bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary safety results of an Italian early-access program (EAP) with cabazitaxel plus prednisone (CbzP) in patients with docetaxel-refractory metastatic castration-resistant prostate cancer (mCRPC).
Authors: Bracarda Sergio , Di Lorenzo Giuseppe , Gasparro Donatello , Marchetti Paolo , Boccardo Francesco , Martoni Andrea , Carteni Giacomo , Fornarini Giuseppe , Baldazzi Valentina , Dogliotti Luigi , Messina Caterina , Sisani Michele 
Published: February 2017

253 Background: A significant number of docetaxel (D) refractory mCRPC patients (pts) have a life expectancy of > 15 months and ask for additional efficacious treatments. In the phase 3 TROPIC trial treatment of mCRPC patients with CbzP who progressed during or after docetaxel resulted in a statistically significant overall survival benefit compared with mitoxantrone / prednisone (Lancet 2010). This survival benefit supported establishment of a global early access program (EAP), allowing pts with mCRPC to have access to the drug prior to its commercial availability. Here we describe preliminary safety results from the EAP in Italy. Methods: We report here the data of the first 16 mCRPC patients (out of the 123 enrolled by 19 Italian centers until Sept 2011 in EAP) treated with Cbz (25mg/m2 Q3W) plus P(10mg bid). Results: Pts were median age 73.5 years (>75 years 38%), ECOG PS-0 81.3% and had received a median of 7 prior cycles of D (median cumulative D dose 562.5mg). Median time from last D dose to inclusion was 7.1 months. Overall, 62.5% (10 Pts) had 2 or more metastatic sites (bone 94%, regional/distant lymph nodes 25% and 44%, lung 12.5%, other sites 19%). A limited number of relevant adverse events (AE) were observed. All grade AEs were seen in 14/16 pts (81.3%), with 4/16 pts experiencing grade 3/4 leukopenia, 8/16 pts grade 3 - 4 neutropenia, one patient with febrile neutropenia and one with hypertransaminasaemia. Grade 1-2 asthenia and fatigue were experienced respectively by 2 pts. No grade 3 / 4 diarrhea, vomiting or constipation were observed and no AEs results in death. All pts received at least 2 cycles of CbzP (2÷5) and only one patient permanently discontinued treatment (disease progression). Conclusions: This preliminary analysis of Italian pts enrolled in the EAP provides real world safety data and suggests a good safety profile of cabazitaxel even in heavily pretreated pts, which is in agreement with Italian experience in TROPIC. Results of the entire Italian cohort with a longer follow-up will be presented.
Meta-analysis of impact of circumcision and vitamin D on occurrence of prostate cancer: Could they act by suppressing anaerobes colonizing areas of prostatic proliferative inflammatory atrophy?
Authors: Oliver R. 
Published: February 2017

259 Background: There is evidence that some false positive PSA tests can reflect prostatic inflammation that leads to Proliferative Inflammatory atrophy (PIA) that promotes malignant change. Report from circumcision trials in Africa suggest that dominant bacterial flora in un-circumcised men was anaerobes. As circumcised men have a lower incidence of PC this presentation reviews the literature on lack of circumcision and that on Vitamin D deficiency and as a cause of diminished host surveillance that could have potential to synergise as causes of PC. Methods: Three papers reporting incidence of PC in Jewish and non-Jewish men undergoing prostate biopsy for prostate symptoms and 7 series reporting case controlled studies published between 1952 and 2001 have provided data on circumcision and PC risk. There were 10 papers referred to in the IARC 2008 report on plasma 25-hydroxyvitamin D and PC. These have been reviewed together with 8 more published from 2008-10 and 3 that have examined impact of an index of life-time sun exposure on PC risk. Results: The 2 of 3 series of prostate biopsy reported 1951-65 demonstrated significant excess and 1 a non-significant excess of PC in the non-Jewish population. Of the 7 case controlled reported from 1971-2001, only 1 reported significant (OR 1.38) and 1 non-significant (OR 1.15) excess of lack of circumcision in those with prostate cancer, the remaining 6 studies having an excess cancer in those who have been circumcised (OR 0.50 – 0.82 pooled risk 0.70). Only 1 of the 18 plasma 25-OH Vit D series showed significant reduction of PC overall (6 did have reduction in prognostic subsets though 2 had higher incidence in the same sub-groups. In contrast all 3 series that have examined an index of life-time sun exposure showed significant reduction of PC (OR 0.18, 0.32 and 0.52 n= 850). Conclusions: The inconsistencies in the circumcision data suggest that it is not the surgery alone but the confounding variable of the hygiene rules that at least contribute to the reduced PC in Jewish men, and mirrors the similar differences seen in the protective value against AIDS of circumcision in Xhosa African and Asian Muslim men.
Receipt of aggressive therapies for muscle-invasive bladder cancer: Results from the National Cancer Data Base.
Authors: Gray Phillip J. , Fedewa Stacey A. , Shipley William U. , Efstathiou Jason Alexander , Virgo Katherine S. , Zietman Anthony L. 
Published: February 2017

