bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes after transperineal template-guided prostate biopsy.
Authors: Hsi Richard A. , Moeller Randall James , Mitchell Marc , Bildsten Scott , Kozlowski Paul , Porter Christopher R. 
Published: February 2017

156 Background: To assess clinical outcomes after transperineal template-guided prostate biopsy (TTPB) including detection rates, pathologic features, clinical relevance and morbidity. Methods: Forty eight men underwent TTPB. All patients had at least one (range 1–4) prior negative transrectal ultrasound-guided (TRUS) prostate biopsy and no prostate cancer diagnosis. The mean pre-biopsy PSA of the entire group was 13.1 ng/ml (range 4.5–46.4). The mean number of cores sampled was 24.7 (range 22–28). Results: The rate of prostate cancer detection was 52% (25/48). Clinically significant prostate cancer, defined as intermediate (n=9) and high (n=11) risk disease using D’Amico criteria, was found in 80% (20/25) of positive biopsy cases. Seventy-two percent of all positive biopsy cores were anatomically located in the anterior or anterolateral positions within the prostate. Urinary retention requiring catheterization after the procedure developed in 6% (3/48) of patients. No patients developed rectal or infectious complications after TTPB. Conclusions: TTPB is a well tolerated procedure resulting in a significant rate of cancer detection. Biopsies were frequently found to be positive in the anterior half of the prostate. Clinically significant disease was found in a high percentage of patients.
Stepwise examination of prostate clinical trials participation to reduce accrual barriers.
Authors: Olatoye Dare , Carducci Michael Anthony , Kanarek Norma 
Published: February 2017

157 Background: Adequate and representative enrollment in therapeutic clinical trials is important to an NCI cancer center. Clinical trial participation is a string of 6 sequential patient and physician decisions beginning with an available therapeutic trial to enrollment in the trial. Opportunities for participation may be lost at any one of these steps. The objective of this study was to calculate transitional probabilities that measure patient, especially minority patient, accrual to clinical trials at the Sidney Kimmel Comprehensive Cancer Center and to describe the barriers for those dropping out at each step. Methods: Records for “first visit” medical oncology patients seen by three SKCCC physicians from January to April 2010 were abstracted. Prostate cancer case reports from the hospital cancer registry and a medical record review provided age, race, Hispanic ethnicity, place of residence, tumor characteristics, and prior treatment history. At each transition step, we calculated the proportion of patients who remained enrollable. Results: Overall, prostate cancer clinical trial participation was 17% (16/94). Minority accrual was similar to Caucasian accrual at 19% and 17% , respectively. Retention at each step of trial participation was highest for “discussed” (98%), “enrolled” (94%), “eligibility” for available trials (79%), and “consented” (71%). Two bottlenecks were qualitatively identified: “trial availability” (65%) and “patient interest” (51%). Forty-two percent of those for whom there was no trial available were older than 70 years and 33% were patients with rising PSA after local therapy and hormone-naïve. The “patient interest” step was shaped primarily by disinterest due to distance to SKCCC (83%). Conclusions: For prostate cancer patients, recruitment to medical oncology clinical trials is robust. Minority patients however are only 17% of all patients seen and half drop out when no trial is available and half of those remaining judged distance to be a problem (hence, no interest). This study approach has clarified which factors are likely to be barriers to participation and is likely useful to making adjustments that can reduce identified barriers by adding to trial portfolio as an example.
Phase I trial of cabazitaxel plus cisplatin in patients with advanced solid tumors.
Authors: Lockhart Albert C. , Sundaram Shankar , Sarantopoulos John , Mita Monica M. , Lane Alex R. , Moseley Jennifer L. , Dedieu Jean-Francois , Stash Diane , Zhi Xin , Mazuir Florent , Mita Alain C. 
Published: February 2017

