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Objectives: To report outcomes of stereotactic body radiotherapy (SBRT) in metastatic castration-resistant prostate cancer (mCRPC) patients with oligoprogression (≤ 5 metastases) during first-line treatment with androgen receptor-targeted therapy (ARTT). Patients and methods: Retrospective multi-institutional analysis of mCRPC patients treated with SBRT to oligoprogressive lesions during ARTT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Survival analysis was performed using the Kaplan–Meier method, univariate and multivariate analysis (MVA) were performed. Results: Data from 34 patients were analyzed. Median NEST-free survival, r-PFS, and OS were 16.97, 13.47, and 38.3 months, respectively. At MVA, factors associated with worse NEST-free survival and r-PFS were polymetastatic burden at diagnosis of metastatic hormone-sensitive disease (hazard ratio [HR] 3.66, p = 0.009; HR 3.03, p = 0.034), PSA ≤ 7 ng/ml at mCRPC diagnosis (HR 0.23, p = 0.017; HR 0.19, p = 0.006) and PSADT ≤ 3 months at mCRPC diagnosis (HR 3.39, p = 0.026; HR 2.79, p = 0.037). Polymetastatic state at mHSPC diagnosis was associated with a decreased OS (HR 4.68, p = 0.029). No patient developed acute or late grade ≥ 2 toxicity. Conclusion: Our results suggest that SBRT in oligoprogressive mCPRC is safe, effective and seems to prolong the efficacy of the ongoing systemic treatment positively affecting disease progression. Prospective trials are needed. [ABSTRACT FROM AUTHOR]

Purpose: To analyse the classification performances of a decision tree method applied to predictor variables in survival outcome in patients with locally advanced rectal cancer (LARC). The aim was to offer a critical analysis to better apply tree-based approach in clinical practice and improve its interpretation. Materials and methods: Data concerning patients with histological proven LARC between 2007 and 2014 were reviewed. All patients were treated with trimodality approach with a curative intent. The Kaplan–Meier method was used to estimate overall survival (OS). Decision tree methods were was used to select important variables in outcome prediction. Results: A total of 100 patients were included. The 5-year and 7-year OS rates were 76.4% and 71.3%, respectively. Age, co-morbidities, tumor size, clinical tumor classification (cT) and clinical nodes classification (cN) were the important predictor variables to the tree's construction. Overall, 13 distinct groups of patients were defined. Patients aged < 65 years with cT3 disease and elderly patients with a tumor size < 5 cm seemed to have highest rates of survival. But the process over-fitted the data, leading to poor algorithm performance. Conclusion: We proposed a decision tree algorithm to identify known and new pre-treatment clinical predictors of survival in LARC. Our analysis confirmed that tree-based machine learning method, especially classification trees, can be easily interpreted even by a non-expert in the field, but controlling cross validation errors is mandatory to capture its statistical power. However, it is necessary to carefully analyze the classification error trend to chose the important predictor variables, especially in little data. Machine learning approach should be considered the new unexplored frontier in LARC. Based on big datasets, decision trees represent an opportunity to improve decision-making process in clinical practice. [ABSTRACT FROM AUTHOR]

We have previously reported that the MEK/ERK pathway sustains in vitro and in vivo transformed phenotype and radioresistance of embryonal rhabdomyosarcoma (ERMS) cell lines. Furthermore, we found that aberrant MEK/ERK signaling activation promotes c-Myc oncoprotein accumulation. In this study, the role of c-Myc in sustaining the ERMS transformed and radioresistant phenotype is characterized. RD and TE671 cell lines conditionally expressing MadMyc chimera protein, c-Myc-dominant negative and shRNA directed to c-Myc were used. Targeting c-Myc counteracted in vitro ERMS adherence and in suspension, growth motility and the expression of pro-angiogenic factors. c-Myc depletion decreased MMP-9, MMP-2, u-PA gelatinolytic activity, neural cell adhesion molecule sialylation status, HIF-1α, VEGF and increased TSP-1 protein expression levels. Rapid but not sustained targeting c-Myc radiosensitized ERMS cells by radiation-induced apoptosis, DNA damage and impairing the expression of DNA repair proteins RAD51 and DNA-PKcs, thereby silencing affected ERMS radioresistance. c-Myc sustains ERMS transformed phenotype and radioresistance by protecting cancer cells from radiation-induced apoptosis and DNA damage, while promoting radiation-induced DNA repair. This data suggest that c-Myc targeting can be tested as a promising treatment in cancer therapy. [ABSTRACT FROM AUTHOR]

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two of the most severe, rare, and life-threatening adverse reactions to medications. Their incidence is approximately two patients per million population per year. Several cases have been reported in the literature in which SJS and TEN have occurred in patients with a neoplasm undergoing radiation therapy and who are taking an anticonvulsant. We report a case of SJS-TEN that developed in a 51-year-old woman with nonresectable non-small-cell lung cancer during treatment with phenobarbital plus radiation therapy for bone metastases but in whom the irradiated areas did not exhibit the SJS skin reaction. To our knowledge, no similar cases have been reported in the literature. [ABSTRACT FROM AUTHOR]