bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-biopsy PSA and biopsy gleason sum; evaluating the independence of two independent variables
Authors: McCann T. , Pierorazio P. M. , Mitchell R. , Desai M. , Olsson C. A. , Benson M. C. , McKiernan J. 
Published: March 2020

14555 Background: Traditionally PSA, Gleason sum and Clinical Stage are considered independent predictors of outcome for prostate cancer. The purpose of this study is to investigate a codependence between prostate specific antigen (PSA) and Gleason sum and whether this relationship has evolved during the PSA era. Methods: The Columbia Urologic Oncology Database was reviewed and 2,522 patients were identified who underwent radical prostatectomy from 1988 to 2005; a retrospective cohort of 1,786 patients with complete data was included. Patients were stratified by Gleason sum into groups with Gleason sum <7, =7 and >7. PSA was correlated to Gleason sum to examine a possible relationship between the two variables. Two-sample t-tests with 95% confidence intervals were utilized to determine differences between groups and were confirmed by ANOVA techniques. A Cox regression model using an interaction term between PSA and Gleason sum was fit to determine if an interaction exists between the two variables. Patients were further stratified into two cohorts by median year of surgery (1998) and the PSA-Gleason sum relationship was evaluated over time. Results: Median patient age was 61.9 years. 1,081 patients were identified with Gleason sum <7. 540 patients had a Gleason sum =7. 165 patients had a Gleason sum >7. The mean PSA values were 6.05, 6.89 and 8.41 for <7, =7 and >7 groups respectively. Differences between the means were statistically significant and validated by the ANOVA technique (p < 0.001). A Cox regression model validated PSA, Gleason sum and clinical stage as independent predictors of outcome. The addition of an interaction term into the Cox regression model between PSA and Gleason sum demonstrated a significant interaction effect between PSA and Gleason sum (p < 0.001). The relationship remained between PSA and Gleason sum within the pre and post 1998 groups (p < 0.001). Conclusions: PSA and Gleason sum are highly interrelated variables, although they each carry additional information that significantly contributes to the prediction of biochemical failure (PSA ≥0.2 ng/ml). For an individual patient, the higher the initial PSA the higher the risk of having a high Gleason sum on biopsy. This relationship has remained constant over the PSA era. No significant financial relationships to disclose.
Cisplatin versus carboplatin-based chemotherapy in inoperable or recurrent urothelial carcinoma: A retrospective analysis
Authors: Bamias A. , Kastritis E. , Bozas G. , Koutsoukou V. , Antoniou N. , Katsifotis H. , Konstantinidis K. , Skolarikos A. , Deliveliotis C. , Dimopoulos M. A. 
Published: March 2020

14558 Background: Cisplatin-based chemotherapy represents the standard for patients with inoperable or recurrent urothelial carcinoma. Carboplatin-based chemotherapy is reserved for not-fit-for-cisplatin patients. Recent data suggest that carboplatin-based chemotherapy may be effective in fit-for-cisplatin patients. We examined the differences in the outcome according to the compound used as first-line treatment. Methods: We selected patients who received first-line combination chemotherapy based on cisplatin or carboplatin. The major end point was survival. Survival curves were estimated with the Kaplan-Meier method, while cox regression analysis was used for multivariate models. Results: 445 patients, treated with cisplatin (330) or carboplatin (115)-based chemotherapy were included in this analysis. After a median follow-up of 52 months, there was no significant difference in survival between the two treatment groups (Table). Subgroup analyses according to PS, distant metastases, Hb, weight loss, showed that the use of cisplatin was independently associated with improved survival only in the PS 2,3 subgroup (see Table). When patients were stratified according to the Bajorin prognostic criteria (PS 0,1 vs. 2,3 and/or distant metastases yes vs. no; J Clin Oncol 1999, 17: 3173), again cisplatin-based chemotherapy was associated with a trend towards improved outcome only in the worst prognostic group (Table). Conclusions: Carboplatin-based chemotherapy may be equally effective to cisplatin-based treatment in patients with inoperable or recurrent urothelial cancer and no or one adverse factors. Cisplatin-based treatment may be beneficial in patients with poor prognosis. Nevertheless, the clinical relevance of this superiority is limited due to the poor outcome and the poor tolerance of cisplatin-based combination chemotherapy in this group of patients. (see Table) Median survival (95% CI) after first-line chemotherapy for advanced urothelial carcinoma. [Table: see text] No significant financial relationships to disclose.
A phase II report of longitudinal bone marker time trends in racially diverse prostate cancer patients receiving zoledronic acid with androgen deprivation
Authors: Phooshkooru V. R. , Spencer H. J. , Kohli M. 
Published: March 2020

