ESTRO 38 Abstract book

S334 ESTRO 38

The role of host immune system in the tumor control and its interaction with commonly used chemo-radio treatment is challenging. In this scenario, the assessment of IL17F -rs641701 as new potential prognostic biomarker in LARC pts could represent a link between immunity and disease control after preopCRT. Its independency from the already acknowledged prognostic factors as TRG, should encourage its use in the clinical practice to improve pts stratification according to the risk of disease progression to better tailor therapeutic approaches in LARC. PV-0628 Association of androgen deprivation duration and cardiovascular mortality in prostate cancer men A. Yorozu 1 , S. Sutani 1 , K. Toya 1 , Y. Shiraishi 1 , S. Saito 2 1 Tokyo Medical Centre- NHO, Department of Radiation Oncology, Tokyo, Japan; 2 Tokyo Medical Centre- NHO, Department of Urology, Tokyo, Japan Purpose or Objective To investigate whether duration of androgen deprivation therapy (ADT) is associated with an increased risk of cardiovascular mortality (CVM) in men treated with brachytherapy and/or external beam radiotherapy (EBRT) for intermediate and high-risk prostate cancer. Material and Methods This is a retrospective analysis of prospectively collected data from men treated between 2003 and 2012 at one institution. Data on 1,628 patients treated for intermediate (n=1,234) or high-risk (n=394) prostate cancer with iodine-125 brachytherapy (n=486), EBRT (n=196), and a combination of brachytherapy and EBRT (n=946) were included. In total, 1,005 patients (61.7%) received neoadjuvant ADT, concurrent with or in the absence of adjuvant ADT. Patients were divided into two groups according to the total duration of ADT: a short course group (n=803) received ≤12 months (median duration: 6 months), and a long course group (n=202) received >12 months (median duration: 24 months) of ADT. The primary endpoint of this study was a CVM, which was defined as a death from myocardial infarction, sudden cardiac arrest, coronary artery disease, cardiac ischemia, malignant arrhythmia, or cerebrovascular stroke. Statistical analysis was conducted using a Kaplan-Meier estimator, a Cox regression model, and a competing risk After a median follow-up time of 7.6 years (interquartile range: 5.6–10.2 years), overall survival was 92.1% at 7 years. In total, 194 men died; there were 53 cardiovascular deaths, 41 prostate cancer deaths, 67 other malignancy deaths, 31 other benign disease deaths, and two deaths due to unknown causes. The 7-year CVM rate was 1.2% in the non-ADT group, 2.1% in the short course ADT group, and 5.3% in the long course ADT group (p<0.001). In terms of baseline patient characteristics, long course ADT was significantly associated with elderly patients, EBRT treatment, high-risk group, and total androgen blockade. Univariate analysis revealed that older age, baseline cardiovascular disease, baseline diabetes, and long course ADT were significantly associated with increased CVM. Competing risk analysis revealed that duration of ADT was significantly associated with CVM, as well as age, baseline cardiovascular disease, and baseline diabetes. The 7-year overall survival rate was 94.3% in the non-ADT group, 92.1% in the short course ADT group, and 84.9% in the long course ADT group (p=0.008). The Cox regression model revealed age and risk group as significant factors associated with overall survival; the duration of ADT was not significantly associated with overall survival. Conclusion Long course ADT is associated with an increased risk of CVM in patients undergoing brachytherapy and/or EBRT for intermediate and high-risk prostate cancer. Age, baseline comorbidities, and duration of combined ADT model. Results

Aviano-National Cancer Institute, Scientific Direction, Aviano, Italy Purpose or Objective Patients (pts) with locally advanced rectal cancer (LARC) exhibit heterogeneous responses to Preoperative Chemoradiotherapy (preopCRT) and prognosis. Risk stratification based on clinical and biologic factors is an area of active investigation in order to personalize treatment. Immunogenetics, the study of polymorphisms (SNPs) in genes involved in immune system activity, could detect biomarkers virtually involved in tumor response to treatment and in prognosis. The aim of this study was to identify immunogenetic biomarkers of early recurrence and long term survival in LARC pts treated with preopCRT and radical surgery. Material and Methods From December ‘93 to November ‘15, LARC pts undergoing preopCRT and surgery were consecutively enrolled at the National Cancer Institute-IRCCS Aviano and IOV-IRCCS Clinica Chirurgica I of Padova University. According to study purposes, pts were split in a training set and in a replication set. Firstly, 147 SNPs in 34 immune-related genes were analyzed in germline DNA samples of the training set. The potential association between these SNPs and the 2yrDFS was analyzed with logistic regression model. Significant SNPs arisen in the training set (p<0.05 after bootstrap analysis) were analyzed in the replication set with logistic regression. Secondly, replicated variants (p<0.10) were tested in the entire population in terms of 5yrMFS, 5yrDFS, and 10yrOS by multivariate Cox regression. Results Clinical and pathological parameters of the 371 LARC pts were well balanced between the discovery (n=234) and the replication set (n=137). Three prognostic biomarkers were significantly associated with the 2yrDFS in the training set ( IL17F -rs641701, IL17F -rs9463772, and STAT3 - rs8069645: p=0.010, p=0.020, and p=0.048, respectively), but only IL17F -rs641701 was significant in the replication set (p=0.099). In the merged population of pts, this SNP was still significantly associated to both 5yrDFS (HR (95%CI)=1.84 (1.01-3.25), p=0.035), and 5yrMFS (HR (95%CI)=2.11 (1.11-4.01), p=0.023). IL17F -rs641701 was also significantly associated with 10yrOS (HR (95%CI)=2.66 (1.51-4.70), p=0.001) (Fig.1), highlighting its pivotal prognostic role. To note IL17F -rs641701 effect on prognosis is independent from Tumor Regression Grade (TRG), as a matter of fact, when stratifying pts according to different TRG, IL17F -rs641701 marker identified subgroups of pts with significantly different prognosis within the same TRG group.

Conclusion