bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of obesity and race in predicting recurrence rates after radical prostatectomy
Authors: Lee D. J. , Ritch C. , Desai M. , McKiernan J. M. 
Published: August 2020

5070 Background: Black men are twice as likely to die from prostate cancer compared to white men. Obese men are known to have higher mortality rates and recurrence rates, and blacks are 1.4 times as likely to be obese than white Americans. However, the relative contribution of BMI and race to biochemical failure (BCF) after radical prostatectomy (RP) has not been well-characterized. We examined the interaction of BMI and race in predicting BCF after RP. Methods: A retrospective analysis of the Columbia Urologic Oncology Database found that 3,736 consecutive men underwent RP between 1988 and 2008. 1,461 men had BMI and race data available. 213 (14.6%) were black men, 1,004 (68.7%) were white, 162 (11.1%) were Hispanic, and 82 (5.6%) were Asian. Overweight and obese men were defined as having a BMI > 25 kg/m2 and a BMI > 30 kg/m2, respectively. BCF was defined as a post-surgery PSA level >0.2 ng/mL on > 2 measurements. Cox regression methods were used to model the relationship between race, BMI and BCF. Results: The 1,461 men had a median age of 60 years, and median pre-operative PSA of 5.5. There was no significant difference in BMI among the four races (p = 0.58). The 5 year disease-free survival for black obese men was the lowest at 69%, compared to non-obese black (71%), obese white (80%), and non-obese white men (80%, p < 0.001). BMI did not have a significant impact on BCF. After adjusting for preoperative PSA level, tumor stage, and Gleason sum, race remained an independent predictor of BCF (HR = 1.65, p = 0.04). An analysis assessing the effect of an interaction between race and BMI demonstrated that hazard ratios for increased BMI did not differ significantly by race. Black men who were normal, overweight and obese were 2.0, 3.0 and 2.5 times more likely than white men to have BCF in the respective weight categories, but the differences were not significant. Conclusions: Black race is an independent predictor of biochemical failure after adjusting for pathologic factors. The impact of BMI on BCF did not vary among different races. However, BMI does contribute to the accurate estimation of the risk of BCF. These findings suggest that elevated BMI does not affect the BCF rates of black men more than in other races, and that other factors may influence the racial variability in disease-free survival and BCF risk. No significant financial relationships to disclose.
Independent validation of the 2002 UICC TNM staging system for papillary renal cell carcinoma in a multicenter cohort
Authors: Wulfing C. , Herrmann E. , Trojan L. , Schrader A. , Becker F. , Stähler M. , Haferkamp A. , Legal W. , Brenner W. , Hartmann A. ,   German Papillary Renal Cancer Study Group
Published: August 2020

5092 Background: Papillary renal cell carcinoma (pRCC) is the second most malignant histologic subtype in nephrectomy specimens. To date, the most recognized staging system to stratify renal cancer patients is the 2002 UICC TNM classification system. Its accuracy for predicting patient outcome for pRCC is unknown. Methods: From ten urologic institutions in Germany follow-up data on 675 patients with pRCC were collected. In most cases histologic slides were available and central pathologic review was performed. The Kaplan-Meier method was used to derive the cumulative cancer-specific survival. For multivariate analysis of prognostic factors, a Cox regression analysis was performed. Results: 498 (74.1%) patients had organ-confined tumor stages (≤pT2). Synchronous distant metastases in the entire group occurred in 58 (8.7%) patients and 69 (11.2%) others developed metastatic disease during follow-up. Cancer-specific survival (CSS) was significantly related to TNM stage and histologic grading in univariate as well as in multivariate analysis (all p < 0.0001). 5-year CSS in pT1b tumors (90.0%) was significantly shorter compared to pT1a tumors (98.3%) (p = 0.017). Patients with ≥pT3 were at high risk for metastases (50.6%), while metastatic disease associated with ≤pT2 tumors occurred in 7.8% (p < 0.0001). Once metastatic disease was present, prognosis was poor (5-year CSS: 7.2%). Age was associated with a worse prognosis in the subgroup of ≥pT3 tumors in univariate (p = 0.026), but not in multivariate analysis. Conclusions: The 2002 UICC TNM staging system is applicable for pRCC. Clinical and radiologic follow-ups should be offered in frequent intervals to patients with venous thrombus and/or locally advanced disease. The role of age remains unclear, but should not be underestimated at risk stratification after tumor resection. No significant financial relationships to disclose.
Safety and efficacy analysis of sunitinib (S), bevacizumab (B), and M-Tor inhibitors in metastatic renal cell cancer (mRCC) patients (pts) with renal insufficiency (RI)
Authors: Gupta S. , Parsa V. , Heilbrun L. , Smith D. , Dickow B. , Heath E. , Vaishampayan U. 
Published: August 2020