14568 Background: Evidence for preventing androgen deprivation (AD) induced osteoporosis with bisphosphonate therapy in prostate cancer patients has emerged largely from trials conducted in caucasian patients. Osteoporosis related skeletal event incidence in African Americans (AA) receiving AD is significantly lower than caucasians and the effect of bisphosphonates therapy uncertain. We conducted a prospective study to evaluate the efficacy of zoledronic acid in preventing osteoporosis in racially diverse population receiving AD. Methods: Asymptomatic, prostate cancer patients (16 caucasians and 6 AA) with normal renal function undergoing AD, started within the last 9 months were randomized to receive (Arm A) CaCO3/vitamin D (500 mg/200U TID) or (Arm B) CaCO3/vitamin D and zoledronic acid (4 mg IV every 3 months for a year). Bone turnover markers including urine N-telopeptide, serum osteocalcin, serum bone specific alkaline phosphatase(BsAP) were serially measured every 3 months and bone mineral density (BMD) measured by DXA at hip, femur, spine and ward’s triangle at 0, 6 and 15 month intervals. Primary endpoint was to obtain BMD changes and bone turnover rates for each treatment arm. Nonparametric methods for analyzing longitudinal data were used to compare DXA-derived BMD measures and bone turnover rate markers in patients receiving zoledronic acid to the control group. Results: Data is presented for 16/22 patients who have completed 15- month follow up. Time trend analysis of bone formation (BsAP, osteocalcin) and resorption (N-telopeptide) markers and DXA measurements of BMD (spine and hip) are shown in the table. Conclusions: This study suggests that zoledronic acid preserves BMD at spine in racially diverse patients and, likewise provides preliminary estimates of BMD changes that occur over 15 months in patients receiving zoledronic acid and placebo. Larger AA cohorts are needed for prospective validation of the observed effect with zoledronic acid. [Table: see text] [Table: see text]
A plasmid DNA vaccine encoding prostatic acid phosphatase (PAP) elicits antigen-specific T cells in patients with stage D0 prostate cancer
Authors: McNeel D. G. , Dunphy E. J. , Johnson L. E. , Frye T. P. , Staab M. J. , Horvath D. L. , Straus J. , Alberti D. , Liu G. , Wilding G. 
Published: March 2020

14570 Background: Prostatic acid phosphatase (PAP) is a tumor antigen in prostate cancer. Clinical trials conducted in patients with metastatic prostate cancer targeting PAP by means of antigen presenting-cell vaccines have suggested clinical benefit in terms of disease progression and overall survival. Ultimately, tumor vaccines may be most effective in the setting of minimal residual disease. We have been investigating plasmid DNA vaccines encoding PAP in rodent models. We found these to be safe and effective in eliciting PAP-specific CD8 T cells and saw evidence of anti-tumor efficacy. We report here the initial immunological results from a dose-escalation portion of a phase I trial testing a DNA vaccine encoding PAP in patients with minimal residual stage D0 prostate cancer. Methods: Patients with clinical stage D0 prostate cancer with rising PSA were vaccinated over a 12-week period, 6 times at 14-day intervals, with a plasmid DNA vaccine encoding PAP (pTVG-HP). Vaccinations were administered intradermally with 100 mcg, 500 mcg, or 1500 mcg doses, and with 200 mcg of GM-CSF co-administered as a vaccine adjuvant. Immunological responses were evaluated by antigen-specific T cell proliferation and IFNγ secretion, and by ELISA for PAP-specific IgG. Results: At present 9 patients have been enrolled in a dose-escalation portion of the trial, and 6 have completed all immunizations. No serious adverse events have been observed, and no patients have discontinued treatment. To date, immunological analysis has been performed for the first, lowest dose cohort. PAP-specific CD4 and CD8 T cell responses, measured by antigen-specific T cell proliferation, were elicited following immunization in 2 of 3 patients. PAP-specific IgG antibodies were not detectable in these patients following vaccination. Conclusions: Intradermal immunization of patients with stage D0 prostate cancer with pTVG-HP has been without evidence of adverse events in doses up to 500 mcg. CD4 and CD8 T cell responses have been observed, consistent with a predominantly cellular immune response, at even the lowest dose of vaccine. Immunological analysis will be performed for patients completing the other dose levels, and all patients will be followed for changes in serum PSA levels. No significant financial relationships to disclose.
Prognostic factors for patients with metastatic urothelial carcinoma treated with cisplatin and 5-fluorouracil-based regimens
Authors: Tsai Y. , Lin C. , Hsu C. , Huang K. , Huang C. , Cheng A. , Vogelzang N. J. , Pu Y. 
Published: March 2020

