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Simple Summary: Neuroendocrine tumors (NETs) are rare neoplasms that often present upregulation of the mammalian rapamycin targeting pathway (mTOR) with consequent uncontrolled growth and proliferation. This pathway is also involved in the metabolism of adipose tissue and in the regulation of skeletal muscle synthesis. The mTOR therefore represents an attractive therapeutic target. Everolimus acts by selectively inhibiting the mTOR pathway with an antiproliferative effect. The aim of this study is to investigate the prognostic and predictive role of body composition indices (muscle and adipose) in metastatic NETs patients treated with everolimus. Neuroendocrine tumors (NETs) are rare neoplasms frequently characterized by an upregulation of the mammalian rapamycin targeting (mTOR) pathway resulting in uncontrolled cell proliferation. The mTOR pathway is also involved in skeletal muscle protein synthesis and in adipose tissue metabolism. Everolimus inhibits the mTOR pathway, resulting in blockade of cell growth and tumor progression. The aim of this study is to investigate the role of body composition indexes in patients with metastatic NETs treated with everolimus. The study population included 30 patients with well-differentiated (G1-G2), metastatic NETs treated with everolimus at the IRCCS Romagnolo Institute for the Study of Tumors (IRST) "Dino Amadori", Meldola (FC), Italy. The body composition indexes (skeletal muscle index [SMI] and adipose tissue indexes) were assessed by measuring on a computed tomography (CT) scan the cross-sectional area at L3 at baseline and at the first radiological assessment after the start of treatment. The body mass index (BMI) was assessed at baseline. The median progression-free survival (PFS) was 8.9 months (95% confidence interval [CI]: 3.4–13.7 months). The PFS stratified by tertiles was 3.2 months (95% CI: 0.9–10.1 months) in patients with low SMI (tertile 1), 14.2 months (95% CI: 2.3 months-not estimable [NE]) in patients with intermediate SMI (tertile 2), and 9.1 months (95% CI: 2.7 months-NE) in patients with high SMI (tertile 3) (p = 0.039). Similarly, the other body composition indexes also showed a statistically significant difference in the three groups on the basis of tertiles. The median PFS was 3.2 months (95% CI: 0.9–6.7 months) in underweight patients (BMI ≤ 18.49 kg/m2) and 10.1 months (95% CI: 3.7–28.4 months) in normal-weight patients (p = 0.011). There were no significant differences in terms of overall survival. The study showed a correlation between PFS and the body composition indexes in patients with NETs treated with everolimus, underlining the role of adipose and muscle tissue in these patients. [ABSTRACT FROM AUTHOR]

Cancer is a risk factor for venous thromboembolism (VTE). Plasma tumor DNA (ptDNA) is an independent predictor of outcome in metastatic castration‐resistant prostate cancer (mCRPC). We aimed to investigate the association between ptDNA and VTE in mCRPC. This prospective biomarker study included 180 mCRPC patients treated with abiraterone and enzalutamide from April 2013 to December 2018. We excluded patients with a previous VTE history and/or ongoing anticoagulation therapy. Targeted next‐generation sequencing was performed to determine ptDNA fraction from pretreatment plasma samples. VTE risk based on survival analysis was performed using cumulative incidence function and estimating sub‐distributional hazard ratio (SHR). At a median follow‐up of 58 months (range 0.5‐111.0), we observed 21 patients who experienced VTE with a cumulative incidence at 12 months of 17.1% (95% confidence interval [CI] 10.3‐23.9). Elevated ptDNA, visceral metastasis, prior chemotherapy and lactate dehydrogenase (LDH) were significantly associated with higher VTE incidence compared to patients with no thrombosis (12‐month estimate, 18.6% vs 3.5%, P =.0003; 44.4% vs 14.8%, P =.015; 24.7% vs 4.5%, P =.006; and 30.0% vs 13.5%, P =.05, respectively). In the multivariate analysis including ptDNA level, visceral metastases, number of lesions and serum LDH, high ptDNA fraction was the only independent factor associated with the risk of thrombosis (HR 5.78, 95% CI 1.63‐20.44, P =.006). These results first suggest that baseline ptDNA fraction in mCRPC patients treated with abiraterone or enzalutamide may be associated with increased VTE risk. These patients may be followed‐up more closely for the VTE risk, and the need for a primary thromboprophylaxis should be taken into account in mCRPC with elevated ptDNA. What's new? Patients with cancer are at increased risk for venous thromboembolism (VTE). Here, the authors test the correlation between plasma tumor DNA (ptDNA) and VTE in patients with metastatic castration‐resistant prostate cancer. In prostate cancer, the concentration of ptDNA prior to treatment can predict clinical outcome. This study enrolled 180 patients who were receiving androgen deprivation therapy. The patients with high ptDNA had a greater incidence of VTE than those with low ptDNA. These results suggest that ptDNA could be a useful tool for assessing VTE risk and improving long‐term survival. [ABSTRACT FROM AUTHOR]

