bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab (Pembro; MK-3475) for advanced urothelial cancer: Results of a phase IB study.
Authors: O'Donnell Peter H. , Plimack Elizabeth R. , Bellmunt Joaquim , Berger Raanan , Montgomery Robert B. , Heath Karl , Dolled-Filhart Marisa , Pathiraja Kumudu , Gause Christine K. , Cheng Jonathan D. , Perini Rodolfo F. , Gupta Shilpa 
Published: February 2017

296 Background: Pembro, an anti-PD-1 monoclonal antibody, has shown antitumor activity in several advanced solid tumors. The safety, tolerability, and antitumor activity of pembro in pts with recurrent or metastatic urothelial cancer was assessed in a cohort of KEYNOTE-012 (Clinicaltrials.gov: NCT01848834). Methods: PD-L1 expression was assessed in archival or newly obtained tumor samples from pts with advanced carcinoma of the renal pelvis, ureter, bladder, or urethra using a prototype immunohistochemistry assay. Only pts with PD-L1 expression in stroma or ≥1% of tumor cells were eligible. Pts received pembro 10 mg/kg every 2 wks until complete response, progression, or unacceptable toxicity. Pts deriving benefit could remain on pembro beyond initial progression. Response was assessed every 8 wks per RECIST v1.1 by the investigator and by independent central review (primary efficacy end point). Results: 33 pts enrolled (n=30 with transitional cell histology; median age, 70 y [range 44-85]; ECOG PS 1, 70%; 2 prior therapies for advanced disease, 52%; liver metastases, 21%). 22 pts (67%) received ≥3 pembro doses. Median follow-up duration was 11 mos (range 10-13), and 7 pts (21%) remain on therapy. At least 1 drug-related AE was reported by 61% of pts, most commonly fatigue (n=6), peripheral edema (n=4), and nausea (n=3). Grade 3-4 drug-related AEs were reported for 4 pts (12%), with only rash seen in >1 pt (n=2). 29 pts received ≥1 dose of pembro and had a baseline scan with measurable disease and were evaluable for response. ORR was 24% (95% CI, 10%-44%) by investigator review, with 7 partial responses. ORR by central review was also 24% (95% CI, 10%-44%), with 3 (10%) complete and 4 (14%) partial responses. Response duration is 16-40+ wk (median not reached) by both investigator and central review. ORR in key subgroups, including visceral vs. nodal metastasis, will be presented. In pts evaluable for response, median PFS is 8.8 wks by investigator review and 8.6 wks by central review. In all pts, median OS is 9.3 mos (6-mo OS rate, 58%). Conclusions: Pembro shows acceptable safety and tolerability and provides promising antitumor activity in pts with advanced urothelial cancer. Evaluation of pembro for the treatment of urothelial cancer is ongoing. Clinical trial information: NCT01848834.
Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma: Predicting response and assessing outcomes.
Authors: Gandhi Nilay M , Baras Alexander S , Munari Enrico , Faraj Sheila , Reis Leonardo O , Liu Jen-Jane , Kates Max , Hoque Mohammad , Berman David , Hahn Noah M. , Eisenberger Mario A. , Netto George J. , Schoenberg Mark , Bivalacqua Trinity 
Published: February 2017

336 Background: To evaluate gemcitabine-cisplatin (GC) neoadjuvant chemotherapy (NAC) for pathologic response (pR) and cancer-specific outcomes following radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) and identify clinical parameters associated with pR. Methods: We studied 150 consecutive cases of MIBC that received GC NAC followed by open RC (2000-2013). A cohort of 121 patients treated by RC alone was used for comparison. Pathologic response and cancer-specific survival (CSS) were compared. We created the Johns Hopkins Hospital Dose Index (JHH-DI) to characterize chemotherapeutic dosing regimens and accurately assess sufficient neoadjuvant dosing regarding patient tolerance. Results: No significant difference was noted in 5-year CSS between GC NAC (58%) and non-NAC cohorts (61%). The median follow-up was 19.6 months (GC NAC) and 106.5 months (non-NAC). Patients with residual non-muscle-invasive disease after GC NAC exhibit similar 5-year CSS relative to patients with no residual carcinoma (p=0.99). NAC pR (≤pT1) demonstrated improved 5-year CSS rates (90.6% vs. 27.1%, p<0.01) and decreased nodal positivity rates (0% vs. 41.3%, p<0.01) compared to non-responders (≥pT2). Clinicopathologic outcomes were inferior in NAC pathologic non-responders (pNR) compared to the entire RC-only treated cohort. A lower pNR rate was seen in patients tolerating sufficient dosing of NAC as stratified by the JHH-DI (p=0.049), congruent with NCCN guidelines. A multivariate decision tree model demonstrated age ≤60 years and clinical stage cT2 as significant of NAC response (p<0.05). Conclusions: Pathologic non-responders fare worse than patients proceeding directly to RC alone. Multiple predictive models incorporating clinical, histopathologic, and molecular features are currently being developed to identify patients most likely to benefit from GC NAC.
Characterization of molecular features of pediatric urothelial bladder carcinomas.
Authors: Collazo Lorduy Ana , Castillo-Martin Mireia , Hyun Grace , Gladoun Nataliya , Cordon-Cardo Carlos 
Published: February 2017

