. The change in values after the first phase and the last phase of chemotherapy was calculated as follows: ADC3-2 = ADC3 − ADC2. We recorded the patient characteristics, including age, gender, pulmonary metastasis, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). The patients were divided into the following 2 groups based on their histological TNR after postoperative: (I) the good-response group (≥90% necrosis, n=13) and (II) the poor-response group (<90% necrosis, n=28). Changes in the ADCs were compared between the good-response and poor-response groups. The different ADCs between the 2 groups were compared, and a receiver operating characteristic analysis was performed. A correlation analysis was performed to assess the correlations of the clinical features, laboratory features, and different ADCs with patients’ histopathological responses to NACT. Results The ADC2 (P<0.001), ADC3 (P=0.004), ADC3-1 (P=0.008), ADC3-2 (P=0.047), and ALP before NACT (P=0.019) were significantly higher in the good-response group than in the poor-response group. The ADC2 [area under the curve (AUC) =0.723; P=0.023], ADC3 (AUC =0.747; P=0.012), and ADC3-1 (AUC =0.761; P=0.008) showed good diagnostic performance. Based on the univariate binary logistic regression analysis, the ADC2 (P=0.022), ADC3 (P=0.009), ADC2-1 (P=0.041), and ADC3-1 (P=0.014) were correlated with the TNR. However, based on the multivariate analysis, these parameters were not significantly correlated with the TNR. Conclusions In patients with COS who are undergoing neoadjuvant chemotherapy, the ADC2 is a promisingindicator for predicting tumor response to chemotherapy in early.

Dataset Information

Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI.

Publications

Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets