Background: Cancer treatment with anthracyclines may lead to an increased incidence of cardiac disease due to cardiotoxicity, as they may cause irreversible myocardial fibrosis. So far, the proposed methods for screening patients for cardiotoxicity have led to only limited success, while the analysis of myocardial extracellular volume (mECV) at cardiac magnetic resonance (CMR) has shown promising results, albeit requiring a dedicated exam. Recent studies have found strong correlations between mECV values obtained through computed tomography (CT), and those derived from CMR. Thus, our purpose was to evaluate the feasibility of estimating mECV on thoracic contrast-enhanced CT performed for staging or follow-up in breast cancer patients treated with anthracyclines, and, if feasible, to assess if a rise in mECV is associated with chemotherapy, and persistent over time.Methods: After ethics committee approval, female patients with breast cancer who had undergone at least 2 staging or follow-up CT examinations at our institution, one before and one shortly after the end of chemotherapy including anthracyclines were retrospectively evaluated. Patients without available haematocrit, with artefacts in CT images, or who had undergone radiation therapy of the left breast were excluded. Follow-up CT examinations at longer time intervals were also analysed, when available. mECV was calculated on scans obtained at 1, and 7 min after contrast injection.Results: Thirty-two female patients (aged 57±13 years) with pre-treatment haematocrit 38%±4%, and ejection fraction 64%±6% were analysed. Pre-treatment mECV was 27.0%±2.9% at 1 min, and 26.4%±3.8% at 7 min, similar to values reported for normal subjects in the literature. Post-treatment mECV (median interval: 89 days after treatment) was 31.1%±4.9%, and 30.0%±5.1%, respectively, values significantly higher than pre-treatment values at all times (P<0.005). mECV at follow-up (median interval: 135 days after post-treatment CT) was 31.0%±4.5%, and 27.7%±3.7%, respectively, without significant differences (P>0.548) when compared to post-treatment values.Conclusions: mECV values from contrast-enhanced CT scans could play a role in the assessment of myocardial condition in breast cancer patients undergoing anthracycline-based chemotherapy. CT-derived ECV could be an imaging biomarker for the monitoring of therapy-related cardiotoxicity, allowing for potential secondary prevention of cardiac damage, using data derived from an examination that could be already part of patients' clinical workflow.
Background Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4–6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment. Methods This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis. Discussion The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression. Trial registration ARMANI is registered at ClinicalTrials.gov ( NCT02934464 , October 17, 2016) and EudraCT(2016–001783-12, April 202,016).
Routine use of the CCI may help in the pretreatment risk stratification of elderly patients with esophageal carcinoma.
Background We investigated the radiodensity of epicardial (EAT), subcutaneous (SAT), and visceral adipose tissue (VAT) before and after treatment with anthracyclines in a population of breast cancer (BC) patients, and in controls not treated with anthracyclines, to detect a potential role of EAT density as a biomarker of changes related to chemotherapy cardiotoxicity. Methods We reviewed BC patients treated with anthracyclines who underwent CT before (CT-t0) and after (CT-t1) chemotherapy, and age- and sex-matched controls who underwent two CT examinations at comparable intervals. On non-contrast scans, EAT was segmented contouring the pericardium and thresholding between -190 and -30 Hounsfield units (HU), and SAT and VAT were segmented with two 15-mm diameter regions of interest thresholded between -195 and -45 HU. Results Thirty-two female patients and 32 controls were included. There were no differences in age (p = 0.439) and follow-up duration (p = 0.162) between patients and controls. Between CT-t0 and CT-t1, EAT density decreased in BC patients (-66 HU, interquartile range [IQR] -71 to -63 HU, to -71 HU, IQR -75 to -66 HU, p = 0.003), while it did not vary in controls (p = 0.955). SAT density increased from CT-t0 to CT-t1 in BC patients (-107 HU, IQR -111 to -105 HU, to -105 HU, IQR -110 to -100 HU, p = 0.014), whereas it did not change in controls (p = 0.477). VAT density did not vary in either BC patients (p = 0.911) or controls (p = 0.627). Conclusions EAT density appears to be influenced by anthracycline treatment for BC, well known for its cardiotoxicity, shifting towards lower values indicative of a less active metabolism.
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