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  • American Society of Clinical Oncology (ASCO)  (20)
  • 1
    Online Resource
    Online Resource
    Do patients with larger prostates have greater toxicity after external beam radiotherapy for localized prostate cancer?
    American Society of Clinical Oncology (ASCO) ; 2007
    In:  Journal of Clinical Oncology Vol. 25, No. 18_suppl ( 2007-06-20), p. 15577-15577
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 18_suppl ( 2007-06-20), p. 15577-15577
    Abstract: 15577 Background: To aim of the study was to assess the impact of prostate volume (PV) on health-related quality of life (HRQOL) before and at different points in time after conformal radiotherapy for prostate cancer. Methods: A group of 180 patients has been surveyed prospectively before (time A), at the last day (B), two months after (C) and sixteen months (median) after (D) radiotherapy (70.2- 72Gy) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Patients in this analysis (n=165) met the prerequisite of responding to the first and last questionnaire. The multi-item scale scores were transformed lineary to a 0–100 scale, with higher scores representing better HRQOL. The group has been divided into a subgroup with a small PV (median 32cc; range 11–45; 83 patients) and a subgroup with a large PV (median 59cc; range 46–151; 82 patients). Results: Treatment plans for large prostates implied a larger planning target volume (averagely 396 vs. 305cc; p 〈 0.01) with a significantly larger dose to the bladder and rectum at all volume levels. Patients with large prostates presented with lower urinary bother (averagely 76 vs. 83; p=0.04), but higher bowel bother scores (averagely 95 vs. 90; p 〈 0.01) before the beginning of treatment. At time B, urinary bother scores decreased stronger for patients with large prostates (averagely 22 vs. 16 points). Comparing posttreatment scores to baseline scores, no significant decrease resulted for urinary function or bother scores for both groups at time C and D. At time D, urinary function scores even increased significantly for patients with large prostates (averagely 4 points). Bowel function and bother scores were still significantly lower for both groups at time C and D (averagely 3–8 points). HRQOL scores did not differ significantly between both patient groups at time D. Conclusions: In spite of a higher dose-load to the organs at risk, lower urinary bother scores before treatment and a higher decrease of urinary scores at the end of radiotherapy for patients with larger prostates, long-term HRQOL scores did not differ significantly between patients with large and small prostates. An improvement of urinary function suggests a regression of hyperplastic prostatic tissue. No significant financial relationships to disclose.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2007.25.18_suppl.15577
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2007
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
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    A phase III randomized trial comparing intermittent versus continuous androgen suppression for patients with PSA progression after radical therapy: NCIC CTG PR.7/SWOG JPR.7/CTSU JPR.7/UK Intercontinental Trial CRUKE/01/013.
    American Society of Clinical Oncology (ASCO) ; 2011
    In:  Journal of Clinical Oncology Vol. 29, No. 7_suppl ( 2011-03-01), p. 3-3
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 7_suppl ( 2011-03-01), p. 3-3
    Abstract: 3 Background: In men with PSA recurrence after radical radiotherapy (RRT), intermittent androgen suppression (IAS) has been suggested by phase II trials to improve quality of life (QoL) but effects on survival are unknown. In this Intergroup randomized phase III trial, we compared IAS vs continuous androgen deprivation (CAD) to test for non-inferiority of IAS with respect to overall survival (OS). Methods: Eligible men had rising PSA 〉 3.0 ng/ml 〉 1 year post RRT, either initial or salvage, for localized prostate cancer. Patients could receive up to 1 year of neo/adjuvant androgen deprivation therapy (ADT) completed 〉 1 year prior. Stratification factors were time since RRT ( 〉 1-3 vs 〉 3 years), initial PSA ( 〈 15 vs 〉 15), prior radical prostatectomy and prior ADT. IAS was delivered for 8 months in each cycle with restart when PSA reached 〉 10 ng/ml off treatment. Primary endpoint was OS; secondary endpoints included time to hormone refractory state (HR), QoL, cholesterol/HDL/LDL, duration of treatment/non-treatment intervals, time to testosterone and potency recovery. The independent DSMC recommended halting the trial after a planned interim analysis demonstrated that a pre-specified stopping boundary for non-inferiority was crossed. Results: 1,386 patients were randomized to IAS (690) or CAD (696) arms. Arms were balanced for important baseline factors. Median follow up was 6.9 years. IAS patients completed a median of 2 x 8 month cycles (range: 1-9). 524 deaths were observed (268 on IAS vs 256 on CAD). Median OS was 8.8 vs 9.1 years on IAS and CAD arms, respectively (HR 1.02, 95%CI 0.86-1.21; p for non-inferiority [HR IAS vs CAD ≥ 1.25] = 0.009). The IAS arm had more disease related (122 vs 97) and fewer unrelated (134 vs 146) deaths. Time to HR was statistically significantly improved on the IAS arm (HR 0.80, 95%CI 0.67-0.98; p = 0.024). IAS patients had reduced hot flashes, but otherwise there was no evidence of differences in AEs, including myocardial events or osteoporotic fractures. Conclusions: In men with PSA recurrence after RRT IAS, given as described herein, is non-inferior to CAD with respect to OS. No significant financial relationships to disclose.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2011.29.7_suppl.3
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2011
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Evaluation of the state of health of patients with localized prostate cancer (cT1-cT2) compared to the normal population.