272 Background: Over 17,000 patients are diagnosed with muscle-invasive bladder cancer (MIBC) in the United States each year. Despite its lethal potential, emerging data has suggested that many patients do not receive aggressive therapy consistent with established practice standards. Using data from American College of Surgeons Commission on Cancer accredited facilities, we seek to characterize treatment patterns for patients with MIBC according to demographic, clinical, pathologic and facility variables. Methods: 28,691 adult patients diagnosed with MIBC (stages II-IV), excluding those with T4b tumors or distant metastases between 2004 and 2008 were selected for analyses from the National Cancer Database. Treatments included radical or partial cystectomy +/− chemotherapy (CT), chemoradiotherapy (CRT), radiotherapy (RT) or CT alone and surveillance. Aggressive therapy (AT) was defined as any open surgery or RT with a total dose ≥50 Gy. Determinants of AT were assessed by multivariate generalized estimating equations accounting for facility clustering. Results: 52.5% of patients received AT (45% were treated surgically while 7.5% received CRT or RT), 11.7% received palliative CT or RT, and 25.9% received surveillance only. Receipt of AT decreased significantly with advancing age (OR 0.29 for age >80 vs. 18-59, p<.001). AT was also received less frequently by minorities (OR 0.72 for blacks p<.001), the uninsured (OR 0.72, p<.001), Medicaid-insured patients (OR 0.81, p=.006) and by those patients treated at low-volume centers (OR 0.63 vs. high-volume, p<.001). Receipt of AT increased with more advanced stage (OR 2.33 for stage III vs. stage II, p<.001) and in patients with non-urothelial histology (OR 1.32 and 1.50 for squamous and adenocarcinoma histology respectively, p<.001). Hydronephrosis was associated with decreased use of AT (OR 0.70, p<.001). Conclusions: Aggressive therapies for MIBC are received less frequently by the elderly and those with historically poorer socioeconomic status. These data indicate a significant unmet clinical need for physician education regarding appropriate selection of patients for cystectomy and RT-based bladder sparing therapy.
Relationship between high microRNA-200C expression and the risk of death from disease in muscle-invasive urothelial carcinoma of the bladder.
Authors: Navai Neema , Williams Michael Brandon , Wen Sijin , Siefker-Radtke Arlene O. , McConkey David James , Dinney Colin P.N. , Adam Liana 
Published: February 2017

