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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 6_suppl ( 2017-02-20), p. 444-444
    Abstract: 444 Background: Multiple approved targeted therapies are available for treatment of mRCC. Though some clinical trials guide treatment selection, there are many gaps without high-level evidence. Both tumor tissue and cfDNA based next-generation sequencing (NGS) testing are frequently performed to help guide treatment. Our objective was to assess type and number of genomic aberrations among tumor tissue and cfDNA. Methods: 14 sequential pts with both tissue and cfDNA NGS testing were selected and genomic profiles were compared. The total number of aberrations detected was statistically evaluated using comparison of the means. The Mann-Whitney test was used to compare the incidence of mutations in identified mutation pathways. Results: There was a discordance in the genetic aberrations detected among tumor versus cfDNA NGS tests, confirming intra-individual genetic diversity. Specifically, alterations in the DNA repair, PI3K, and epigenetic pathways were more common in tissue based testing (Table). Additionally, the median number of mutations identified was significantly lower for cfDNA based NGS testing (median 1.5) compared to tissue based NSG testing (median 10.0) (p 〈 0.0001). Conclusions: Discordance in the type of genomic aberrations in tissue versus cfDNA testing suggests intra-individual genetic diversity and may have implications in treatment selection when using these tests. Lower number of aberrations detected by the cfDNA testing may have occurred due to lower sensitivity of NGS by cfDNA compared to the tissue based NGS. The higher frequency of aberrations on tissue based testing suggests that tissue based testing should be used preferentially in clinical trials and practice. This data is hypothesis generating and needs further investigation in a larger cohort. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 6_suppl ( 2017-02-20), p. 189-189
    Abstract: 189 Background: Tumor tissue and tumor cfDNA next-generation sequencing (NGS) tests are obtained in pts with metastatic prostate cancer and have demonstrated a diverse genomic landscape. High-level evidence does not exist for utilizing these tests to guide treatment selection in these pts. Targeted therapies are available for metastatic prostate cancer treatment and clinical trials are investigating drugs targeting specific molecular pathways. The objective of this study was to assess type and number of genomic aberrations between tumor tissue and cfDNA. Methods: Pts with metastatic prostate cancer who had both tissue and cfDNA results were selected and genomic profiles were compared between these two technologies. The mean number of tissue mutations was compared to cfDNA mutations for all pts using the t-test. The mutations for both tests were then categorized into five pathways: DNA repair, cell cycle regulation, PI3K, epigenetics, and androgen receptor (AR). For each pathway, the total number of patients with a mutation was compared between tissue and cfDNA using the Mann-Whitney test. Results: Nineteen pts were identified with both tissue and cfDNA results. The mean number of mutations identified was significantly less with cfDNA (95% CI, 2.7-5.3) compared to tissue (95% CI, 7.0-9.7; P 〈 0.0001). There were significantly more patients with PI3K pathway mutations identified in the tissue compared to cfDNA (73.7% vs 21.1% P = 0.0018), as well as epigenetic mutations (47.4% vs 0.0% P = 0.0012). There was no difference in the number of patients identified to have DNA repair, cell cycle regulation, and AR variances between the two tests. Conclusions: The lower number of aberrations detected by the cfDNA test may have occurred due to lower sensitivity of cfDNA compared to tissue based NGS. Discordance in the type of genomic variances between the two tests suggests intra-individual genetic diversity, and these results may have implications in treatment selection of pts with metastatic prostate cancer. Data are hypothesis generating and need further investigation in a larger cohort.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 6_suppl ( 2017-02-20), p. 261-261
    Abstract: 261 Background: AA is approved for Mcrpc with co-administration with P to prevent MCE toxicity such as hypertension, hypokalemia and edema. However, use of P is often not desirable by the relatively asymptomatic patients because of potential for detrimental effects of long term corticosteroid therapy. Epe is a non-steroidal mineralocorticoid antagonist demonstrated to abrogate MCE. Here we report real world experience of use of Epe with AA in men with mCRPC who wished to avoid concomitant P. Methods: Incidence and grade (CTCAE v4) of MCE, along with baseline demographics, disease characteristics, and progression free survival (PFS) in men with mCRPC treated with AA (1000 mg daily), not willing to be treated with P (and thus received treatment with Epe 50 mg daily) were collected retrospectively, and compared with those treated with AA + P (10 mg daily) during the same time period (Table). Continuous variables were assessed by Wilcoxon rank sum or student t-test, and categorical variables were assessed by Fischer’s Exact test or chi-square as appropriate. PFS was compared by Kaplan-Meier. Results: Baseline and disease characteristics, median PFS, and toxicities of all grades were similar in both cohorts (Table). Conclusions: In real world population of men with mCRPC treated with AA, corticosteroids may be avoided by concomitant treatment with Epe. Data need further validation in a larger cohort. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
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