bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of GemRIS (gemcitabine-releasing intravesical system, TAR-200) on antitumor activity in muscle-invasive bladder cancer (MIBC).
Authors: Daneshmand Siamak , Pohar Kamal S. , Steinberg Gary D. , Aron Manju , Cutie Christopher 
Published: September 2018

e16000 Background: Efficacy of current intravesical cytotoxic therapy for bladder cancer is limited by suboptimal dwell times and dose, and may result in local toxicities. GemRIS™ is a novel drug-device combination product that continuously delivers gemcitabine into the bladder over 7 days. Preclinical models demonstrated that GemRIS was well tolerated and resulted in no appreciable systemic exposure. Methods: This Phase 1b study evaluating the safety and tolerability of 2 GemRIS system deployments of 7 days each, separated by a 14-day rest period, in patients with confirmed MIBC scheduled for radical cystectomy (RC). A secondary endpoint included pathologic tumor response. Patients were required to have grossly visible tumor measuring > / = 3 cm in size at study entry. Pharmacokinetic (PK) analyses were conducted in blood and urine. Response to GemRIS was assessed grossly and by histopathologic analysis. Results: 10 subjects were dosed with GemRIS and underwent RC. There were no treatment-related SAEs or discontinuations; no subject requested GemRIS removal. There was no evidence of treatment-related cytopenias and no events that resulted in a delay in RC. PK analyses have demonstrated measurable levels of gemcitabine in the urine with no detectable levels in plasma. Eighty percent (8/10) of patients experienced a reduction in exophytic tumor volume; 40% exhibited complete ablation of muscle invasive disease within this short 4-week course of therapy. Conclusions: GemRIS has demonstrated encouraging preliminary efficacy and safety. Further evaluation of GemRIS in MIBC is warranted. Clinical trial information: NCT02722538. [Table: see text]
Diagnostic value of DNA aneuploidy for urothelial carcinoma.
Authors: Zhang Pei , Liang Chao Zhao , Li Jun 
Published: September 2018

e16007 Background: The incidence and mortality of urologic cancer are increasing in China and worldwide. Early diagnosis is the key to improve survival. DNA-Image-Cytometry (DNA-ICM) is to assist in the early microscopical diagnosis and grading of various types of tumors, measuring the DNA-contents of their cells. This study investigates the role of DNA aneuploidy in improving diagnostic sensitivity and specificity for urothelial carcinoma. Methods: 274 voided urine samples (204 cases from patients with urothelial carcinomas and 70 cases from patients with benign urinary system diseases) were analyzed with DNA-ICM and liquid-based cytology (LBC) .Fresh urine samples were collected in the morning of the analysis. Sedimented cell-preparations were obtained through centrifugation (cytospins) for DNA-ICM. The sensitivity and specificity of DNA ICM and LBC were calculated by comparing with the pathology in cells with moderate and severe dysplasia. Results: Sensitivity of DNA-ICM was 70.3% which was much higher than that of liquid-based cytology (27.2%)(P < 0.01). Specificity of DNA-ICM was 100% while specificity of LBC was 98.6%. The sensitivity of DNA-ICM in upper urinary tract urothelial cell carcinoma(UTCUs) were 68.75%, lower than 75.00% in bladder urothelial cell carcinomas, there was no significant differences between them(P > 0.01). Conclusions: DNA single cell cytometry represents a highly relevant tool in the objective identification of urothelial carcinoma with a sufficient sensitivity and specificity. Enhancing its extended use as an adjuvant strategy for the early screening of the urothelial carcinoma during routine analyses is benefical. DNA-ICM is an effective screening method for urothelial cancer. Its use to monitor the treatment should be further validated in larger series.
Patients treated with bladder preserving trimodality chemoradiation therapy (BPTMCRT) off-trial compared to those on trials.
Authors: Ahamad Anesa Waheda , Martinez Alvaro , Salenius Sharon , Ross Rudi , Fernandez Eduardo 
Published: September 2018

