Purpose To evaluate the predictive performance of the prostate health index (PHI) and PHI density (PHID), for clinically significant prostate cancer (csPCa) in patients with a PI-RADS score ≤3. Materials and Methods Patients tested for total prostate-specific antigen (tPSA, ≤100 ng/mL), free PSA (fPSA), and p2PSA at Peking University First Hospital were prospectively enrolled. Possible predictive factors of csPCa were analyzed using the receiver operating characteristic (ROC) curve. Results were expressed as area under the curve (AUC) with 95% confidence intervals (CI). The cutoff values of PHI and PHID were determined. Results We enrolled 222 patients in this study. The prevalence of csPCa in the PI-RADS ≤3 subgroup (n=89) was 22.47% (20/89). Age, tPSA, F/T, prostate volume, PSA density, PHI, PHID, and PI-RADS score were significantly associated with csPCa. PHID (AUC: 0.829 [95% CI: 0.717–0.941]) was the best predictor of csPCa. PHID >0.956 was set as the threshold of suspicious csPCa with a sensitivity of 85.00% and a specificity of 73.91%, avoiding 94.44% of unnecessary biopsies but missing 15.00% csPCa. A threshold of PHI ≥52.83 showed the same sensitivity but a rather lower specificity of 65.22% that avoided 93.75% of unnecessary biopsies. Conclusions PHI and PHID have the best predictive performance of csPCa in patients with PI-RADS score ≤3. A threshold value of PHID ≥0.956 may be used as the criterion for biopsy in these patients.

Purpose/Objective(s): Mature toxicity outcomes from the first phase I trial using stereotactic body radiotherapy (SBRT) to the prostate bed for recurrent prostate cancer have been recently reported. From that study, we herein report inter-and intra-fractional positional changes in the clinical target volume (CTV) and rectum with the use of an endorectal balloon. Materials/Methods: Prostate bed SBRT was delivered over 5 fractions in escalating doses of 35, 40, and 45 Gy. Three fiducial markers were planted in the CTV volume. A subset of 10 patients on the trial received both preand post-treatment CBCT for each fraction and were the subject of this analysis. An endorectal balloon was placed during both simulation and daily treatments. Patients were instructed to maintain a full bladder. On pre-treatment CBCT we localized to the anterior surface of the balloon to align the anterior rectal wall and CTV. Inter-fractional variation was measured using registrations based on pelvic anatomy. Intra-fractional changes in balloon position were assessed with soft-tissue registration. The t-test was used to evaluate the significance of correlation coefficient with significance level set at 0.05. Results: The average daily air-filled balloon volume (AEstandard deviation) was 77.0AE5.0 cc (range: 60.6 cc e 88.5 cc), and the average pre-treatment bladder volume was 235.0AE109.7 cc. Compared to the planning CT, the pretreatment bladder volume changed by-35.0AE87.9 cc (range:-227.1 e 123.1 cc). Relative to the planning positions, the anterior rectal wall had an average inter-fractional shift of-1.6AE5.6 mm (range:-15.2 e 7.5 mm) in the anteroposterior (AP) direction at the mid-section of the balloon (negative value: shifts posteriorly), with ! 3mm shift in 66% of total fractions. Correlation between daily bladder volume variations and anterior rectum position variations in the AP direction was statistically significant (Pearson's correlation coefficient Z 0.76, p Z 0.02). The average time between the pre-and posttreatment CBCT scans was 9.8AE4.0 minutes (range: 6 e 29 minutes). The post-treatment bladder volume increased significantly (p < 0.01) by an average of 58.9AE51.6 cc. The balloon volume changed by <5% in each treatment. The center-of-mass of the balloon had average intra-fractional variation of 0.3AE0.8 mm in the left-right (LR) direction (range:-1.3 e 2.5 mm),-0.9AE2.4 mm in the AP direction (range:-11.0 e 3.0 mm), and-1.7AE2.2 mm in the superoinferior (SI) direction (range:-10.9 e 0.7 mm) (negative value: shift anteriorly). No correlation was seen between increased bladder volume and intrafractional AP shifts, since the majority of greater than 3 mm shifts were attributed to one patient. Conclusion: Although not statistically significant, we observed higher than expected intrafractional AP and SI shifts. Our future phase II trial will incorporate larger margins to account for this finding.