Body composition parameters (BCp) have been associated with outcome in different tumor types. However, their prognostic value in patients with HER2-positive metastatic breast cancer (BC) receiving first line treatment with dual anti-HER2 antibody blockade is unknown. Preclinical evidences suggest that adipocytes adjacent to BC cells can influence response to anti-HER2 treatments. We retrospectively analyzed Computed Tomography (CT)-based BCp from 43 patients with HER2-positive metastatic BC who received first line pertuzumab/trastuzumab-based treatment between May 2009 and March 2020. The impact of baseline CT-based BCp on progression-free survival (PFS) was tested using Kaplan–Meier estimates and univariate and multivariate Cox regression models. We found a significantly worse PFS for patients with high baseline subcutaneous fat index (median 7.9 vs 16.1 months, p = 0.047, HR = 2.04, 95%CI 1–4.17) and for those with high total abdominal fat index (8.1 vs 18.8 months, p = 0.030, HR = 2.17, 95%CI 1.06–4.46). Patients with baseline sarcopenia did not show shorter PFS compared to those without sarcopenia (10.4 vs 9.2 months, p = 0.960, HR = 0.98, 95%CI 0.47–2.03). Total abdominal fat index remained a significant predictor of PFS at multivariate analysis. Our findings suggest that a high quantity of total abdominal fat tissue is a poor prognostic factor in patients receiving trastuzumab/pertuzumab-based first-line treatment for HER2-positive metastatic BC. [ABSTRACT FROM AUTHOR]

Objectives. To characterize tumour baseline blood flow (BF) in two lung cancer subtypes, adenocarcinoma (AC) and squamous cell carcinoma (SCC), also investigating those “borderline” cases whose perfusion value is closer to the group mean of the other histotype. Materials and Methods. 26 patients (age range 36-81 years) with primary Non-Small Cell Lung Cancer (NSCLC), subdivided into 19 AC and 7 SCC, were enrolled in this study and underwent a CT perfusion, at diagnosis. BF values were computed according to the maximum-slope method and unreliable values (e.g., arising from artefacts or vessels) were automatically removed. The one-tail Welch’s t-test (p-value <0.05) was employed for statistical assessment. Results. At diagnosis, mean BF values (in [mL/min/100g]) of AC group [(83.5 ± 29.4)] are significantly greater than those of SCC subtype [(57.0 ± 27.2)] (p-value = 0.02). However, two central SCCs undergoing artefacts from vena cava and pulmonary artery have an artificially increased mean BF. Conclusions. The different hemodynamic behaviour of AC and SCC should be considered as a biomarker supporting treatment planning to select the patients, mainly with AC, that would most benefit from antiangiogenic therapies. The significance of results was achieved by automatically detecting and excluding artefactual BF values. [ABSTRACT FROM AUTHOR]

Background: Cancer patients undergo routine computed-tomography (CT) scans and, therefore, iodinated contrast media (ICM) administration. It is not known whether a time-dependent correlation exists between chemotherapy administration, contrast enhanced CT and onset of acute ICM-related adverse reactions (ARs). Methods: All consecutive contrast-enhanced CTs performed from 1 January 2010 to 31 December 2012 within 30 days of the last chemotherapy administration were retrospectively reviewed. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. We analyzed time to CT evaluation calculated as the time elapsed from the date of the CT performed to the date of the last chemotherapy administration. Patients were classified into 4 groups based on the antineoplastic treatment: platinum-based, taxane-based, platinum plus taxane and other group. Results: Out of 10,472 contrast-enhanced CTs performed, 3,945 carried out on 1,878 patients were considered for the study. Forty acute ICM-related ARs (1.01%; 95% CI, 0.70-1.33) were reported. No differences were seen among immediate (within 10 days of the last chemotherapy administration), early (11-20 days) and delayed (21-30 days) CTs. Median time to CT in patients who experienced an acute ICM-related AR by treatment group was not statistically different: 20 days (range 6-30), 17 days (range 5-22), 13 days (range 8-17), 13 days (range (2-29) for the platinum, taxane, platinum plus taxane and other group, respectively (P =0.251). Conclusions: Our results did not reveal any correlation between time to CT and risk of acute ICM-related ARs in cancer patients. [ABSTRACT FROM AUTHOR]

Background. The impact of cytotoxic agents on the risk of acute allergy-like adverse reactions (ARs) to intravenous iodinated contrast media (ICM) injections is unknown. Methods.We retrospectively reviewed 13,565 computed tomography (CT) scans performed in a consecutive cohort of cancer patients from January 1, 2010 to December 31, 2012. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. The following matched comparisons were made: tax code, gender, primary tumor, antineoplastic therapy, and date of last cycle. Concomitant antineoplastic treatment was classified into five groups: platinum, taxane, platinum plus taxane, other, and no treatment group (no therapy had been administered in the previous 24 months). Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) to evaluate the risk of acute ICM-related ARs. Results. Of 10,472 contrast-enhanced CT scans, 97 (0.93%; 95% CI:0.74-1.11) ICM-relatedARs were reported, 11 of which (0.1%) were severe, including one fatality. The overall incidence was significantly higher in patients aged,65 years (p5.0062) and in the platinumplus taxane and taxane groups (p5.007),whereas no correlation was found with gender, number of previous CT scans, site of disease, or treatment setting.Multivariate analysis confirmed an increased risk for patients aged ,65 years (OR: 1.73;95%CI: 1.14-2.63) and for the taxane group (in comparison with the no treatment group; OR: 2.06; 95% CI: 1.02-4.16). Conclusion. Among cancer patients, concomitant treatment with taxanes and younger age would seem to be risk factors for ICM-related ARs. The Oncologist 2014;19:823-828 [ABSTRACT FROM AUTHOR]