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Background: Predicting recurrence after stereotactic body radiotherapy (SBRT) in non-small cell lung cancer (NSCLC) patients is problematic, but critical for the decision of following treatment. This study aims to investigate the association of imaging features derived from the first follow-up computed tomography (CT) on lung cancer patient outcomes following SBRT, and identify patients at high risk of recurrence.Methods: Fifty nine biopsy-proven non-small cell lung cancer patients were qualified for this study. The first follow-up CTs were performed about 3 months after SBRT (median time: 91 days). Imaging features included 34 manually scored radiological features (semantics) describing the lesion, lung and thorax and 219 quantitative imaging features (radiomics) extracted automatically after delineation of the lesion. Cox proportional hazard models and Harrel's C-index were used to explore predictors of overall survival (OS), recurrence-free survival (RFS), and loco-regional recurrence-free survival (LR-RFS). Five-fold cross validation was performed on the final prognostic model.Results: The median follow-up time was 42 months. The model for OS contained Eastern Cooperative Oncology Group (ECOG) performance status (HR = 3.13, 95% CI: 1.17-8.41), vascular involvement (HR = 3.21, 95% CI: 1.29-8.03), lymphadenopathy (HR = 3.59, 95% CI: 1.58-8.16) and the 1st principle component of radiomic features (HR = 1.24, 95% CI: 1.02-1.51). The model for RFS contained vascular involvement (HR = 3.06, 95% CI: 1.40-6.70), vessel attachment (HR = 3.46, 95% CI: 1.65-7.25), pleural retraction (HR = 3.24, 95% CI: 1.41-7.42), lymphadenopathy (HR = 6.41, 95% CI: 2.58-15.90) and relative enhancement (HR = 1.40, 95% CI: 1.00-1.96). The model for LR-RFS contained vascular involvement (HR = 4.96, 95% CI: 2.23-11.03), lymphadenopathy (HR = 2.64, 95% CI: 1.19-5.82), circularity (F13, HR = 1.60, 95% CI: 1.10-2.32) and 3D Laws feature (F92, HR = 1.96, 95% CI: 1.35-2.83). Five-fold cross-validated the areas under the receiver operating characteristic curves (AUC) of these three models were all above 0.8.Conclusions: Our analysis reveals disease progression could be prognosticated as early as 3 months after SBRT using CT imaging features, and these features would be helpful in clinical decision-making. [ABSTRACT FROM AUTHOR]

Anthracycline-based cardiotoxicity is concerning for women with breast cancer and portends a dose-dependent risk of developing left ventricular dysfunction. Overall, the prevalence of heart failure (HF) is ≈2% of the total US population; however, BRCA-deficient mice have shown increased HF. We evaluated for the inherent risk of HF in women with BRCA mutations to determine whether treatment with anthracycline-based therapy increased this risk. We obtained results on BRCA mutation carriers regarding cancer treatment and HF, identified through the BRCA patient advocacy organization Facing Our Risk for Cancer Empowered (FORCE) and the Moffitt-based Inherited Cancer Registry. In our patient group (232 BRCA1 and 159 BRCA2 patients; 10 with both mutations), 7.7% reported HF, with similar proportions in BRCA1 versus BRCA2 carriers (7.4% and 8.2%, respectively). These proportions are significantly higher than published rates (p < 0.001). There was no statistically significant difference in HF rates comparing anthracycline-treated versus anthracycline-naïve patients however (7.1% vs. 8.3%; p = 0.67). In addition, 9.1% of BRCA1 carriers and 8.2% of BRCA2 carriers reported arrhythmias. BRCA mutation carriers showed increased risk of cardiotoxicity versus the general population and an overall increased risk of cardiotoxicity from anthracycline-based therapy. Our study supports data that BRCA carriers have increased non-cancer mortality from cardiotoxicity. A prospective trial to determine HF and conduction abnormalities in this population is warranted. [ABSTRACT FROM AUTHOR]

Optimal conditioning therapy for hematopoietic cell transplantation (HCT) in acute myelogenous leukemia (AML) remains undefined. We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1 mg/kg every 6 hours for 4 days) and cyclophosphamide (60 mg/kg IV x 2 days) - (Bu/Cy) with 100 consecutive AML patients treated with pharmacokinetic targeted IV busulfan (AUC < 6000 μM/L*min per day x 4 days) and fludarabine (40 mg/m2 x 4 days) - (t-IV Bu/Flu). The Bu/Cy and t-IV Bu/Flu groups significantly differed according to donor relation, stem cell source, aGVHD prophylaxis, remission status, primary vs. secondary disease, median age, and % blasts prior to HCT (p < 0.01 for each). Conditioning with t-IV Bu/Flu reduced early toxicity including idiopathic pneumonia syndrome (IPS) and hepatic veno-occlusive disease (VOD). Additionally, the trajectory of early NRM (100 day: 16% vs. 3%, and1 year: 25% vs. 15% for Bu/Cy and t-IV Bu/Flu, respectively) favored t-IV Bu/Flu. Grade II-IV aGVHD (48% vs. 82%, p < 0.0001), as well as moderate/severe cGVHD (7% vs. 40%, p < 0.0001) differed between the Bu/Cy and t-IV Bu/Flu groups, due to the predominance of peripheral blood stem cells in the t-IV Bu/Flu group. Pharmacokinetic targeting of intravenous busulfan in combination with fludarabine is associated with reduced conditioning regimen related toxicity compared to oral busulfan and cyclophosphamide. However, multivariable analysis did not demonstrate significant differences in overall survival (p = 0.78) or non-relapse mortality (p = 0.6) according to conditioning regimen delivered. [ABSTRACT FROM AUTHOR]