    American Society of Clinical Oncology (ASCO) ; 2010
    In:  Journal of Clinical Oncology Vol. 28, No. 15_suppl ( 2010-05-20), p. 6115-6115
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 28, No. 15_suppl ( 2010-05-20), p. 6115-6115
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2010.28.15_suppl.6115
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2010
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Online Resource
    A phase III randomized trial of intermittent versus continuous androgen suppression for PSA progression after radical therapy (NCIC CTG PR.7/SWOG JPR.7/CTSU JPR.7/ UK Intercontinental Trial CRUKE/01/013).
    American Society of Clinical Oncology (ASCO) ; 2011
    In:  Journal of Clinical Oncology Vol. 29, No. 15_suppl ( 2011-05-20), p. 4514-4514
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 15_suppl ( 2011-05-20), p. 4514-4514
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2011.29.15_suppl.4514
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2011
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Randomized trial of p53 targeted adjuvant therapy for patients (pts) with organ- confined node-negative urothelial bladder cancer (UBC)
    American Society of Clinical Oncology (ASCO) ; 2009
    In:  Journal of Clinical Oncology Vol. 27, No. 15_suppl ( 2009-05-20), p. 5017-5017
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 15_suppl ( 2009-05-20), p. 5017-5017
    Abstract: 5017 Background: Retrospective studies suggest that p53 mutation and associated immunohistochemical (IHC) detectable expression are prognostic for recurrence in pts with organ confined UBC and may be predictive for benefit from MVAC adjuvant chemotherapy. Methods: Pts with pT1–2N0M0 UBC following radical cystectomy and bilateral pelvic lymph node dissection were eligible. IHC for p53 was centrally performed and pts with ≥10% nuclear reactivity were offered randomization to 3 cycles of adjuvant MVAC vs. observation. P53 negative and p53 positive pts who declined randomization were observed. Primary endpoint was recurrence-free survival (RFS) in the randomized population. Secondary endpoints were RFS in p53 negative versus p53 positive pts and overall survival in each of these groups. Using a one-sided log-rank test with α = 0.05 and β = 0.15, 190 p53 positive patients were planned to be randomized to detect an absolute improvement in RFS at 3 years (yrs) from 50% to 70% (corresponding hazards ratio of 0.51). Results: 521 pts were registered, 499 underwent successful p53 assessment (male: 80%, 〈 65 yrs: 57%, Caucasian: 91%, pathologic stage P1/P2: 37%/63%, lymphovascular invasion: 20% yes/28% unknown), 272 (55%) were p53 positive and 114 were randomized (42%). Further accrual was halted based on data safety monitoring board review of futility analysis on the first 100 randomized pts. P53 positive tumors were higher grade (97% vs 93% grade 3/4, p = 0.04) and less likely to express p21 (59% vs 84%, p 〈 0.001). Overall 5-yr RFS was 80 ± 2% with no difference based on p53 status. P53 positive patients declining were older but otherwise similar to those accepting randomization. Only 67% of pts randomized to MVAC received all 3 cycles with 12 (21%) receiving none. There was no difference in RFS in the randomized population (overall 5 yr RFS 83 ± 4%, hazard ratio = 0.88, p = 0.78). Conclusions: The prognostic and predictive value of p53 IHC were not confirmed in this prospective study, but the lower than expected event rate and failures to receive assigned therapy severely compromised the study's power. The value of p53 mutations is being assessed. No significant financial relationships to disclose.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2009.27.15_suppl.5017
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2009
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    Comparative efficacy of local versus systemic salvage therapies for recurrent prostate cancer after primary radiotherapy.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 6_suppl ( 2020-02-20), p. 221-221
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 221-221
    Abstract: 221 Background: We sought to compare two common salvage strategies for radio-recurrent prostate cancer: androgen deprivation therapy (ADT: PR7 RCT NCT00003653) or local salvage ablation using cryotherapy (CRYO: single institution study Williams, Eur Urol. 2011;60(3):405). Methods: Pre-salvage therapy prognostic variables common to the two datasets (Gleason score at initial treatment, time from original RT, use of ADT at time of original RT, PSA at time of salvage, patient age) were used for propensity matching between patients from previously published ADT (1) and CRYO (2) datasets. Progression free survival (PFS, defined as time from initial treatment to development of castrate resistance or death); Disease Specific Survival (DSS, defined as time from salvage to prostate cancer related death) and Overall Survival (OS, defined as time from salvage to death from any cause) were compared between the propensity matched cohorts using Log-Rank and Cox PH regression statistics. Raw linear propensity scores included in the PH model to account for residual variability. A planned subset analysis examined the effect of neoadjuvant ADT among the CRYO cohort (no CRYO patients had adjuvant ADT). Results: Overall, 1119/1386 (ADT) and 172/187 (CRYO) patients were included in the propensity matched analysis. Median follow up was 6.7 yrs (ADT) and 18.7 yrs (CRYO). Median PFS (95% CI) was 10.7 yrs (9.5, 12.3) for CRYO vs. 7.0 yrs (6.1, 10.0) for ADT (HR 0.63 (0.44, 0.89), p = 0.009). Median OS was also longer for CRYO vs. ADT: 12.3 (11.0, 13.8) vs. 10.2 (9.4, not reached) yrs (HR 0.69; p = 0.02). 