345 Background: Bladder cancer is a rare entity in the pediatric population making it difficult to define surveillance protocols and long term outcomes. Notably, most pediatric tumors are low grade and non-muscle invasive and do not recur. In order to determine the source of the different natural history between pediatric population and adults, we hypothesized that pediatric bladder cancer may potentially stem from different molecular pathways than its adult form. Our main objective was to study the molecular pathogenesis in this rare disease using immunohistochemical (IHC) and mutational analysis of the main known genes involved in bladder cancer. Methods: Paraffin-embedded tissue slides of bladder tumors from three pediatric patients were retrospectively identified from our institution's pathology archives (1990-present) and re-evaluated. Clinical data was reviewed. FGFR3, H-RAS, and PI3K mutational analysis of the most well-known mutated spots was conducted by PCR amplification and Sanger sequencing. IHC analysis was conducted using antibodies against p53, Pten, Rb, EGFR, Her2Neu and ki-67. Results: Two patients had low-grade Ta disease, whereas the other tumor was classified as a Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP). None of the lesions recurred. Two patients were female and one was male. The ages at diagnosis were 13, 11, and 17, with a mean follow-up of 5.2 years (Range: 1.5-8.0 years). All specimens showed H-RAS G12V mutation, whereas they were characterized by wild-type FGFR3 and PI3K. Nuclear p53 was not detected, whereas PTEN and Rb expression were maintained. EGFR was homogenously expressed in the three cases, and Her2Neu was negative. The proliferation rate analyzed by Ki-67 expression was very low in all cases (<5%). Conclusions: Pediatric tumors may arise from a pathway that is not initiated by FGFR3 or p53 mutations, but by H-RAS mutations. This distinction may explain the relatively few recurrences seen in the pediatric population. Molecular investigation of larger series of pediatric tumors is warranted, and will aid in determining the surveillance and the clinical follow up, if any, needed in this rare entity.
Effectiveness of chemotherapy administration and time to cystectomy following neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) in the academic and community settings.
Authors: Rose Tracy Lynn , Deal Allison Mary , Basch Ethan M. , Godley Paul Alphonso , Rathmell Kimryn , Kim William Y. , Whang Young E. , Dunn Mary , Nielsen Matthew Edward , Pruthi Raj , Wallen Eric , Woods Michael , Smith Angela , Milowsky Matthew I. 
Published: February 2017

359 Background: Neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy is the standard of care for MIBC. Many patients are referred to an academic medical center (AMC) for cystectomy but receive NAC in the community setting. It is unknown if administration of NAC in the community is associated with differences in type of NAC received, pathologic response rate (pT0), and time to cystectomy as compared to NAC administered at an AMC. Methods: This is a retrospective study of 135 patients referred to a single AMC with MIBC (cT2a-T4-Nx-M0) between 1/2012 and 1/2014. We analyzed patient demographics, clinical stage, treatment, pT0 and time to cystectomy in patients who received NAC at our AMC compared to those referred to the community setting. Comparisons were made using Wilcoxon rank-sum, Fisher’s exact test, and multivariable linear regression. Results: Median age was 70, 73% were male, and 83% Caucasian. Most patients (73.3%) had clinical stage II disease. 94 (69.6%) underwent cystectomy and of those, 47 (50%) received NAC. 34% received NAC at our AMC and 66% in the community. Age, sex, clinical stage, and renal function did not differ significantly between those who received NAC in the community and those at our AMC. Those who received NAC in the community had a similar total dose of cisplatin (median 280 mg/m2 for both groups, p=0.89) and pT0 rate (25% vs. 30%, p=0.72) compared to those who received NAC at our AMC. However, community administration of NAC was associated with a significantly prolonged time from initial visit to cystectomy (median number of days 128 vs. 162, p<0.01). This remained significant after adjusting for age and renal function (p=0.04). Conclusions: Patients with MIBC treated with NAC in the community as compared to an AMC received similar chemotherapy and achieved comparable pT0 rates suggesting the effective implementation of NAC in the community setting. However, those who received NAC in the community had a significantly longer time from initial visit to cystectomy, suggesting a delay in the transfer of care between settings and an area for improvement.
Effect of early detection of asymptomatic visceral recurrence after radical cystectomy on prognosis in patients with muscle invasive bladder cancer.
Authors: Hatakeyama Shingo , Yamamoto Hayato , Imai Atsushi , Yoneyama Takahiro , Hashimoto Yasuhiro , Koie Takuya , Kusaka Ayumu , Ohyama Chikara 
Published: February 2017

