bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temsirolimus in platinum-resistant metastatic urothelial cancer: A phase II trial.
Authors: Gerullis Holger , Eimer Christoph , Georgas Evangelos , Bangner Jens Willem , Otto Thomas 
Published: February 2017

302 Background: This investigator initiated phase II trial assessed temsirolimus, an inhibitor of mamalian target of rapamycin (mTOR), as second-line therapy in patients with locally advanced or metastatic TCCU after failure of platinum-containing therapy. Methods: 15 patients were enrolledin this phase II trial from June/2009 to June/2011. Primary endpoint was overall survival, as secondary endpoints we defined time to disease progression, safety and QoL along treatment. Patients with progressive TCCU after prior platinum-based chemotherapy received 25 mg of temsirolimus for 8 weeks. Evaluation for response was acomlished every 8 weeks according to the RECIST criteria, QoL assessment was done every 4 weeks using the QLC-C30 questionnaire, adverse events (AEs) were recorded and graded using NCI-CTC criteria. Results: We enrolled 15 patients in this study, of whom 14 (93%) were available for activity and safety assessment. We treated 10 (71%) male and 4 female (29%) patients median age was 64.7 years (45-76). Patients received on average 13 (3-15) infusions of temsirolimus. Median overall survival was 3.5 months (107 days). Median time to disease prgression was 2.5 months. Four patients with transient stable disease were observed. QoL assessment along treatment revealed a reduction of EORTC-QLQ-C30 (Global Health Status-Subscale) from initial 7.86 to 5.00. Temsirolimus was well tolerated, mostly observed were fatigue (Grade 3-4) in 2 patients, pancytopenia (Grade 3-4) in 2 patients, thrombopenia (Grade 3-4) in 2 patients. All other adverse events were grade 1-2 in nature. Conclusions: The primary endpoint was not met with an overall survival of 3.5 montsh only. Therefore the trial was closed after 14 patients. Temsirolimus seems to have poor activity in patients with progressive metastasized TCCU after platinum-containing first-line therapy.
Neoadjuvant cisplatin/gemcitabine (CG) chemotherapy for muscle-invasive transitional cell carcinoma of the bladder (TCCB): A single-institution experience.
Authors: North Scott A. , El-Gehani Faraj , Venner Peter 
Published: February 2017

304 Background: Despite evidence of a survival advantage for neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy (RC) for muscle-invasive TCCB, many patients are not treated. While many Canadian centers use CG chemotherapy in this setting, there is little data on pathologic response rate, often considered an important predictor of long term outcome. This retrospective study was undertaken to determine the use of neoadjuvant treatment prior to RC at our institution and assess pathologic response rates at time of RC for patients receiving neoadjuvant CG. Methods: A retrospective chart review was performed on all patients undergoing RC between January 1, 2007 and June 30, 2011 in Edmonton, Alberta, Canada. Data were collected on patient demographics, pre-treatment clinical stage information, type and amount of chemotherapy administered, and pathologic data from RC specimens. Results: A total of 251 RC were performed during the study period. Eighty-three RC were performed for non-muscle invasive TCC: 15 non-malignant causes, 27 refractory superficial TCC, 41 non-TCC malignant histology. A total of 168 RC were performed for T2-T4 TCC. Median age at diagnosis was 68 years. Ninety-two (55%) patients received neoadjuvant CG. Seventy-five (45%) patients went straight to RC. Reasons for neoadjuvant GC not being given include: medical contraindication in 43 patients (56%), patient refusal in 9 patients (12%) and lack of referral to Medical Oncologist in 24 patients (32%). Of a possible 116 patients who would have been eligible to receive neoadjuvant chemotherapy, 92/116 (79%) were treated. Of the 92 patients receiving chemotherapy prior to RC, 19 (21%) of the surgical specimens were pathologically free of cancer (pT0) at the time of surgery and 18 (20%) had only superficial disease remaining. By contrast, only three (4%) of the 75 patients who went to immediate RC achieved pT0 status and 5 (7%) had remaining superficial disease. Conclusions: The use of neoadjuvant chemotherapy prior to RC at our institution is higher than quoted in published literature. The use of neoadjuvant GC improves the chances of eliminating residual cancer in the RC specimen.
Pathologic down-staging and complete pathologic response with gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder.
Authors: Psutka Sarah P. , Olumi Aria F. , Feldman Adam S. , Saylor Philip James , Kaufman Donald S. , Lee Richard J. 
Published: February 2017

