The 17-Gene Genomic Prostate Score Test Is Prognostic for Outcomes After Primary External Beam Radiation Therapy in Men With Clinically Localized Prostate Cancer.

PURPOSE: The Oncotype DX Genomic Prostate Score (GPS) assay has been validated as a strong prognostic indicator of adverse pathology, biochemical recurrence, distant metastasis (DM), and prostate cancer (PCa)-related death (PCD) in men with localized PCa after radical prostatectomy. However, it has yet to be tested in men undergoing external beam radiation therapy (EBRT), for whom assessing PCa progression risk could inform decisions on treatment intensity. We analyzed whether GPS results are associated with time to biochemical failure (BCF), DM, and PCD after EBRT in men with localized PCa and whether the association is modified by race. METHODS AND MATERIALS: We conducted a retrospective study of men with localized PCa treated with EBRT at the VA Health Care System in Durham, NC from 2000 to 2016. Study endpoints were time to BCF per the Phoenix criteria, DM, and PCD. The association of GPS results, per 20-unit increase or dichotomous variable (0-40 vs 41-100), was evaluated with each endpoint using univariable and multivariable Cox proportional hazards models. Results were then stratified by race. RESULTS: A total of 238 patients (69% Black) met the eligibility criteria. Median follow-up for patients who did not experience BCF was 7.6 years. GPS results per 20-unit increase were significantly associated with BCF (hazard ratio [HR], 3.62; 95% confidence interval [CI], 2.59-5.02), DM (HR, 4.48; 95% CI, 2.75-7.38), and PCD (HR, 5.36; 95% CI, 3.06-9.76) in univariable analysis. GPS results remained significant in multivariable models adjusted for baseline clinical and pathological factors, with HRs being similar to the univariable analysis. There was no significant interaction between the GPS assay and race (P = .923). HRs for BCF were similar in Black men (HR, 3.88; 95% CI, 2.40-6.24) versus non-Black men (HR, 4.01; 95% CI, 2.42-6.45). CONCLUSIONS: Among men treated with EBRT, the GPS assay is a strong, independent prognostic indicator of time to BCF, DM, and PCD, and performs similarly in Black and non-Black men.

Association of the 12-Gene Breast DCIS Score® Assay With Local Recurrence in Patients With Ductal Carcinoma In Situ Treated on Accelerated Partial Breast Radiotherapy Protocols.

BACKGROUND: The following analysis explores clinicopathologic factors and the 12-gene Breast DCIS Score test result in order to better define an appropriate DCIS (ductal carcinoma in situ) population eligible for APBI (accelerated partial breast radiotherapy). METHODS: This exploratory analysis aimed to retrospectively measure the association between the 12-gene Oncotype DX Breast DCIS Score® assay (Redwood City, CA) and relevant clinicopathologic factors with locoregional recurrence in a pooled cohort of women treated with local excision and APBI on prospective phase II (NCT01185145) and phase III (NCT01185132) clinical trials. Univariable Cox proportional hazards regression was used to determine whether there was an association between local recurrence and DCIS Score result risk group (≥ 39 vs < 39) and clinicopathologic factors. RESULTS: This analysis included 104 evaluable patients (n = 18 from NCT01185145 and n = 86 from NCT01185132). The median age was 60 years (range: 40-79). Seventy-nine percent of patients were postmenopausal. The median span of DCIS was 10 mm (range 2-45 mm). Two-thirds of the cohort presented with necrosis (71%). The distribution of DCIS Score® results ranged from 0 to 82, with 69% of patients having a DCIS Score result < 39. The median follow-up time was 8.2 years in NCT01185145 versus 3.0 years in NCT01185132. There were 6 local ipsilateral breast recurrences. DCIS Score result was significantly associated with local recurrence in univariable modeling, hazard ratio = 10.3 (95% CI 1.7, 198.4); p = 0.010. None of the clinicopathologic characteristics resulted in any significant association with locoregional recurrence. CONCLUSION: The Breast DCIS Score assay demonstrated risk stratification in this cohort of patients treated with local excision and APBI pooled from two clinical trials. These results are consistent with those recently published utilizing whole breast radiotherapy. Due to the small number of local recurrence events and limited follow-up time, further investigations are needed to confirm findings.

A Comparison of Predicted Ipsilateral Tumor Recurrence Risks in Patients With Ductal Carcinoma in Situ of the Breast After Breast-Conserving Surgery by Breast Radiation Oncologists, the Van Nuys Prognostic Index, the Memorial Sloan Kettering Cancer Center DCIS Nomogram, and the 12-Gene DCIS Score Assay.