361 Background: It is unknown whether routine follow-up with computed tomography (CT) to detect asymptomatic visceral recurrence after radical cystectomy improves patient survival. We accessed the impact of symptoms at recurrence on patient survival after radical cystectomy and survival after recurrence. Methods: A total 348 radical cystectomy for muscle invasive bladder cancer (MIBC) were performed at our institution between January 1996 and December 2013. All patients had regular followup examinations with urine cytology every 3 months, blood biochemical test, and CT of the chest and abdomen every 6 months. Additional examinations were required for symptomatic recurrence. We investigated the first site and date of tumor recurrence. Overall survival in patients with recurrence stratified by the mode of diagnosis (asymptomatic vs. symptomatic) was estimated using the Kaplan-Meier methods and compared with the log rank test. Cox proportional hazard regression models were used to evaluate the impact of the mode of diagnosing recurrence on survival. Results: A total 91 patients (20%) experienced recurrence after surgery. Seven patients (8%) were excluded due to missing data. Finally, 84 patients were enrolled in this retrospective study. Of those, 46 (55%) were asymptomatic and 38 (45%) were symptomatic. Recurrence sites included lymph nodes in 46 patients (55%), local recurrence in 23 (27%), bone in 14 (17%) and visceral organs in 21 (25%). The most common symptoms at recurrence were pain in 20 patients (53%). Overall survival after radical cystectomy and recurrence were significantly shorter in patients with asymptomatic recurrence. The median survival after surgery and after tumor recurrence in patients with asymptomatic vs. symptomatic recurrence were 33 and 14 vs. 13 and 5 months, respectively (P=0.0142 and P=0.0001). Multivariate analysis showed that a symptomatic recurrence was one of the independent factors for overall survival after surgery and recurrence. Conclusions: Routine CT followup after radical cystectomy for early detection of asymptomatic recurrence may contribute better prognosis in patients with MIBC.
Is measuring serum levels of microRNA miR-371a-3p superior to the classical biomarkers of testicular germ cell tumors?
Authors: Dieckmann Klaus-Peter , Spiekermann Meike , Ruf Christian G , Oechsle Karin , Belge Gazanfer 
Published: February 2017

376 Background: There is need for more serum biomarkers of testicular germ cell tumors (GCTs) because the management of GCT is largely based on marker monitoring but only 60% of patients express the classical markers AFP and beta HCG. We measured serum levels of microRNA miR-371a-3p (miR-371) in GCT patients with the aim of establishing a new biomarker. Methods: Serum samples of 130 consecutive patients with GCT (75 seminoma, 55 nonseminoma; 90 clinical stage 1, 40 higher stages) were examined for miR-371a-3p before and after treatment. 105 young males with nonmalignant testicular diseases and 10 patients with non-GCT testis tumors served as controls. Serum levels of miR-371a-3p were measured by quantitative polymerase chain reaction with quantification in relation to miR-20a as internal standard. Measurements were correlated with clinical data, analysis involved descriptive statistical methods. Results: Over 90% of all patients had higher serum levels of miR-371a-3p than controls. After treatment, all elevated levels decreased to the normal range. All metastasized patients had significantly higher mean levels than stage 1 patients, serum levels appear to correlate with tumor bulk. Upon chemotherapy levels decreased with each cycle of therapy. After orchiectomy in stage 1 cases, serum levels dropped by 95% within 24 hours. Nonseminomas had higher mean levels than seminoma. Teratoma does not express miR-371a-3p. The levels remained low during follow-up. Conclusions: Serum levels of microRNA miR-371a-3p appear to comprise of all attributes of a valuable serum biomarker of germ cell tumors. This marker is also expressed in seminoma and it apparently outperforms the classical markers. Evaluation in a large scale multicentric study is warranted.
Receipt of inguinal lymph node dissection in patients with T2 penile cancer: Results from the National Cancer Database.
Authors: Haseebuddin Mohammed , Handorf Elizabeth , Waingankar Nikhil , Wong Yu-Ning , Viterbo Rosalia , Greenberg Richard Evan , Uzzo Robert G. , Kutikov Alexander , Smaldone Marc C. , Chen David Y. T. 
Published: February 2017

