bluuebunny/crossref_metadata_2025_split huggingface dataset:
A review of the stage, recurrence, treatment, and outcomes in penile cancer at a tertiary referral center.
Authors: Franklin Andrew , Koehne Elizabeth , Haden Tyler , Ross Gilbert , Stephen Weinstein , Wakefield Mark , Pokala Naveen , Hoyt Daniel 
Published: February 2017

495 Background: This was a retrospective review analyzing the epidemiological and pathological association of penile cancer as well as the clinical results in patients managed at the University of Missouri Hospital and Clinics (UMHC) and Harry S Truman VA. Methods: Records were obtained of patients with a pathological diagnosis of penile cancer from 2001−2014 at UMHC and at the Harry S Truman VA. These charts were retrospectively reviewed. Information regarding patient demographics, pathology, treatment, and outcomes were recorded. Results: Forty-four patients with a pathologic diagnosis of penile cancer were identified. Mean age at diagnosis was 64 with 41 being White, 2 unknown, 1 Black, and 1 Hispanic. Seventy-two percent had tobacco exposure, with 66% of all patients having smoked greater than 10 years. HPV was present in 20%. Circumcision status was reviewed showing overall 61% were circumcised, with 4.5% being circumcised before the age of 18. Premalignant lesions were identified in 36% of the patients, with condyloma acuminate being the most common followed by Lichen Sclerosus and severe dysplasia. The vast majority (98%) of penile cancers were squamous cell carcinoma (SCCa), with only one patient having a Buschke−Lowenstein tumor. Invasive SCCa without nodal involvement was the most common pathologic stage (41%) followed by nodal positive disease (36%) and CIS (23%). Of those with node positive disease, 56% were dead less than 5 years after nodal involvement. Ninety-nine procedures with curative intent were performed, with a mean of 2.25 procedure per patient. However, only 79 of the procedures led to a sustainable cure. Of those patients with metastatic disease 13.6% underwent chemotherapy and 9.1% received radiation. Conclusions: Our study reflects the trends in stage, recurrence, treatment, and outcomes at two large centers for penile cancer. In this patient group the majority had exposure to tobacco and almost exclusively had SCCa. A durable cure may require multiple operative interventions. Nodal involvement carries a poor prognosis and high risk of death in less than 5 years once diagnosed.
Expression of Aldo-keto-reductase 1B1 (AKR1B1) in tubulocytic carcinoma of kidney.
Authors: Hashimoto Yasuhiro , Tanaka Toshikazu , Imai Atsushi , Hatakeyama Shingo , Yoneyama Takahiro , Koie Takuya , Ohyama Chikara 
Published: February 2017

507 Background: Tubulocystic carcinoma of the kidney (TubCC) is a new entity of tumor not listed in the 2004 WHO classification. The tumor comprised tubules forming duct-like structures exhibiting hobnail change, and resembled collecting duct carcinoma (CDC) by immunostaining; thus, this tumor was named low grade CDC. Since then, similar tumors have been reportedly called tubulocystic carcinoma (TubCC)We explored the possibility whether Aldo-keto-reductase-1B1 (AKR1B1), osmoregulatory protein and abundant in collecting duct, can be used as a marker for the pathologic diagnosis of TubCC. Methods: We prepared anti-AKR1B1 monoclonal antibodies, examined expression of AKR1B1 protein in the human normal kidney. Immunohistochemical expressions of AKR1B1 was examined on normal kidney, 4 cases of TubCC, 10 cases of papillary renal cell carcinoma (pRCC), and 10 cases of invasive urothelial carcinoma (iUC). Results: AKR1B1 expression distributed preferentially in the renal medulla and not in the cortex, reflected by its high concentration in medulla (2.12 ±1.35 μg/mg) compared with cortex (0.13 ± 0.03 μg/mg). Immunohistochemically, AKR1B1 was strongly positive in 3 of 4 TubCC cases. AKR1B1 was negative in cases of either iUC or pRCC. Conclusions: Although the present study was small and preliminary, AKR1B1 may be a more specific and potentially useful marker for TubCC. [Table: see text]
Renal function in advanced renal cell carcinoma patients treated with sorafenib: Subset analyses of post-marketing surveillance in Japan with over 3,200 consecutive cases.