14583 Background: Combination of cisplatin and 5-fluorouracil (5-FU) has activity in metastatic urothelial carcinoma (UC). To identify patient subgroups most likely to benefit and compare survival to that in previously described patient series, long-term survival, as a function of known and suspected prognostic variables, was determined. Methods: The survival status of 79 patients with metastatic urothelial cancer treated on two phase II trials of cisplatin and 5-FU-based regimens was updated. P-HDFL regimen (n = 35) was cisplatin 35 mg/m2 IV 24hr D1, 8; 5-FU 2,600 mg/m2 and leucovorin 300 mg/m2 IV 24hr D1, 8, 15; repeated every 28 days (Cancer 2006, in press). TP-HDFL regimen (n = 44) was paclitaxel 70 mg/m2 IV 1hr D1, 8; cisplatin 35 mg/m2 IV 24hr D1, 8; 5-FU 2,000 mg/m2 and leucovorin 300 mg/m2 IV 24hr D1, 8; repeated every 21 days (Proc ASCO 22:407b, 2003 [abstr 1637]). Univariate and multivariate Cox proportional hazards models were constructed. Results: Karnofsky performance status (KPS) <80%, presence of visceral metastasis, and alkaline phosphatase ≥220 U/l are three significant poor prognostic factors for survival. The percentage of patients who harbored zero-risk, one- or two-risk, and three-risk categories was 27%, 61%, and 13%, respectively. Among patients with no risk factors, the median survival time was not reached yet after a median follow-up of 43.0 months. Patients with one or two risk factors had a median survival duration of 12.3 months (95% CI 8.6–16.0). Patients with all three risk factors had a median survival of 4.6 months (95% CI 1.4–7.9). There was a significant difference in survival between the three groups (P < .0001). Conclusions: Previously described prognostic factors, including KPS <80%, visceral metastasis, and alkaline phosphatase ≥220 U/l, for survival in metastatic UC were confirmed in patients treated with cisplatin and 5-FU-based regimen. No significant financial relationships to disclose.
Clinical course of patients with metastatic papillary renal cell carcinoma
Authors: Steiner T. , Roigas J. , Kirchner H. , Doehn C. , Heynemann H. , Siebels M. , Loening S. , Jocham D. , Fornara P. , Rohde D. , Stieff C. G. 
Published: March 2020

14591 Background: For a long time it has been discussed, whether patients (pts.) with metastatic papillary renal cell carcinoma (mRCC pap) demonstrate different behaviour compared to those with clear cell mRCC. Methods: Clinical data of 61 pts. with mRCC pap were retrospectively assessed at 8 treatment centres. Results: Median follow-up was 20 (1–114) months, median age at time of diagnosis was 62 (24–85) years. Men were affected predominantly (50/61 pts.; 82%). 21 pts. (34%) showed metastases at time of diagnosis. The remaining 40 pts. had metachroneous metastatic disease. Mean time to metastases development was 30.4 (3–143; median 16.5) months. Metastatic sites were: lung (37; 61%), bone (24; 38%), liver (20; 33%), lymph nodes (24; 38%). Local recurrences occurred in 17 pts. (28%). Others sites of metastatic disease were brain in 6 pts. (10%), peritoneal carcinosis in 5 pts. (8%) and others. A surgical approach was performed primarily in 11 pts. (18%): lung 2; local recurrence and lymphomas 7; liver 1; brain 1. 26/61 pts. with metastatic disease received an immuno- (interferon-a ± interleukin-2) or immunochemotherapy (in combination with vinblastine or 5-fluorouracile) as first line treatment. In total, 42/61 pts. (69%) received an interferon- or interleukin-based immunotherapy. No treatment at all was performed in 12 pts. (20%) because of poor performance status. 5/42 pts. (11.4%) achieved an objective response to immuno(chemo)therapy. In the Kaplan-Meier-analysis, median overall survival after diagnosis of metastatic disease was estimated to be 13 ± 1.5 (95% CI 9.9–16) months for the entire study group and 12 ± 2.5 (95% CI 7.1–16.3) from the beginning of systemic treatment. Conclusions: Clinical data of a large population of pts. with mRCC pap have been assessed in this retrospective analysis for the first time. Compared to pts. with clear cell mRCC, these patients are characterized by: I) more frequent local recurrences; II) lower remission rates to immuno(chemo)therapeutic approaches; III) poorer prognosis with regard to overall survival. These findings should be taken into account when planning future studies. No significant financial relationships to disclose.
The biologic therapy of prostate cancer using plasminogen activator inhibitor-1 (PAI-1)
Authors: Chen S. , Henry D. O. , Wong M. K. 
Published: March 2020

