bluuebunny/crossref_metadata_2025_split huggingface dataset:
A model for predicting overall survival in men with metastatic castrate-resistant prostate cancer (CRPC) for whom first-line chemotherapy failed.
Authors: Halabi Susan , Lin Chen-Yen , Small Eric Jay , Armstrong Andrew J. , Kaplan Ellen B. , Petrylak Daniel Peter , Sternberg Cora N. , Shen Liji , Oudard Stephane , De Bono Johann Sebastian , Sartor A. Oliver 
Published: February 2017

24 Background: Several prognostic models for overall survival (OS) have been developed and validated in men with chemotherapy naïve mCRPC. The primary objective was to develop and validate a prognostic model that can be used to predict OS in men who have failed first-line chemotherapy. Methods: Data was used from a phase III trial of 755 mCRPC men who had developed progressive disease following first-line chemotherapy and were randomized to cabazitaxel plus prednisone or mitoxantrone plus prednisone (TROPIC trial). The data was randomly split into training (n=507) and testing (n=248) sets. A separate data, consisting of 488 men previously treated with docetaxel who were randomly assigned to either satraplatin and prednisone or placebo and prednisone, was used as the validation set (SPARC trial). Penalized regression method was used to identify important prognostic factors. Adaptive Lasso selected nine variables of OS. A predictive score was computed from the estimated regression coefficients and used to classify patients into low (<-1.29) and high (>= -1.29) risk groups in the testing datasets. The model was assessed for its predictive accuracy using time dependent area under the curve (AUC) on the testing sets (TROPIC and SPARC trials). Results: The final selected model included: ECOG performance status, time since last docetaxel use, measurable disease, presence of visceral disease, pain, duration of prior hormonal use, hemoglobin, prostate specific antigen and alkaline phosphatase. In the TROPIC testing set, the median OS in high and low risk groups were 11 and 17 months, respectively, with a hazard ratio (HR)=2.47 (p-value<0.0001). Using the SPARC set, the median OS were 11 and 20 months in the high and low risk groups, respectively, with a HR=1.94 (p<0.0001). The time dependent AUC were 0.73 and 0.70 on the testing sets. Conclusions: A prognostic model of OS in the post-docetaxel mCRPC setting was developed and validated and risk groups were identified. This model can be used to select patients based on their prognosis to participate in clinical trials. Prospective validation is needed.
Post-treatment prognostic model for patients (pts) with metastatic urothelial cancer (UC) treated with first-line chemotherapy.
Authors: Galsky Matt D. , Moshier Erin L. , Krege Susanne , Lin Chia-Chi , Hahn Noah M. , Ecke Thorsten , Sonpavde Guru , Pond Gregory Russell , Godbold James H. , Oh William K. , Bamias Aristotelis 
Published: February 2017

256 Background: Models to predict the outcome of pts with metastatic UC, based on pre-treatment variables, have previously been developed. However, pts often request “updated” prognostic estimates based on their response to treatment. This is particularly relevant in first-line treatment of metastatic UC, a disease state for which a fixed number of cycles of chemotherapy are typically administered. Methods: Data were pooled from 317 pts enrolled on eight trials evaluating first-line cisplatin-based chemotherapy in metastatic UC. Variables were combined in a Cox proportional hazards model to produce a nomogram to predict survival from end of treatment. The nomogram was validated externally using data from a trial of MVAC versus docetaxel plus cisplatin (n=148). Results: The median survival from end of treatment was 10.65 months [95% CI 9.20 – 13.24]; 69% of patients had died. Baseline (white blood count, ECOG performance status, number of visceral metastatic sites) and post-treatment (treatment response, duration of treatment, reason for treatment discontinuation) variables were evaluated. The Cox proportional hazard model is shown in the Table. The duration of treatment and reason for treatment discontinuation were not significantly associated with survival. The four significant variables were included in a nomogram. The nomogram achieved a bootstrap-corrected concordance index of 0.68. Upon external validation, the nomogram achieved a concordance index of 0.67. Conclusions: A model derived from pre- and post-treatment variables was constructed to predict survival from the end of first-line chemotherapy in pts with metastatic UC. This model may be useful for pt counseling and for stratification of trials exploring “maintenance” treatment. [Table: see text]
Survival of upper tract urothelial carcinoma: A population-based analysis.
Authors: Porten Sima P. , Gopalakrishnan Vancheswaran , Nogueras-Gonzalez Graciela M. , Kamat Ashish M. , Siefker-Radtke Arlene O. , Dinney Colin P.N. , Matin Surena F. 
Published: February 2017