Authors: Oya Mototsugu , Kabu Koki , Adachi Masatoshi , Ito Yuichiro , Akaza Hideyuki 
Published: February 2017

518 Background: Patients with advanced renal cell carcinoma (RCC) are predisposed to impaired renal function due to prior nephrectomy and existing renal mass. Moreover, treatment with molecular targeted agents may also affect renal function. We retrospectively analyzed post marketing all-patients surveillance to assess the effect of sorafenib on the renal function of advanced renal cell carcinoma (RCC) in real-world use. Methods: We have collected safety/efficacy data of over 3,200 consecutive Japanese patients with advanced RCC treated with sorafenib under daily medical practice (1). Using this database, the effect of sorafenib on renal function was analyzed in a post-hoc manner, by calculating estimated glomerular filtration rate (eGFR) from age, gender, and serum creatinine at each time point. Results: The eGFRs at baseline (n=2,943), 12 months after sorafenib treatment (n=636, and the time of discontinuation (n=1712) of all patients were 54 ± 21, 57 ± 24, and 59.6 ± 31.8 mL/min/1.73 mm2, respectively, and showed no significant differences. The mean eGFRs of each segment at baseline and 12 months were 110 ± 26 and 96 ± 39 in G1(eGFR ≥90), 70 ± 8 and 73 ± 23 in G2 (eGFR ≥60 and <90), 52 ± 4 and 57 ± 15 in G3a (eGFR ≥45 and <60), 39 ± 4 and 43 ± 11 in G3b (eGFR ≥30 and <45), 24 ± 4 and 30 ± 10 in G4 (eGFR ≥15 and <30), 7 ± 3 and 11 ± 12 in G5 (eGFR <15), respectively. The median daily dose were 726mg (G1), 522mg (G2), 524mg (G3a), 517mg (G3b), 483mg (G4), and 400mg (G5). The incidence of renal AEs seemed to be higher in G4 and G5 (14% and 6%, respectively) than the other groups. The objective response rate ranged from 29.2% in G3a to 18.3% in G5, and the overall survival were higher in G3a and G3b (1 year survival rate: 81.5% and 78.4%, respectively), and lower in G1 (1 year survival rate: 50.2%). Conclusions: This study demonstrated that little impact on renal function of advanced RCC patients treated with sorafenib during observational period with sufficient clinical response and safety irrespective of the baseline eGFR value.
Everolimus (E) versus axitinib (A) as second-line therapy (2L) in metastatic renal cell carcinoma (mRCC): Retrospective experience at Gustave Roussy.
Authors: Guida Annalisa , Albiges Laurence , Loriot Yohann , Massard Christophe , Fizazi Karim , Escudier Bernard J. 