10 year DSS event rate was 16.5% CRYO vs. 18.5% ADT but was not statistically different. Neoadjuvant ADT did not affect outcomes in CRYO. Conclusions: A 3-year PFS and 2-year OS benefit was noted for the CRYO vs. ADT cohorts while no difference was noted in DSS. Potential explanations include residual bias not corrected for in the propensity scoring, variable follow-up duration, adverse effects from differing cumulative exposure to ADT or a combination of these factors. Prospective comparisons are required to control for these potential biases and compare other important outcomes such as side effects and quality of life.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.6_suppl.221
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Online Resource
    Persistence of immunotherapy survival effects of sipuleucel-T and relationship to postrandomization docetaxel use in phase III studies.
    American Society of Clinical Oncology (ASCO) ; 2010
    In:  Journal of Clinical Oncology Vol. 28, No. 15_suppl ( 2010-05-20), p. 4551-4551
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 28, No. 15_suppl ( 2010-05-20), p. 4551-4551
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2010.28.15_suppl.4551
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2010
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Online Resource
    Utilizing metformin to enhance the efficacy of androgen-deprivation therapy in the treatment of prostate cancer.
    American Society of Clinical Oncology (ASCO) ; 2011
    In:  Journal of Clinical Oncology Vol. 29, No. 7_suppl ( 2011-03-01), p. 22-22
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 7_suppl ( 2011-03-01), p. 22-22
    Abstract: 22 Background: Prostate cancer (PCa) incidence varies by geographic location, with developed countries exhibiting higher levels of disease. Some attribute this to the “Westernized lifestyle” of high energy diets and limited physical activity with consequent obesity. Obesity and related diseases like diabetes, cause hyperinsulinemia, which upregulates pro-survival insulin/insulin-like growth factor signalling. Previous work shows diet-induced hyperinsulinemia enhances PCa tumor growth in vivo. Metformin, a diabetic treatment, reduces hyperinsulinemia, and also exhibits anti-neoplastic properties. We assessed the potential benefit of combining a standard PCa treatment (bicalutamide) with metformin in vitro and in vivo. Methods: The effect of bicalutamide and/or metformin on colony formation rates was assessed in LNCaP, PC3, DU145 and PC3AR2 PCa cell lines using clonogenic assay. Western blot and cell cycle analyses were used to elucidate mechanisms of interaction between the drugs. The combination treatment regimen was assessed in vivo using a murine xenograft model. Results: Micromolar bicalutamide or millimolar metformin caused significant dose-dependent reduction in colony formation rates (p 〈 0.001). Combination treatment further significantly reduced colony formation rates (p 〈 0.005). Differing mechanisms of interaction occurred in AR positive and negative cell lines. Following combination treatment LNCaP cells exhibited altered cell proliferation (decreased PCNA) and perturbed cell cycle kinetics (G1/S arrest). PC3 cells showed evidence of enhanced apoptosis (increased BAX, decreased caspase 3, phospho-Akt). Preliminary in vivo results show significantly diminished tumor growth following combination treatment (p 〈 0.0001). Conclusions: Combining bicalutamide and metformin significantly reduces PCa cell colony formation rates further than either monotherapy. In AR positive cells this effect is mediated by reducing cell proliferation rates, whereas in AR negative cells combination treatment promotes apoptosis. This combination drug regimen may potentially improve prostate-cancer specific survival via the direct anti-neoplastic properties outlined. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2011.29.7_suppl.22
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2011
    detail.hit.zdb_id: 2005181-5
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  • 9
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    Online Resource
    The association between statin use and outcomes in patients initiating androgen deprivation therapy.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 7_suppl ( 2015-03-01), p. 145-145
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 7_suppl ( 2015-03-01), p. 145-145
