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  • 1
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    Online Resource
    Patients with an extremely high prostate-specific antigen at prostate cancer diagnosis: A single institution analysis.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. 309-309
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 309-309
    Abstract: 309 Background: High prostate specific antigen (PSA) at diagnosis is associated with worse outcomes in patients (pt) with prostate cancer. However, treatment selection and clinical outcome in those diagnosed with an extremely high PSA ( 〉 500 ng/ml) are not well characterized, and we aim to better study this unique pt population. Methods: Using the Mount Sinai Genitourinary (GU) Cancer Biorepository, an IRB approved database containing all consented GU cancer pts seen between 2010-2018, we identified 23 pts with a PSA 〉 500 at prostate cancer diagnosis. Descriptive analysis was performed to capture clinical characteristics, treatment selection and response, and outcomes in this cohort. Results: The median age and PSA at diagnosis were 64 (54-85) and 1057 ng/ml (528-11,418). At presentation, 1 pt had localized versus 22 pts had metastatic disease, 3 were asymptomatic, and sites of metastasis included lymph nodes (LN) only (n=3), bone only (n=8), or LNs and bone (n=11). Pts were initiated on either first line androgen deprivation (ADT) or ADT plus docetaxel if seen after 2015 (1 refused). All pts had 〉 90% PSA response to first line therapy, with median PSA nadir 4.38 ng/ml (0.06-153), duration of response 6 months (1-33), and time to castration-resistant prostate cancer (CRPC) 14.5 months (5-99). There are differences in treatment selection and outcomes for pts treated with ADT vs. ADT plus docetaxel first line (see table). Conclusions: In pts with PSA 〉 500 at prostate cancer diagnosis, we have observed significant heterogeneity in clinical presentation and response to treatment. In pts treated with first line ADT plus docetaxel, we observed 2 of 7 pts with extended treatment response ( 〉 42 months). Differences in disease biology may account for this observation, and molecular characterization will be needed to better understand this subset. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.7_suppl.309
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Online Resource
    Influence of prostate cancer disease state and therapeutic selection on peripheral whole-blood RNA signature.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 7_suppl ( 2015-03-01), p. 166-166
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 7_suppl ( 2015-03-01), p. 166-166
    Abstract: 166 Background: Prostate cancer is a heterogeneous disease with differences in tumor stromal interactions contributing to variability in treatment response and outcome. Gene expression of peripheral blood cells is altered by interactions with neoplastic tissue. We previously developed a peripheral whole blood six-gene signature prognostic for survival in mCRPC. Here we evaluate how different clinical disease states and treatment with different therapeutic agents impact this signature. Methods: Whole blood was collected in PAXgene Blood RNA tubes in two cohorts of prostate cancer patients, one at Mount Sinai (n=135), the other in Munich (n=59), in the context of prospective clinical studies. Whole blood RNA was extracted and the six target genes were amplified using qPCR. Scores were derived using normalized cycle threshold (ΔCT) values of the six genes, according to the model: 2 x ABL2 + SEMA4D + ITGAL – C1QA – TIMP1 – CDKN1A. Patients were categorized by disease state in the Mount Sinai cohort, and by treatment received in the Munich cohort, for data analysis. Results: CRPC is the only disease state with a mean six-gene score (18.06) above the high-risk cutoff (17.9), and is significantly higher than localized or hormone sensitive advanced disease (16.07, 16.52, respectively; p=0.0002). Among patients with localized disease, there was no significant difference in the mean six-gene scores for patients with low-, intermediate-, and high-risk disease (16.07, 15.33, 16.66, respectively; p=0.27). In CRPC patients treated with docetaxel, there are significant changes to the six-gene score over the course of treatment (p=0.002), with a notable percentage decrease (-6.2%) at the 2-8 week timepoint that is not observed in patients treated with abiraterone or enzalutamide. Conclusions: Gene expression profiling of whole blood is influenced by the clinical state of prostate cancer as seen by differences to the six-gene score from localized to castrate resistant disease. Cytotoxic chemotherapy appears to modulate the six-gene score, something not seen with AR-directed therapies. Further investigation will be needed to understand the significance of these changes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.7_suppl.166