Published: February 2017

527 Background: Currently both E and A are standard treatments for patients (pts) with mRCC after failure of first line therapy (1L)with VEGF-targeted therapy. There is no comparative study reported so far, and this study aims to evaluate these 2 drugs in a large center. Methods: Patient characteristics, safety and outcome data from all mRCC pts who received E or A as 2L at Gustave Roussy from April 2007 to May 2015 have been compared. Progression-free Survival (PFS) and Overall Survival (OS) were assessed by the Kaplan-Meier method and compared with the log-rank test. Results: 81 pts were treated with E and 45 pts with A. The table shows patient characteristics. The 2 groups were similar. The most common 1L was sunitinib (79% in E group and 82.2% in A group). Median follow up was 29 mo (95%CI 26 – 31), 26 mo for A and 33 mo for E (p=0.046). Median OS was 21.5 mo for E and 14.9 mo for A (p = 0.23). Median PFS was 5.3 and 7.7 mo for E and A respectively (p = 0.39). Disease control rate was 69% and 73% (p=0.31) and partial response was achieved in 4% and in 24% of pts (p=0.002), respectively in E and A cohort. At time of analysis E is ongoing in 3 pts (4%) and A in 9 pts (20%) (p=0.008). Third-line therapy (3L) was administrated in 62% of pts after E and in 33% after A (p=0.003). The most common 3L after E is A (48%) and vice versa the most common after A is E (71%). Median PFS of 3L after E is 9.1 mo (12.1 mo for A and 8 mo when 3L is not A (p=0.17)). Median PFS of 3L after A is 7.8 mo (95%CI 4-12). Conclusions: No statistically significant difference for PFS and OS were observed. Nevertheless, A showed more PR than E, while more pts received 3L after E. A remains very active in 3L. [Table: see text]
Metastatic papillary renal cell carcinoma: A retrospective study from two large academic centers in Sweden.
Authors: Stenman Maria , Nearchou Andreas Demetrios , Sandström Per , Lindskog Magnus , Harmenberg Ulrika 
Published: February 2017

535 Background: Non-clear cell renal cell carcinoma (nccRCC) constitute about 10-15% of all metastatic renal cell carcinoma (mRCC) and typically include papillary, chromophobe and collecting duct histologies. Despite differences in clinical behavior between subtypes they are often grouped as one due to small patient numbers. Hence, there is a lack of knowledge on type-specific prognosis and treatment options. Methods: Patients diagnosed with metastatic nncRRC (56 out of 526 patients; 10.8%) during the years 2005-2013 were retrospectively identified using data from medical records at two large academic centers in Sweden. The characteristics and outcome of those with papillary subtype (n = 44; 79% of nccRCC) was analyzed. Results: Metastatic papillary RCC patients were more often male (82%), had a median age of 69 years and 48% had M1 disease. 9% were type I, 41% type II, 4% mixed and 41% papillary NOS. 89% had a nephrectomy and 56% received at least one line of systemic therapy. The median overall survival (OS) of all papillary patients was 10.1 months. Factors associated with OS included performance status (PS; OS 25.8 months for ECOG PS 0-1 patients vs OS 3.1 months for ECOG PS > 1 patients, p = 0.00002), and systemic therapy (OS 23.4 months vs 3.8 months for patients not treated systemically, p = 0.002). Systemic therapies (ST) included VEGF targeting agents (88%), mTOR inhibitors (50%), or interferon (21%) for all lines. The most common first line ST was VEGF targeting agents (75%). 42% received one line, 33% two lines, and 25% three or more lines of ST. Characteristics of patients treated with ST included lower age at diagnosis, higher proportion of M1 disease and better PS. The reasons for not giving systemic treatment were primarily poor performance status or comorbidities. ECOG PS > 1 (p = 0.04) and poor MSKCC risk group (p = 0.02) were predictive of OS among patients treated with ST. Conclusions: Patients with metastatic papillary RCC and good performance status (ECOG PS 0-1) seem to benefit from systemic therapy using drugs primarily evaluated for clear cell RCC. However, patients not eligible for systemic therapy due to poor performance status or other reasons have a dismal prognosis.
Comprehensive genomic profiling of renal cell carcinoma with sarcomatoid dedifferentiation to pinpoint recurrent genomic alterations.
Authors: Malouf Gabriel G. , Ali Siraj Mahamed , Wang Kai , Balasubramanian Sohail , Ross Jeffrey S. , Miller Vincent A. , Stephens Philip J. , Khayat David , Mouawad Roger , Pal Sumanta K. , Su Xiaoping , Sircar Kanishka , Tamboli Pheroze , Jonasch Eric , Tannir Nizar M. , Wood Christopher G. , Karam Jose A. 