307 Background: Neoadjuvant chemotherapy (NC) with MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) improves survival in muscle invasive urothelial cancer (MI−UC) with patients who achieve pathologic complete response (PCR) following radical cystectomy (RC). Gemcitabine/cisplatin (GC) NC is increasingly employed due to lower toxicity, however, its effectiveness as neoadjuvant therapy is controversial and multiple studies have reported poor utilization of this therapy, despite recent recommendations advocating for broader use. We describe pathologic and clinical outcomes following NC and RC. Methods: We retrospectively evaluated patients with MI−UC who received NC between 2003 and 2011 (n=38). Those who were treated with neoadjuvant radiation therapy (n= 15) were excluded. We compared initial clinical stage at surgery to final pathological stage and assessed overall−median progression free−survival. Mean follow−up was 25 months (SD 21.6, range 3 –76 months). Results: Twenty-three patients who received NC were included. Nineteen patients (82.6%) were treated with GC, 3 (13.0%) with MVAC, and 1 (4.3%) with gemcitabine/paclitaxel. The median time from start of NC to RC was 119 days (IQR 98.5−146). 10/19 (52.6%) patients treated with GC achieved PCR (pT0) from clinical stage T2 (n=5), cT3 (n=2) and cT4 (n=3), and 6 (31.2%) were downstaged to pT1 and pTIS from cT2. Two patients treated with MVAC were downstaged to pT1 and one achieved PCR. Median recurrence-free survival was 13 months (IQR 6−19 months) with 8 patients developing recurrent or metastatic UC following RC. At median follow-up of 19 months (IQR 8−31.2 months, Range 1−71 months), 15/23 (65.2%) patients were disease free, all of whom had received GC NC prior to cystectomy. Conclusions: Neoadjuvant GC for MI−UC was associated with a 52.6% PCR rate at RC and was well tolerated. These data compare favorably with published data on GC and MVAC as NC, and warrant further study.
The impact of preoperative ASA and serum albumin on early complication and survival rate of patients undergoing radical cystectomy for bladder cancer.
Authors: Djaladat Hooman , Fairey Adrian Stuart , Cai Jie , Miranda Gus , Schuckman Anne , Skinner Eila C. , Daneshmand Siamak 
Published: February 2017

313 Background: American Society of Anesthesiologist (ASA) score is used to evaluate the physical status of patients before surgery. Serum albumin is also a known marker of nutritional status. We evaluated the impact of preoperative ASA score and serum albumin on early complication and survival of pts who underwent radical cystectomy for bladder cancer. Methods: 1,964 patients with bladder cancer underwent cystectomy between 1971 and 2008 at the USC. Preoperative serum albumin and ASA score were available in 1471 and 1140 patients respectively. Post cystectomy early complication was defined as any postoperative event leading to lengthening hospital stay or re-admission within 90 days of surgery. Recurrence free survival (RFS) and overall survival (OS) for these cohorts were reviewed. Results: The demographic data of pts based on their serum albumin and ASA score is presented in table 1. Median follow up was 12.4 years (0 - 36.6 yrs). Low serum albumin (<3.4 g/dL) and high ASA score (3 or 4) were associated with higher early complication rate (43% vs. 33%, p= 0.03 and 40% vs. 28%, p= 0.0001 respectively). In multivariable analysis, low serum albumin was an independent predictor of RFS (HR 1.35, 95% CI 1.00-1.81) and OS (HR 1.62, 95% CI 1.29-2.04). High ASA score was an independent predictor of OS (HR 1.45, 95% CI 1.13-1.85), but not RFS. Conclusions: Preoperative low serum albumin and high ASA score are independently predictive of post cystectomy decreased overall survival. Low serum albumin is also a risk factor for recurrence after cystectomy. These parameters potentially could be used in nomograms to predict postoperative prognosis in patients undergoing radical cystectomy. Demographic data in 1,471 and 1,140 patients who underwent cystectomy for bladder cancer based on preoperative serum albumin and ASA score, respectively. [Table: see text]
HPV status in relation to clinicopathologic variables in patients with penile cancer at Los Angeles County-USC Medical Center.
Authors: Schwartz Rachel L. , Jayaratna Isuru Sampath , Mitra Anirban Pradip , Da Silva Diane , Kast W Martin , Chen Moli , Ma Yanling , Quinn David I. , Dorff Tanya B. , Schuckman Anne 
Published: February 2017

