bluuebunny/crossref_metadata_2025_split huggingface dataset:
An elevated body mass (BMI) index predicts for better clinical outcomes in men with metastatic hormone refractory prostate cancer (HRPC)
Authors: Halabi S. , Ou S. , Vogelzang N. J. , Small E. J. 
Published: March 2020

4556 Background: Previous articles have reported that an elevated BMI was associated with an increased risk of biochemical failure in hormone sensitive patients. We asked the question as to whether an elevated BMI predicts for worst clinical outcomes, namely overall survival (OS) and prostate-cancer survival (PCS), among 1,216 men with HRPC. Methods: Patients were enrolled on eight clinical trials conducted by the Cancer and Leukemia Group B (CALGB). Eligible patients had progressive prostate cancer during androgen deprivation therapy (with documented castrate levels of testosterone), an ECOG performance status of 0–2, adequate hematologic, renal and hepatic function. We used the NIH definition to classify patients as: normal (<25 kg/m2), overweight (25–29 kg/m2 ), mildly obese (30–34 kg/m2), and moderately to severely obese (≥35 kg/m2). PCS was defined as the time from study entry to the time of death due to prostate cancer. The proportional hazards model was used to explore the prognostic significance of BMI in predicting OS and PCS. Results: The median BMI was 27.7 kg/m2 (inter-quartile range = 25.2–31.0 kg/m2 ). Twenty three percent (285/1216) of the patients had normal BMI, 46% (555/1216) were overweight, 23% (280/1216) were mildly obese, and 8% (96/1216) were moderately to severely obese. In multivariate analysis, adjusting for age, race, performance status, hemoglobin, PSA, LDH, alkaline phosphatase, testosterone, years since diagnosis, presence of visceral disease and Gleason scores, BMI was a statistically significant predictor of OS and PCS. Compared to normal men, the hazard ratios (HR) of overweight patients was 0.80 (95% CI = 0.69–0.93, p-value = 0.003), for mildly obese patients was 0.86 (95% CI = 0.72–1.02, p-value = 0.087) and for moderately to severely obese men it was 0.60 (95% CI = 0.47–0.78, p-value < 0.001). In addition, the HRs for PCS for overweight patients was 0.83 (95% CI = 0.70–0.97, p-value = 0.023), was 0.88 (95% CI = 0.72–1.06, p-value = 0.179) for mildly obese and for moderately to severely obese was 0.62 (95% CI = 0.47–0.81, p-value = 0.001) compared to men with normal BMI. Conclusions: Contrary to what was reported, these findings demonstrate an inverse relationship between BMI and clinical outcomes in men with HRPC. [Table: see text]
Clinical outcome of taxane-resistant (TR) hormone refractory prostate cancer (HRPC) patients (pts) treated with subsequent chemotherapy (ixabepilone (Ix) or mitoxantrone/prednisone (MP)
Authors: Lin A. M. , Rosenberg J. E. , Weinberg V. K. , Kelly W. K. , Michaelson M. D. , Hussain M. , Wilding G. , Gross M. E. , Small E. J. 