PURPOSE: To compare ipsilateral breast event (IBE) risks in patients with ductal carcinoma in situ of the breast (DCIS) post-lumpectomy, as estimated by breast radiation oncologists, the Van Nuys Prognostic Index, the Memorial Sloan Kettering Cancer Center (MSKCC) DCIS nomogram, and the 12-gene Oncotype DX DCIS score assay. METHODS AND MATERIALS: Consecutive DCIS cases treated with lumpectomy from November 2011 to August 2014 with available DCIS score results were identified. Three radiation oncologists independently estimated the 10-year IBE risk. The Van Nuys Prognostic Index and MSKCC nomogram 10-year IBE risk estimates were generated. Differences and correlations between the IBE estimates and clinicopathologic factors were evaluated. RESULTS: Ninety-one patients were identified for inclusion. Forty-eight percent would have been ineligible for the E5194 study. The mean risk of IBE from the DCIS score assay was 12.4%, compared with a range of 18.9% to 26.8% from other sources. The mean IBE risk from the DCIS score assay was lower regardless of E5194 eligibility. The MSKCC nomogram and DCIS score assay risk estimates were weakly correlated with each other (P = .23) and were each moderately correlated with the other risk estimates (P = .41-.56). When applying the radiation oncologists' treatment recommendations based on their proposed risk cutoffs, evaluating risk according to the DCIS score assay led to the highest proportion of patients recommended excision alone. CONCLUSIONS: IBE risk estimates for this general community cohort of DCIS cases vary significantly among commonly available clinical predictive tools and individual radiation oncologist estimates. Surgical margins and tumor size continue to factor prominently in radiation oncologist decision algorithms. The differences found between the IBE risk estimate methods suggests that they are not interchangeable and the methods that rely on clinicopathologic features may tend to overestimate risk.

Liquid biopsy mutation panel for non-small cell lung cancer: analytical validation and clinical concordance.

Molecular testing for genomic variants is recommended in advanced non-small cell lung cancer (NSCLC). Standard tissue biopsy is sometimes infeasible, procedurally risky, or insufficient in tumor tissue quantity. We present the analytical validation and concordance study of EGFR variants using a new 17-gene liquid biopsy assay (NCT02762877). Of 144 patients enrolled with newly diagnosed or progressive stage IV nonsquamous NSCLC, 140 (97%) had liquid assay results, and 117 (81%) had both EGFR blood and tissue results. Alterations were detected in 58% of liquid samples. Overall tissue-liquid concordance for EGFR alterations was 94.0% (95% CI 88.1%, 97.6%) with positive percent agreement of 76.7% (57.7%, 90.1%) and negative percent agreement of 100% (95.8%, 100%). Concordance for ALK structural variants was 95.7% (90.1%, 98.6%). This assay detected alterations in other therapeutically relevant genes at a rate similar to tissue analysis. These results demonstrate the analytical and clinical validity of this 17-gene assay.

Young-Onset Colon Cancer and Recurrence Risk by Gene Expression.

The incidence and mortality from colorectal cancer in younger adults (younger than 55 years) is increasing. We reviewed the complete database of a gene-expression test, Oncotype DX Colon Recurrence Score test, to determine age-related differences in recurrence score (RS) and single-gene results (7 cancer-related of the 12-gene assay). We included 20 478 stage II and III A and B colon cancer patients submitted to Genomic Health. RS results were grouped by low-, intermediate-, and high-risk groups. Single-gene scores were described using median and interquartile range. Of all patients 72.5% and 72.6% of those younger than 40 years had low-risk RS. Comparing older with younger patients, RS or single-gene expression did not differ by age group or stage. Young-onset colon cancer does not differ by expression of the RS component genes. Most patients with stage II and III colon cancer have low-risk disease as measured by the 12-gene assay, regardless of age.

Validity of Pedometers to Measure Step Counts During Dance.