257 Background: Urothelial carcinoma involving the upper tract (UTUC) accounts for only 5% of urothelial malignancies; thus the majority of data are from single institution series or highly selected patient populations. We sought to examine contemporary trends in overall (OS) and disease-specific survival (DSS) for UTUC using a large, population based dataset. Methods: Patients within the Surveillance, Epidemiology, and End Results (SEER) database with de novo UTUC from 1973-2008 were included and analyzed in 5 year increments to evaluate disease trends. Univariate and multivariate for OS and DSS competing risks analysis were performed adjusting for age, gender, and race for renal pelvis and ureteral tumors. Results: A total of 14,237 patients met inclusion criteria. For renal pelvis tumors (n=9,318), overall survival was 54.4% at 3 years. On multivariate analysis factors that were significant predictors of OS were: age (HR 1.03, p<0.001), and year of diagnosis (HR 1.32, p<0.001). Competing risks regression estimated DSS of 60.5% at 5 years, with male gender, black race, and year of diagnosis remaining significant after adjusting for covariates (p<0.05). For ureteral tumors (n=4,919), overall survival was 56.1% at 3 years. On multivariate analysis, age was a significant predictor of OS (2.73, 95%CI 2.52-2.93, p<0.001). Competing risks regression estimated DSS of 61.9% at 5 years, with female race, and year of diagnosis remaining significant after adjusting for covariates (p<0.05). For both renal pelvis and ureteral tumors, the more contemporary era (1997-2002, 2003-2008) showed worse survival than prior eras (p<0.05). Conclusions: Disease-specific survival for patients with renal pelvis and ureteral UTUC appears to be worse in the contemporary era. While sociodemographic factors (age, gender, and race) appear to impact prognosis, it is unclear what factors may be contributing to this decline. This data adds to the growing literature supporting a paradigm change in the treatment of this disease.
Identification of prognostic groups in patients with hormone-sensitive metastatic prostate cancer at the present time: An analysis of the GETUG 15 phase III trial.
Authors: Gravis Gwenaelle , Fizazi Karim , Joly Florence , Oudard Stephane , Priou Frank , Latorzeff Igor , Delva Remy , Krakowski Ivan , Laguerre Brigitte , Rolland Frederic , Theodore Christine , Deplanque Gael , Ferrero Jean-Marc , Pouessel Damien , Mourey Loic , Beuzeboc Philippe , Zanetta Sylvie , Esterni Benjamin , Habibian Muriel , Soulie Michel 
Published: February 2017

26 Background: Patients with upfront metastases at the time of prostate cancer (PC) diagnosis are less frequent than in the past in Western countries, but still represent 5-10% of all patients and almost one half of PC patients will eventually die of the disease. Prognostic factors (lymph node metastases/appendicular vs axial bone disease, performance status > 1, Gleason score > 8 and PSA > 65 ng/ml) have been proposed (Glass et al., 2003), leading to the definition of three subgroups with good, intermediate and poor prognosis. However, the current natural history of metastatic prostate cancer has not been well described. Methods: Patients with hormone sensitive metastatic PC were randomized to receive continuous androgen deprivation therapy (ADT) plus docetaxel (75 mg/m²/21d up to 9 cycles) and prednisone or ADT alone. Glass risk groups were used as stratification factors. Results: From October 2004 to December 2008, 385 pts were included. They were distributed into good (50%), intermediate (29%), and poor (21%) prognosis groups. The median follow up was 50 months [95% CI: 49 - 54]. The primary endpoint analysis showed no difference in overall survival (OS) (HR: 1.01 [95%CI: 0.75-1.36]) between the 2 arms but a significant PFS improvement was observed in the docetaxel group (HR: 0.75 [0.59-0.94] p=0.0147) (Gravis, ESMO 2012). The median OS in the ADT alone arm was 54 months [42-NR]. It was 69 [95% CI: 60.9-NR], 47 [95% CI: 37.7-NR, HR = 1.6] and 37 [95% CI: 28.5-58.9, HR = 2.12] months respectively in the good, intermediate, and poor prognosis groups (p=0.001) in the whole cohort. No interaction between prognosis groups and treatment was found. A detailed analysis using the Cox model will be presented. Conclusions: At the present time, median life expectancy of patients with metastatic PC seems to exceed 4 years. Subgroups with favorable or unfavorable outcome can be identified. Clinical trial information: NCT00055731.
The role of VEGF/mTOR/AKT pathway in patients with advanced urothelial carcinoma of the bladder cancer.
Authors: Moritz Rudolf , Hartmann Arndt , Giedl Johannes , Eltze Elke , Hertle Lothar , Herrmann Edwin 
Published: February 2017