Published: February 2017

537 Background: Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is found in five percent of all renal cell carcinoma (RCC) cases, and has a significantly worse prognosis relative to matched highgrade RCC with only epithelial elements. The genomic features underpinning sRCC are not well understood, and at present, there are no specific or effective therapies for sRCC. Methods: We conducted comprehensive genomic profiling (CGP) on paired epithelial and sarcomatoid areas of 3 sRCC cases. In the course of routine clinical care, CGP was performed on another 23 sRCC harboring diverse epithelial components. CGP was conducted using a hybrid capture next generation DNA sequencing assay(NGS) of 236 cancer-related genes plus 19 genes frequently rearranged in cancer. Results were compared with 56 similarly sequenced cases of clear cell RCC devoid of sarcomatoid component, and with clear cell TCGA. Results: Two of three sRCC cases that underwent CGP of both their epithelial and the sarcomatoid components demonstrated identical mutational profiles, and a third case demonstrated commonly disrupted genes. Of the 23 sRCC, TP53(43%), CDKN2A(30%), VHL(26%) and NF2(22%) were the most frequently altered genes. NF2 mutations were mutually exclusive with TP53 but not with VHL mutations. Conclusions: Two of three sRCC cases that underwent CGP of both their epithelial and the sarcomatoid components demonstrated identical mutational profiles, and a third case demonstrated commonly disrupted genes. Of the 23 sRCC, TP53(43%), CDKN2A(30%), VHL(26%) and NF2(22%) were the most frequently altered genes. NF2 mutations were mutually exclusive with TP53 but not with VHL mutations.
Outcome of octogenarian versus (vs) young patients (pts) with metastatic renal cell carcinoma (mRCC), treated with sunitinib (su).
Authors: Kushnir Igal , Rosenbaum Eli , Sella Avishay , Sarid David , Gottfried Maya , Maimon Natalie , Peer Avivit , Neumann Avivit , Neiman Victoria , Kovel Svetlana , Gez Eliahu , Mermershtain Wilmosh , Rouvinov Keren , Carducci Michael Anthony , Eisenberger Mario A. , Hammers Hans J. , Sinibaldi Victoria J. , Berger Raanan , Keizman Daniel 
Published: February 2017

538 Background: Su is a standard treatment (tx) for mRCC. Octogenarian pts (aged ≥ 80) are often considered to be unfit for su tx, and recommendations for their tx is limited by the paucity of clinical trials data in this population. We aimed to study baseline characteristics and outcome of octogenarian vs young (aged ≤45) pts with mRCC treated with su. Methods: We performed an international multicenter retrospective study of pts with mRCC, who were treated with su in 8 centers across 2 different countries. We compared baseline characteristics and outcome of octogenarian versus young pts. The effect of very old age on response rate (RR), progression free survival (PFS) and overall survival (OS), was tested with adjustment of other known confounding risk factors using a chi-square test and partial likelihood test from cox model. Furthermore, univariate and multivariate analyses of association between clinicopathologic factors and age, and outcome were performed using the entire pt cohort. Results: Between 2004-2013, 36 octogenarian (group 1; median age 83) and 37 young (group 2; median age 42) mRCC were treated with su. The groups were balanced regarding the following baseline clinicopathologic characteristics: gender, HENG risk, past nephrectomy, mRCC histology, ≥ 2 metastatic sites, lung/liver/bone metastasis, prior targeted tx, smoking status, use of angiotensin system inhibitors (ASIs), pre-tx neutrophil to lymphocyte ratio (NLR) >3, and sunitinib induced hypertension (HTN). In group 1 vs 2, 53% vs 27% (p=0.006) had dose reduction/treatment interruption d/t side effects. Clinical benefit (partial response + stable disease) in group 1 vs 2 was 76% vs 84%, while 24% vs 16% had disease progression within the first 3 months of tx (p=0.09). Median PFS was 11 vs 8 months (p=0.1). Median OS was 22 vs 20 months (p=0.7). In multivariate analyses of the entire pt cohort (n=73), age was not significantly associated with PFS or OS. Conclusions: Su is active in octogenarian mRCC pts. Vs young pts, a significantly higher proportion of octogenarian pts had dose reduction/treatment interruption d/t side effects.