329 Background: Penile squamous cell carcinoma (PSCC) is a disfiguring and deadly disease. US cancer registry reports a higher incidence in certain minority communities including those over-represented at LAC-USC. Human papilloma virus (HPV) infection is strongly associated with PSCC. This study examined correlations of HPV presence and subtype with PSCC patient clinicopathological variables. Methods: After IRB approval, a retrospective review of PSCC patients at LAC-USC between 1996-2010 was completed. HPV presence and genotype was detected from primary tumors of 33 patients by DNA amplification followed by reverse line blot hybridization. Associations with patient and tumor characteristics were examined by contingency analyses. Results: 20 (60.6%) patients were HPV+, and 85% of all HPV+ cases harbored at least one high-risk viral strain (80% of all positive cases had HPV 16, 5% HPV 31, 10% HPV 66). 20% of all positive cases harbored low-risk HPV 11; HPV strains 6 or 35 were not detected in any specimen. 3 patients were positive for multiple strains. Overall median age at diagnosis was 53 (range: 24-77) yrs. Median age was 56 yrs and 49 yrs for HPV+ and HPV- patients, respectively. HPV infection showed a trend towards being more prevalent in patients beyond the fifth decade of life, although this did not reach statistical significance (p=0.10). 22 (66.7%) patients were Hispanic; this ethnicity comprised 60% and 77% of HPV+ and HPV- cases, respectively (p=0.31). This cohort included Stage 0 (n= 1, n= 0), Stage 1 (n= 4, n=2), Stage 2 (n= 4, n= 4), Stage 3 (n=5, n= 1), and Stage 4 (n= 4, n= 5) HPV+ and HPV- patients, respectively. Neither HPV status nor presence of nodal metastasis was significantly associated with stage (p=0.50, p=0.52 respectively). Tumor grade was available for 30 (90.9%) cases; while HPV+ cases tended to have higher proportion of moderately-poorly differentiated tumors than HPV- cases (77.8% vs. 58.3%), this was not statistically significant (p=0.32). Conclusions: An overwhelming majority of HPV+ cases harbored at least one high-risk viral strain. Several interesting associations of HPV status with age and grade were noted, although the study was underpowered to show significance.
Large retroperitoneal lymph nodes (RPLN) as a predictor for venous thromboembolism (VTE) in patients (pts) with germ cell tumor (GCT) receiving first-line chemotherapy (chemo).
Authors: Tran Ben , Moore Malcolm J. , Amir Eitan , Jewett Michael A , Anson-Cartwright Lynn , Sturgeon Jeremy F. G. , Chung Peter W. M. , Warde Padraig Richard , Bedard Philippe 
Published: February 2017

332 Background: VTE causes significant morbidity and mortality in GCT pts. While an existing and validated predictive model identifies VTE risk in chemo pts with any cancer (Khorana model), a predictive model specific to GCT does not exist. Many GCT pts present with bulky RPLN that produce venous stasis in the lower extremities. The objective of this study was to explore the association between large RPLN and VTE in GCT pts receiving chemo and compare large RPLN as a predictor for VTE in GCT pts to the non-GCT specific Khorana model. Methods: Clinical data from our institutional GCT database was complemented by review of radiology, pharmacy and medical records. All GCT pts receiving 1st line chemo between 1-Jan-00 and 31-Dec-10 were included. Large RPLN were defined as ≥5cm in maximal diameter. Factors used in the Khorana model (baseline BMI, hemoglobin, white cell count and platelets) were collected. We compared the predictive accuracy of large RPLN versus Khorana score ≥3 using receiver operator characteristic (ROC) curve statistical analyses. Results: The cohort consisted of 260 GCT pts, median age 31.5 years, predominantly testis primary (235, 90%) and good risk (171, 66%). 17 (7%) developed VTE prior to the start of chemo. 19 (7%) were given prophylactic anticoagulation, none of whom developed VTE. Of the remaining 224 pts, 20 (9%) developed VTE during chemo. In a univariate analysis, large RPLN was strongly associated with VTE (OR 7.74, p<0.001), as were Khorana score ≥3 (OR 9.81, p<0.001) and hospital admission during chemo (OR 3.96, p=0.004). ROC curve analyses demonstrated large RPLN was a significant individual predictor for VTE (AUC 0.588, p=0.03), however, Khorana score ≥3 was a better predictor (AUC 0.664, p=0.02). Adding large RPLN to create a modified Khorana score provided marginal gains (AUC 0.682, p=0.02). Conclusions: Although large RPLN at diagnosis predicts for VTE in GCT pts, the Khorana predictive model is superior. Given the high rate of VTE in GCT pts receiving chemo, we recommend prophylactic anticoagulation for pts at increased risk, including pts with Khorana score ≥3, pts requiring hospital admission or pts with large RPLN.
Effect of preoperative antiangiogenic treatment and subsequent discontinuation on angiogenesis in the primary tumor in patients with RCC.
Authors: Bex Axel , Griffioen Arjan W. , Mans Laurie A. , de Graaf Annemarie M. A. , Nowak-Sliwinska Patrycja , Bosch Steven , de Hoog Celine , de Jong Trees A. M. , Vyth-Dreese Florry , Jonasch Eric 
Published: February 2017