162 Background: Cabazitaxel (Cbz) is a novel taxane with broad in vivo efficacy in taxane-sensitive and -resistant tumors. Clinical activity of Cbz was confirmed in the Phase III TROPIC trial ( NCT00417079 ); Cbz significantly improved overall survival compared with mitoxantrone in patients (pts) with metastatic castration-resistant prostate cancer whose disease had progressed during or after a prior docetaxel-containing regimen. Therapeutic synergism of Cbz/cisplatin (Cis) has been demonstrated in tumor-bearing mice. Methods: The primary objective in part 1 of this Phase I study ( NCT00925743 ) was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of Cbz/Cis. Secondary objectives were safety, pharmacokinetics (PK) and efficacy. The primary objective of part 2 was to determine the antitumor activity at the MTD. Eligible pts were ≥ 18 yrs, ECOG PS ≤ 1, with confirmed metastatic or unresectable solid tumors for which Cis therapy was considered appropriate. A 3 + 3 dose escalation with a starting dose (level 0) of 20/75 mg/m2 (Cbz/Cis), administered IV Q3W, was used. The MTD was the highest dose at which 0/3 or ≤ 1/6 pts experienced a DLT in Cycle 1. Results: Pts (N = 25; 10 in part 1; 15 in part 2) with a median age of 56 yrs were enrolled. The most frequent primary tumors were lung (n = 4), prostate, ovary and pancreas (each n = 2). 2 of 6 evaluable pts experienced a DLT at dose level 0 (Grade 3 acute renal failure; febrile neutropenia). The MTD was 15/75 mg/m2 as no DLTs were observed. Eighteen pts were treated at the MTD and 60 cycles were administered (median = 3; range 1–8). The most frequent non-hematologic treatment-related adverse events (all Grade/Grade 3–4) were nausea (78%/22%), vomiting (72%/11%), fatigue (61%/17%), anorexia (67%/11%) and diarrhea (44%/0%). Incidence of Grade 3–4 neutropenia was 78% and 1 pt had febrile neutropenia. No PK interactions between Cbz and Cis were observed. Stable disease was seen in 11 pts. No objective responses were reported. Conclusions: The MTD of Cbz/Cis was 15/75 mg/m2. The combination had a manageable safety profile consistent with that of a platinum/taxane combination. No PK interactions were seen. Further investigations into the combined treatment combination are planned.
A cohort compassionate-use program with cabazitaxel plus prednisone for patients with metastatic castration-resistant prostate cancer: Interim results.
Authors: Bavbek Sevil E. , Malik Zafar , Di Lorenzo Giuseppe , Scholz Hans-Jorg , van Oort Inge M , Ng Siobhan , Ozguroglu Mustafa , Gerritsen Winald R. , Mueller Stefan , Marttila Timo , Anton-Aparicio Luis M. , Albers Peter , Gschwend Juergen , Bensfia Samira , Ecstein-Fraïssé Evelyne B , Bracarda Sergio , Heidenreich Axel 
Published: February 2017

172 Background: In the Phase III TROPIC trial ( NCT00417079 ), cabazitaxel/prednisone (CbzP) improved overall survival compared with mitoxantrone/prednisone in patients (pts) with mCRPC who had progressed on or after prior docetaxel (D) (HR 0.70; P < 0.0001). The survival benefit observed supported the establishment of 2 programs (based on local regulations): a compassionate use (CUP) and an early access program (EAP) ( NCT01254279 ). Methods: The aims of both programs are to provide drug to pts with mCRPC who may benefit from CbzP prior to commercial availability, and further evaluate CbzP safety profile. Total enrollment for both programs is targeted to be 1,600 pts from 250 centers in Europe, Asia, Latin America and Canada. Eligible pts will receive CbzP (25 mg/m2 Q3W plus oral prednisone 10 mg daily) until disease progression, death, unacceptable toxicity or physician/pt decision. Results: Baseline characteristics and safety data are available for the first 399 pts. Median age was 68 yrs (range 43–89); 90.2% were ECOG PS 0–1. Median cumulative dose of prior D was 675 mg/m2 (median 9 cycles). For pts whose disease progressed following D, the median time from last dose of D to progression was 4 months; 53.3% of pts experienced disease progression either during or < 3 months after D. 61% of pts had ≥ 2 metastatic sites; the most common were bone (93.2%) and regional lymph nodes (34.4%). A median of 4 cycles of CbzP was administered and 4 pts received ≥ 10 cycles. Median relative dose intensity was 99.2% (range 80.1–104.9). G-CSF was administered to 34.3% of pts in Cycle 1 (6.3% therapeutic, 26.6% prophylactic). Overall, 71.4% of pts experienced adverse events (AEs) (all grades) considered related to study drug. The most common Grade 3–4 AEs included neutropenia 11.3%, febrile neutropenia 6.3%, anemia 2.8%, fatigue 2%, neutropenic sepsis 1.8%, vomiting 1.3% and diarrhea 1%. 8 (2%) treatment-related deaths were reported. Conclusions: The CUP/EAP programs provide additional safety data for CbzP in a routine clinical practice population of pts with mCRPC. Treatment with CbzP was tolerable, with a manageable toxicity profile consistent with the data reported for the TROPIC trial.
Cardiovascular mortality following short-term androgen deprivation in clinically localized prostate cancer: An analysis of RTOG 94-08.
Authors: Efstathiou Jason Alexander , Paulus Rebecca , Smith Matthew R. , Jones Christopher U. , Leibenhaut Mark H. , Husain Siraj M. , Rotman Marvin , Souhami Luis , Sandler Howard Mark , Shipley William U. 
Published: February 2017