279 Background: Bladder cancer represents both a common and highly morbid disease with limited tools for prognostication. Recently molecular studies have led to promising targets to inform disease behavior, including microRNAs (miRNA). miRNAs are non-coding RNAs, with widespread effects on cellular function. Our group has demonstrated that the miR200 family members play an integral role in epithelial to mesenchymal transition (EMT) via an inverse relationship with ZEB1 and a direct relationship with E-cadherin. EMT is seen as a necessary step for invasion and metastasis, however, studies have indicated a significant role for mesenchymal to epithelial transition (MET) to drive proliferation after cells have reached metastatic locations. Members of the miR200 family have been shown to induce MET and we hypothesize that miR200c, as a surrogate marker for MET, and will predict disease survival in muscle invasive urothelial carcinoma (MIUC). Methods: A clinically diverse sample set was obtained consisting of 101 unique specimens upon which real-time PCR miRNA analysis was performed. Regression tree analysis and best-fit modeling was used to establish the most discriminating relative miR200c expression level to predict disease specific survival. Fisher exact test was carried out to compare clinical variables, Kaplan-Meier estimate of survival distribution based on miR200c expression and univariate log-rank test was used to compare survival distributions between groups. Multivariate analysis was done via the proportional hazards model. A p-value of <0.05 was considered significant for all statistical analyses. Results: Patients with high miRNA200c had significantly more deaths (69 vs. 47%). In multivariable analysis of patients with MIUC miR200c expression was associated with the highest risk of death (RR 2.7). Lymph node involvement (RR 2.0) and age > 65yrs (RR 2.4) were also strong predictors of survival. High miR200c had lower median survival for all patients (59 vs 16 months; p = 0.039) and those with MIUC (41 vs 8 months; p = 0.0004). Conclusions: High miR200c expression is associated with a higher risk of death from bladder cancer in patients with muscle invasive disease.
Bladder cancer patterns of pelvic failure: Implications for adjuvant radiation therapy.
Authors: Baumann Brian Christopher , Guzzo Thomas J. , He Jiwei , Vaughn David J. , Keefe Stephen Michael , Vapiwala Neha , Deville Curtiland , Bekelman Justin E. , Tucker Kai , Hwang Wei-Ting , Malkowicz S. Bruce , Christodouleas John Paul 
Published: February 2017

293 Background: Local-regional recurrences (LF) after radical cystectomy with or without chemotherapy are common in patients with locally advanced disease. Adjuvant radiation (RT) could reduce LF, but toxicity discouraged its use. Modern RT with reduced morbidity has rekindled interest but requires knowledge of pelvic failure patterns to design appropriate clinical target volumes. Methods: 5-yr LF rates after radical cystectomy plus pelvic lymph node dissection with or without chemotherapy were determined for 8 pelvic sites among 442 patients with urothelial carcinoma of the bladder. The impact on the pattern of failure of pathologic stage, margin status, nodal involvement, and extent of node dissection was assessed using competing risk statistical methods. The percentage of patients whose sites of LF would be completely encompassed within various hypothetical clinical target volumes for post-operative radiation were calculated. Results: Stage pT3-4 patients had higher 5-yr LF rates in virtually all pelvic sites compared to pT0-2 patients. Among pT3-4 patients, margin status significantly altered the pattern of failure while extent of node dissection and pathologic nodal involvement did not. Stage pT3-4 patients with negative margins failed predominantly in the iliac/obturator nodes. Failures in the cystectomy bed and presacral region were significantly higher in pT3-4 patients with positive rather than negative margins. 76% of pT3-4 patients with negative margins who failed would have had all sites of LF included within clinical target volumes encompassing the iliac/obturator nodes, but only 57% of pT3-4 patients with positive margins would have their LF sites covered by such target volumes. Including the cystectomy bed and presacral region in the clinical target volume when margins were positive increased the percentage of encompassed failures to 91%. Conclusions: In adjuvant RT protocols, the obturator and iliac regions should be targeted in pT3-4 tumors with negative margins; coverage of presacral region and cystectomy bed is advised for pT3-4 with positive margins.
Neoadjuvant chemotherapy for muscle-invasive bladder cancer at the University of Southern California.
Authors: Fairey Adrian Stuart , Daneshmand Siamak , Dorff Tanya B. , Dorin Ryan Paul , Leiskovsky Gary , Quinn David I. , Schuckman Anne , Cai Jie , Miranda Gus , Skinner Eila C. 
Published: February 2017