Published: March 2020

4558 Background: The clinical course of TR HRPC pts has not previously been evaluated in a large, prospective study. No standard treatment exists for this pt population, although MP is frequently used. Ix is an epothilone B analogue with activity against TR cell lines. Methods: Metastatic HRPC pts with disease progression during or within 60 days of stopping T chemotherapy were eligible. In a 2-arm, non-comparative randomized phase II study, pts were assigned to receive either: 1) M 14 mg/m2 IV q3wks and P 5 mg PO BID or 2) I × 35 mg/m2 IV q3wks. Crossover was allowed for progression or toxicity. The study’s primary endpoint was to detect a ≥ 50% PSA decline by Consensus Criteria in at least 25% of 2nd-line pts (H0 = 10%, α = 0.04, β = 0.18 for each arm). Pts were followed for survival. Results: Forty-one evaluable pts each were accrued to Ix and to MP. The median follow-up is 5.0 months (range: 0.3–19.5). The median number of cycles administered to each 2nd-line arm is 3 (range: Ix: 1–8, MP: 1–12). Median survival from protocol entry is 13.0 months with Ix and 12.5 months with MP. Confirmed 2nd-line post-therapy (rx) ≥50% PSA declines were observed in 17% of Ix pts (95% CI = 7–32) and 20% of MP pts (95% CI = 9–35). Of pts with measurable disease, partial responses were observed in 1/18 pts on 2nd-line Ix (6%; 95% CI = 0.1–27.3) and in 1/15 pts on 2nd-line MP (7%; 95% CI = 0.2–31.9). Median duration on 2nd-line Ix and MP was 2.2 months and 2.3 months, respectively. Crossover to 3rd-line rx occurred in 39% of Ix pts and 68% of MP pts. Confirmed 3rd-line post-rx ≥50% PSA declines were observed in 3/24 Ix pts and in 4/13 MP pts. The most common grade 3/4 toxicity associated with 2nd-line rx was neutropenia as previously reported (41% of Ix pts, 54% of MP pts). Conclusions: This prospective trial has characterized TR HRPC pts as having an observed median survival of approximately 1 year. This may be a useful reference for the screening of effective agents in the 2nd-line setting for TR HRPC. Both Ix and MP appear to have only modest activity as 2nd- and 3rd-line rx in this highly selected TR HRPC population. This study was supported by Bristol-Myers Squibb and the Prostate Cancer Foundation. No significant financial relationships to disclose.
Neoadjuvant GM-CSF and thalidomide in men with high-risk prostate carcinoma undergoing radical prostatectomy
Authors: Garcia J. A. , Magi-Galluzzi C. , Rothaermel J. , Elson P. , Zhou M. , Klein E. , Dreicer R. 
Published: March 2020

4564 Background: Granulocyte macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that stimulates dendritic cells (DC’s) and promotes uptake of tumor antigens by DC’s leading to T cell cross-priming. Thalidomide is an anti-inflammatory agent with immunomodulatory and antiangiogenic activity. Administration of GM-CSF and Thalidomide can induce PSA responses in 20–25% of patients (pts) with Hormone-Refractory Prostate Cancer (HRPC). In an effort to further evaluate this novel combination we conducted a phase II trial in pts with locally advanced PCA. Methods: High-risk PCA pts undergoing radical prostatectomy (RP) were eligible. ECOG 0–1, adequate organ function, and no prior hormonal therapy were required. All pts received GM-CSF at 250 μg administered SC three times weekly. Thalidomide was escalated to reach the study dose of 200 mg/day. Patients were assessed every 4 weeks with therapy continuing to a maximum of 8 weeks. The primary endpoints were pathologic response, rate of PSA decline and toxicity. High-throughput tissue microarrays (TMAs) were also used to assess exploratory tissue endpoints including tumor expression of PTEN, CD3, Ki-67, and CD68 by immunohistochemistry. Results: To date 22 of a total planned of 29 pts are enrolled. Median age is 59 (43–72), median PSA of 10.4 (3.6–64.8). Baseline Gleason Scores (9 pts-GS7, 10 pts-GS8, and 3 pts GS9). 19/22 pts received all 8 weeks of therapy. Three pts discontinued therapy early due to toxicity or drug intolerance. A maximum PSA decline of 15–55% was observed in 86% of pts. Grade (G) 1–2 toxicities included dizziness/paresthesias (68%), constipation (64%), injection site reactions (64%) and fatigue (50%). Only one pt developed G3 toxicity (DVT). Tumor tissue expression of PTEN, Ki-67, CD3 and CD68 was significantly higher in treated pts when compared with matched controls (PTEN p = 0.03, Ki-67 p = 0.004, CD3 p < 0.001, and CD68 p < 0.001). Conclusions: Neoadjuvant therapy with GM-CSF and Thalidomide is well tolerated, and does not appear to impact on the perioperative morbidity of RP. This combination therapy appears to induce overexpression of PTEN, Ki-67, CD3 and CD68 in PCA tissue. Ongoing tissue and serum immune studies are underway to better define the significance of these tissue findings. [Table: see text]
Public health impact of PSA doubling time after radical prostatectomy on prostate cancer specific and overall survival
Authors: Freedland S. J. , Humphreys E. B. , Mangold L. A. , Eisenberger M. , George D. J. , Partin A. W. 