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Evolving patterns of metastatic renal cell carcinoma: A meta-analysis.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. 563-563
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 563-563
    Abstract: 563 Background: Advances in diagnostic and treatment modalities have resulted in better outcomes in metastatic renal cell carcinoma (mRCC) patients. With new therapies extending survival, we hypothesize that pattern of metastatic disease has evolved over time. We assessed the pattern of metastases as reported in baseline characteristics of prospective clinical trial patients between 1990 and 2018. Methods: This study identified all phase I-III mRCC therapeutic clinical trials published between January 1990 and July 2018 in PubMed and ClinicalTrials.gov. Studies that included patients with other cancers or did not report metastases were excluded. Data was stratified to examine differences in three listed treatment eras for first-line therapy. Linear regression models were used to evaluate temporal trends and subcategorized as either First Line Only treatments (FLO) or Second-Line and Beyond (SLB). Results: 127 clinical trials encompassing 16534 subjects were identified. Between 1990 and 2018, rates of lymph node metastases in the FLO population increased significantly at 1.03% per year ( P 〈 0.05). The rate of lung and liver metastases in FLO showed a trend of increase at 0.48% and 0.04% per year, respectively, but decreased -0.73% and -0.15% per year in the SLB population. Moreover, rate of bone metastasis showed a trend of increase in both populations, particularly between the VEGF/TKI and Immunotherapy/TKI eras in the SLB population (18.89% to 29.19%). Conclusions: Notable changes were found in the pattern of metastasis in patients with mRCC. Increasing rate of bone metastasis may warrant dedicated bone imaging for routine staging in patients with mRCC. These evolving patterns may have important implications in treatment selection and prognosis in this patient population. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.7_suppl.563
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 4
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    Online Resource
    Characterization of PSA at death in patients with metastatic castration-resistant prostate cancer.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. 184-184
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 184-184
    Abstract: 184 Background: Prostate Specific Antigen (PSA) is a valuable prognostic and predictive biomarker in prostate cancer (PC). Currently, the significance of PSA at death is undefined. In this single institution retrospective study, we aim to characterize the significance of PSA at death in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: Using the Mount Sinai Genitourinary (GU) Cancer Biorepository, an IRB approved database containing all consented GU cancer patients seen between 2010-2018, we stratified patients into the following cohorts based on their PSA at death: 〈 10, 10-100, 100-1000, and 〉 1000 ng/ml. We excluded data of patients who had less than 3 visits to the Mount Sinai Hospital. A descriptive analysis was performed to assess clinical characteristics of disease, treatment response, and outcomes. Results: We identified 1097 PC patients, and 101 were found to be deceased following a diagnosis of mCRPC. Cohorts of higher PSA level at death were associated with: a lower Gleason score at diagnosis, a longer time to castration resistance, higher burden of metastatic disease at death (non-visceral and visceral), and longer OS in patients with mCRPC (see table). Conclusions: In this study, PSA at death is associated with several important clinical characteristics and outcome, including overall survival. These differences may be attributed to their underlying biologic behavior. These results are hypothesis generating, and larger studies will be needed to further assess the significance of these findings. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.7_suppl.184
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 5
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    Effect of concurrent beta-blocker (BB) use in patients receiving immune checkpoint inhibitors for metastatic urothelial (mUC) and renal cell carcinomas (mRCC).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. 467-467
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 467-467
