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  • American Society of Clinical Oncology (ASCO)  (7)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 5_suppl ( 2012-02-10), p. 274-274
    Abstract: 274 Background: Serine peptidase inhibitor Kazal type 1 (SPINK1) overexpression has been associated with poor outcomes. In one small study, loss of SPINK1 expression in urothelial carcinoma of the bladder (UCB) was associated with advanced tumor stage. We assessed the expression of SPINK1 in normal urothelium and UCB and analysed the association of SPINK1 with pathological features and clinical outcomes of patients treated with radical cystectomy (RC). Methods: The study used TMAs containing samples from 438 consecutive UCB patients treated with RC. 62 cases of normal urothelium were included as controls. A monoclonal antibody was used for immunohistochemical SPINK1 staining. SPINK1 expression of UCB was evaluated by two pathologists, blind to clinical outcome. Samples demonstrating less than 50% staining extent and 0 to 1 intensity (scale 0 to 3), were considered to have loss of expression. Results: SPINK1 expression was noted in umbrella cells of normal urothelium in 32/62 controls (52%). UCB of 254 patients (57.9%) exhibited loss of SPINK1 expression. Loss of SPINK1 expression was significantly associated with advanced pathological stage (p=0.002) and presence of lymph node (LN) metastasis (p=0.04). Within a median follow-up of 130 month (IQR 98.4), loss of SPINK1 expression was associated with an increased risk of disease recurrence (5-year RFS: 52±3 vs. 61±4 months; p=0.02) and cancer-specific mortality (5-year CSS: 59±3 vs. 68±3 months; p=0.03). In multivariable Cox regression analyses that adjusted for the effects of age, gender, tumor stage and grade, concomitant CIS, LN status and adjuvant chemotherapy, SPINK1 was not associated with disease recurrence (p=0.09) or cancer-specific death (p=0.12). Conclusions: While umbrella cells in normal urothelium commonly expresses SPINK1, more than half of UCB specimen exhibit loss of SPINK1 expression. Loss of SPINK1 expression is strongly correlated with local disease stage and LN metastasis. SPINK1 revealed no independent prognostic value for outcome prognostication, but it is a very promising marker for tumor staging which could be used for tailored follow-up protocols and possibly as a target for therapy as it has similarities with epidermal growth factor.
    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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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 5_suppl ( 2012-02-10), p. 268-268
    Abstract: 268 Background: Circulating tumour cells (CTC) are frequently detectable in the peripheral blood of patients with urothelial cancer of the bladder (UCB) prior to radical cystectomy (RC). We hypothesize that CTC can predict advanced stages, nodal status and disease outcome after radical cystectomy and therefore represent an optimal biomarker for treatment decision making and patient counseling. Methods: Blood samples of 120 consecutive, clinically non-metastatic UCB patients scheduled for RC were prospectively investigated for CTC. Preoperatively collected blood samples (7.5 ml) were analysed for CTC using the CellSearch system (Veridex, USA). Uni- and multivariable models evaluated the association of CTC status and number of CTC with clinical and nodal stage and disease outcome. Results: CTC were detectable in 30/120 patients (25%) with an average number of 5.7±18.3 CTC (range:1-100; median:1). Eighteen patients (60.0%) had 1 CTC/7.5mL, 8 patients (26.7%) had 2-5 CTC and 4 patients (13.3%) had 〉 5 CTC, respectively. CTC status was not associated with tumour stage, grade, lymph node metastases or lymphovascular invasion. Moreover, increasing numbers of CTC were not associated with higher stages or increasing numbers of lymph node metastases. However, at a median follow-up of 18 months (range:1-48 months) CTC detection prior to RC was an independent risk factor for disease recurrence (p 〈 0.001, HR=4.9, 95%CI 2.1–11.7) and cancer-related death (p=0.002, HR=4.9, 95%CI 1.7-13.6). Disease recurrence and cancer-related death were not associated with the number of detected CTC. Conclusions: Although CTC can not predict pathological or nodal stage, they are associated with inferior disease outcome. Detection of even 1 CTC/7.5 mL blood in UCB patients prior to RC is an independent predictor for disease recurrence and cancer-related death. These findings are very important for future investigations, as they are in contradiction to theories supporting a cut-off value of 5 or more CTC needed for accurate outcome prediction. Therefore, CTC may represent a feasible biomarker for monitoring response to neoadjuvant and adjuvant chemotherapy.