e16014 Background: We assessed characteristics and outcome of patients treated with radiotherapy for muscle-invasive bladder cancer off-trial at forty-four community-based radiotherapy centers in the United States compared to those on clinical trials. Methods: We retrospectively reviewed 155 patients who had been treated from August 2010 to June 2014. Overall survival (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method. Results were compared to a pooled analysis of six RTOG protocols. Results: Characteristics were significantly inferior versus those on RTOG studies: lower rate of complete transurethral resection of bladder tumor: 36.8% versus 70.7% (p<0.0001), poorer performance status (PS): 36.8% were 0 to 1 versus 100% (p<0.0001), higher median age: 79 years versus 66 (p<0.0001), more medically inoperable: (51.0%) versus 0% in RTOG (p<0.001). Forty-seven percent had refused surgery. Fewer patients underwent concurrent chemotherapy: 56.1% versus 100% (p<0.0001). Median radiotherapy dose was similar: 64.8 Gy. At median follow-up of 12.6 months (range, 3.1-49.2), 36-month OS was 51.3% for those who refused surgery versus 24.5% for medically inoperable (p=0.009); 36-month OS was 58.1% post complete TURBT versus 29.8% if incomplete (p=0.07); 18-month PFS was 74.9% for PS 0-1 versus 36.3% for >1 (p=0.04). PS >1 patients were deceased or censored by 24 months. The 36-month OS was 54.3% with chemoradiation therapy (CRT) versus 17.2% without chemotherapy (p=0.03). Among CRT patients, the 36-month OS was 38.9% for medically inoperable versus 66.3% for those who refused surgery (p=0.04), similar to the pooled analysis of prospective RTOG protocols. Conclusions: The 66.3% 36-month OS for patients who refused surgery and received CRT suggests that it is appropriate to offer BPTMCRT to these patients in free standing centers. However, we may not be able to translate clinical trial protocols to many patients in this setting due to their poor functional reserve. More treatment options are needed for these patients given the aging population.
Differences in survival between symptomatic versus asymptomatic recurrence following cystectomy for bladder cancer.
Authors: Osterman Chelsea K , Alanzi Jaber , Kaufman Elizabeth L , Narayan Vivek , Boursi Ben , Cambareri Christine , Malkowicz S. Bruce , Mamtani Ronac 
Published: September 2018

e16021 Background: The benefit of surveillance after curative treatment in bladder cancer is controversial, but might be justified if early detection of asymptomatic recurrence improves survival. Prior studies demonstrating a benefit of surveillance may have been impacted by lead-time bias, which is the overestimation of survival duration due to earlier detection of disease. To avoid this bias, we examined time-dependent differences in survival with symptomatic vs. asymptomatic diagnosis of recurrence after cystectomy. Methods: We conducted a retrospective cohort study among 463 cystectomy patients between 1987 and 2011 at the University of Pennsylvania. Patients were followed by standardized protocol and classified by mode of recurrence detection (asymptomatic or symptomatic). Primary outcome was all-cause mortality. To reduce lead-time bias, we used cox regression models with varying cohort-entry times to assess the impact of mode of recurrence on survival from both time of cystectomy (Model 1) and time of recurrence (Model 2), adjusted for time to recurrence. Results: 197 patients (42.5%) recurred; 71 were asymptomatic (36.0%), 107 were symptomatic (54.3%), and 19 (9.6%) were unknown. In all models, relative to asymptomatic patients, patients with symptomatic recurrence had significantly increased risk of death (Model 1 HR 1.74, 95% CI 1.13-2.68, Model 2 HR 1.98, 95% CI 1.27-3.10) and had lower 1 year overall survival (30.43% vs. 55.66%). Group differences in median survival (246 days) were greater than the estimated lead-time (10 days). Conclusions: Symptomatic recurrence is associated with worse outcomes than asymptomatic recurrence, even after lead-time bias adjustment. These data support consensus guidelines for intensive surveillance post-cystectomy. Similar methods to account for lead-time bias should be considered in future studies evaluating the benefit of surveillance following curative cancer resection.
Immunosenescence in testicular cancer survivors treated with chemotherapy.
Authors: Bourlon Maria Teresa , Velazquez Hugo Eduardo , Hinojosa Juan , Lima Guadalupe , Rios-Corzo Ricardo , Jimenez-Martinez Karina , Zarco-Letzel Gabriela , Llorente Luis , Atisha-Fregoso Yemil 
Published: September 2018