5108 Background: S, T (temsirolimus) and E (everolimus) are primarily metabolized in the liver, while the metabolism of B is unclear. There are limited data on the clinical toxicity profile and efficacy of these agents in pts with RI. Methods: The primary objective was to assess the safety and efficacy of S, B, T and E in pts with RI. Medical records of pts with mRCC at Wayne State University, treated on S, B, T or E were reviewed. Pts with a calculated creatinine clearance (CrCl) of ≤ 60ml/min [chronic kidney disease stage 3 or higher per K/DOQI guidelines by the National Kidney Foundation] were deemed to have RI. Data on safety and efficacy of the therapy were collected and analyzed with respect to renal function. Results: 19 of 51 (37%) pts had RI. Pts with RI had a higher median rise in blood pressure (BP) with S and B than pts with normal renal function. Patients with RI had an increased incidence of rash and higher dose interruption rates with m-TOR inhibitors. No major differences in toxicities including cardiac, thyroid, renal, lipid profile abnormalities or hyperglycemia were observed. Similar efficacy was seen in all groups. Conclusions: More than a third of pts with mRCC receiving targeted therapy have RI, hence highlighting the importance of evaluating tolerability of therapies in pts with RI. Therapy with S, B and T/E is well tolerated and efficacy appears to be maintained. Closer monitoring for hypertension is needed in pts receiving S and B. [Table: see text] No significant financial relationships to disclose.
Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma (mRCC) with severe renal impairment or on haemodialysis
Authors: Josephs D. H. , Hutson T. E. , Pickering L. M. , Larkin J. M. , Choueiri T. K. , Patel T. V. , Mcdermott D. F. , Powles T. , Harper P. G. , Chowdhury S. 
Published: August 2020

5109 Background: Sunitinib is currently a standard of care for the treatment of mRCC. Due to the inclusion criteria of clinical trials, no studies of sunitinib have enrolled patients with severe renal impairment or those undergoing haemodialysis, and thus further investigation of the effect of sunitinib in this population is required. Methods: Clinical databases were used to identify all patients with mRCC treated with sunitinib in five institutions internationally. Medical records were searched to identify only those patients with a creatinine clearance (CLcr) of <30ml/min or who had end stage renal disease (ESRD) requiring haemodialysis. Baseline characteristics, toxicity data and progression free survival (PFS) were collected. Results: 21 patients met inclusion criteria with 9 (43%) undergoing haemodialysis. Baseline characteristics include a median age of 62 years (range 44–80); 90% of patients had ECOG PS of 0 or 1; 38% of patients had > 2 metastatic sites and 86% had prior nephrectomy. The estimated median PFS of this cohort was 38 weeks (range 2–120) although progression has not yet been reached in 8 (38%) patients. PR or SD was observed as best response in 17 (81%) patients. The most common treatment-related adverse events (AEs) included fatigue, diarrhoea, hand foot skin reaction (HFSR), nausea and vomiting and rash. Grade 3 treatment related AEs including fatigue, HFSR, diarrhoea and rash occurred in a total of 7 (33%) of patients. Only one patient experienced grade IV toxicity (HFSR). Conclusions: These data suggest that patients treated with sunitinib who have severe renal impairment, or ESRD on haemodialysis, have a PFS that is comparable to patients with normal renal function. In addition sunitinib appears to be reasonably well tolerated in this group of patients. These preliminary results warrant confirmation in a larger cohort of patients. [Table: see text]
Cost implications of intravenous bevacizumab treatment in patients with renal cell carcinoma (RCC): A retrospective claims database analysis
Authors: Dial E. , Duh M. , Fournier A. , Antras L. , Rodermund D. , Neary M. P. , Oh W. K. 
Published: August 2020