    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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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 11 ( 2007-04-10), p. 1316-1322
    Abstract: We tested the hypothesis that the prediction of renal cancer–specific survival can be improved if traditional predictor variables are used within a prognostic nomogram. Patients and Methods Two cohorts of patients treated with either radical or partial nephrectomy for renal cortical tumors were used: one (n = 2,530) for nomogram development and for internal validation (200 bootstrap resamples), and a second (n = 1,422) for external validation. Cox proportional hazards regression analyses modeled the 2002 TNM stages, tumor size, Fuhrman grade, histologic subtype, local symptoms, age, and sex. The accuracy of the nomogram was compared with an established staging scheme. Results Cancer-specific mortality was observed in 598 (23.6%) patients, whereas 200 (7.9%) died as a result of other causes. Follow-up ranged from 0.1 to 286 months (median, 38.8 months). External validation of the nomogram at 1, 2, 5, and 10 years after nephrectomy revealed predictive accuracy of 87.8%, 89.2%, 86.7%, and 88.8%, respectively. Conversely, the alternative staging scheme predicting at 2 and 5 years was less accurate, as evidenced by 86.1% (P = .006) and 83.9% (P = .02) estimates. Conclusion The new nomogram is more contemporary, provides predictions that reach further in time and, compared with its alternative, which predicts at 2 and 5 years, generates 3.1% and 2.8% more accurate predictions, respectively.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2007
    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. 5_suppl ( 2012-02-10), p. 188-188
    Abstract: 188 Background: Many patients with a negative prostate biopsy (PBx) but persistent clinical suspicion of prostate cancer (PCa) undergo repeat PBx. Although higher rates of low grade PCa on repeat PBx have been reported, we hypothesize that a considerable risk of clinically significant PCa remains. Methods: We retrospectively reviewed the data from a cohort of 25,584 patients who underwent one or more PBx at two institutions. To ensure current standards, we only included patients biopsied from 2004 to 2010 with a minimum of ten cores taken. Statistical analysis was performed using SPSS v.17.0. Results: 6,729 men met the inclusion criteria, 764 (11.4%) of whom underwent a second PBx after negative initial biopsy. Overall, 3669 (54.6%) men were diagnosed with PCa on first PBx whereas 199 (26.0%) had a positive second PBx (p 〈 0.01, Table 1). Cancers detected on the second PBx were more likely to be Gleason 6 than cancers detected on initial PBx (60.8% vs. 46.1%, p 〈 0.01). We further categorized men as having low risk PCa, as defined by PSA 〈 10ng/mL, Gleason sum 6, clinical stage ≤T2a, and ≤2 biopsy cores positive. The proportion of low risk patients was significantly higher in repeat PBx compared to initial PBx (36.2% vs. 23.6%, p 〈 0.01). Conclusions: Despite having a negative initial PBx, over a quarter of men who underwent a repeat biopsy in our large cohort had PCa detected. Despite the pathologic characteristics being more favorable on repeat PBx, almost two-thirds of these men still had intermediate or high-risk PCa. In conclusion, men in whom there is persistent suspicion for PCa despite a negative PBx should be counseled that repeat biopsies detect a high number of clinically significant PCa. [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. 4_suppl ( 2014-02-01), p. 114-114
    Abstract: 114 Background: High-risk prostate cancer (HRPC) is a challenging disease and the role of surgery is often considered in the context of a multimodal approach. The indication for adjuvant therapy after surgery for HRPC patients who have specimen-confined disease (R0, pN0, 〈 pT3b) is still difficult. The current study aims to analyze postoperative pathological features which help to predict CSS in specimen-confined HRPC and thus may aid in the decision to administer adjuvant EBRT or ADT. Methods: From a multi-institutional retrospective cohort of 5876 HRPC patients treated by radical prostatectomy and pelvic lymph node dissection, 1391 patients with specimen-confined disease were selected. Following surgery, adjuvant EBRT and/or ADT were delivered according to institutional protocols. Patients were subdivided into four groups according to pT stage (pT≥3 and pT 〈 3) and final Gleason score (GS≥8 and GS 〈 8). Kaplan-Meier plots with log-rank tests and a Cox proportional hazards model were applied to study CSS. All significance levels were set at 0.05. MedCalc was used for all statistical analyses. Results: Median age was 65 years (43-84). Of all patients, 346 (24.9%) had GS≥8 and 794 (57.1%) had pT≥3 at definitive histopathology. Patients were classified into COMBO groups: C1 (478; 34.4%; GS 〈 8,pT 〈 3), C2 (567; 40.8%; GS 〈 8, pT≥3), C3 (119; 8.6%; GS≥8, pT 〈 3), C4 (227; 16.3%; GS≥8, pT≥3). Adjuvant EBRT and ADT, respectively, were delivered in C1 2%/2%, C2 15%/22%, C3 3%/10%, C4 18%/25%. Kaplan Meier plots demonstrated statistically different 10-yr CSS between groups: C1 97.4%, C2 95.2%, C3 89.9% and C4 84.4% (p 〈 0.0001). COMBO groups were also compared using a Cox model and results are shown in the Table. Conclusions: COMBO groups demonstrated to be able to subdivide specimen-confined HRPC into 4 demarcated groups with significantly different CSS. This subdivision could be considered an easy-to-use tool which can help for counseling patients for adjuvant treatment strategies. [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: 2014
