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  • American Society of Clinical Oncology (ASCO)  (48)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. 9012-9012
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 209-209
    Abstract: 209 Background: NEPC includes both pure small cell carcinoma and mixed tumors with varying degrees of adenocarcinoma and neuroendocrine histology. It arises de novo or is treatment associated (TA) post androgen deprivation therapy. Clinical outcome data and prognostic biomarkers are limited and were thus explored. Methods: Patients with high grade prostate cancer and morphologic and/or immunohistochemical (IHC) NEPC features were included in this retrospective multicentre study. Clinical stage, Gleason score, and serum biomarkers were recorded. Kaplan-Meier method and log-rank test calculated and compared overall survival (OS) from time of NEPC diagnosis.Cox proportional hazards regression assessed prognostic impact of serum biomarkers at diagnosis and de novo vs TA status, adjusting for clinical stage and castration resistance. Results: 135 NEPC cases were identified. 124 (92%) were mixed tumors. 56 (41%) arose de novo. 79 (59%) were TA. 77% of those with a Gleason score (N=85/110) were grade group 5. Median PSA pre-NEPC biopsy was 11.6 ng/mL. At NEPC diagnosis, 19 (14%) had localized disease (median OS 123.0 mo); 33 (24%) non-metastatic castrate-sensitive disease (median OS 42.3 mo); 6 (4%) non-metastatic castrate-resistant disease (median OS 14.3 mo); 35 (26%) metastatic castrate-sensitive disease (median OS 17.6 mo); and 42 (31%) metastatic castrate-resistant disease (median OS 9.6 mo). Median OS for those with visceral metastases was 8.6 mo (95% CI 6.0 – 14.6), compared to patients with non-visceral metastases (11.1 mo; 95% CI 13.7 – 21.5) and no metastases (42.3 mo; 95% CI 47 – 89). Anemia (adjusted HR 1.66; 95% CI 1.05 - 2.16, p = 0.031) and NLR 〉 3 (adjusted HR 1.51; 95% CI 1.01 - 2.52, p = 0.045) were associated with increased risk of death. De novo disease, elevated LDH, serum PSA, and Gleason score were not prognostic. Conclusions: This study identifies NEPC clinical outcomes by stage, with survival poorer than expected in pure prostate adenocarcinoma. Anemia and elevated NLR 〉 3 are prognostic biomarkers that may help risk stratify and guide treatment intensification, including platinum-based chemotherapy. Further biomarker characterization of NEPC through IHC-staining pattern and genomic analysis is currently underway by this group.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 175-175
    Abstract: 175 Background: Clinically relevant outcomes in nmCRPC treated with androgen receptor-axis-targeted therapies (ARAT) may be inferior in patients with tumors harboring mutations bypassing androgen receptor signalling. This final update of a retrospective, multicenter analysis explores the association between genomic mutations in the PI3K-AKT and DDR signalling pathways with ARAT treatment outcomes in nmCRPC patients. Methods: Relevant clinical endpoint were collected for high-risk nmCRPC patients treated with an ARAT at APCaRI affiliated cancer centers, including median metastasis-free survival (MFS), overall survival (OS), PSA decline ≥ 50% (PSA50), and second progression free survival (PFS2). Archival tumor tissue was accessed for next generation gene sequencing, examining for genomic alterations in 500 genes, including those involved in the DDR and the PI3K-AKT signalling pathways. Comparison of outcomes of patients with DDR and PI3K-AKT pathway mutations was conducted using Cox proportional hazards regression using wildtype cases as the reference group, adjusting for PSA doubling time and pelvic lymphadenopathy. Results: Of the 37 patients included, 30 (82%) received apalutamide, 5 (13%) received darolutamide, and 2 (6%) received enzalutamide. 10 patients (27%) had PI3K-AKT pathway mutations (4 PTEN, 3 PIK3Ca, 2 PIK3C2G, 1 PIK3C2b), 8 patients (22%) had DDR gene mutations (3 ATM, 2 CHEK1, 1 BRCA2, 1 CDK12, 1 CHEK2, 1 FANCD2, 1 FANCL), and 1 patient (3%) had 2 MLH1 mutations (microsatellite instability). Of those who had subsequent treatment, 1 received enzalutamide and 5 received abiraterone. Patients with PI3K-AKT pathway mutations had significantly shorter MFS (4.8 mo; HR 4.2; 95% CI 1.2 – 15.0; p = 0.025). Those with DDR mutations had a trend towards shorter MFS (23.3 mo HR 3.7; 95% CI 0.71 – 13.4; p = 0.134). OS data remains immature. 4 (11%) patients did not achieve PSA50, including a patient with 2 MLH1 mutations. Conclusions: This final analysis demonstrates that nmCRPC with PI3K and DDR signalling pathway mutations have poor clinical outcomes when treated with ARAT, likely secondary to decreased reliance on the androgen receptor signalling pathway. These results highlight the potential value of exploring targeted therapies, such as PARP or AKT inhibitors in patients with these mutations.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 8579-8579