Published: March 2020

4568 Background: Among patients treated with radical prostatectomy (RP) with a PSA recurrence, we previously found men with a PSA doubling time (PSADT) <3 months were at increased risk of prostate cancer death, though these men constituted a small subset of patients. We sought to determine the actual and predicted number of prostate cancer deaths stratified by PSADT. Methods: We retrospectively studied 379 men treated with RP between 1982 and 2000 with a PSA recurrence. We calculated the actual and 15-year actuarial number of prostate cancer deaths in each of the following PSADT categories: <3, 3.0–8.9, 9.0–14.9, and ≥15.0 months. Results: Median follow-up after PSA recurrence was 7 years. During this time, there were 76 prostate cancer deaths; the majority (51%) were among men with a PSADT of 3.0–8.9 months. Though men with a PSADT <3 months were at the greatest risk of death, this group accounted for only 20% (n=15) of all prostate cancer deaths. Using actuarial 15-year estimates of prostate cancer specific survival, 50% of all prostate cancer deaths were among men with a PSADT of 3.0–8.9 months while men with a PSADT <3 months accounted for only 13% of prostate cancer deaths. Using actuarial 15-year estimates of all-cause and prostate cancer specific mortality, among men with a PSADT <15 months, prostate cancer was estimated to be the cause of death in 94% (145/155). Only among men with a PSADT >15 months was the risk of competing causes of mortality high enough such that the majority of deaths were not attributed to prostate cancer. Conclusions: Among a select cohort of men treated with RP who experienced a PSA recurrence, prostate cancer was estimated to account for 75% of all deaths. Though men with a PSADT <3 months were at the greatest risk, the majority of deaths occurred among men with a PSADT of 3.0–8.9 months. Efforts to reduce prostate cancer mortality should focus on men with intermediate PSADT times (3.0–15.0 months) as they represent the greatest public health concern among men with PSA recurrence following RP. [Table: see text] No significant financial relationships to disclose.
Erythropoietin receptor expression in bladder cancer
Authors: Belda Iniesta C. , De Castro Carpeño J. , Casado Saenz E. , Feliu Batlle J. , Bernabeu F. , Alves J. , Cejas P. , Sereno M. , Perona R. , Gonzalez Baron M. 
Published: March 2020

4584 Background: Several groups have implicated erythropoietin receptor (EPOR) expression in cancer progression, angiogenesis and cell survival. No clinical data about its implication in bladder cancer has been reported. So, our main objective was to determine the expression of EPOR in bladder cancer specimens after radical cystectomy and its potential relation with disease free survival (DFS) and overall survival (OS). Methods: Patients diagnosed with invasive grade 3 bladder cancer were included after radical cystectomy. None of them had node involvement after pathological examination. Data about pathological stage (pT), DFS and OS were recorded. EPOR expression was analyzed by immunohistochemistry in paraffin embedded samples. An expert uro-pathologist ensured enough tumoral proportion in every sample. EPOR antibody was targeted against the extracellular domain of this receptor (Santa Cruz, CA). Positive immunostaining was defined when more than 80% tumoral cells showed a cytoplasmatic staining pattern. Results: Of the 75 consecutive patients included (pT1 = 11; pT2 = 21; pT3 = 21; pT4 = 22), 40 (53.3%; 95% CI 42.61- 64.23) had EPOR expression. No correlation was observed between EPOR expression and pathological stage. Median DFS was 10 months for patients with EPOR expression and was not reached for individuals without receptor expression after 22 months of follow-up (logrank test p < 0.0001). Furthermore, univariate analysis showed that pathological stage had no statistical influence. Finally, multivariate analysis showed only EPOR expression as predictor for DFS and OS (p = 0.0009). Conclusions: EPOR expression is a strong prognostic factor after radical cystectomy in grade 3 bladder cancer patients without node involvement. No significant financial relationships to disclose.