350 Background: Angiogenic changes in primary tumor tissue of renal cell carcinoma (RCC) patients treated with VEGF-targeted therapy has not been previously studied. Methods: A total of 57 primary tumor samples from various retrospective and prospective studies of presurgical sunitinib or bevacizumab were used. In these studies targeted therapy was given with the primary tumor in situ prior to cytoreductive nephrectomy, to investigate impact of therapy on primary tumors. Primary tumor tissues were assessed for microvessel density (MVD), proliferating endothelial cells, pericyte coverage, apoptosis of tumor or endothelial cells and molecular expression of angiogenesis regulators. Results of tumors pretreated with sunitinib discontinued at different intervals before surgery, were compared to similar analyses of untreated and bevacizumab-pretreated tumors. Results: Sunitinib and bevacizumab pretreatment resulted in a significant reduction of MVD, as well as an increase in vascular pericyte coverage in the primary tumor (sunitinib samples) consistent with efficient angiogenesis inhibition. Expression of several key regulators of angiogenesis were found to be suppressed in sunitinib pretreated tissues, among which VEGFR-1 and -2, angiopoietin-1 and -2 and PDGF-B. Apoptosis was induced both by sunitinib and bevacizumab pretreatment. Interestingly, in sunitinib pretreated tissues a dramatic increase of the number of proliferating endothelial cells was observed, which was not the case in bevacizumab pretreated and untreated tumors. A positive correlation with the interval between halting the therapy and surgery was found, suggesting a compensatory angiogenic response caused by the discontinuation of sunitinib treatment. Conclusions: This study describes the antiangiogenic response in human primary renal cancers upon treatment with VEGF targeted therapy. Treatment discontinuation of tyrosine kinase inhibitors with short half life leads to accelerated angiogenesis. The results of the current study contribute important data to the ongoing discussion on the discontinuation of treatment with tyrosine kinase inhibitors.
Phase III AXIS trial for second-line metastatic renal cell carcinoma (mRCC): Effect of prior first-line treatment duration and axitinib dose titration on axitinib efficacy.
Authors: Rini Brian I. , Escudier Bernard J. , Michaelson M Dror , Negrier Sylvie , Gore Martin Eric , Oudard Stephane , Clark Joseph , Tarazi Jamal Christo , Rosbrook Brad , Kim Sinil , Motzer Robert John 
Published: February 2017

354 Background: Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. In the phase 3 AXIS trial of axitinib vs sorafenib for second-line mRCC, axitinib significantly prolonged median progression-free survival (mPFS) (6.7 vs 4.7 months; hazard ratio 0.665; P<0.0001). Here, we evaluated the effect of prior sunitinib treatment duration and axitinib dose titration on subsequent axitinib efficacy. Methods: Eligible patients had clear-cell mRCC; measurable RECIST-defined progressive disease after 1 prior first-line systemic therapy; and Eastern Cooperative Oncology performance status (PS) 0/1. Patients were stratified by PS and prior therapy, and randomized 1:1 to either axitinib, at a starting dose of 5 mg twice daily (BID), or sorafenib, 400 mg BID. Patients without toxicity >grade 2 and BP <150/90 mmHg without antihypertensive medication for >2 weeks were eligible to increase axitinib dose to 7 mg BID and then to 10 mg BID. Results: The mPFS for patients receiving at least one total daily axitinib dose >10 mg (dose-titrated group; n=132) was 6.6 months [95% CI 4.7–8.3] and 8.3 months [95% CI 6.0–10.2] for patients receiving axitinib ≤10 mg (n=227). A total of 194 patients (53.7%) in the axitinib arm and 195 patients (53.9%) in the sorafenib arm had prior sunitinib treatment. The mPFS for patients with duration of prior sunitinib treatment ≥6 months and <6 months were 4.8 months [95% CI 4.5–6.5] and 4.6 months [95% CI 2.8–8.3] for axitinib patients; and 4.6 months [95% CI 2.9–4.9] and 2.9 months [95% CI 2.8–4.6), for sorafenib patients. The mPFS for duration of prior sunitinib ≥9 months and <9 months were 6.3 months [95% CI 4.6–6.7] and 4.5 months [95% CI 2.8–6.4] for axitinib patients; and 4.6 months [95% CI 2.8–4.9] and 2.9 months [95% CI 2.8–4.7]) for sorafenib patients. Conclusions: Duration of prior sunitinib ≥9 months may be associated with a longer PFS on second-line VEGFR tyrosine kinase inhibitors. Both axitinib dose-increased and non-increased patients had longer PFS compared with the sorafenib arm.
Genomic analysis of translocation renal cell carcinoma: Association of frequent 3p loss and poor outcome.
Authors: Malouf Gabriel , Monzon Federico A. , Couturier Jerome , Molinie Vincent , Escudier Bernard J. , Camparo Philippe , Tamboli Pheroze , Wood Christopher G. , Tannir Nizar M. 
Published: February 2017

