558 Background: Accurate prediction of risk of distant recurrence (DR) in HR+, HER2-negative early-stage breast cancer (EBC) is important for optimizing adjuvant therapy decisions, including treatment escalation with CDK4/6 inhibitors (CDK4/6i). Current guidelines recommend consideration of CDK4/6i for node-positive, clinically high-risk EBC, including N1 patients. However, it is not known which patients will benefit, and guideline recommendations suggest that the risks may outweigh benefits for patients with low risk of distant recurrence. Identification of these patients will help prevent over-treatment. RlapsRisk BC (RR) is an AI pathology-based test that integrates features from H&E-stained whole-slide images with clinicopathologic data (age, tumor size, nodal status) to assess risk of distant recurrence in HR+, HER2-negative EBC. The RR model was previously developed and validated using 7 retrospective cohorts totaling 6,039 patients. Here we report validation of RR in the NSABP B-28 cohort of HR+ HER2-negative N+ patients who received post-operative chemoendocrine therapy. Methods: This blinded independent validation study of the pre-specified RR included a subset of NSABP B-28 patients with HR+ and HER2-negative EBC (n=731) and digitized whole slide images from primary tumors. The primary endpoint was distant recurrence-free interval (DRFI). The objective was to validate the prognostic utility of RR score for DR. Univariable and multivariable Cox models were performed. Results: The evaluable cohort had a median follow-up of 11.1 years and included 504 (69%) patients with N1 disease, 87% grade 2/3 tumors, and a median tumor size of 21mm. Across the entire cohort, RR classified 58% of patients as low-risk and 42% as high-risk. RR (high vs low) was significantly associated with DRFI: HR=3.1 (95% CI: 2.3-4.3; p < .001). Estimated 10-year DR-free was 87.5% (95% CI: 83.9-90.4%) for low-risk vs. 65.0% (95% CI: 59.1-70.2%) for high-risk patients. In a multivariable Cox model, the histology-only score remained significant after adjusting for clinicopathologic data: HR=1.6 (95% CI: 1.4-1.9; p < .001). In the N1 subgroup, RR identified 65.7% of patients as low-risk with an estimated 10-year DR-free of 90.6% (95% CI: 86.9-93.4%), compared to 69.8% (95% CI: 62.2-76.2%) for high-risk. Conclusions: RR demonstrates robust prognostic performance in clinically high-risk N+, HR+, HER2-negative EBC patients from the NSABP-28 trial, in which the majority of patients had N1 disease. Our results demonstrate that approximately two-thirds of N1 patients, identified as low-risk by RR, exhibited favorable long-term outcomes with standard chemoendocrine therapies alone. As the clinical landscape shifts toward broader CDK4/6i use, RR could be used to identify N1 patients for whom the benefit of treatment intensification may be minimal.

Objective:To assess the factors associated with the use of active surveillance (AS) in NCCN favourable intermediate-risk (FIR) prostate cancer (PCa) patients who received the 17-gene Genomic Prostate Score (GPS) assay. Material and Methods:Contemporary data were collected from academic and large community group practices across the United States. Eligible patients had localized PCa classified as FIR per NCCN guidelines and received a GPS report between May 2017 and April 2019. Higher GPS results (scale: 0-100) were associated with a higher risk of adverse outcomes. The proportion of patients selecting AS was calculated with 95% confidence intervals. Uni-and multivariable logistic regression analyses were performed to determine the association between AS selection and relevant covariates. Results:There were 324 eligible patients (Gleason Score 3 + 4, 79%; PSA 10-20 ng/ml, 19%; clinical stage T2b-T2c, 2%; median percent positive cores, 16.7%; median GPS result, 26). The distribution of GPS results was 0-19 (23%), 20-40 (60%), and 41-100 (16%). Overall, 31% (95% CI 26%, 36%) selected AS: 58% (46%, 69%) with GPS 0-19, 27% (21%, 33%) with GPS 20-40, and 6% (1%, 16%) with GPS 41-100. In univariable models, the Gleason score, percent positive cores, PSA, and GPS results were significantly associated with AS selection. In a multivariable model, the percent positive cores and the GPS result remained significantly associated with AS selection. AS persistence was 91% (82%, 95%) at 12 months. Conclusions:The GPS result and percent positive cores appear associated with AS use after controlling for relevant clinical variables in NCCN FIR prostate cancer patients.