e16037 Background: Cytotoxic (Ctx) chemotherapy can cure patients with advanced testicular cancer. Notwithstanding, Ctx agents could promote molecular aging and induce cellular senescence in vivo. This phenomenon has been studied in breast cancer patients exposed to adjuvant chemotherapy, however, the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy remains unknown. Methods: Case-control study. Cases were 18-55 yo TCS, treated with chemotherapy (≥3 BEP cycles), disease-free for ≥3 m. Controls were healthy subjects matched by sex and age ± 1 y. Selected subpopulations of isolated peripheral blood mononuclear cells (PBMC) depicted in Table, were analyzed flow cytometry. Statistics: Adjusted counts or relative percentage for each population were compared using student-t test or Mann-Whitney U test as appropriate. Results: We included 15 TCS and 15 controls. Mean age was 32.6 yo (24-54 y). Mean time since last chemotherapy was 53.13 months (3-192 m). All 15 patients were treated with at least 3 BEP cycles ± TIP/VIP cycles. There were no differences in total leucocyte (5128 ± 1917 vs 5850 ± 2141, p=0.36), and lymphocyte (1539 ± 592 vs 1889 ± 825, p=0.4) counts among cases and controls. Cases have a diminished percentage of CD3+ (63 ± 10 vs 71 ± 11, p=0.05) and CD4+ cells (36±8 vs 43 ± 9, p=0.03). There were no differences in pct of CD8+ or CD19+. However, there was an increase in late differentiated CD8+/CD57+ cells (31 ± 14% vs 20 ± 11%, p=0.02); and a decrease in CD4+/CD28+ cells (90 ± 9% vs 97 ± 4%, p=0.02) in cases. We observed paradoxical changes in B cell subpopulations with an increment in naïve (79 ±10 vs 67% ± 14% p=0.02) and a decrease in memory (18 ± 9 vs 31 ± 13%, p=0.01) B cells. Conclusions: TCS after chemo develop changes compatible with immunesenescence in T cell (CD3+) compartment, and an increment in naïve B cells. [Table: see text]
Retrospective review of clear cell and non-clear cell renal carcinomas: Characteristics and course in the pre-TKI (tyrosine kinase inhibitor) and post-TKI era.
Authors: Gupta Kanika , Nizam Amanda , Millado Kristen , Liu Jiaqi , Guebre-Xabiher Hiwot , Nguyen Hong , Siegel Robert S. , Aragon-Ching Jeanny B. 
Published: September 2018

e16052 Background: Renal cell carcinoma (RCC) confers a lifetime risk of 1.6% of developing cancers. Early, localized cancers have high cure rates after surgical treatment, but locally advanced/distant metastatic disease remains a devastating disease. The use of TKIs has been considered a mainstay of treatment for clear cell pathology, but other histologic subtypes such as papillary, chromophobe, and mixed subtypes, which is considered non-clear cell RCC, also make up a heterogeneous pattern and course of disease. This retrospective study characterizes renal cell carcinomas and their treatments. Methods: A retrospective chart review of the last 15 years was performed using data from a single-institution center at the George Washington University Cancer Center Tumor Registry Data. Statistical analysis was performed using the Fisher’s test, Chi-squared test, T-test, and Kaplan-Meier survival curves. Results: 1043 patients with RCC were identified. Preliminary data analysis was performed on 92 of these patients. 48 had pure clear cell renal cell carcinoma (CCRCC) and 44 had non-clear cell carcinoma (NCC). Mean age of diagnosis was similar for both groups (58.25 years for CCRCC vs 62.14 years for NCC, p = 0.0977). However, hemoglobin levels at diagnosis were statistically significantly lower for CCRCC (p = 0.0261), as were calcium levels (p = 0.0187). All patients underwent surgical or local treatment. Only 2 patients received chemotherapy and 5 patients received molecularly targeted therapy. While not statistically significant, patients with CCRCC had surgery sooner after diagnosis than NCC (71 days vs 92 days), had longer time to metastatic disease (1033 days vs 820 days), and improved overall survival (1955 days vs 1446 days). Conclusions: NCC was a less favorable pathology than CCRCC with apparent later institution of surgical intervention as well as shorter time to metastatic disease and worse overall survival. Identifying patients with more aggressive disease earlier allows for the potential role for more aggressive therapies that may result in improved outcomes.
Survival outcomes and patterns of utilization of cytoreductive nephrectomy in the tyrosine kinase inhibitors (TKI)-era in metastatic clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC): Analyses from the National Cancer Database (NCDB).
Authors: Aragon-Ching Jeanny B. , Wang Hongkun , Trump Donald L. 
Published: September 2018