14596 Background: Treating prostate cancer through the expression of intrinsic biologic modifiers is a relatively unexplored aspect of prostate cancer therapy. Plasminogen Activator Inhibitor-1 (PAI-1) is expressed at low levels in prostate cancer cells. PAI-1 is both an anti-angiogenesis agent, and also potently inhibits tumor proteases responsible for tumor invasion and metastases such as uPA and tPA. Thus we hypothesized that stimulation of tumor endogenous PAI-1 would result in a particularly powerful and profound prostate cancer regression. We present proof-of-concept from our experimental models that demonstrate significant tumor regression in experimental prostate tumors and supports this hypothesis. Methods and Results: Human prostate adenocarcinoma (PC3 cell line) xenograft tumors engineered to conditionally express either PAI-1 or Green Fluorescent Protein (GFP, control) were used to test our hypothesis. Stable cell lines were created that conditionally express either GFP or PAI-1 under the regulation of a doxycycline-responsive promoter (Tet-On). Thus gene expression is switched on in the presence of doxycycline. PC3 tumors were inoculated and allowed to reach at least 200 mm3 in size whereby the tumor-bearing mice were given doxycycline-doped drinking water. Genes were significantly turned on within 48 hours as monitored by the appearance of a GFP signal in control mice. The induction of PAI-1 results in significant inhibition of tumor growth as compared to GFP control. Importantly, in vitro induction of PAI-1 expression in PC-3 has no direct effects on cell growth as compared to any PC-3 control. Histological analysis of these tumors revealed a rich nexus of fine angiogenic vessels at the interface between control tumors and surrounding stroma. PAI-1 secreting tumors were significantly smaller and were pale, bland, and lacked peritumoral vessels. Protease activity measured by in-situ zymography directly on these tumors revealed that this was significantly reduced in PAI-1 expressing tumors as compared to GFP controls. Conclusion: PAI-1 expression results in tumor inhibition through direct anti-angiogenic effects and inhibition of tumor protease activity. No significant financial relationships to disclose.
Use of zoledronic acid (ZA) and interleukin-2 (IL-2) to activate and expand Vγ9Vδ2 T cells for therapeutic use in patients with metastatic renal cell carcinoma (mRCC)
Authors: Malkovsky M. , McNeel D. G. , Wallace M. , Schell K. , Wilding G. , Eikhoff J. , Staab M. J. , Horvath D. , Straus J. , Liu G. 
Published: March 2020

14607 Background: Approximately 3–6% of human peripheral blood lymphocytes express the γδ T cell receptor (TCR). The majority of these cells express the Vδ2 TCR variable segment associated with the Vγ9 segment. Vγ9Vδ2 T cells can recognize phosphorylated nonpeptidic microbial metabolites and alkylamines. This recognition of phosphorylated molecules requires neither antigen uptake/processing, nor MHC class I/II expression, allowing for a rapid response to immune challenge. Aminobisphosphonates are a class of agents capable of activating human Vγ9Vδ2 T cells. Here we conduct a study using ZA with low-dose IL-2 in order to augment Vγ9Vδ2 T cells for therapeutic use in mRCC. Methods: Patients with immunotherapy naïve mRCC were treated with ZA (4 mg IV d1) with IL-2 (ranging from 1–7 MU/m2 SQ days 1–5, repeated weekly × 3, in 4 week cycles). Blood was collected at various timepoints between day 1 and 15 of the first cycle of therapy to assess the relative frequency, proliferative capacity, and cytolytic activity of each subjects’ Vg9Vd2 T cells. Clinical responses were assessed using RECIST criteria. Results: To date, 7 patients have received treatment on protocol. No objective clinical responses were observed by RECIST criteria but prolonged stable disease (with one minor response) was observed in 2 patients (on study for 280 and 224 days respectively) on this trial. A relative increase in Vγ9Vδ2 T cell frequency could be detected by day 8 of therapy including one patient with an increase in Vγ9/Vδ2 positive T cells from 9.6 to 19.4%. Results of the change in Vγ9Vδ2 T cell frequency, proliferative capacity, and cytolytic activity against RCC cell lines will be presented in detail. Conclusions: Modest amplification of Vγ9Vδ2 T cell frequency was seen; however, not to the degree appreciated in preclinical models. At present, we are planning a dose-titration of ZA with fixed dosed IL-2 in order to optimize this therapeutic strategy. The exploitation of Vγ9Vδ2 T cells as a therapy for mRCC is novel, and the current study suggests this approach deserves further evaluation. No significant financial relationships to disclose.
Urinary dysfunction appears to be the primary determinant of castration versus observation for prostate cancer patients with PSA failure
Authors: Zagory J. A. , Chang C. , Knight S. , Lyons E. A. , Bennett C. L. 
Published: March 2020