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Purpose/Objective(s): Lung and cardiac toxicity were found to be negative prognostic factors of survival in patients with lung or breast cancer who received radiotherapy as part of their treatment. Their roles in patients with operable esophageal carcinoma (EC) who received neoadjuvant chemoradiotherapy are not well established. The purpose of this study was to determine the impacts of lung and / or heart dose on survival outcome in patients with EC receiving trimodality therapy. Materials/Methods: The medical charts and treatment plans of 127 patients with EC treated with trimodality therapy in two institutions between January 2010 and December 2015 were reviewed. Clinical factors and dosimetry parameters were collected to analyze their impacts on survival outcome by using the Kaplan-Meier method and Cox proportional hazards model. Results: Of all the patients, with a majority of clinical stage III disease (n Z 96, 75.6%), squamous cell histology (n Z 121, 95.3%), and smoking history (n Z 120/127, 94.5%), 91 patients (71.7%) underwent pre-treatment feeding jejunostomy. The median dose of radiotherapy was 5,000 cGy (range: 4,000-6,600 cGy). At a median follow-up of 27.7 months (range: 4.7-92.8 months), the median survival of all the patients was 32.7 months (95% confidence interval [CI], 24.9-40.5 months). In the Cox proportional hazards model, pathological complete response (PCR); (hazard ratio [HR], 0.232; 95% CI, 0.127-0.422; p < 0.001), the Eastern Cooperative Oncology Group (ECOG) performance status (HR, 2.111; 95% CI, 1.297-3.437; p Z 0.003), and volume of lung receiving at least 20 Gy (V20); (HR, 1.089; 95% CI, 1.045-1.134; p < 0.001) significantly predicted mortality risk, but not heart mean dose (HR, 1.000; p Z 0.844]. Patients with PCR and lung V20 & 20% had a longer median survival time than those without PCR and with lung V20 >20% (67.5 and 65.7 months vs 24.6 and 27.7 months, respectively; p < 0.001 and < 0.001, respectively). Conclusion: Lung V20 >20% was associated with poor outcomes in patients with EC receiving trimodality therapy. The heart mean dose was not a negative prognostic factor of survival. Limiting the lung radiation dose during radiotherapy in EC patients could potentially improve the outcomes. Future study should aim to reduce the lung dose using novel radiotherapy technique or modalities with a goal of optimizing the outcomes in patients with operable EC.

Purpose/Objective(s): Androgen deprivation therapy (ADT) is commonly used in patients with metastatic disease, locally advanced or high risk prostate cancer (PCa). There is conflicting evidence regarding the association between ADT and cardiovascular disease (CVD). Most studies have examined men >65 years, who have a higher risk of CVD. This study aims to understand the relationship between ADT and CVD risk in younger men (40 to 64 years). Materials/Methods: Retrospective review of a national health insurance claims database of privately insured individuals (MarketScan) from January 1 to December 31, 2011 identified 124,164 newly diagnosed PCa patients. The patients were followed through December 31, 2014. The study included 24,631 non-metastatic PCa patients after applying exclusion criteria. All participants were free of CVD before January 1st, 2011. In full cohort study, we identified 1522 PCa patients receiving >Z3months of pharmacologic ADT or orchiectomy as the study cohort and 23,109 PCa patients with no ADT/<3months of ADT as the comparison cohort. The primary end point was CVD, a composite of coronary artery disease (CAD), myocardial infarction (MI) and stroke, identified using ICD-9-CM codes. Multivariable Cox proportional hazards models were used to assess CVD risk among PCa patients on pharmacologic ADT>Z3months/orchiectomy and no ADT/<3months of ADT groups adjusting for potential confounders such as age, region, residence, diabetes, hypertension, hyperlipidemia, prostatectomy, and radiation therapy. Sensitivity analyses were performed based on type and duration of ADT. Results: The mean age of PCa patients with ADT>Z3months/orchiectomy was 57.02AE3.56 years and the no ADT/<3months of ADT group was 56.16AE 4.22 years. We identified 3376 incident CVD cases during 2012-2014. In full cohort study, pharmacologic ADT>Z3months/orchiectomy was associated with higher risk of developing CVD compared to no ADT/ <3months of ADT, adjusted HR (aHR) 1.27; 95% CI (1.13 to 1.43). Treatment with GnRH agonists was associated with increased incidence of CAD (aHR 1.39; 95% CI, 1.14 to 1.68) and stroke ((aHR 1.65; 95% CI, 1.28 to 2.11), except for MI (aHR 1.05; 95% CI, 0.60 to 1.83). Similarly, combined androgen blockade was also associated with an increased risk of incident CAD (aHR 1.33; 95% CI, 1.10 to 1.61) and stroke (aHR 1.63; 95% CI, 1.28 to 2.07) except for MI (aHR 1.03; 95% CI, 0.60 to 1.77). Furthermore 1 to 2 years of ADT duration was associated with 61% higher risk of CAD (aHR 1.61; 95% CI, 1.14 to 2.28) and 72% higher risk of stroke (aHR 1.72; 95% CI, 1.07 to 2.75) except for MI (aHR 1.60; 95% CI, 0.65 to 3.92) Conclusion: In this large study of nonmetastatic PCa patients younger than age 65, there was higher incidence of CVD in patients with ADT >Z3months/orchiectomy compared to no ADT/<3months of ADT. Longer duration of ADT was positively associated with increased risk of CAD and stroke.