e16068 Background: Use of TKIs is standard of care for metastatic ccRCC and cytoreductive nephrectomy has improved survival even in metastatic ccRCC. The use of cytoreductive nephrectomy in the TKI era post-2005 for nccRCC histologies is unknown. We sought to determine trends and explore differences in characteristics of ccRCC and nccRCC, use of cytoreductive nephrectomy and survival outcomes for varying stages. Methods: Using a de-identified dataset acquired from the NCDB from 2004 to 2014, extraction of demographic information on patients divided into ccRCC versus nccRCC. Descriptive statistics was used for summarizing patients’ characteristics. Chi-Square test was used for comparing categorical variables. Two-sample t-test was used for comparing continuous variables. Kaplan-Meier method was used to analyze patients’ survival data. Results: 302,339 (82%) ccRCC and 66,530 (18%) nccRCC patients were identified. nccRCC included papillary (n = 42,251), sarcomatoid (n = 5769), chromophobe (n = 17,671) and collecting duct (n = 839). The median age for both groups was 63 years, more common in males (ccRCC = 61%; nccRCC = 69%), and mostly Caucasians (ccRCC = 86%; nccRCC = 75%). Most patients were treated in comprehensive community and academic research programs (ccRCC = 81%; nccRCC = 83%). Majority of patients were diagnosed with AJCC Stage I (ccRCC = 57%, nccRCC = 62%). Stage IV was diagnosed in 14% of ccRCC and 9% of nccRCC. The utilization of nephrectomy declined for ccRCC at 36% in the year 2014 compared to 44% in 2005, whereas it declined more for nccRCC with 47% in 2014 compared to 70% in 2005. The median survival time for Stage I was comparable in both groups (ccRCC = 140 mos, 95% CI 138.8 – 142.16; nccRCC = 140 mos, 95% CI 138 – unestimable). However, median survival was worse for stage IV in nccRCC (ccRCC = 9 mos; 95% CI 8.8 – 9.17; nccRCC = 7.43 mos; 95% CI 7.16 – 7.79). Conclusions: In stage IV patients with nccRCC, cytoreductive nephrectomy is used less often and overall survival appears inferior compared to ccRCC.
Dynamics of immune-mediated thyroid dysfunction in patients with advanced renal cell carcinoma receiving checkpoint inhibitor therapy.
Authors: Osorio Juan Carlos , Patil Sujata , Coskey Devyn Taylor , Carlo Maria Isabel , Feldman Darren R. , Hellmann Matthew David , Voss Martin Henner 
Published: September 2018

e16071 Background: Checkpoint inhibitors (CPI) are quickly gaining relevance in the management of metastatic renal cell carcinoma (RCC). Treatment is generally well tolerated, but immune-induced thyroid dysfunction (TD) is reported in up to 10% of patients (pts) across trials. The dynamics of this phenomenon are undefined; hence there are no proposed standards for endocrine surveillance on therapy. Here we report on a cohort of RCC pts treated with CPI at Memorial Sloan Kettering Cancer Center with serial prospective assessment of thyroid function on therapy. Methods: Thyroid function tests (TFT) were assessed at baseline and serially on therapy. We recorded trends for hyper- and hypothyroidism and determined median time to development of TD by standard statistical methods. T4 replacement therapy was investigated by individual chart review. The association of TD with outcomes on CPI therapy was assessed by non-parametric tests. Results: Of 59 pts with serial TFT assessment, 20 were hypothyroid and 39 were euthyroid at baseline. 50% of previously hypothyroid pts required adjustment of T4 dosage. Thirteen of 39 euthyroid pts (36%) developed new TD requiring thyroid replacement. TD occurred early (median time to onset: 1.4 months, range 0.9-9.6), and in six of the 13 pts (46%), transient thyroiditis preceded hypothyroidism. None of the pts with thyroiditis required treatment, and the median duration from onset of thyroiditis to development of hypothyroidism was 1.5 months (range 0.7-2.8). All pts with hypothyroidism required replacement therapy; none required discontinuation of immunotherapy due to TD. TD was not associated with difference in objective response rate (fisher’s exact, p = 0.163), regression in target lesions (wilcoxon rank-sum, p = 0.135), or PFS (log rank p = 0.8214). Conclusions: TD is common in RCC pts receiving CPI therapy. In this cohort, onset of TD was early, thyroiditis was always transient, and no new cases were detected beyond 10 months. Confirming these findings in larger cohorts will provide meaningful data to guide management of TD when using this new class of agents outside of clinical trials.
Organ-preserving surgery for localized renal cell carcinoma: Current approaches.
Authors: Dimitriadi Sergey N , Kit Oleg Ivanovich , Frantsiyants Elena Mikhaylovna , Ushakova Natalya Dmitrievna , Rozenko Dmitry , Shvyrev Dmitry Aleksandrovich , Faenson Aleksandr V. , Goncharov Sergey I. 
Published: September 2018