5112 Background: Angiogenesis inhibitor (AI) therapies are promising novel treatments for patients with RCC. However, IV therapy may impose transportation burdens for patients, infection risk from IV catheters and increased costs. The incremental costs associated with IV vs. oral administration of selected AI therapies (oral sunitinib or sorafenib, or IV bevacizumab off-label) for the treatment of RCC were evaluated. Methods: Patients with ≥ 2 RCC claims (ICD-9 189.0, 198.0) were identified from a large US commercial health insurance claims database from 1/02 to 12/07. Patients receiving bevacizumab (N=109) were matched 1:1 to patients receiving sorafenib or sunitinib, and observed from their first AI therapy claim until the last treatment date. Inpatient, outpatient and pharmacy costs were calculated on a per- patient per-month (PPPM) basis over the treatment period. Cost comparisons between the IV AI group and each separate oral AI group were performed using multivariate Tobit regressions for each category separately, adjusting for age, gender, region, health plan, time from first RCC claim and first metastasis claim to treatment initiation. Results: Mean total medical cost was $13,351, $6,998, and $8,213 PPPM for bevacizumab, sorafenib, and sunitinib, respectively (p<0.05 for equality). Adjusted incremental total medical cost for the bevacizumab group was $5,045 PPPM higher than for sorafenib (p<0.05), and $4,902 PPPM higher than for sunitinib (p<0.05). Bevacizumab patients incurred higher incremental PPPM outpatient services cost by $7,687 and $7,995 compared to sorafenib and sunitinib, respectively (both p<0.05) largely driven by the cost of bevacizumab itself. Conclusions: Patients with RCC treated with bevacizumab incur an incremental $58,826 to $60,546 total medical cost per patient per year compared to those treated with sunitinib or sorafenib. Oral AI therapies may result in cost savings to patients and healthcare payers over IV therapies. [Table: see text] [Table: see text]
Radical prostatectomy in clinically localized prostate cancer—The risk of extraprostatic spread by NCCN risk group and its implications for adjuvant therapy: An analysis of 23,988 patients
Authors: Schreiber D. , Rineer J. , Olsheski M. , Vongtama D. , Wortham A. , Sura S. , Nwokedi E. , Han P. , Choi K. , Rotman M. 
Published: August 2020

5125 Background: Swanson et al recently reported an update of SWOG 8794 (ASTRO 2008, oral presentation) revealing a 10% absolute overall survival benefit at 15 years with adjuvant radiation therapy for patients with extraprostatic extension (EPE) or positive margins after radical prostatectomy (RP). In this population based analysis, we analyze and report on the pathologic rates of EPE or positive margins in clinically localized prostate cancer as well as how often these patients have received adjuvant radiation therapy. Methods: The Surveillance, Epidemiology and End Results (SEER) registry was used to identify patients between 2004–2005 with clinically staged T1-T2c prostate cancer who underwent RP. Patients were stratified using NCCN risk groups into low (T1c- T2a, PSA less than 10ng/ml, Gleason 2–6), intermediate (T2b, PSA 10–20ng/ml, Gleason 7), and high (T2c, PSA greater than 20ng/ml, Gleason 8–10). Results: 23,988 patients were identified: 6,314 in the NCCN low risk group (LR), 12,052 in the NCCN intermediate risk group (IR), and 5,622 in the NCCN high risk group (HR). Overall, 68.2% of patients had organ-confined disease with negative margins. However, the risk of EPE or positive margins increased with the NCCN risk group, PSA value, and Gleason score (see table ). Of those who met criteria for adjuvant radiation, 11.9% received the treatment: 4.7% of the LR group, 9.2% of the IR group and 18.9% of the HR group. Conclusions: This is, to our knowledge, the largest reported multi-institutional surgical series of clinically localized prostate cancer. Patients can use this data to be counseled on their risk of requiring adjuvant radiation based on their pre-treatment parameters. This data also reveals that nearly one third of all patients met the indications for adjuvant radiation, but only a small percentage of them received this treatment. [Table: see text] No significant financial relationships to disclose.
Initial phase II experience of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration-resistant prostate cancer (mCRPC)
Authors: Slovin S. F. , Beer T. M. , Higano C. S. , Tejwani S. , Hamid O. , Picus J. , Harzstark A. , Scher H. I. , Lan Z. , Lowy I. ,   Prostate Cancer Clinical Trials Consortium
Published: August 2020