    Abstract: 467 Background: Stress-induced adrenergic signaling suppresses the immune system. A pre-clinical mouse model has shown that pharmacologic beta-blockade can stimulate CD8+ T-cell activity, and as a result improve efficacy of checkpoint inhibitors (CPI) to inhibit growth in solid tumors. Herein, we investigate the effect of BB on outcomes of patients receiving immunotherapy in mUC and mRCC. Methods: Using the Mount Sinai Genitourinary (GU) Cancer Biorepository, an IRB approved database containing all consented GU cancer patients seen between 2010-2018, we identified patients with either UC or RCC that have received CTLA-4 and/or PD-1/PD-L1 blockade. Patients who received only 1 dose of CPI were excluded from this analysis. A descriptive analysis was performed to assess clinical characteristics and treatment response. Overall Survival (OS) was calculated with Kaplan-Meier curves and cox proportional hazard models. Results: We identified 34 evaluable patients with mUC and 14 with mRCC that received CPI (Table). The median age at initiation was 69 years (39–91 years) and 81.2% (39/48) received prior chemotherapy and/or molecular targeted therapies. The mean duration of therapy was longer in the BB group compared to non-BB group (10.6 vs. 4.0 mo). For patients with mUC, the overall response rate (ORR) was 62.5% vs. 12.5% in favor of the BB group. For the patients with mRCC, the ORR was 40.0% vs. 10.0% in favor of the BB group. There were more outstanding responders ( 〉 1 year) in the BB group when compared with the non-BB group (41.2% vs. 6.5%). Patients with BB use had significantly improved median OS (NR vs. 11.6 mo, p = 0.004) when compared to those who did not receive BB. Conclusions: In this single-center cohort, the concurrent use of BB receiving CPI therapy is associated with an improved ORR, duration of therapy, and OS. Although this is hypothesis generating, the addition of BB is a promising strategy to improve response of immunotherapy, and prospective validation of this approach will be needed. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.7_suppl.467
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 6
    Online Resource
    Online Resource
    Influence of prostate cancer disease state and therapeutic selection on peripheral whole-blood RNA signature.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. 5046-5046
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. 5046-5046
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.5046
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Online Resource
    PRINT: Prostate cancer intensive, non-cross reactive therapy for CRPC—Early observations of feasibility and efficacy.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. 310-310
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 310-310
    Abstract: 310 Background: Optimal sequencing of approved therapeutic agents in mCRPC is not known. The standard approach, is to treat until resistance then switch. The PRINT trial explores the efficacy of treating mCRPC with a rapidly-cycling, non-cross reactive regimen as a way to more effectively treat an intrinsically heterogeneous disease, to delay or prevent drug resistance, and minimize treatment toxicity. Methods: Patients were treated with 3 consecutive treatment modules, each of 12 weeks' duration: 1. abiraterone acetate 1000 mg PO daily and prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV and carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily and radium-223 50 kBq/kg IV q4 weeks (in those with bone metastases). After completion of this 9 month regimen, patients are followed on ADT alone. Primary endpoint is PSA or radiographic time to disease progression. Results: From 3/2017 to 10/2018, 28 of 40 planned men with mCRPC were enrolled, 19 (67.9%) with bone metastases. PSA response rates ( 〉 90%/ 〉 50%), compared to baseline, following each treatment module: 1. 50%/78.6%; 2. 50%/92.7%; 3. 64.39%/92.7%. Currently, 14 patients have completed the study regimen with median follow up of 3.6 months, 8 of whom continue without any additional therapy. Of the patients evaluable for primary endpoint, median time to PSA progression is 96+ days (95% CI 82-110+ days). The regiment was well tolerated, grade 3/4 adverse effects include: hyperglycemia (17.9%), diarrhea (7.1%), anemia (3.6%), fatigue (3.6%), neutropenia (3.6%), thrombocytopenia (3.6%). Measurable response and molecular correlate data will be presented. Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross reactive regimen is feasible, demonstrates significant antitumor benefits, and is well tolerated. Further follow up will determine if PRINT delays progression compared with standard approaches. Clinical trial information: NCT02903160.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.7_suppl.310
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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