Physician treatment selection in the prospective Metastatic Renal Cell Cancer (MaRCC) Registry.
Authors: Kyriakopoulos Christos , Harrison Michael Roger , Bhavsar Nrupen Anjan , Wolf Steven Paul , Costello Brian Addis , Stadler Walter Michael , Hammers Hans J. , Vaishampayan Ulka N. , Appleman Leonard Joseph , Creel Patricia A. , Samsa Greg P. , Richardson Eric M. , Johnson Kathleen A. , Borham Azah , George Daniel J. 
Published: February 2017

563 Background: Clinical trials mRCC pts are different from real world pts, resulting in bias in the literature. The MaRCC Registry is designed to survey questions not asked in tri als, such as why physicians make certain management decisions. This analysis describes reasons for physician treatment (tx) selection in the first 109 real world pts enrolled in a multicenter, prospective, observational registry. Methods: MaRCC Registry will enroll 500 pts from up to 60 US academic (ACAD) and community (COMM) sites with ~2 years of recruitment and ≥ 3 years of follow-up. Key inclusion criteria are age ≥ 18 years and diagnosis of mRCC with no prior systemic therapy (STx) for mRCC at study entry. Pts currently not on STx but who are being observed are permitted. Key endpoints include descriptive characteristics of txs, tx and patient outcomes, medication adherence, and health resource utilization. Results: At data cutoff, 105 pts have been accrued with known STx status; median age 64 (Q1-3 range, 56-70); 66% male; 75% ACAD; 87% clear cell histology; and 31% stage IV at diagnosis. Initial management decision was: 40% deferred systemic therapy (DSTx), 22% pazopanib, 18% clinical trial, 10% sunitinib, and 6% other. Among STx pts (N = 61), the most common categories for therapy choice as selected by providers were likelihood of clinical benefit (41%) followed by pt characteristics (30%). Within the clinical benefit category, the most common reason was OS/PFS (31%). Within the pt characteristic category the most common reasons included performance status/frailty (12%) or prognostic factors (12%). Common reasons for DSTx pts (N = 44) were active surveillance (AS) with disease present (39%), AS without disease present following a procedure (11%), or local therapy (7%). ACAD sites had higher percentages of pts with DSTx undergoing AS with disease present and local therapy. Conclusions: This is the first report describing factors driving physician decision making in management of mRCC. Management choices are not captured in other prospective or retrospective studies. Early experience suggests that clinical benefit and pt characteristics were common reasons for initial STx. Side effect profile rarely determined initial STx selection.
Can PSA density and free-to-total PSA ratio improve our ability to predict prostate cancer on biopsy? Results from a prospective, multi-institutional, and contemporary cohort.