264 Background: Activation of the mTOR pathway can be observed in various tumor entities. In advanced urothelial carcinoma of the bladder (BCA) its role still is unclear. The aim of our study was to examine activation of the mTOR cascade in BCA and its correlation with survival data. Methods: Tissues from 268 patients undergoing radical cystektomy were collected to assess the diagnostic and prognostic value of mTOR, HIF1-alpha, p4EB-P1, pAKT and VEGF using tissue microarray-based immunohistochemistry. Results: Overexpression of mTOR pathway enzymes is frequently detected for HIF1-alpha (29.8%), pAKT (53.2%), mTOR (43.3%), p4EB-P1 (28.4%) and VEGF (58.5%). Overexpression of pAKT was a significant predictor of progression (PFS) in pT1 (p=0.026) and pT2 (p=0.018) tumors. Overall survival (OAS) was significantly shorter for patients with pT1 (p=0.021) and pT2 (p=0.026) tumors in this subgroup. HIF1-alpha overexpression leads to significant earlier recurrence of BCA following radical cystektomie in the subgroup of pT3 tumors (p=0.046). High levels of mTOR were predictive for cancer related death (p=0.021) in pT2-tumors. Conclusions: Activation of mTOR-pathway, especially pAKT is of prognostic value in patients with advanced BCA and might be useful as a target for future therapies.
Reproductive organ involvement in female patients undergoing radical cystectomy.
Authors: Djaladat Hooman , Skinner Eila C. , Miranda Gus , Cai Jie , Daneshmand Siamak 
Published: February 2017

274 Background: Anterior pelvic exenteration is traditionally the treatment of choice for women with invasive bladder carcinoma. Female reproductive organ involvement is reported to be low, but there is not enough evidence to abandon this part during radical surgery. We evaluated the pathological involvement of reproductive organs (RO) in female patients undergoing radical cystectomy for invasive bladder urothelial carcinoma. Methods: 2,098 patients with bladder cancer underwent cystectomy between 1971 and 2008 at USC, of whom 458 were female. 411 (90%) had urothelial and 47 had non-urothelial bladder cancer. The cohort of female cystectomy patients with pathologic RO involvement is reviewed and their RFS and OS are discussed. Results: In the TCC group, 20 patients (4.8%) had RO involvement by urothelial cancer (UC-RO); 10 (2.5%) had vaginal, 2 (0.5%) cervical and one (0.25%) only uterus involvement with the rest (7) having a combination. In non-UC group, only two (4%) had RO involvement. In the UC-RO cohort, median age was 71 yo (38-89). Only one patient (5%) underwent orthotopic diversion. 19 cases (95%) were high grade TCC. Clinical stage T4a was diagnosed in 25% of cases preoperatively. Associated CIS, multifocality, LVI and histologic type of cancer had no significant correlation with RO involvement. Patients with a palpable mass or hydronephrosis were 5 times more likely to have RO involvement (P<0.001). RO involvement was associated with higher chance of positive lymph nodes (60%) (P=0.001). Three (15%) and seven (35%) patients underwent neo-adjuvant and adjuvant chemotherapy respectively. Urethral pathology was positive in 1 patient. 5 (25%) developed local recurrence and 9 (45%) developed distant metastasis at a median follow up of 12.2 yrs (0.1 to 35.5 yrs). Two-year RFS and five-year OS in UC-RO group were both 10%. Conclusions: The risk of RO involvement in female patients undergoing cystectomy for bladder cancer is about 5%, with the vagina being the most commonly involved organ. A palpable mass and/or hydronephrosis are a strong predictor of RO involvement, although other clinical criteria are not predictive.
A phase II multicenter study of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) chemotherapy with pegfilgrastim support in patients (pts) muscle-invasive urothelial cancer (MIUC): Safety, pathologic, radiologic, and molecular correlates.
Authors: Choueiri Toni K. , Jacobus Susanna J. , Qu Angela Q. , Sweeney Christopher , Appleman Leonard Joseph , Tretter Christopher P.G. , Bubley Glenn J. , Elfiky Aymen , Park Rachel , Stack Edward C. , Signoretti Sabina , Walsh Meghara K. , Steele Graeme , Hirsch Michelle S. , Krajewski Katherine Maragaret , Taplin Mary-Ellen , Rosenberg Jonathan E. , Ross Robert W. 
Published: February 2017