383 Background: Per the NCCN guidelines, inguinal lymph node dissection (ILND) is recommended for patients with intermediate (T1b) or high (Any T2 or Grade 3) risk disease even in the absence of palpable inguinal nodes. Our objective was to assess temporal trends in utilization of ILND and to determine factors associated with the receipt of ILND using National Cancer Database (NCDB). Methods: The NCDB was queried for all patients diagnosed with T2 penile cancer from 1998-2011. Temporal trends for receipt of ILND were assessed. Adjusting for patient, demographic, and clinicopathologic characteristics, multivariable logistic regression models were used to examine the association between available covariates and receipt of ILND. Results: Of 2019 patients identified over the study period, 693 (34.3%) underwent ILND. Rates of ILND did not significantly improve from 1998 to 2011 (34.2 to 40.0%; p = 0.09). Significant differences were observed in patients undergoing ILND with respect to age (p<0.001), Hispanic ethnicity (p=0.04), insurance status (p<0.001), and facility type (p<0.001), while no changes were seen with respect to race, income, education, urban/rural location, tumor grade, or Charlson co-morbidity score. Following adjustment, patients with high grade disease (OR 1.35 [CI 1.1-1.7]) and those treated at academic centers (OR 3.2 [CI 2.2-4.7]) were more likely to receive ILND, while patients >70 years of age (OR 0.41 [CI 0.28-0.60]) were less likely to receive ILND. Conclusions: In the NCDB, less then 35% of patients with T2 penile cancer receive ILND and the rates have not significantly changed over the last decade. Referral of patients with this uncommon, highly morbid lethal disease to experienced centers may increase adherence to guideline recommended care.
The proportion and characterization of patients with metastatic renal cell carcinoma who are never treated or have delayed treatment with targeted therapy: Results from a large prospective cohort.
Authors: Bains Param , Heng Daniel Yick Chin , Knox Jennifer J. , Bjarnason Georg A. , Kollmannsberger Christian K. , Hotte Sebastien J. , Kapoor Anil , Vanhuyse Marie , Reaume M. Neil Neil , Czaykowski Piotr , Soulieres Denis , Basappa Naveen S. , Saarela Olli , Wood Lori 
Published: February 2017

424 Background: The proportion and characterization of patients (pts) with metastatic renal cell carcinoma (mRCC) who never start or delay starting targeted therapy (TT) is unknown. It is important to understand and characterize these pts. Methods: Data from the Canadian Kidney Cancer information system (CKCis) database were utilized. CKCis data were collected prospectively from 14 REB-approved academic centers in Canada. The study population included pts with mRCC managed from 2006 (when VEGFR TT became available) to 2014. Results: 920 pts met the inclusion criteria, but 67 pts had <6 months (mo) follow up and were excluded. Thus, 853 pts make up the study cohort with a median follow up of 21 mo. The cohort was divided into 3 groups: early (started TT within 6 mo), delayed (started TT after 6 mo), and never (never started TT). The groups consisted of 406 pts (47.6%), 182 pts (21.3%), and 265 pts (31.1%), respectively. In those that started TT, median time to initiation was 3.2 mo; 69% by 6 mo, 82% by 12 mo, 92% by 24 mo, and 99.7% by 5 yrs. Multiple baseline characteristics were determined, compared, and will be presented. On univariable analysis, pts never treated were older, had a longer interval from original diagnosis to metastases (mets), fewer metastatic sites, fewer liver mets, more lung-only mets, more metastectomies, and less radiation (RT). On Cox regression analysis, pts were less likely to initiate TT if they were older, had earlier year of diagnosis of mets, had metastectomy, never had RT, fewer sites of mets, and brain mets. Median survival from time of metastatic diagnosis was 1.53 yrs, 3.54 yrs, and 1.41 yrs in the early, delayed, and never treated groups, respectively. Conclusions: 31% of pts with mRCC never received TT in this cohort of pts treated in academic centers, which may underrepresent the reality in the community. Baseline characteristics in the delayed treatment group were better and likely represent a more indolent biology. More data on the untreated group will be presented as it comprises a heterogenous group of pts: potentially those lost to follow up, those treated with metastectomy, pts too ill with limited survival, and pts felt to have excellent outcomes without treatment.
A phase Ib dose-escalation study of TRC105 (anti-endoglin antibody) in combination with axitinib in patients with metastatic renal cell carcinoma.
Authors: Choueiri Toni K. , Michaelson M Dror , Posadas Edwin M. , Sonpavde Guru , McDermott David F. , Walsh Meghara K. , Wall Kevin C. , Seon Ben K. , Jivani Manoj A. , Adams Bonne J. , Theuer Charles P. 
Published: February 2017

