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  • American Society of Clinical Oncology (ASCO)  (2)
  • Kanesvaran, Ravindran  (2)
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  • American Society of Clinical Oncology (ASCO)  (2)
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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 273-273
    Abstract: 273 Background: The Decipher 22-gene genomic classifier (GC) has been shown to predict for metastasis and survival in predominantly Caucasian and African-American men from Western cohorts. There is however little data on the clinical utility of GC in Asian prostate cancer (PCa). We investigated if GC prognosticates for metastasis-free survival (MFS) in an Asian cohort of localized PCa. Additionally, we performed comparative genomic analyses between our Asian patients and non-Asian cases from a large Decipher GRID database (Veracyte, San Francisco, CA). Methods: We used a cohort of PCa patients who were treated at a single institution from East Asia between 2006 to 2021. Patients underwent active surveillance or radical prostatectomy (RadP) and/or radiotherapy (RT) +/- hormonal therapy (HT). The GC assay (Decipher Biosciences, CA) was performed on diagnostic biopsies, following central review of the Gleason’s grade (GG) and tumor cellularity by an expert GU pathologist. MFS was the primary endpoint for survival analysis. Comparative analyses of 273 gene-signatures were performed against the full and a propensity-score matched (PSM) cohort identified from the Decipher GRID database. Adjusted p-values from Wilcoxon tests were used to select from these signatures. Results: We profiled 126 unique patient tumors, comprising of 19 (15.1%) NCCN-defined low-/favorable intermediate-, 22 (17.5%) unfavorable intermediate-, 34 (27.0%) high-, and 51 (40.5%) very high-risk groups. 24 (19.0%) patients had RadP as primary treatment, 98 (77.8%) had RT +/- HT, while 4 (3.2%) underwent active surveillance or HT alone. Using the GC, 70 (55.6%), and 56 (44.4%) were stratified as low/intermediate- (≤0.6) and high-risk ( 〉 0.6), respectively. GC high-risk was significantly associated with an inferior MFS than GC low/intermediate-risk ( HR 5.22 [95% CI:1.08–25.3], P = 0.04). Comparison between our Asian and the full unmatched GRID cohort (N = 80,703) revealed a lower proportion of ERG+ PCa (14% vs 41%, P 〈 0.001) and a higher proportion of PAM50 basal subtypes (41% vs 30%, P 〈 0.001), as well as a lower T-cell exclusion (median 0.080 vs 0.097; P 〈 0.001) and angiogenesis (-0.37 vs -0.08; P 〈 0.001) signature scores. These trends were also observed when comparing with the PSM-subset (N = 630; 5:1 ratio for NCCN, GG, age at diagnosis, and assay quality score). Interestingly, both high angiogenesis and T-cell exclusion signatures were associated with a worse MFS ( HR not available due to no events for low angiogenesis, P = 0.0015 by log-rank test; HR 5.12 [1.03–26.5], P = 0.046, respectively). Conclusions: We validated the Decipher 22-gene GC for prognostication of MFS in a predominantly high-risk PCa cohort. We also identified several gene expression signatures that were significantly different between Asian PCa and other cohorts. These observations may have implications for customizing treatment recommendations to an Asian popula tion.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: JCO Global Oncology, American Society of Clinical Oncology (ASCO), Vol. 9, No. Supplement_1 ( 2023-08), p. 75-75
    Abstract: 75 Background: Aberrations of the DDR pathway have been shown to be prognostic of survival and predictive of PARP inhibition in PCa. We have previously reported on the prevalence of germline DDR mutations based on a 32-gene set in localized PCa in EA men, and observed comparable rates with that of White men. Here, we performed additional analyses investigating for associations between DDR variants to the somatic transcriptome of localized PCa. Methods: We utilized a prospectively recruited cohort of 172 EA patients, with centrally assessed Gleason’s score (GS) by an expert pathologist. Germline profiling was performed by whole exome sequencing (100X) using the Illumina Novaseq (CA). Joint genotyping was performed to annotate variants that were deemed to be pathogenic (P)/likely pathogenic (LP)/conflict of interest pathogenic (CIP) based on the CADD and REVEL scores. Tumor transcriptome was profiled using the Decipher Genomic Classifier (GC, Veracyte, CA) based on the Affymetrix ST array (ThermoFisher, CA). Results: Among the subset of 172 EA men, we observed DDR variants in 26 (15%) patients, which was comparable to the larger cohort of 890 men from the same institution. Among the DDR mutations, 2 (7.7%) were classified as P/LP, while 24 (92.3%) were CIP. Decipher GC scores were comparable between patients with and without DDR mutations (median GC score 0.87 vs 0.53, Mann-Whitney U P=0.10). For luminal-basal subtyping by either the PAM50 and Prostate specific subtyping models, we did not observe a difference for the basal (P=0.48) and luminal subtypes (P=0.21). Interestingly, DNA repair gene-set expression were comparable between patients with DDR mutations versus those without (median score -0.2 vs -0.17). However, we observed microenvironment differences for immune-related genes, where patients harboring DDR mutations manifested a less immune-suppressive environment versus those without (PDL2: -0.15 vs 0.2; Treg: 0.09 vs 0.13; MDSC: 0.03 vs 0.07, respectively). Conclusions: Herein, we report an extension of our previous work (Lua, et al. ASCO GU, 2023), where we show potential linkages between the germline DDR variant status and the tumor transcriptome. Our findings suggest the influence of germline DDR variants that extends beyond tumorigenesis.
    Type of Medium: Online Resource
    ISSN: 2687-8941
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 3018917-2
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