278 Background: ddMVAC is associated with high responses rate (RR) in advanced urothelial cancer (UC). We embarked on a study in MIUC to determine pathologic RR and its correlation with clinical and radiological outcomes as well as DNA excision repair pathway biomarkers (ERCC1, PAR, BRCA1, and BRCA2). Methods: Patients with cT2-T4, N0-1, M0 UC, and adequate kidney and marrow function were enrolled on a prospective multicenter phase II trial. Four cycles of ddMVAC were given followed by radical cystectomy (RC). The primary endpoint was pathologic downstaging to <pT1N0M0. The treatment would be considered effective if 17 of 37 eligible patients (46%) met the primary endpoint (85% power, 1-sided type I error 0.1). Secondary endpoints included safety, imaging response (by contrast-enhanced imaging, largely MRI), and biomarker correlates. Results: Between 12/08 and 4/12, 39 pts (cT2:42%; cT3:42%, cT4:16%, N1:45%) were enrolled. 91% had bladder primary, and 95% received 4 cycles of ddMVAC. Median follow up was 18 months. One patient developed distant metastases before RC. Of 39 eligible pts, 49% (90% CI 35-63) downstaged to <pT1N0M0 (pT0N0=26%), and the primary endpoint was met. 14/17 (82%) of pts with cN1 disease had pN0 at surgery; no pts with cN0 was found to have pN(+). Toxicities >Grade 3 related to chemotherapy were observed in 10% of pts and included mucositis, hand-foot skin reaction, hypokalemia and neutropenia. No neutropenic fevers were seen. Median and 18-month disease-free survival (DFS) is provided in Table. Tissue biomarker analyses will be presented. Conclusions: ddMVAC regimen is well tolerated and results in significant pathologic and radiologic downstaging in pts with MIUC. Clinical trial information: NCT00808639. [Table: see text]
Efficacy and safety of valrubicin in non–muscle-invasive bladder cancer in older and younger patients.
Authors: Cookson Michael S. , Lihou Christine Francis , Harper Samira Q. , Li Thomas , Chitra Surya , Tutrone Ronald 
Published: February 2017

309 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report the effectiveness and safety of valrubicin, stratified by patient age, from a US multicenter, observational, retrospective study. Methods: Medical records of adults with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted between March and September 2011. The median age (75 [range 42–95] years) was the stratification cutoff. Kaplan-Meier analyses were performed for event-free survival (EFS), worsening-free survival (WFS), and progression-free survival (PFS). Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 [range, 2–18] instillations). Median EFS, WFS, and PFS were similar in patients ≤75 vs >75 years old (see Table); 1-year rates were 17.8% vs 15.4%, respectively, for EFS; 16.1% vs 14.3% for WFS; and 80.2% vs 81.4% for PFS. 11 (19%) patients aged ≤75 years vs 4 (7%) aged >75 years underwent radical cystectomy; 28 (48%) vs 28 (51%), respectively, experienced ≥1 local adverse reaction; 3 (5%) vs 4 (7%) experienced ≥1 serious adverse event; and 4 (7%) vs 1 (2%) discontinued as a result. Conclusions: In patients with NMIBC treated with intravesical valrubicin, effectiveness and safety are similar in patients aged ≤75 and >75 years. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc. [Table: see text]
Low-grade micropapillary urothelial carcinoma: Does it exist? A SEER analysis of management and outcomes.
Authors: Vourganti Srinivas , Harbin Andrew , Singer Eric A. , Shuch Brian , Metwalli Adam R. , Agarwal Piyush K. 
Published: February 2017