14621 Background: After undergoing definitive treatment for a primary localized disease, prostate cancer patients may experience a rise in their prostate specific antigen (PSA) levels. Treating PSA failure with hormonal treatment has many health related quality of life (HRQOL) implications, including urinary, bowel, sexual, and male hormonal problems. Predictors of choice between hormonal treatment versus watchful waiting have not been investigated. Methods: Patients were approached after consecutive rises in PSA levels (n = 31). Patients completed HRQOL and decision satisfaction questionnaires, and a literacy assessment. Results: Patients were between 56 and 85 years old; 55% were African American. 71% of African Americans and 50% of whites had low functional literacy. 58% of patients chose hormonal therapy to treat their PSA rise; 81% of patients reported urinary problems. All patients reported decision satisfaction (see Table). Factors associated with castration versus watchful waiting were primarily related to poor urologic function, and were not specifically prostate cancer related (dysuria, nocturia, urination frequency). Conclusions: Primary treatment of urinary dysfunction, rather than castration, should be evaluated as initial therapy for prostate cancer patients with PSA failure. [Table: see text] No significant financial relationships to disclose.
Zoledronic acid (ZA) to prevent bone loss during combined androgen blockade with finasteride (CAB+F) for clinically localized or recurrent non-osseous prostate cancer (PC)
Authors: Tucker S. , Binder RN S. , Chua RN C. , Houts PhD A. C. , Fortner PhD B. V. , Schwartzberg L. S. 
Published: March 2020

14628 Background: Androgen suppression (AS) is increasingly used as primary therapy for early PC and recurrent PSA-only PC. AS decreases bone mineral density (BMD), increases markers of osteoclastic and osteoblastic activity, and increases fracture risk. CAB+F is a maximal form of AS which has not been described in prospective trials. We present the first analysis of a prospective study of ZA to prevent bone loss in men receiving CAB+F. Methods: We performed a prospective non-randomized study of ZA in men receiving CAB+F for non-osseous PC. CAB+F consisted of 48 weeks of an LH-RH agonist and antiandrogen (bicalutamide or flutamide) plus finasteride 5 mg QD. Men received ZA 4 mg intravenous at entry and every 3 months. Calcium 1000 mg and calcitriol 0.5 mcg were given QD. Baseline and serial measures of osteocalcin (OC) and deoxypyridinoline (DPD) were assayed. Baseline BMD of the lumbar spine (LS) was measured by DEXA. Quality of life (QOL) was measured with a validated symptom-based scale for pen-based computers. Results: From 7/2004 through 12/2005, 26 men with PC met eligibility criteria and enrolled. ECOG status at entry was 0 for all. Mean age was 64 (range 46–81), mean PSA was 10.6 ng/mL (range 3.23–33.0) and median Gleason sum (GS) was 7 (range 5–9). Mean testosterone was 455 ng/dL. High risk PC (PSA > 20, or GS > 7, or T3 stage) was seen in 7/26 men. In preliminary analysis of men completing 48 weeks of CAB+F (n = 13), mean (±SD) LS BMD (gm/cm2) increased significantly from 1.245 (±0.170) to 1.425 (±0.198) (p = 0.002). Baseline mean OC (ng/ml) decreased from 7.69 (±0.20) to 2.50 (±1.48) and baseline mean DPD (nmol/mmol Cr) decreased from 6.75 (±5.72) to 4.20 (±2.03). All men achieved PSA < 0.1 by 24 weeks. Serial QOL data is significant for decreased sexual interest and mild fatigue compared with baseline. No grade 3 or 4 toxicities were seen. Expanded QOL and toxicity data will be described. Conclusion: ZA given at baseline and every 3 months in conjunction with maximal AS, CAB+F, significantly improves BMD of the lumbar spine and suppresses biochemical markers of both bone resorption and formation. No significant financial relationships to disclose.