18 Background: Androgen deprivation therapy (ADT) is associated with greater risk of diabetes and coronary heart disease in men with prostate cancer but there is significant controversy surrounding its potential impact on cardiovascular mortality especially among men with lower rates of cancer-specific death. We assessed the relationship between ADT and mortality in a large randomized trial of men treated with or without short-course ADT and radiation therapy (RT) for clinically-localized prostate cancer. Methods: Between 1994-2001, 1979 eligible men (median age 71) with clinically-localized (T1-2, PSA<20) prostate cancer were enrolled on a phase III trial (RTOG 94-08) and randomized to RT and 4 months of neoadjuvant/concurrent ADT or RT alone. Fine-Gray proportional hazards model was used to evaluate the relationship between treatment arm and mortality (disease-specific and cardiovascular). Covariates included PSA, Gleason score, T-stage, age, race, weight, prevalent cardiovascular disease (CVD), diabetes (DM), and hypertension. Results: After a median follow-up of 8.2 years, use of ADT improved overall and disease-specific survival but there was no ADT-related increase in cardiovascular mortality or non-prostate cancer death. There were a total of 191 cardiovascular-related deaths. At 10-years, cardiovascular mortality for men treated with RT+ADT was 9.8% vs 10.7% for men treated with RT alone. In multivariate analyses, treatment arm was not significantly associated with an increased risk of cardiovascular mortality [adjusted hazard ratio (HR)=0.93, 95% confidence interval (CI) 0.69-1.26, p=0.64]. Traditional cardiac risk factors, including prevalent CVD and DM, were significantly associated with greater cardiovascular mortality. Results were similar when limiting analyses to patient subsets at high risk for cardiovascular mortality and at low risk for disease-specific mortality. Conclusions: Use of short-course ADT improves overall and disease-specific survival but does not appear to increase cardiovascular mortality in men with clinically-localized prostate cancer. Supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from NCI.
Does low-risk prostate cancer detection change with repeat biopsies?
Authors: Najari Bobby B. , Rink Michael , Hansen Jens , Heuer Roman , Eichelberg Christian , Ahyai Sascha A. , Haese Alexander , Steuber Thomas , Heinzer Hans , Fisch Margit , Kluth Luis A. , Huland Hartwig , Graefen Markus , Scherr Douglas , Shariat Shahrokh F. , Chun Felix K. 
Published: February 2017

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]
Neuroendocrine prostate cancer (NEPC) after androgen deprivation therapy (ADT): Clinical characteristics.
Authors: Akhtar Naveed Hassan , Beltran Himisha , Afzal Muhammad Zubair , Ecker Caryn , Nanus David M. , Tagawa Scott T. 
Published: February 2017