PURPOSE: To obtain validity evidence for the measurement of step counts by spring-levered and piezoelectric pedometers during dance. METHODS: Thirty-five adults in a college dance class participated in this study. Participants completed trials of 3- and 5-min of different styles of dance wearing Walk4life MVP and Omron HJ-303 pedometers, while their steps were visually counted. Pearson correlation, paired t-test, mean absolute percent error (MAPE), and mean bias were calculated between actual step and pedometer step counts for the 3- and 5-min dances separately. RESULTS: For the Walk4life trials the correlations were .92 and .77 for the 3- and 5-min dances. No significant differences were shown by t-test for the 3- (P = .16) and 5-min dances (P = .60). However, MAPE was high, 17.7 ± 17.7% and 19.4 ± 18.3% for the 2 dance durations, respectively. For the Omron, the correlations were .44 and .58 for the 3- and 5-min dances, respectively. No significant differences were shown by t-test for the 3-min (P = .38) and for the 5-min (P = .88) dances. However, MAPE was high, 19.3 ± 16.4% and 26.6 ± 15.2% for the 2 dance durations, respectively. CONCLUSIONS: This study demonstrated that pedometers can be used to estimate the number of steps taken by a group of college students while dancing, however caution is necessary with individual values.

Tobacco use among adults initiating treatment for HIV infection in rural Uganda.

We conducted a longitudinal study of tobacco use among adults initiating antiretroviral therapy (ART) in Mbarara, Uganda where 11 % of men and 3 % of women use tobacco according to the 2011 Demographic and Health Survey. In a prospective cohort, self-reported tobacco use was assessed before starting ART and reassessed every 3-4 months. Plasma cotinine, a nicotine metabolite, was measured in a subset of adults pre-ART to verify self-report. Among 496 subjects, 50 (10 %) reported current tobacco use (20 % of men, 6 % of women). Most (53 %) adults with elevated cotinine levels (>15 ng/mL) reported no tobacco use. By 6 months after ART initiation, 33 % of tobacco users had quit (95 % CI 20-46 %). By 5 years, 64 % quit (95 % CI 47-77 %). Self-reported tobacco use among rural Ugandans starting ART was twice as common as among the local background population and use may be underreported. ART initiation could be an opportunity for tobacco cessation interventions.

The impact of lower extremity mass and inertia manipulation on sprint kinematics.

Resistance sprint training is a sprint-specific training protocol commonly employed by athletes and coaches to enhance sprint performance. This research quantified the impact of lower extremity mass and inertia manipulation on key temporal and kinematic variables associated with sprint performance. A 3-dimensional analysis of 40 m sprinting was conducted on 8 elite sprinters under normal conditions and resisted sprint training. Results of the study showed that lower extremity additional mass training (at 10% individual segment weight) led to a significant reduction in sprint time for both the 10-m to 20-m and the 30-m to 40-m splits and the total 40 m measure. The stride velocity throughout the 20-m to 30-m phase of the sprint trials was also shown to be significantly reduced in the lower extremity mass and inertia manipulation condition. Importantly, no significant differences were observed across the remaining spatiotemporal variables of stride length, stride frequency, total stride time, and ground contact time. For coaches and athletes, the addition of specific lower extremity mass could improve the athlete's sprint performance without any measured effect on the technique of highly trained elite sprinters.

Longitudinal risk of intracranial hemorrhage in patients with arteriovenous malformation of the brain within a defined population.

BACKGROUND AND PURPOSE: Accurate estimates for risk and rates of intracranial hemorrhage (ICH) in the natural course of patients harboring brain arteriovenous malformation (BAVM) are needed to provide a quantitative basis for planning clinical trials to evaluate interventional strategies and to help guide practice management. METHODS: We identified patients with BAVM at the Kaiser Permanente Northern California health maintenance organization and documented their clinical course. The influences of age at diagnosis, gender, race-ethnicity, ICH at presentation, venous draining pattern, and BAVM size on ICH subsequent to presentation were studied using the multivariate Cox proportional hazards model and Kaplan-Meier curves. RESULTS: We identified 790 patients with BAVM (51% female; 63% white; mean age+/-SD at diagnosis: 38+/-19 years) between 1961 and 2001. Patients who presented with ICH experienced a higher rate of subsequent ICH than those who presented without ICH under multivariate analysis (hazard ratio, 3.6; 95% CI, 1.1 to 11.9; P<0.032). The effect was similar across race-ethnicity and gender. This difference in ICH rates was greatest in the first year (7% versus 3% per year) and converged over time. The effect of subsequent ICH on functional status was similar to that of the initial ICH. CONCLUSIONS: Presentation with ICH was the most important predictor of future ICH, confirming previous studies. Future ICH had similar impact on functional outcome as incident ICH. Intervention to prevent ICH would be of potentially greater benefit to patients presenting with ICH, although the advantage decreases over time.