Taken together this report highlights distinct features of A

Taken together, this report highlights distinct features of AA CaP integrin inhibitor with emphasis on new findings on recurrent deletions of the LSAMP locus in AA CaP which associates with disease recurrence and identifies an aggressive subset of prostate cancers. These findings have broader implication towards the understanding of cancer genomes of currently underrepresented populations towards the development of ethnically informed diagnostic, prognostic marker and tailored therapeutic approaches.
Authorship contributions
Acknowledgements This research was supported by funds from the Center for Prostate Disease Research, Uniformed Services University Program, HU0001-10-2-0002 to DGM, the NCI/EDRN ACN12011-001-0 to SS, the NCI RO1 CA162383-05 grant to SS, the H.L. Snyder Medical Foundation to MLF, the KMR-12-1-2012-0216 and OTKA-114560 grants to DR and IC, the Otto Mønsteds Foundation to IC and ZS, and the Mazzone Foundation, the Breast Cancer Research Foundation, the Novo Nordisk Foundation, grants by MTA-TKI643/2012, KTIA_NAP_13-2014-0021 to ZS. The funders did not have any role in the in study design, data collection, data analysis, interpretation or writing of the report. The authors thank Dr. Madhvi Upender, Dr. Ahmed A. Mohamed, Dr. Allissa Dillman, Dr. Nicholas Griner, Dr. Shashwat Sharad, Dr. Zhaozhang Li, and Ms. London Toney for the experimental support and Mr. Stephen Doyle for his assistance with the art and graphics. The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of the Army, Department of Defense or the US Government.
Introduction Severe but also moderate toxicities after curative-intent radiotherapy (RT), such as a poor cosmetic outcome following breast cancer can have a negative impact on quality of life and a marked effect on subsequent psychological outcome (Al-Ghazal et al., 1999). A number of factors are known to increase the risk of radiation toxicity including intrinsic radiosensitivity (Azria et al., 2012). While toxicity risks for populations of patients are known, the determination of an individual\'s normal tissue radiosensitivity is seldom possible before treatment. Therefore, current practice standards commonly prescribe radiation dose according to clinical scenarios, without regard to the genotype or phenotype of the individual being irradiated. In that context, we (Ozsahin et al., 2005) and others (Bordon et al., 2010; Foro et al., 2014; Schnarr et al., 2009) have developed retrospectively or prospectively in small cohorts a rapid (72h) radiosensitivity assay based on flow cytometric assessment of radiation-induced CD8 T-lymphocyte apoptosis (RILA). An excellent negative predictive value was found in the case of high RILA value and less grade ≥2 late toxicity (Ozsahin et al., 2005). In addition, all severe side-effects (grade ≥2) were observed in patients with low values of RILA. We assumed that the assay had clear potential as a useful biomarker for selecting individuals likely to display an increased probability of toxicity to RT. In 2006, we obtained a PHRC (Programme Hospitalier de Recherche Clinique) grant from the French National Cancer Institute to improve the level of evidence of the RILA assay. We then started two prospective multicenter trials (NCT00893035) to evaluate RILA as a predictor of late effects after adjuvant RT of breast cancer (trial 1, n=502) or after curative intent RT in prostate cancer (trial 2, n=372). We report here the final results of trial 1 with a median follow-up of 38.6months.
Methods
Results
Discussion In the present multicenter study, we confirmed prospectively that a decreased percentage of grade ≥2 bf+ was observed for increasing values of RILA with an excellent NPV of 91%. RILA identified independently and with more than 90% accuracy patients who will not develop severe late fibrosis among other factors like hormonotherapy and in a lesser extent tobacco smoking. In addition, we observed no grade 3 bf+ in patients with RILA ≥12%. In multivariate analysis, no correlation between RILA and acute events was found. Finally, the recurrence rates were higher in the RILA <12% group but without statistical significance.