426 Background: Resistance to VEGF-targeted therapy is a major challenge in contemporary treatment of metastatic renal cell carcinoma (mRCC), and endoglin (CD105) activation may be an important mechanism leading to resistance. Endoglin is an essential angiogenic receptor expressed on proliferating tumor vessels and mRCC cancer stem cells that is upregulated following VEGF inhibition. TRC105 is an anti-endoglin monoclonal antibody that potentiates bevacizumab (Bev) and VEGF receptor tyrosine kinase inhibitors (VEGFR TKI) in preclinical models. Methods: Heavily-pretreated mRCC pts with ECOG PS 0-1, and acceptable organ function were treated with TRC105 weekly (8 mg/kg and then 10 mg/kg) in combination with axitinib (initially at 5 mg PO BID and then escalated per patient tolerance to a maximum of 10 mg PO BID). Results: Eighteen mRCC pts (median age=61.5; M:F 16:2; median number of prior therapies=3, including >1 VEGFR TKI, clear cell=13, prior axitinib allowed) were treated. TRC105 dose escalation proceeded from 8 mg/kg (n=3) to 10 mg/kg (n=15) without dose limiting toxicity. Low grade AEs characteristic of each drug were not increased in frequency or severity at the recommended phase 2 doses of the two drugs. Three pts (18%) were PR by RECIST and 8 of 17 pts (47%) exhibited >10% tumor reduction. Median PFS is not mature and is at least 5.8 months in the overall population and at least 5.9 months in ccRCC pts. The single patient who progressed on axitinib immediately prior to study entry remains progression free at month 5 with minor tumor regression. Conclusions: TRC105 at 8 and 10 mg/kg was well tolerated with axitinib in mRCC pts with signs of activity. A multicenter randomized phase II trial of axitinib +/- TRC105 is accruing at this time. Clinical trial information: NCT01806064.
Specificity of radiographic lymphadenopathy for lymph node metastasis in renal cell carcnioma.
Authors: Mossanen Matthew , Dighe Manjiri , Wilson Bryan , Lin Daniel W. , Wright Jonathan L. , Harper Jonathan D. , Gore John L. 
Published: February 2017

442 Background: Approximately 30% of patients with renal cell carcinoma (RCC) will have metastatic disease at the time of diagnosis. Patients without preoperative lymphadenopathy (LAD) radiographically rarely have positive nodes at the time of nephrectomy. We sought to evaluate the specificity of radiographic LAD for lymph node metastases in patients with and without clinical metastatic RCC. Methods: We retrospectively reviewed all nephrectomies performed at our institution from 2003-2013. We identified patients with clinical stage classification T2-T3 (cT2-T3) RCC and stratified patients by clinical N and M classification. Lymphadenectomy was performed at surgeon discretion. Performance statistics for preoperative imaging for pathologic lymph node metastases and multivariable logistic regressions models to identify patient characteristics associated with lymph node metastases were generated. Results: A total of 223 patients were identified. Of these, 85 (38%) had clinical evidence of metastatic disease while 138 (62%) did not. In patients with clinical metastatic disease, LND was performed in 68%; of those without clinical metastatic disease, LND was performed in 48%. Radiographic LAD for those with clinical metastatic disease (26/85 patients, 31%) had sensitivity of 94%, specificity of 49%, positive predictive value (PPV) of 43%, and negative predictive value (NPV) of 95% for pathologically confirmed lymph node involvement. Radiographic LAD for patients without clinical metastatic disease (37/138 patients, 27%) had sensitivity of 90%, specificity of 52%, PPV of 25%, and NPV of 96% for pathologically confirmed lymph node involvement. On multivariate logistic regression analysis (adjusted for age, gender, smoking status, obesity, non-clear cell histology, and grade) having clinical metastatic disease was significantly associated with pathologic node positivity (RR = 3.37, 95% CI 1.19 – 20.6). Conclusions: Radiographic lymphadenopathy is a nonspecific finding in patients with RCC and LND is not routinely performed at our institution. However, in the setting of clinical metastatic disease, radiographic LAD is more likely to represent pathological lymph node metastases.