    Abstract: 8579 Background: The ERIVANCE BCC study is the pivotal trial of vismodegib (GDC-0449), a first-in-class small-molecule inhibitor of Hedgehog signaling, for treatment of locally advanced (laBCC) and metastatic BCC (mBCC), for whom there are no other effective therapy options. The study met the primary endpoint of overall response rate by independent review (Sekulic, Melanoma Res 2011). Here we report a 6-mo update of investigator-assessed (I-A) efficacy and safety endpoints as of May 26, 2011. Methods: This multicenter, international, nonrandomized 2-cohort study enrolled patients (pts) with laBCC (deemed inoperable or for whom surgery would be significantly disfiguring), and mBCC pts with RECIST-measurable disease. Pts received 150 mg oral vismodegib daily. Results: 104 pts (71 laBCC/33 mBCC) enrolled at 31 sites in the US, Europe, and Australia. I-A efficacy endpoints are shown in the table. One-year survival rate was 77.3% (95% CI 62.48–92.09%) for mBCC and 93.1% (95% CI 86.49–99.63%) for laBCC. Adverse events (AEs) in 〉 30% of pts were muscle spasms, alopecia, dysgeusia, weight decrease, fatigue, nausea, and amenorrhea (33.3%; 2/6 pts). Serious AEs were reported in 32 pts (31%). No additional fatal AEs were reported since the prior data cut (n=7, 7%; none considered related to vismodegib). Conclusions: This 6-mo update of I-A efficacy and safety endpoints from the ERIVANCE BCC study supports the significant clinical benefit of vismodegib in both laBCC and mBCC reported at the primary analysis. Median DOR and PFS increased numerically with follow-up. The AE profile was consistent with the prior data cut. These results further support the efficacy of vismodegib for treatment of advanced BCC. [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: 2012
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. 9081-9081
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e21090-e21090
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e21090-e21090
    Abstract: e21090 Background: Given the reported association between incisional procedures performed on cancer patients and subsequent increases in metastasis, as well as the established inverse relationship between metastasis and patient survival, this study establishes the extent to which incisional core needle biopsies (CNB) affects tumor growth and metastatic dissemination in two distinct breast cancer animal models. Methods: Using the chick embryo system (CES) and murine breast cancer model (MuBC)the impact of CNB on cancer metastases was evaluated. Human MDA-MB-231 and MDA-MB-435 cancer cells were used in the xenograft / CES, and murine 4T1 Breast cancer cells for the syngeneic MuBC . In each model, tumors were biopsied in half of the animals while the other half were left undisturbed (CES:n=40, MuBC:n=40). The impact of CNB on tumor growth, necrosis and metastases was assessed. Metastases levels in the CES was determined by quantitative PCR for human alu sequence DNA in chick tissue extracts. Metastatic burden in the MuBC model was evaluated by microscopic quantification of metastatic areas in sectioned and H-E stained mouse organs. Results: When biopsied and un-biopsied groups were compared, both models showed significant difference in pulmonary metastasis. MDA-MB-435 CES (p=0.025) and 4T1 MuBC (p=0.026). MDA-MB-231 CES showed no significant change in lung metastases in the CES but did however show increased Chorioallantoic Membrane (CAM) metastasis (p=0.018) and both cell lines showed statistically significant alteration in Liver metastasis, (MDA-MB-231 CES (p=0.006); MDA-MB-435 CES (p=0.004)). Interestingly only MDA-MB-435 (CES) tumor growth was significantly increased after CNB (p=0.002). Conclusions: These results offer the first experimental evidence that core needle biopsies result in an increased risk of metastatic dissemination and affect metastatic tropic behavior. They also reinforce the concept of a multi-step metastatic pathway and suggest involvement of extrinsic factors that influence the extravastion and intravasation steps. The clinical implications are considerable and follow-up studies examining potential mechanisms and countermeasures are urgently required
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 5023-5023
    Abstract: 5023 Background: Given the low specificity of the current standard of care diagnostic tests for prostate cancer (PCa), there is an unmet clinical need for higher specificity tests to counter overdiagnosis of grade group (GG) 1 PCa. The aim of the study was to create optimized neural network risk models using PSA, free PSA, and other useful clinical features, and to validate the accuracy of the risk models to predict GG ≥2 PCa using real-world samples and data. Methods: Men aged 40-75 years with PSA 〉 =3ng/mL and a biopsy referral were recruited into cohorts from sites in Canada (Kipnes Urology Centre (KUC), Edmonton, AB, and Prostate Cancer Centre (PCC), Calgary, AB) and the United States (Johns Hopkins University (JHU), Baltimore, ML and UCLA, Los Angeles, CA). Risk models to predict all GGs or GG ≥2 PCa were fit using data from KUC and JHU (train cohort n = 1037) while fixed models were validated on PCC (n = 401) and UCLA (n = 945). Prediction models were created using neural networks to generate the patient’s risk score. To compare the risk model test with PSA, the high-grade cancer detection sensitivity was fixed, and the number of biopsies needed to achieve that sensitivity was evaluated. Threshold values for the training cohort were determined using at least 95% sensitivity and maximum specificity. Threshold values for other clinical features and risk calculator outputs were set to match the test sensitivity when possible. Results: The optimized neural network risk models test had