301 Background: There is a paucity of data on neoadjuvant GC (gemcitabine, cisplatin) chemotherapy in patients with muscle-invasive bladder cancer (MIBC). Our aim was to compare pathologic and survival outcomes of neoadjuvant GC and M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin) chemotherapy in patients with MIBC. Methods: A retrospective analysis of prospectively collected data from the University of Southern California (USC) Bladder Cancer Database was performed. Between 1985 and 2011, 116 patients received neoadjuvant chemotherapy prior to radical cystectomy and extended pelvic lymph node dissection for clinical stage T2-T4N0M0 bladder cancer. The outcomes were pathologic complete response (pT0N0), pathologic tumor downstaging (pT0N0, pTaN0, pT1N0, or pTisN0), overall survival (OS), and recurrence-free survival (RFS). The Kaplan-Meier method and Cox proportional regression models were used to analyze survival data. Results: The median follow-up duration was 4.5 years (range, 0 to 19.8 years). Fifty-eight patients each received GC and M-VAC chemotherapy. There were no statistically significant differences between the GC and M-VAC groups with regard to pathologic complete response (27.3% versus 17.1%, p=0.419) or pathologic tumor downstaging (45.5% versus 37.1%, p=0.498). The predicted 5-year OS (29% versus 38%, Log rank p=0.634) and RFS (36% versus 35%, Log-rank p=0.891) rates did not differ between the GC and M-VAC groups. However, in a subset of 37 patients with pathologic lymph node positive disease, the predicted 1-year RFS rate differed between the GC and M-VAC groups (0% versus 32%, log rank p=0.019). Multivariable analysis showed a trend toward an independent association between type of neoadjuvant chemotherapy and RFS (GC versus M-VAC: HR 1.64, 95% CI 0.93 to 2.89, p=0.089). Conclusions: Pathologic complete response, pathologic tumor downstaging, and survival did not differ in patients who received neoadjuvant GC and M-VAC chemotherapy. However, GC was associated with poorer RFS in a subset of patients with pathologic lymph node positive disease. Randomized controlled trials comparing neoadjuvant chemotherapy regimens are urgently needed.
Preliminary results of perioperative outcomes and oncologic efficacy from a single-institution randomized controlled trial of open versus robotic-assisted radical cystectomy.
Authors: Messer Jamie Christopher , Fitzgerald John Patrick , Ercole Barbara , Svatek Robert Scott , Parekh Dipen J. 
Published: February 2017

305 Background: In the past decade minimally invasive robotic assisted approaches have emerged as a viable option for the treatment of many urologic malignancies. Robotic-assisted radical cystectomy (RARC) for bladder cancer has been reported with the potential for lower blood loss, less transfusion requirement, and shorter hospital stay in prior studies. We present preliminary data from a single institution prospective randomized clinical trial of open radical cystectomy (ORC) versus RARC. Methods: Prospective randomized single institution series evaluating the feasibility of ORC versus RARC for consecutive patients was performed from July 2009 to June 2011. Oncologic efficacy was assessed based on the surrogates of total number of lymph nodes removed and positive surgical margins. Perioperative morbidity was assessed evaluating for estimated blood loss, transfusion requirements, length of stay and perioperative morbidity. Results: To date 46 patients have been randomized with data available on 39 patients for analysis. Each group was similar with regards to age, sex, race, BMI, comorbidities, and previous abdominal procedures, operative time, and final pathologic stage. We observed no significant difference between oncologic outcomes of positive surgical margins (5% vs 5.263%, p 0.48) or number of LN removed (11 vs 23, p 0.40) for the RARC versus ORC groups respectively. The RARC group was noted to have decreased estimated blood loss (400 mL vs 800 mL, p 0.008) and a trend towards decreased rate of excessive length of stay (>5 days) (65% vs 84%, p 0.17) for the RARC versus ORC groups. The robotic group had a trend towards decreased rate of transfusion however this was not statistically significant (40% versus 53%, p 0.26). Conclusions: Our preliminary findings from a single institution randomized trial of RARC versus ORC indicates that RARC has equivalent oncologic outcomes as measured by positive surgical margins and total number of lymph node removed. RARC demonstrates Perioperative benefits of decreased blood loss, fewer excessive hospital stays, and a trend toward fewer transfusions that was not significant.
Intravesical (IVe) valrubicin for treatment of carcinoma in situ (CIS) of the bladder: Use in clinical practice.
Authors: Cookson Michael S. , Lihou Christine Francis , Harper Samira Q. , Lang Zhihui 
Published: February 2017