360 Background: Translocation renal cell carcinoma (RCC) is a rare subtype of kidney cancer that is characterized by translocations involving TFEB or TFE3 genes. We recently reported that adults with translocation RCC have worse prognosis than pediatric and adolescent patients (Malouf et al, J Urol, 2011), however little is known about the genetic and epigenetic differences between these groups. Methods: Cytogenomic analysis was performed with 250K SNP microarrays (Affymetrix) on 19 tumor specimens of translocation RCC (Age <18 (n=6); Age >=18 (n=13) and 2 established cell lines (UOK109, UOK146). Changes in global DNA methylation levels were measured by using pyrosequencing of highly repetitive LINE-1 sequences on 27 tumor samples. Results were correlated with the patients’ clinical data. Results: 3p loss was observed in 8 patients (42%) and was associated with other chromosomal alterations frequently seen in clear-cell RCC such as 9p loss. Patients with 3p loss showed poor overall survival (OS) as compared to patients without 3p loss (Median OS 12.7 month vs. not reached) [p=0.03]. There was no association found between 3p loss and clinico-pathological variables such as AJCC stage, age and gender. The UOK146 cell line also showed 3p and 9p loss. Young patients (<18 years) displayed fewer number of genetic abnormalities as compared to older patients (p=0.02). Moreover, Line-1 methylation was found to be lower in adult as compared to young patients (76.7% vs. 71.1%, p=0.02). Conclusions: Our results show that a subset of translocation RCC is characterized by a genetic profile similar to that of clear-cell RCC and these tumors seem to behave aggressively. Studies to determine the presence of VHL mutation in these tumors are underway. Adult patients display higher genetic abnormalities and lower Line-1 methylation as compared to young patients. These results might explain the different behavior of pediatric and adult translocation RCC.
Updated results of a prospective noninterventional study of everolimus after failure of the first VEGF-targeted therapy.
Authors: Staehler Michael D. , Goebell Peter J. , Kube Ulrich , Kindler Manfred , Koepke Thomas , Janssen Jan , Schmitz Joerg , Weikert Steffen , Kloss Susanne , Steiner Gabriel , Jakob Andreas , Steiner Thomas , Overkamp Friedrich , Bergmann Lothar , Guderian Gernot , Doehn Christian 
Published: February 2017

361 Background: Everolimus (EVE, Afinitor) is approved for the treatment of metastatic renal cell cancer (mRCC) after failure of VEGF-targeted therapy. The option to treat mRCC with six approved targeted agents has sparked debate on proper sequencing of these agents. However, data beyond clinical trials is limited. Here, we report prospective non-interventional data on EVE in routine use after failure of the first VEGF-targeted therapy. Methods: A prospective, single arm, open label, multi center non-interventional study for patients with mRCC was initiated in Germany in 08/2009 to determine effectiveness defined as time between first EVE intake until disease progression due to any cause (TTP) and treatment duration. Targeted enrollment is 400 patients. A first interim analysis was conducted 3 months after 100 patients had been enrolled and was presented previously (Bergmann et al., J Clin Oncol 29: 2011 [suppl; abstr 4552]). Here we present a second interim analysis to corroborate the results of the first interim analysis. Patients were analyzed 14 months after the first 100 patients had been enrolled. Results: 59 sites included 113 patients between August 2009 and July 2010. At the cut-off date of the first interim analysis (12 November 2011), these patients had been followed for a median of 116 days. The safety population consisted of 99 patients with documented EVE treatment. The median treatment duration had not yet been reached at the time of the first interim analysis. Median time to progression (TTP) was 9.7 months (95% CI: 6 months; n.d.). A total of 230 AEs were reported in 61% of patients including 18 SAEs in 12 patients (12%). These preliminary results are substantiated in this interim analysis with a total observation period of at least 14 months (cut-off date 30 September 2011). Updated data on effectiveness and safety of EVE will be presented. Conclusions: This non-interventional study on EVE in treatment of mRCC after prior failure of VEGF-targeted therapy provides first evidence on routine use of EVE. Further analysis of this ongoing study affords insight into effectiveness and safety of EVE in routine use after failure of the first VEGF-targeted therapy.