Authors: Rai Samarpit , Soodana-Prakash Nachiketh , Pavan Nicola , Nahar Bruno , Patel Amil , Dong Yan , Satyanarayana Ramgopal , Parekh Dipen , Punnen Sanoj 
Published: February 2017

57 Background: Several studies have reported an increased value of PSA density (PSAD) and free−to−total PSA ratio (f/t PSA) over PSA alone in predicting prostate cancer (PCa). Despite this, they remain underutilized. This study analyzed a cohort of men referred for prostate biopsy (PB) to determine if PSAD and f/t PSA enhanced the prediction of any PCa and/or significant PCa (Gleason score ≥ 7) compared to PSA. Methods: 1,370 prospectively enrolled patients were referred for a PB across 26 urological centers. A phlebotomy was performed immediately prior to PB for PSA and f/t PSA measurement. PSAD was calculated using prostate volume obtained during the trans−rectal ultrasound (TRUS) guided PB. The area under the receiver operating characteristic curve (AUC) was used to assess the added discriminative value of PSAD and f/t PSA when added to a base model consisting of PSA, age, prior biopsy status, and DRE for the prediction of any and significant PCa. Results: Of the 1,290 men in the final cohort, 301 (23%) and 284 (22%) men were diagnosed with low−grade (Gleason score = 6) and significant PCa respectively. The median PSAD values in men with no PCa, low−grade PCa, and significant PCa were 0.09, 0.11, and 0.17 ng/mL/cc, respectively (P < 0.0001). The median f/t PSA in men with no PCa, low−grade PCa, and significant PCa was 0.21, 0.17, and 0.12 respectively (P < 0.0001). The AUC for a model incorporating PSAD showed superior predictive value compared to the base model for diagnosing any PCa (AUC 0.76 versus 0.70, P < 0.0001) and significant PCa (AUC 0.82 versus 0.77, P < 0.0001). Similarly, a model with f/t PSA showed superior predictive value compared to the base model for diagnosing any PCa (AUC 0.73 vs 0.70, P < 0.0001) and significant PCa (AUC 0.82 versus 0.77, P < 0.0001). While PSAD showed superior predictive value over f/t PSA for predicting any PCa (AUC 0.76 versus 0.73, P = 0.0062), there was no difference in their discrimination of significant PCa. Conclusions: PSAD and f/t PSA add substantial predictive power to the diagnostic armamentarium for any and significant PCa. Their calculation may reduce the number of unnecessary biopsies being performed for PCa detection.
Molecular profiling of renal medullary carcinoma to reveal frequent alterations in chromatin remodeling genes and to identify EZH2 as a relevant therapeutic target.
Authors: Gao Jianjun , Malouf Gabriel G. , Su Xiaoping , Yao Hui , Rao Priya , He Rong , Xiong Liangwen , Karam Jose A. , Matin Surena F. , Mouawad Roger , Comperat Eva , Khayat David , Wood Christopher G. , Tannir Nizar M. 
Published: February 2017

571 Background: Renal medullary carcinoma (RMC) is a rare and highly aggressive malignancy that affects primarily young adults with sickle cell trait. The prognosis of RMC is poor with a median survival of about 12 months from diagnosis. It has been previously shown that loss of heterozygosity of SMARCB1 occurs in the majority of cases leading to protein loss. However, a comprehensive molecular profiling of this disease remains unknown. Methods: Whole-exome sequencing (WES) of 9 RMC matched tumor-normal cases and 1 unmatched case were performed. In addition, single nucleotide polymorphism (SNP) analysis was done using the Affymetrix SNP 6.0 array. To test differentially expressed genes between RMC cases and normal kidney, RNA sequencing was carried out. The effect of EZH2 inhibition on in vitro RMC tumor cell proliferation was assessed using the MTT assay. Results: WES analysis of 9 paired RMC cases identified 233 non-synonymous somatic mutations (median: 21; range: 12-44). We observed frequent mutations in chromatin remodeling genes in 7 of 10 RMC cases, including mutations in SMARCB1 (n = 2) and SMARCA5 gene (n = 1). SNP analysis demonstrated that only the case with SMARCA5 somatic mutation harbored SMARCB1 monoallelic loss. However, all RMC cases had loss of SMARCB1 protein by immunohistochemistry. Ingenuity pathway analysis using RNA sequencing data identified EZH2 as one of the top over-expressed upstream regulators (Z-score = 3.7; p-value = 1.6x10-6). RT-PCR and western blot analyses confirmed that EZH2 expression is elevated at both mRNA and protein levels corresponding to SMARCB1 loss in RMC tumors. In vitro assessment of a novel RMC tumor cell line derived from the case harboring SMARCB1 deletion showed that EZH2 inhibitor GSK343 inhibited proliferation of this cell line. Conclusions: Our data reveal that 30% of RMC cases showed inactivation of SMARCB1 through somatic mutations or monoallelic loss, suggesting that additional epigenetic mechanisms may lead to gene inactivation. In addition, our data suggest that EZH2 may be a relevant therapeutic target in RMC.