Nuclear magnetic resonance spectroscopy of expressed prostatic secretions: Metabolite citrate and derivatives are potential markers of prostate cancer
Authors: Crawford D. , Serkova N. , Gamito E. , Jones R. , O’Donnell C. , Hedlund T. 
Published: March 2020

4623 Background: Nuclear magnetic resonance spectroscopy (NMRS) along with a novel method for determining absolute concentrations of metabolites were utilized to analyze expressed prostatic secretions (EPS) from men with prostate cancer (PCa) and from healthy controls. Methods: Flash frozen EPS samples from 66 men (40 with PCa and 26 controls) were analyzed by high-resolution 1H-NMR spectroscopy using a Bruker 500 MHz DRX NMR spectrometer with a 1-mm microprobe. The total number of scans per fully relaxed 1H-NMR spectrum was n = 40 with water suppression. Absolute concentrations of endogenous metabolites (citrate, spermine, myo-inositol, lactate, alanine, phosphocholine, glutamate, acetate, hydroxybutyrate) were quantified using trimethylsilyl-propionic acid as an external standard reference. Stepwise multivariable logistic regression (LR) was used to model the risk of PCa based upon the levels of the measured metabolites. Results: The average age of the EPS donors was 54.7 ± 9.8 years. The median Gleason score for the men with PCa was 6 (range 5–9). The Wilcoxon rank sum test indicated that citrate, spermine, inositol, citrate/spermine, and citrate/lactate were all significant predictors of PCa (p < .001). The LR models indicated that the absolute concentration of citrate was highly predictive of PCa with lower concentrations resulting in a higher risk of cancer. The area under the receiver operating characteristic curve (AUROC) for citrate alone was 0.79 (95% CI 0.75–0.83). Using relative concentrations (metabolite ratios) in a two-variable LR model, citrate/spermine and citrate/lactate were also predictive of PCa with an AUROC of 0.76 (95% CI 0.71–0.81). Conclusions: The results suggest that absolute concentration of citrate and its derivatives in EPS as measured by NMRS have promising potential as accurate markers of prostate cancer. No significant financial relationships to disclose.
Effect of bicalutamide 150 mg on PSA progression in M0 prostate cancer: Results from the Early Prostate Cancer program
Authors: See W. A. , McLeod D. G. , Iversen P. , Wirth M. P. , Armstrong J. , Navani S. 
Published: March 2020

4624 Background: Prostate-specific antigen (PSA) progression is the first sign of prostate cancer recurrence after primary therapy. In the Early Prostate Cancer (EPC) program, men with locally advanced disease who received bicalutamide 150 mg (CASODEX) in addition to standard care (radiotherapy [RT], radical prostatectomy [RP], or watchful waiting [WW]) had significantly improved objective progression-free survival (PFS) vs standard care alone. In the RT setting, this translated into improved overall survival (OS). Here, we compare PSA-PFS in the 3rd analysis of the EPC program with the results for objective PFS. Methods: The EPC program consists of 3 trials in which patients (all M0) with either localized (T1–2, N0/Nx) or locally advanced (T3–4, any N; or any T, N+) prostate cancer were randomized to receive standard care plus either bicalutamide 150 mg (n = 4052) or placebo (n = 4061). The primary end points were OS and objective PFS. PSA-PFS was a secondary end point. A PSA progression event was defined as PSA rising to ≥2× baseline or ≥0.4 ng/mL in men with non-quantifiable baseline PSA, death, or objective progression. PSA-PFS and objective PFS were analyzed for stage/therapy subgroups using a Cox proportional hazards model. Results: At 7.4 years’ median follow-up, bicalutamide plus standard care was associated with significantly improved PSA-PFS vs placebo (p < 0.001), irrespective of primary therapy or disease stage. However, PSA-PFS benefit only translated into a significant objective PFS benefit in locally advanced disease ( table ). Conclusion: Adding bicalutamide 150 mg to standard care significantly improves PSA-PFS for men with early, non-metastatic prostate cancer. The significant improvement in PSA-PFS was only accompanied by a significant improvement in objective PFS in locally advanced disease. Consequently, a significant PSA-PFS benefit cannot always be assumed to translate into a significant objective PFS benefit. [Table: see text] [Table: see text]
Diethylstilbestrol and docetaxel: A phase II study in patients with metastatic, androgen independent prostate cancer
Authors: Montgomery B. , Lin D. , Ryan C. , Garzotto M. , Beer T. M. 