e16077 Background: Introduction of modern organ-preservingapproaches in surgical treatment of kidney cancer is limited by the duration of warm ischemia used during the partial nephrectomy (PN), including surgery for elective indications. Some resection procedures require prolonged warm ischemia time resulting in acute kidney injury and development of renal failure in the postoperative period. The purpose of the study was to analyze the effectiveness of a new organ-preserving surgery method for kidney cancer. Methods: 46 patients with clinically localized renal cancer, R.E.N.A.L. score 6-10, underwent PN for elective indications. Patients were divided into two groups: the first group – 20 patients (8 patients – laparoscopic PN (LPN), 12 – open PN (OPN)) with bilateral perirenal procaine blockade (BPPB) before the resection. The second group included 26 patients (19- LPN, 7– OPN) receiving surgery without BPPB. BPPB was performed under US-control. 50 ml of 0.25% procaine solution was successively injected to the perinephric fat in upper, middle and lower kidney segments at both sides. Acute kidney injury (AKI) was diagnosed by serum creatinine level increase by 50% of the initial level and higher. Results: Patients in both groups were comparable by age – 58.35±7.5 (44–70) and 58.7±5.6 (50–65) years, and resection difficulty by R.E.N.A.L. score – 7.35±1.1 (6–10) and 7.15±1.2 (6–10), respectively. Median warm ischemia time did not differ significantly in both groups and was 20.0±2.99 (15–25) and 18.42±2.93 (15–25) min., respectively. Morphologically, all patients were diagnosed with renal cancer, surgical margins were negative. 9 (34.6%) patients of the second group developed AKI, while no AKI was registered in the first group. Urinary fistula and delayed bleeding were not observed. Conclusions: The results suppose renal protective effect of BPPB during partial nephrectomy for kidney cancer with warm ischemia time of 15-25-minutes.
Prospective phase II study of sunitinib rechallenge in metastatic renal cell carcinoma (mRCC): A G.I.O.N. trial.
Authors: Porta Camillo , Ferrari Vittorio D. , Zucali Paolo Andrea , Fornarini Giuseppe , Bernardo Antonio , Falconeri Andrea , Ferrari Alessandra , Santarossa Sandra , Pappagallo Giovanni L. , Bearz Alessandra 
Published: September 2018

e16081 Background: Sunitinib is a 1st-line standard of care in mRCC. Lack of cross-resistance to sequential VEGF-targeting drugs and the possibility of a successful rechallenge with Sunitinib have been postulated. Whether mRCC patients (pts) could benefit from rechallenge with Sunitinib after progressing on 1st-line Sunitinib and 2nd-line Everolimus was the aim of this phase II study Methods: 39 mRCCpts were prospectively treated with Sunitinib (50 mg/daily, 4:2); main inclusion criteria were: histologically proven RCC with clear cell component, previous 1st-line Sunitinib with a Disease Control Rate lasting at least 10 months, 2nd-line Everolimus, and written informed consent. The primary end-point of this study was 6-months progression-free survival (PFS). A Simon’s 2-stage design was used; after testing Sunitinib on 12 pts in the first stage, the trial would have been terminated if 5 or fewer had a PFS of less than 6 months. Otherwise, the trial would have proceeded to the second stage, enrolling a total of 38 pts. If the total number of pts free of progression at 6 months would have been less than or equal to 18, Sunitinib would have been rejected Results: As a whole, 39 pts (30 males, 9 females) were enrolled. The study quickly moved from the first stage to its completion and ultimately succeeded; indeed, 6-months PFS was 60%, median PFS being 8.6 months (average: 9.59, range: 0.7-24.6 months). In terms of safety no unexpected toxicities were observed. Tx-related grade 3-4 AEs observed in ≥5% of the pts were: hand-foot skin reaction, fatigue, nausea, hypertriglyceridemia, hypophosphatemia, hypocalcemia, hyperglycemia, and neutropenia. One case each of myocardial infarction, atrial flutter and spontaneous pneumothorax were also reported, but resolved Conclusions: Despite an ineluctable time-lead-bias, median PFS on Sunitinib rechallenge was high (8.6 months), clearly showing that many pts may become sensitive again to VEGFRs-inhibition. Although many agents are presently available from 2nd-line on, in countries where treatment options are still limited, Sunitinib rechallenge could still represent a reasonable treatment option. EudraCT number: 2012-000473-23. Clinical trial information: 2012-000473-23.