533 Background: In randomized studies (NSABP B-20, SWOG 8814, TAILORx, RxPONDER), the predictive effect of the 21-gene Breast Recurrence Score assay (RS) on chemotherapy (CT) benefit has been evaluated in patients with node-negative (N0) and node-positive (N+) breast cancer. Retrospective analyses of TAILORx and RxPONDER demonstrated differences in outcome by racial/ethnic groups (RG); however, there were no differences in CT benefit for any of the clinical outcome measures. In this study we characterized the association between the RS result and breast cancer-specific mortality (BCSM) and chemotherapy benefit in BCSM in RG in the recently updated, population-based SEER registries. Methods: Eligible patients were from the SEER 17 registries, November 2022 submission, and had non-metastatic, hormone receptor-positive, HER2-negative, node negative (N0) breast cancer diagnosed between 2006 and 2019 with a RS result. Analyses were weighted using the inverse of estimated propensity of using CT (yes vs. none/unknown). Prognosis was ascertained by estimating breast cancer specific survival (BCSS) at 9 years among patients with CT recorded as none/unknown by RG. The log-rank test was used to compare BCSM by RG. Multivariable Cox models, including RS result (26-100 vs. 0-25) x CT interaction, were used to assess whether RS result was predictive of CT benefit. Analyses were performed in the overall cohort and in Hispanic (H), non-Hispanic Asian and Pacific Islander (NHAPI), non-Hispanic Black (NHB), and non-Hispanic White (NHW) RGs. Results: There were 145,642 eligible patients and 3,212 breast cancer deaths. Median follow-up was 68 months. NHB patients had higher median RS result and CT usage than other groups (p < .001). In N0 patients, higher RS result was associated with lower 9-year BCSS, both overall and by race/ethnicity (p < .001). In Cox multivariable models (Table), the interaction between RS result by CT was significant among all N0 patients (p < .001) and in NHB patients (p = 0.005), NHW patients (p = 0.002), and H patients (p = 0.019), but not in NHAPI patients (p = 0.766). Analyses of patients with N+ disease and more detailed analysis of CT benefit according to RS results by RG are underway and will also be presented. Conclusions: Real-world evidence from the SEER registries in over 145,000 patients confirms the 21-gene assay is prognostic for BCSS in all groups by race and ethnicity. The RS result was predictive of CT benefit in N0 patients overall and in Hispanic, NHB, and NHW patients, but not in NHAPI patients in this analysis. [Table: see text]

Background and Purpose Clinico-pathological factors alone are insufficient to select patients at low risk of recurrence after breast conserving surgery and systemic therapy for the omission of radiotherapy (RT). We conducted a study to validate the prognostic and predictive value of the 16-gene signature, Profile for the Omission of Local Adjuvant Radiation (POLAR), for radiation response in the Scottish Conservation Trial (SCT). Materials and Methods Transcriptome-wide profiling was performed on formalin fixed paraffin embedded (FFPE) samples from patients from the SCT with invasive BC randomised to ± RT following breast conserving surgery (BCS). Patients with follow-up data for locoregional recurrence and gene expression data were included in the analysis of POLAR. Results 224 patients were included in the analysis. The continuous standardised POLAR score was prognostic for LRR in the no RT arm after adjusting for relevant covariates (HR=1.78 [1.20-2.64], p=0.003). POLAR was the only factor to remain significant in multivariable Cox PH models. In the subgroup of node-negative patients with ER+/HER2-negative tumours (N=137), there was a statistically significant RT benefit for patients with cancers with a POLAR high score (HR=0.31 [0.11-0.88], p=0.028) but not for patients with cancers with a POLAR low score (HR=0.5 [0.1-2.4], p=0.39). Conclusion For patients with early-stage invasive BC, treated with BCS but without RT, POLAR is prognostic for LRR. Additionally, in women with ER+, HER2-negative, node-negative BC, POLAR may identify a group of women with low risk of LR that do not benefit from adjuvant RT .

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 analy-sis. 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. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

The validated 17-gene Oncotype DX Genomic Prostate Score® (GPS™) assay risk-stratifies prostate-cancer patients with localized disease. The assay has primarily been utilized in lower risk patients deciding between active surveillance versus definitive therapy. In this retrospective cohort study, we analyze the association of the GPS result with time to biochemical recurrence post-prostatectomy in patients with National Comprehensive Cancer Network® (NCCN) intermediate and higher risk prostate cancer. The 141 patients included in the study were from the NorthShore University HealthSystem diagnosed 2014-2019 with NCCN intermediate (n = 109) or higher risk (n = 32) prostate cancer, treated with radical prostatectomy 2015-2019. The association of GPS result with time to biochemical recurrence was evaluated using univariable and multivariable Cox proportional hazards models in 120 patients with unfavorable intermediate or higher risk. Median (interquartile range) follow-up time was 28 (20 to 38) months. The GPS result was significantly associated with time to biochemical recurrence as both a continuous and dichotomous variable in univariable (hazard ratio [HR] per 20 GPS units 2.36, 95% CI 1.45-3.80, p < 0.001; HR for GPS result 41-100 vs 0-40 3.28, 95% CI 1.61-7.19, p < 0.001) and in multivariable models accounting for NCCN risk group (HR per 20 GPS units 2.14, 95% CI 1.31-3.46, p = 0.003; HR for GPS result 41-100 vs 0-40 3.00, 95% CI 1.43-6.72, p = 0.003) or biopsy Gleason Score and diagnostic PSA or PSA density. These results indicate that the GPS assay was a strong predictor of biochemical recurrence after radical prostatectomy in this unfavorable intermediate and higher risk prostate cancer patient population.

BackgroundThe 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).MethodsThis 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.ResultsThis 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.ConclusionThe 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.

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance I (MP23)1 Apr 2020Prostate Cancer: Localized: Active Surveillance I (MP23) View All Author Informationhttps://doi.org/10.1097/JU.0000000000000856AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Expand All Advertisement PDF downloadLoading ...

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.

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.

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.