5138 Background: IPI is a fully human, monoclonal anti-CTLA-4 antibody capable of enhancing anti-tumor immunity. In preclinical models, XRT releases tumor antigens and enhances anti-tumor activity of CTLA-4 blockade. In the dose escalation part of this Phase I/II trial 10 mg/kg dosing of IPI with or without prior priming by single fraction XRT was feasible. We now report initial phase II results. Methods: 45 patients (pts) with mCRPC and ECOG PS of 0–1 received 10 mg/kg q3 weeks (wks) X 4 of IPI in 3 groups: (1) IPI alone n=16, (2) IPI + XRT n=15 chemotherapy naïve (NoCHEMO), and (3) IPI + XRT n=14 chemotherapy experienced (CHEMO) pts. XRT (800 cGy) was given to up to 3 involved bony sites (GI tract sparing) just prior to starting IPI. PSA was monitored monthly, with scans q 3 months. Endpoints were to confirm safety and an initial assessment of activity. Results: 17 pts (38%) experienced 26 immune-related adverse events (irAEs) including diarrhea/colitis (12), rash/pruritus (6), hepatitis (4), endocrinopathy (4). 11 pts (24%) experienced 13 ≥ Grade 3 irAEs: GI (9; 20%) and hepatitis (4; 9%); all resolved with immunosuppression. 10 of 45 pts (22%; 95% CI 10–34%) had confirmed PSA declines ≥ 50% as follows in the table below. Median time to PSA decline was 5.7 wks (r 3 to 21 wks); median duration 23 wks (r 3 to 84+ wks). In one pt dosed with IPI alone, PSA ≤ 0.05 ng/ml, as well as a CR of bone, nodal and prostate lesions continue for 54+ and 84+ wks, respectively. Conclusions: irAEs in the 10 mg/kg cohorts are similar in type and rate to IPI in melanoma. irAEs and PSA declines occurred in chemotherapy naïve and post chemotherapy patients, and with or without XRT. Addition of XRT to 10 mg/kg is well tolerated. Time to response can be delayed, with a durable median response of 23 wks. Further study of IPI in mCRPC is warranted, with or without XRT as a potential immunosupportive maneuver to augment clinical responses to IPI. [Table: see text] [Table: see text]
A phase II study of patupilone in patients (pts) with metastatic castration- resistant prostate cancer (CRPC) who have progressed after docetaxel
Authors: Beardsley E. K. , Saad F. , Eigl B. , Venner P. , Hotte S. , Winquist E. , Ko Y. J. , Sridhar S. S. , Chi K. N. 
Published: August 2020

5139 Background: Chemotherapy for pts with CRPC who have progressed after docetaxel remains to be defined. Patupilone is an epothilone with broad spectrum pre-clinical activity including in taxane resistant models. Methods: Multicenter, 2-stage design. Pts with metastatic CRPC with progressive disease during or within 6 months of receiving docetaxel were eligible. Patupilone was initially given 10mg/m 2 IV every 3 weeks. PSA response rate (≥50% decline) was the primary endpoint (H0 = 15%, H1 = 25%, α = 0.1, β = 0.2). Secondary endpoints were measurable disease response, serial pain and analgesics scores, progression free survival (PFS) and overall survival (OS). Results: 83 pts were enrolled from March 2007-June 2008. 401 cycles administered (median 5, range 1–15). Baseline characteristics (range): median age 67 (47–85), PSA 212 (2.6–11520), hemoglobin 118 (89–160), median time to progression after docetaxel 1.0 months (0.0–6.0), number of prior chemotherapy regimens 1:2:3+ in 45:28:10 pts, ECOG PS 0–1:2 in 73:10 pts, disease in bone/lymph nodes/viscera in 76/47/14 pts respectively. In the first 6 pts, gastrointestinal serious adverse events (AE) occurred in 4 pts (diarrhea and vomiting) which lead to a dose reduction of patupilone to 8 mg/m2 for subsequent patients. Grade 3/4 related adverse events at this dose included fatigue (16%), diarrhea (13%) and anorexia (5%). There were no grade 3/4 hematologic AEs. In 78 pts evaluable for PSA response, PSA declines of ≥30% and ≥50% have occurred in 44/78 (56%) and 35/78 (45%) with a confirmed PSA response in 25 pts (32%). Partial response occurred in 5% and stable disease in 64% of 44 evaluable pts. Pain response (2 point decline on 6 point scale) occurred in 36 (51%) of 71 pts eligible for analysis. Median PFS for PSA and non-PSA outcomes (measurable disease/symptomatic progression or death) was 7.6 months (3.7–11.5) and 5.6 months (3.9–7.3) respectively. Follow up for OS is continuing. Conclusions: Patupilone 8 mg/m2 every 3 weeks was well tolerated and associated with encouraging PFS, PSA and pain responses in pts with docetaxel resistant/refractory disease. Further investigation of patupilone in this population is warranted. [Table: see text]
Results of a phase II study of picoplatin with docetaxel and prednisone in first-line treatment of castration-resistant prostate cancer (CRPC)
Authors: De Jager R. L. , Roman L. , Lopatkin N. , Karlov P. , Breitz H. , Earhart R. 
Published: August 2020