317 Background: IVe valrubicin is indicated for bacillus Calmette-Guérin (BCG)-refractory CIS when cystectomy is not an option. An ongoing retrospective clinical-practice chart review is being conducted to examine use of valrubicin since its reintroduction (Oct 2009). Methods: Records were analyzed for adults with non-muscle invasive bladder cancer (NMIBC) treated with valrubicin. Results: In this ongoing study, 62 patients received valrubicin (date range; 10/7/2009-6/10/2011). Most were male (52, 84%) and white (49, 79%); median age was 79 y (range, 49–89). 49 patients (79%) had a history of CIS + papillary tumors, 8 had CIS (13%), 4 had papillary (7%), 1 had NMIBC unspecified (1%). 57 patients (92%) received prior IVe therapy (median [range], 2 [0–11] courses); 13 patients (21%) received 1 course, 16 (26%) 2 courses, and 28 (45%) ≥3 courses. Immunotherapy (eg, BCG, unspecified) was the most common prior treatment (54 patients, 87%; median [range], 2 [0–7] courses); 17 patients (27%) received 1 course, 15 (24%) 2 courses, and 22 (35%) ≥3 courses. Prior IVe chemotherapy was less common (21 patients, 34%). 47 patients (76%) had ≥1 transurethral resection of the bladder tumor (median [range], 2 [0–9] for n=62 patients). Fewer had undergone ≥1 fulguration procedures (27, 44%). Most valrubicin courses (49/67, 73%) used the recommended 6 instillations (median [range], 6 [2–7]). Retention time (median [range], 120 [0–180] min) was recorded for 89/381 instillations (23%). Adverse events (AEs) were observed for 31 patients (50%); most AEs (102/106, 96%) were mild or moderate. 3 patients (5%) had serious AEs (treatment-relationship unknown). Median followup for all patients was 5.2 mo (range, 0–13.9). 13 patients (21%) underwent cystectomy at a median of 5.3 mo (range, 1-13) from the last valrubicin dose. 2 patients died, at 1.1 (metastatic disease) and 11.9 mo after finishing valrubicin. Conclusions: Patients treated with valrubicin in clinical practice often had concomitant papillary tumors and were heavily pretreated. One in 8 patients had no record of previous immunotherapy. Drug administration adhered closely to labeled instructions and was well tolerated. Funding: Endo Pharmaceuticals.
Paclitaxel-based high-dose chemotherapy (HDCT) for relapsed or refractory germ cell tumors (GCTs): Clinical outcome and quality of life (QOL) in long-term survivors.
Authors: Pal Sumanta Kumar , Sun Virginia , Carmichael Courtney , Ferrell Betty R. , Frankel Paul Henry , Margolin Kim Allyson 
Published: February 2017

325 Background: HDCT is a viable and potentially curative approach for patients with relapsed or refractory GCTs. However, no comparative data exist to define the optimal chemotherapeutic strategy. Herein, long-term follow-up data and QOL assessments are provided for an expanded cohort of patients treated with high-dose paclitaxel, etoposide, carboplatin, and ifosfamide (TECTIC). Methods: Details of the TECTIC regimen and clinical follow-up data for an initial 33 patients have been previously reported (Margolin Biol Blood Marrow Trans 2005). Surviving patients were surveyed using a modified EORTC Quality of Life Questionnaire-30 (QLQ-C30) and the Functional Assessment of Cancer Therapy-Taxane (FACT-T) questionnaire; results were compared to relevant historical cohorts using a 2-sample t-test. Cardiovascular morbidity (CM) was ascertained through queries regarding use of antihypertensive (AH) or cholesterol-lowering (CL) agents, and presence/absence of diabetes mellitus (DM). Results: Forty-six patients received protocol-based therapy. Of these, 17 patients were progression-free at a median of 112.7 mos (49.5-170.2), and 6 patients remain alive following progression with a median overall survival (OS) of 64.4 mos (43.6-147.1). Median progression-free survival (PFS) and OS were 11.8 mos (95%CI 5.8-NR) and 21.7 months (95%CI 12.7-NR), respectively. Of the 23 patients still alive, 18 patients were accessible and consented to telephonic interview. As compared to historical cohorts (Rossen J Clin Oncol 2009), survivors had a higher global health scale score (87.04 v 75.62; P=0.02) but a lower physical functioning score (68.89 v 92.66; P=0.0001) by the QLQ-C30 scale. No difference in FACT-T scores were observed as compared to historical cohorts (Cella Cancer 2003). Four patients (22%) had DM. Three patients (17%) and 4 patients (22%) reported use of AH and CL agents, respectively. Conclusions: HDCT with the TECTIC regimen produces durable remissions in patients with relapsed or refractory GCTs, with acceptable QOL and CM in long-term survivors.