190 Background: NEPC is an aggressive variant of PC that may arise de novo or, more commonly, from existing prostate adenocarcinoma following the use of ADT. With additional agents targeting the AR signaling pathway, NEPC transformation may become more commonly clinically significant. Methods: With IRB approval, we retrospectively identified 48 metastatic (met) PC patients (pts) who met NEPC (or anaplastic) criteria for trial enrollment: a) PC with >50% immunohistochemical (IHC) staining for NE markers chromogranin (CgA), synaptophysin, or neuron specific enolase (NSE) OR Histological/cytological confirmed adenocarcinoma with clinical progression despite medical/surgical castration and at least one of the following: b) Predominant liver or brain mets c) Serum CgA > 5x upper limit of normal (ULN) or NSE > 2x ULN d) Short interval (<6 months) to development of CRPC following ADT. Results: Overall 48 pts met the criteria of NEPC. All pts received prior ADT, 54.2% received prior chemotherapy (84.6% docetaxel). The table demonstrates overall and subgroup demographics and survival from time of NEPC diagnosis. One pt with a history of long-term ADT including abiraterone after docetaxel demonstrated complete transformation to small cell phenotype, losing AR, PSA, PSMA, and Erg expression on IHC, only retaining FISH evidence of Erg rearrangement (along with AURKA and MYCN amplifications), confirming prostate origin of his emergent liver and lung metastases. Conclusions: NEPC arising from prostatic adenocarcinoma is an emerging issue, leading to one of the most lethal forms of PC. As we further refine clinical and molecular diagnostic criteria, therapeutic studies targeting this population warrant further exploration. [Table: see text]
Biochemical outcomes for patients with intermediate-risk, organ-confined prostate cancer treated with I-125 interstitial brachytherapy monotherapy.
Authors: Tran Anna Thi Huyen , Mandall Paula , Swindell Ric , Hoskin Peter , Bottomley David , Wylie James 
Published: February 2017

192 Background: Treatment with low dose rate brachytherapy (LDR-BT) monotherapy is well established for low risk prostate cancer. The routine use of LDR-BT in intermediate risk (IR) is more controversial and is often combined with additional external beam radiotherapy (EBXRT). We report the biochemical outcome of a large cohort of patients with IR disease treated with LDR-BT monotherapy. Methods: A multi-institutional prospective database identified 615 patients with IR prostate cancer treated with I-125 interstitial BT between 2003–2007. IR was defined using Memorial Sloan-Kettering Cancer Centre (MSKCC) definition of either T2b, or Gleason score (GS) 7 or raised initial PSA (iPSA) 10.1-20ng/ml. Patients receiving additional EBXRT were excluded. Biochemical failure was defined by both ASTRO (3 rises past nadir) and Phoenix criteria (nadir plus 2). Kaplan-Meier methods were used to estimate biochemical no evidence of disease rates (bNED) and univariate analyses used to identify potential prognostic factors. Results: The median age was 64 years (range 49–82). Forty-three patients had stage T2b, 180 had iPSA 10.1-20 and 392 had GS 7 disease. Only 108 received androgen deprivation therapy (ADT) prior to implant. Median follow up was 5.0 years. The 5-year bNED rates (95% confidence interval) by ASTRO are 85.5% (82.0–88.3%) and for Phoenix 83.7% (80.0–86.7%). Use of ADT, GS 3+4 versus 4+3, and dosimetric indices were not significant prognostic variables. When stratified by risk factor (T2b, GS7 or raised iPSA) raised iPSA correlated to poorer outcome only by Phoenix criteria (by Phoenix p=0.001, by ASTRO p=0.311). Conclusions: We have demonstrated good biochemical control for IR patients treated with LDR-BT alone. No additional benefit was seen with the use of ADT. We believe LDR-BT alone is an effective treatment option in selected IR prostate cancer patients with comparable outcome to other treatment modalities such as surgery or EBXRT.
Urinary TMPRSS2: Use of ERG and PCA3 to predict tumor volume and Gleason grade in an active surveillance cohort—Results from the Canary/EDRN Prostate Active Surveillance Study.
Authors: Lin Daniel W. , Newcomb Lisa F , Brown Elissa C , Brooks James D , Carroll Peter , Feng Ziding , Gleave Martin E. , Lance Ray , Sanda Martin G. , Thompson Ian Murchie , Wei John , Nelson Peter 
Published: February 2017