Published: March 2020

4627 Background: The combination of diethylstilbestrol (DES) and docetaxel has additive to synergistic activity against prostate cancer in preclinical models and DES inhibits expression of taxane resistant tubulin isoforms. The objective of this study is to determine the effects of the combination of DES and docetaxel on PSA, overall response, and toxicity. Methods: Twenty nine patients with metastatic androgen independent prostate cancer progressing by rising PSA or scan were treated with DES 5 mg daily the day prior to docetaxel and 1 mg daily continuously in combination with Docetaxel 36mg/m2 IV weekly for 3 weeks of a 4 week cycle. Prophylactic anticoagulation was used in all patients. All patients were assessed by PSA monthly and CT or bone scans every 3 cycles. Dose modifications for hematologic, hepatic and renal toxicity were made. The RECIST criteria and PSA decline by >50% which was maintained for 4 weeks were used. Results: The median age is 69 years (56–84), SWOG PS 0 (0–1), alkaline phosphatase 120 U/L (45–523), Hgb 12.6 g/dL (9.2–16.3), PSA 67 ng/dL (6–1962). The median number of cycles is 5. The median follow up after completion of therapy is 6 mos (1–18). Soft tissue metastases were present in 46% of patients and bone metastases in 96%. Twenty four patients are evaluable for response and toxicity. Of these, 18 patients (75%) had PSA responses and the PSA declined by >90% in 9 patients (38%). The overall response for was 75%. 11 patients suffered grade 3/4 toxicity. Two patients died of causes unrelated to therapy and another died from a steroid induced ulcer. The median number of cycles for responding patients is 9. Two patients developed thrombosis and were positive for Factor V mutations. Conclusions: The combination of DES and docetaxel is well tolerated and toxicity is indistinguishable from docetaxel alone. The overall response rate was 75%, with approximately half of responding patients achieving a PSA < 4.0, suggesting that DES improves the therapeutic index of docetaxel substantially and is an effective regimen using easily administered drugs. (Supported by Sanofi Aventis). [Table: see text]
Serum c-erbB-2 ectodomain (ECD) correlates with immunohistochemical c-erbB-2 expression and predicts an aggressive clinical outcome in hormone-independent prostate cancer (HIPC) patients (pts) treated with docetaxel (D)
Authors: Domingo-Domenech J. , Gallardo E. , Filella X. , Fernandez E. , Fernandez P. , Gascon P. , Mellado B. 