5140 Background: Picoplatin (Pico) was designed to overcome platinum resistance and has the potential for improved safety compared to other platinum agents. Previously, a PSA response rate of 25% was observed when Pico monotherapy was infused at 120 mg/m2 Q3W (N = 20). Recently, a 34-patient Phase I study was performed to investigate the safety and efficacy of Pico in combination with docetaxel (D) + prednisone (pred) as first-line therapy for metastatic CRPC. Picoplatin therapy was well-tolerated at a dose of 120 mg/m2 and 19 of 32 evaluable pts (59%) achieved a confirmed PSA response. Methods: 32 patients with chemotherapy-naïve CRPC and disease progression received Pico (120 mg/m2) and D (75 mg/m2) Q3W with pred 5 mg po bid for up to 10 cycles. PSA responses were defined as a reduction from baseline of at least 50% maintained for at least 4 weeks. CT and bone scans were also evaluated. Tumor response was measured using RECIST. Results: Patients received a median of 10 cycles (range = 1–10). Median baseline PSA was 340.8 ng/mL (range 5.6–3019). One pt had no baseline PSA data. Of the 24 patients with evaluable post-treatment PSA, 83% (95% CI 64–93%) had PSA decreases <50% of baseline, and in 8 of these (33% of the evaluable population), PSA reached normal levels (< 4 ng/mL). In the intent-to-treat population, the PSA response rate was 63% (95% CI 45–77%). 13 patients evaluated by CT scan had measurable disease; 6 pts had SD by RECIST, 4 had PD, and 3 were not evaluable. The most common adverse events were alopecia (36%), asthenia (32%), neutropenia (29%), increased creatinine (23%), and thrombocytopenia (19%). No neurotoxicity ≥ grade 2 was observed. Conclusions: Picoplatin was safely administered to patients with CRPC as 1st-line therapy at 120 mg/m2 Q3W with full doses of docetaxel and prednisone, resulting in a PSA response rate of 83% of evaluable patients. These results support further development of picoplatin as a novel combination with docetaxel for the treatment of CRPC. [Table: see text]
Cediranib (AZD2171) in docetaxel-resistant, castration-resistant prostate cancer (CRPC)
Authors: Karakunnel J. J. , Gulley J. L. , Arlen P. , Mulquin M. , Wright J. , Turkbey I. B. , Choyke P. , Figg W. D. , Dahut W. 
Published: August 2020

5141 Background: There is no standard therapy for prostate cancer patients who have progressed following docetaxel therapy. VEGF is implicated in tumor blood vessel formation and in disease progression in several solid tumors. Cediranib is an oral, small molecule inhibitor of receptor tyrosine kinases which influence VEGF. Methods: Patients must have clinical and/or radiographic evidence of progression on docetaxel with no limit on the number of prior chemotherapy regimens or radioisotopes. The starting dose is 20 mg daily, imaging is every 2 months. The primary objective is a 30% 6 month probability of progression free survival as determined by clinical (not by PSA rise alone) and radiographic criteria Simon two stage optimal design is being utilized with twelve patients enrolled in the first cohort. If 2 or more patients are progression-free at 6 months, the cohort will be expanded to 35 evaluable patients. Patients receiving cediranib were scanned by DCE-MRI pre- and post-treatment. A two compartment model was used to analyze the volume transfer. Results: Thirty-four of a planned 35 patients have been enrolled and 4 remain on active treatment (2–7 months). There have been 13 of 23 evaluable patients with tumor shrinkage and 4 have met the criteria for partial response. Decreases in lymph node metastases as well as in lung, liver and bone lesions have occurred. PSA levels have not corresponded well with imaging responses. Adverse events have been similar to other drugs in this class including hypertension, dysphonia and fatigue. Grade 3 toxicities included vomiting (2), prolonged QTc interval (1) and muscle weakness (3), weight loss (3), dehydration (4), fatigue (6), hypoxia (1), renal failure (1), transaminitis (3), and anorexia (1). There have been 30 patients who were evaluated by DCE-MRI. Targeted lesions included bone (17) and soft tissue (15). Conclusions: The safety profile and early activity makes cediranib a promising drug in CRPC post docetaxel. Preliminary data suggests that cediranib does have direct effect on the microcirculation and vasculature. Additional accrual is required to better characterize the response rate, the discrepancy between PSA and standard imaging changes and establish evidence of clinical correlation for DCE-MRI. No significant financial relationships to disclose.