2 Background: Active surveillance is an increasing alternative for the management of low risk prostate cancer; however, there is a crucial need for better biomarkers to distinguish men with indolent versus aggressive disease. Both PCA3 and TMRPSS2-ERG (T2-ERG) are biomarkers that show promise in that they may be associated with more aggressive disease. This study examines the correlation of these biomarkers with higher volume or grade cancer in an active surveillance cohort. Methods: Post-DRE urine was collected prospectively as part of the multi-institutional Canary/EDRN Prostate Active Surveillance Study (PASS). PCA3 and T2-ERG levels were analyzed in urine collected from 401 men at study entry. Many of the men had undergone previous biopsies after initial prostate cancer diagnosis, and 20% of the urine specimens were associated with a negative serial biopsy. Biomarker scores were correlated to clinical and pathologic variables, including tumor volume - measured by percent of biopsy core involvement - and Gleason score, using non-parametric and univariate analyses. Results: Both PCA3 and T2-ERG scores were significantly associated with higher volume disease. For negative repeat biopsy, 1-10%, 11-34%, >34% positive cores, median (95% CI) PCA3 scores were 27 (24-31), 26 (22-33), 40 (29-51), 47 (26-90), p = 0.003 [Kruskal Wallis test (KW)], and median T2-ERG scores were 5 (2-8), 9 (4-14), 21 (14-40), 23 (4-115), p < 0.0001 (KW). Both PCA3 and T2-ERG scores were also significantly associated with presence of higher grade disease. For negative biopsy, Gleason 5 - 6, and Gleason >7, the median PCA3 scores were 27 (24-31), 31 (27-35), 48 (31-92), p = 0.02 (KW), and median T2-ERG scores were 5 (2-8), 14 (9-18), 29 (13-78), p = 0.001 (KW). The odds ratio for a positive biopsy versus a negative biopsy (ref) on modeling was 1.37 (1.04-1.81), p = 0.02 for PCA3 and 1.30 (1.12-1.51), p = 0.0006 for T2-ERG. Conclusions: Both PCA3 and T2-ERG appear to stratify risk, for men on active surveillance, of having aggressive cancer as defined by tumor volume or Gleason score and may have clinical applicability in selecting men with low volume/low grade disease for active surveillance.
Use of VEGFR1 expression in benign pelvic lymph nodes to predict biochemical recurrence in patients with high-risk prostate cancer.
Authors: Pal Sumanta Kumar , Zhang Wang , Deng Jiehui , Liu Yong , Reckamp Karen L. , Liu Xueli , Nelson Rebecca A. , Wilson Timothy G. , Lau Clayton , Yu Hua , Figlin Robert A. 
Published: February 2017

205 Background: High-risk prostate cancer (PCa) is a heterogeneous disease, and biomarkers that accurately predict clinical outcome within this subset are lacking. The pre-metastatic niche (PMN) represents one possible biomarker—this harbinger of future metastasis may be characterized by infiltration of VEGFR1+ cells [Kaplan et al Nature 139:820, 2005]. Given the predilection of PCa to spread to nodal sites, the association between VEGFR1 expression in benign pelvic lymph nodes and clinical outcome was examined. Methods: The City of Hope Prostate Cancer Registry (COH PCR) was used to identify 46 patients with high-risk PCa (baseline PSA > 20, pT3a-4 disease, or biopsy Gleason 8–10) who had undergone radical prostatectomy and pelvic lymph node dissection (PLND). The COH PCR prospectively collects clinical data associated with patients undergoing prostatectomy at the institution, and warehouses available clinical specimens. Benign tissue specimens derived from PLND were acquired for each patient, and were stained for VEGFR1 expression. VEGFR1+ cell clusters were counted within 8 distinct 40x fields, and the cluster count was averaged. Results: VEGFR1+ clustering in benign PLND specimens was a significant predictor of biochemical recurrence on multivariate Cox proportional hazards analysis, and outperformed other variables including established prognostic factors such as age, extracapsular spread, seminal vesicle invasion, and the aforementioned high-risk features. Patients with increased VEGFR1+ clustering pelvic lymph node tissue had a shorter interval to biochemical recurrence (HR 0.18, P<0.10). Conclusions: These preliminary results indicate that increased VEGFR1+ cell clustering in benign nodal tissue may predict poorer clinical outcome in patients with high-risk PCa. VEGFR1+ cells (a purported constituent of the PMN) represents a targetable entity. A randomized, phase II study employing axitinib (VEGFR1 IC50=1 nM) as neoadjuvant therapy in patients with high-risk PCa is nearing initiation at City of Hope ( NCT01385059 ).