Published: March 2020

4632 Background: The overexpression of c-erbB-2 has been described as a common event associated to the hormone-independent progression in prostate cancer. The clinical implications of c-erbB-2 expression in HIPC pts are not fully established. In this study we investigated the clinical significance of c-erbB-2 serum levels in HIPC pts treated with D and the correlation between serum c-erbB-2 ECD and c-erbB-2 tissue expression. Methods: Pts with HIPC treated with D were tested for serum c-erbB-2 ECD levels by immunoassay before chemotherapy. In pts with available biopsy specimens of hormone-independent tumor, c-erbB-2expression was determined by immunohistochemistry in paraffin-embedded tissue sections. PSA response to D, time to PSA progression and survival were analyzed. Results: Forty-one pts were included in the study. Median follow-up time was 23.3 (3.7–43.1) months. Median time to D progression was 4.1 (0,4–15.1) months and median survival was 11.3 (1,6–43.1). Serum c-erbB-2 correlated with PSA (r=0.351, p=0.025), inversely with time to PSA progression (r = −0.338, p = 0.033) and inversely with survival (r = −0.305, p = 0.05). Median time to PSA progression in pts with high serum c-erbB-2 (≥15 ng/ml) was 1.5 months compared to 4.6 months in pts with low levels (p = 0.0003). Survival in pts with high c-erbB-2 was 11 months and in pts with low c-erbB-2 was 15 months (p = 0.053). HIPC tissue samples from 10 pts were assessed for c-erbB-2 expression. Immunohistochemical c-erbB-2 positive staining (score +2 and +3) was detected in 4 (40%). C-erbB-2 staining showed correlation with serum c-erbB2 levels. Pts with positive staining had 19.1 ± 1.78 ng/ml and negative pts 8.8 ± 2.6 ng/ml (p = 0.001).The 4 pts with tissue c-erbB-2 overexpression had serum c-erbB-2 levels >15 ng/ml, while pts with no c-erbB-2 overexpression in tissue had also low c-erbB-2 levels in serum. Conclusions: High c-erbB-2 ECD in serum is associated with a worse clinical outcome of HIPC. Our data suggest that the determination of c-erbB-2 ECD in serum translates the c-erbB-2 status in the hormone-independent tumor and may be useful to select pts for c-erbB-2-targeted therapy. No significant financial relationships to disclose.
Meta-analysis of neo-adjuvant androgen deprivation therapy (AD) in localised prostate cancer
Authors: Kumar S. , Harrison C. , Shelley M. , Mason M. 
Published: March 2020

4643 Background: AD before primary therapy, either prostatectomy (P) or radiotherapy (RT) is increasingly used in routine practice. Clinical trials of surgical series have shown an improvement in pathological variables but with limited survival data. A few RT studies have shown a clinical benefit. We performed a systematic review and meta-analysis to assess the true impact of NA treatment. Methods: Data from published clinical trials of patients with non-metastatic PC were extracted for quality, and included design, participants and comparisons and meta-analysis was performed for comparable data. The primary endpoint was overall survival (OS) and secondary endpoints included disease-specific, disease-free survival (DFS) and disease recurrence rates. Analysis was performed using Revman 4.2.8. For dichotomous data the odds ratio was calculated with 95% confidence interval (CI) and the results were tested for homogeneity at a significance level of p < 0.1. A fixed effects model was used if there was no evidence of heterogeneity between studies. Results: AD before P led to a significant reduction in disease recurrence (number (n) of patients 973 in 3 trials-overall odds ratio OR 0.74; 95% CI 0.55–1.0; p = 0.05). In addition there was a significant reduction of positive surgical margins (n 1802 in 8 trials-OR 0.34; 95% CI 0.27–0.42; p < 0.00001).There were no comparable data for pooled analysis of DFS or OS. The use of AD before RT resulted in a significant improvement in disease-specific survival (n 1082 in 3 trials-OR 1.37; 95% CI 1.06–1.77; p =0.02) and DFS (n 991 in 2 trials-OR 1.86; 95% CI 1.93–2.40; p < 0.00001). The data for biochemical DFS was heterogenous due to differences in definition of PSA recurrence but the overall effect was highly significant in favour of AD (n 1097 in 3 trials-OR 1.93; 95% CI 1.45–2.56 p < 0.00001). There was a trend to improvement of OS at 1, 2 and 5 years, not statistically significant. Conclusions: Despite a significant improvement in pathological variables with AD before surgery, available evidence is limited regarding a survival benefit which requires prolonged follow-up of patients. In selected patients undergoing RT, the addition of AD results in improved disease specific survival and DFS, likely improvement of biochemical DFS and trend to improvement in OS. No significant financial relationships to disclose.