315 Background: Micropapillary Urothelial Bladder Carcinoma (MPBC) is a rare aggressive variant histology of bladder cancer. Management of non-muscle invasive (NMI) MPBC is controversial, as bladder sparing strategies routinely used when managing TCC have resulted in worse outcomes. In order to better understand its behavior, we reviewed all MPBC pts in the SEER database and compared them with TCC pts. Methods: Data was collected from SEER 17. Age, sex, race, grade, stage, treatment, and cause of death were collected. Kaplan-Meier (KM) and Cox proportional hazards (CPH) models were performed. Results: From 2001-2008, 120 pts with MPBC were identified, 0.1% of all bladder cancer. Mean age was 70.3 yrs, 76.7% were male, and 90.8% were Caucasian. No difference in age, sex, or race was detected between MPBC and TCC pts. MPBC presented with more high grade (HG) disease (86.1% vs. 38.7%, p<0.0001) and with higher stage (40.8% NMI vs. 90.4% NMI, p < 0.0001). KM analysis demonstrated that NMI MPBC had significantly worse overall survival (OS) than NMI TCC (not controlling for grade, p<0.0001). Low grade (LG) NMI MPBC pts had worse OS and cancer specific survival (CSS) as compared to LG TCC pts (p=0.0037, p<0.0001 respectively), and did no better than HG NMI MPBC pts. No difference was detected between HG NMI MPBC and HG NMI TCC pts. A CPH model controlling for stage, grade, treatment, age, race, and sex detected no significant survival difference in MPBC vs. TCC (HR 1.04, p=0.7966). For NMI MPBC (n=49), only 4 pts underwent definitive therapy (2 had cystectomy and 2 received EBRT). During the median follow-up period of 31 months, no cancer specific deaths occurred in this group of pts. However, in those not receiving definitive therapy (n=45), 7 cancer specific deaths occurred (15.6%). Conclusions: MPBC is a rare variant with high stage and grade presentation. Controlling for stage and grade, no difference could be detected in survival between MPBC and TCC. However, LG NMI MPBC behaved similarly to both HG MPBC and HG TCC in regards to survival outcomes. We propose that all MPBC (regardless of grade) be managed as HG disease, and that strong consideration for definitive therapy should be given even in the setting of NMI disease.
Long-term survival rates after chemotherapy (CTx) in patients (pts) with nonseminomatous (NS) germ cell tumors (GCT) with teratoma (T).
Authors: Patil Sujata , Feldman Darren Richard , Bajorin Dean F. , Motzer Robert John , Sheinfeld Joel , Tickoo Satish , Reuter Victor E. , Bosl George J. 
Published: February 2017

334 Background: Debate surrounds the clinical importance of T in NSCGT pts who receive CTx. The WHO no longer distinguishes between mature (MT) and immature teratoma (IT). Two studies suggested that immunohistologic (IHC) markers of apoptosis, p53 and Ki67 expression were independent markers of outcome in pts with embryonal carcinoma (JCO 21: 2679, 2003) and a differentiation genotype was an independent marker of worse outcome in NSGCT (JCO 27: 5240, 2009). We extend these analyses to NSGCT with and without T. Methods: In an IRB-approved study, archived pre-CTx tumor was obtained from 191 pts who received platinum-based CTx for initial treatment of NSGCT between 4/75 and 5/1996. Histology was confirmed and % cells displaying apoptosis (TUNEL assay) or expressing p53 and Ki67 (IHC) determined at MSKCC. 110 pts’ tumors had ≥ 1 NSGCT cell types without T and 81 had MT (n=39) and/or IT (n=52); 10 pts had both. Tumors with T had ≥ 1 additional NSGCT cell types. Overall survival (OS) differences were tested using Kaplan-Meier, Cox regression and log-rank test. Results: Median age was 27 years; primary site was testis (96%) and mediastinum (3%). 57% were IGCCCG good risk, 29% intermediate risk with no difference with and without T (P=0.53). With median follow-up of 7 yrs, 5-yr OS was 84% (95% CI: 75-90) without T and 72% (61-81) with T, and at 10 yrs 84% (75-90) and 65% (52-76), respectively (P=.06). OS differed by T subgroup: 5-yr OS was 80% if IT alone; 75% if both IT and MT; 61% if MT alone (P=.001). Adjusting for risk strata, this difference remained significant (P=.02). For IT, %Ki67 expression was borderline associated with OS (P=.06), but not %apoptosis (P=.56) or %p53 (P=.93). For MT, %apoptosis was associated with OS (P=.01) but not %Ki67 (P=.70) or %p53 (P=.29). Conclusions: The presence of T, particularly MT, in mixed NSGCT was associated with worse OS than tumors without T. T subtype was important: OS was associated with %Ki67 for IT and %apoptosis for MT. These data suggest that the presence of T should be considered in treatment decision-making. The absence of T subtyping in the WHO classification will likely result in a loss of prognostic information.