    Abstract: 145 Background: Studies are conflicting regarding the association between statin use and biochemical recurrence after surgery or radiotherapy for localized prostate cancer. A handful of studies have observed favorable associations between statins and prostate cancer-specific (PCSM) and overall mortality (OS), however, this has not been studied in an advanced disease cohort nor has the combination of statins and androgen deprivation therapy (ADT) been specifically studied. Methods: Patients with PSA 〉 3 ng/mL after 〉 1 year following primary or salvage radiotherapy (RT) were enrolled in a randomized trial of intermittent (IAD) vs. continuous (CAD) ADT (NCT00003653). Statin use at baseline and during the study was captured and modeled as a time-dependent covariate. The primary end-point was OS. Models were adjusted for age, time from RT to ADT and PSA at baseline. As results were nearly identical between the IAD and CAD arms they are reported as aggregates unless otherwise indicated. Results: Of 1,364 patients enrolled, 585 (43%) reported statin use during the study. Statin users were younger (72.7 vs. 73.8, p=0.001) and less likely to have PSA 〉 15 (20 vs. 25%, p=0.04). Median follow-up was 6.9 years and 524 deaths occurred. Statin use was associated with a reduced risk of overall death (HR: 0.64; 95% C.I. 0.53 – 0.78, p 〈 0.001) and PCSM (HR: 0.64, 95% C.I. 0.48 – 0.86, p=0.003). Statin users had 14% longer time to castration resistance but this did not reach statistical significance (p=0.15). In the IAD arm, statin users had more off-treatment intervals (p=0.04) and longer time off-treatment (median: 0.85 vs. 0.64 years, p=0.06). Across 6 functional domains, statin users reported better quality of life scores. Conclusions: In men treated with ADT following primary or salvage RT, statin use was associated with improved overall and prostate cancer-specific survival and improved quality of life. In patients treated with IAD, statin use was associated with more off-treatment intervals and longer time off-treatment. A prospective trial of statins in men commencing ADT is warranted to confirm this observation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.7_suppl.145
    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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  • 10
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    Online Resource
    Utilizing metformin as a radiosensitizing agent in the treatment of prostate cancer.
    American Society of Clinical Oncology (ASCO) ; 2011
    In:  Journal of Clinical Oncology Vol. 29, No. 7_suppl ( 2011-03-01), p. 89-89
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 7_suppl ( 2011-03-01), p. 89-89
    Abstract: 89 Background: External beam radiation therapy (EBRT) is a well recognized curative prostate cancer (PCa) treatment modality utilizing ionizing radiation (IR). In addition to mediating DNA damage, IR upregulates several intracellular pro-survival pathways including the insulin- like growth factor (IGR) signaling network. This may contribute to the intrinsic radioresistance exhibited by certain tumors. Diabetic patients with PCa experience poorer outcomes following EBRT than their non-diabetic counterparts. Some attribute this to diabetes-induced chronic hyperinsulinemia with consequent upregulation of pro-survival insulin/IGF signalling. Previous work by our group showed diet-induced hyperinsulinemia to enhance PCa tumor growth in vivo. Metformin, a diabetic treatment, alleviates hyperinsulinemia, and also exhibits anti-neoplastic properties. We postulate that pre-treatment with metformin to correct hyperinsulinemia may protect cells from radiation-mediated pro-survival insulin/IGF signaling. Thus we assessed the radiosensitizing potential of metformin using in vitro and in vivo PCa models. Methods: The effect of IR and/or metformin on colony formation rates was assessed in LNCaP, PC3, DU145 and PC3AR2 PCa cell lines using clonogenic assay. The combination treatment regimen was assessed in vivo using a murine xenograft model. Western blot and cell cycle analyses are ongoing to try and elucidate any mechanisms of interaction between metformin and IR. Results: Monotherapy with IR (1-8Gy) or metformin (0.01-10.0mM) caused significant dose-dependent reduction in colony formation rates (p 〈 0.001). Combination treatment further significantly reduced colony formation rates (p 〈 0.03). Preliminary results from our in vivo study show diminished tumor growth in response to combination treatment (p 〈 0.0001), and are currently subject to ongoing statistical analyses. Conclusions: Our in vitro findings confirm combining metformin with IR significantly reduces PCa cell colony formation rates further than either monotherapy. Recapitulation of these results in vivo would provide justification for translating this work into a phase II clinical trial of metformin as a radiosensitizing agent. No significant financial relationships to disclose.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2011.29.7_suppl.89
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2011
    detail.hit.zdb_id: 2005181-5
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