the highest area under the curve (AUC 0.81) for predicting GG ≥2 PCa on the validation cohorts compared to four other risk calculators; Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC) with free PSA (0.78, p-value 〈 0.001), Prostate Biopsy Collaborative Group risk calculator (PBCG, 0.73, p-value 〈 0.0001), European Randomized study of Screening for Prostate Cancer risk calculator 3 (ERSPC-3, 0.72, p-value 〈 0.0001), and PCPTRC with no free PSA (0.71, p-value 〈 0.0001) and PSA (0.66, p-value 〈 0.0001). At a threshold of 18.6%, this test provided 94% sensitivity, 37% specificity, 49% positive predictive value, and 90% NPV for predicting GG ≥2 PCa. If a biopsy was performed only when the tests’ risk score prediction was ≥17.8% for GG ≥2 PCa, 36-44% of unnecessary prostate biopsies could be avoided while missing 4-12% of patients with GG ≥2 prostate cancer. Conclusions: This neural network risk model is a tool that can be used to inform the physician of a patient’s risk of having GG ≥2 PCa on prostate biopsy. Using this novel test in the clinic is expected to significantly reduce the number and burden of unnecessary prostate biopsies. [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: 2023
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 5530-5530
    Abstract: 5530 Background: The accuracy of the extracellular vesicle-fingerprint score (EV-FPS) test to predict clinically significant prostate cancer (PCa; Gleason grade (GG) ≥ 3) from indolent disease (GG ≤ 2) and avoid unnecessary prostate biopsies was determined at the point of prostate biopsy decision. Methods: Clinical data, health information, and blood samples were collected from a prospective validation cohort of 415 men, without prior PCa diagnosis, referred to urology clinics for prostate biopsy or transurethral prostate surgery (June 2014-Dec 2016). The patient’s EV-FPS risk score was calculated by combining machine learning model-analyzed microflow cytometry data from EV biomarkers with logistic regression-analyzed patient-centric clinical features. The plasma-derived EV biomarkers were prostate-specific membrane antigen, polysialic acid and ghrelin-growth hormone receptor. The patient clinical features were; age, ethnicity, PCa family history, PSA levels, abnormal digital rectal examination (DRE) and prior negative prostate biopsy. Together, the biomarkers and clinical features provided specificity for clinically significant PCa. Results: The EV-FPS test identified clinically significant PCa patients with high accuracy (0.81 area under curve) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cut-off after test validation; 95% of the patients with GG ≥ 3 would have been found before biopsy, 35% biopsies would have been avoided and diagnosis of GG ≥ 3 PCa would have been missed in only 5% of the cohort. Conclusions: This minimally invasive EV-FPS test accurately predicted clinically significant PCa in men with high EV-FPS risk scores, high PSA level and/or abnormal DRE. Therefore, men with low EV-FPS risk scores could potentially avoid unnecessary prostate biopsies. Clinical care cut-offs to calculate the number of biopsies that could have been avoided, and the percentage of GG ≥ 1 to GG ≥ 3 PCa that could have had a delayed diagnosis. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 9
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  JCO Clinical Cancer Informatics , No. 3 ( 2019-12), p. 1-12
    In: JCO Clinical Cancer Informatics, American Society of Clinical Oncology (ASCO), , No. 3 ( 2019-12), p. 1-12
    Abstract: An online clinical information system, called Predictive Research Online System Prostate Cancer Tasks (PROSPeCT), was developed to enable users to query the Alberta Prostate Cancer Registry database hosted by the Alberta Prostate Cancer Research Initiative. To deliver high-quality patient treatment, prostate cancer clinicians and researchers require a user-friendly system that offers an easy and efficient way to obtain relevant and accurate information about patients from a robust and expanding database. METHODS PROSPeCT was designed and implemented to make it easy for users to query the prostate cancer patient database by creating, saving, and reusing simple and complex definitions. We describe its intuitive nature by exemplifying the creation and use of a complex definition to identify a “high-risk” patient cohort. RESULTS PROSPeCT was made to minimize user error and to maximize efficiency without requiring the user to have programming skills. Thus, it provides tools that allow both novice and expert users to easily identify patient cohorts, manage individual patient care, perform Kaplan Meier estimates, plot aggregate PSA views, compute PSA-doubling time, and visualize results. CONCLUSION This report provides an overview of PROSPeCT, a system that helps clinicians to identify appropriate patient treatments and researchers to develop prostate cancer hypotheses, with the overarching goal of improving the quality of life of patients with prostate cancer. We have made available the code for the PROSPeCT implementation at https://github.com/max-uhlich/e-PROSPeCT .
    Type of Medium: Online Resource
    ISSN: 2473-4276
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 1 ( 2021-01-01), p. 66-78
    Abstract: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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