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 6_suppl ( 2013-02-20), p. 474-474
    Abstract: 474 Background: White blood cell count (WBC) and C-reactive protein (CRP) are reliable biomarkers in clear cell renal cell carcinoma (ccRCC). Nevertheless, accepted cut-offs values for risk stratifications are missing. This study re-evaluated the prognostic and predictive significance of preoperatively WBC and CRP that independently predicts patient prognosis and to determine optimal cut-off values for CRP. Methods: 327 patients with surgery for ccRCC were retrospectively evaluated from 1996 to 2005. Cox-proportional hazard models were used, adjusted for the effects of tumor stage, tumor size, Fuhrman grade, and Karnofsky-Index; and to evaluate the prognostic significance of WBC and CRP; and to identify cut-off values. Identified cut-offs were correlated with clinico-pathological parameters and used to estimate cancer-specific survival (CSS). To prove any additional predictive accuracy of the identified cut-off it was compared to a clinico-pathological base model using Harrell c-index. Results: In univariable analyses WBC was a significant prognostic marker at a concentration of 9.5/µl (HR: 1.83) and 11.0/µl (HR: 2.09) and supported a CRP value of 0.25 mg/dL (HR: 6.47, p 〈 0.001) and 0.5mg/dL (HR: 7.15, p 〈 0.001) as potential cut-off values. If adjusted by the multivariable models WBC showed no clear breakpoint, but a CRP-value of 0.25mg/dL (HR: 2.80, p = 0.027) proved to be optimal. Reduced CSS was proven for CRP 0.25 mg/dL (median: 69.9 vs. 92.3 months). Median follow-up was 57.5 months with 72 (22%) tumor related deaths. The final model built by the addition of CRP 0.25mg/dL did not improve predictive accuracy (c-index = 0.877) than compared to the clinico-pathological base model (c-index =0.881) which included TNM-stage, grading and Karnofsky-Index. Conclusions: Multivariable analyses revealed an optimal breakpoint of CRP at a value of 0.25mg/dL best to stratify patients at risk of cancer-specific mortality, but CRP 0.25mg/dL added no additional information in the prediction model. Therefore we cannot recommend to measure CRP as the traditional parameters of TNM-stage, grading and Karnofsky-Index were already of high predictive accuracy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 4_suppl ( 2014-02-01), p. 140-140
    Abstract: 140 Background: High-risk prostate cancer (HRPC) is a challenging disease and the role of surgery is often considered in the context of a multimodal approach but patients with positive section margins (R1) disease have not always the same cancer-specific survival (CSS). The current study aims to analyze current postoperative pathological features in order to predict CSS of HRPC patients with R1, but with negative lymph nodes (pN0), treated with surgery. Methods: From a multi-institutional retrospective cohort of 5,876 HRPC patients treated by radical prostatectomy and pelvic lymph node dissection, 1541 patients with pN0 and R1 were selected. Following surgery, adjuvant EBRT and/or ADT were delivered according to institutional protocols. Patients were subdivided into four groups according to pT stage (pT≥3 and pT 〈 3) and p-Gleason score (pGS≥8 and pGS 〈 8). Kaplan-Meier plots with log-rank tests and a Cox proportional hazards model were applied to study CSS. All significance levels were set at 0.05. MedCalc was used for all statistical analyses. Results: Median age at surgery was 66 years (42-89). Of all patients, 399 (25.9%) had GS≥8 and 999 (64.8%) had pT≥3 at definitive histopathology. Patients were classified as COMBO groups: C1 (423; 27.4%; GS 〈 8,pT 〈 3), C2 (674; 43.7%; GS 〈 8, pT≥3), C3 (83; 5.4%; GS≥8, pT 〈 3), C4 (362; 23.5%; GS≥8, pT≥3). Adjuvant EBRT and ADT, respectively, were delivered in C1 3%/5%, C2 15%/21%, C3 21%/20%, C4 28%/40%. Kaplan-Meier plots demonstrated statistically different 10-yr CSS between groups: C1 97%, C2 93.8%, C3 85.1% and C4 77.3% (p 〈 0.0001). COMBO groups were also compared using a Cox model and results are shown in the Table. Conclusions: COMBO groups demonstrated to be able to subdivide margin-positive, pN0 HRPC into 4 demarcated groups with significantly different CSS. This subdivision could be considered an easy-to-use tool which can help for counseling patients for adjuvant treatment strategies. [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: 2014
    detail.hit.zdb_id: 2005181-5
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