bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial differences in treatment decision-making patterns and decisional regret in patients with localized prostate cancer.
Authors: Kim Daniel J. , Hurwitz Lauren , Cullen Jennifer , Hudak Jane , Colston Maryellen , Travis Judith , Elsamanoudi Sally , Rosner Inger L. 
Published: February 2017

48 Background: Racial disparities in prostate cancer (PCa) incidence, health-related quality of life (HRQoL), treatment outcomes, and decisional regret have been reported. This study evaluated decision-making in African American (AA) and Caucasian (CA) patients with localized PCa to better understand HRQoL domains associated with post-treatment regret. Methods: This is a prospective cohort study evaluating patients with low- and intermediate-risk PCa in a racially diverse, equal access health-care setting who enrolled in a multidisciplinary clinic at Walter Reed National Military Medical Center. Demographic, clinical, and treatment outcomes data were collected. Validated questionnaires were administered, including the Control Preferences scale, Decision Regret scale (DRS), Expanded Prostate Cancer Index Composite (EPIC), and Medical Outcomes Study Short Form (SF36). Questionnaires were given at fixed intervals post-treatment. Results: A total of 297 (37.8%) AA and 489 (62.2%) CA patients were included in this study. AA patients were more likely to elect radiation therapy (RT) and less likely to elect radical prostatectomy (RP) or active surveillance. AA patients preferred more physician involvement in decision-making. Significantly higher regret was observed for AA patients after RP at 6 and 24 months, compared to CA patients. Only 6-month urinary bother was associated with regret in AA patients while, among CA patients, regret was associated with mental health and sexual bother. Among XRT patients, multiple HRQoL domains were associated with regret in AA patients, while only 36-month mental health was associated with regret in CA patients. Conclusions: Several key differences were noted across race in terms of HRQoL domains that were associated with patient regret. This cohort is now being followed for patient satisfaction with medical care. Such data may further help physicians tailor conversations with patients during treatment decision making to optimize HRQoL and minimize regret.
Comparison of survival outcomes for African American and Caucasian men with advanced penile cancer in Florida.
Authors: Ritch Chad , Pavan Nicola , Rai Samarpit , Soodana-Prakash Nachiketh , Balise Raymond R , Parekh Dipen , Gonzalgo Mark L. 
Published: February 2017

490 Background: Studies suggest that there may be disparity in clinical outcomes for African−American men (AAM) compared to Caucasian men (CM) with penile squamous cell carcinoma (SCC). We sought to determine whether there was a survival difference for African American versus Caucasian men, particularly in locally advanced and metastatic cases of penile SCC where disease mortality is highest. Methods: Using the Florida Cancer Data System, we identified men diagnosed with penile SCC, from 2004 to 2014. We excluded men who were diagnosed on autopsy or at the time of death and with < 6 months of follow up. Demographic variables including: age, follow−up, stage, race and treatment type were compared between AAM and CM. Treatment type was categorized as surgery alone or surgery plus additional therapy (chemotherapy and/or radiation). For locally advanced and metastatic disease, we compared treatment type and overall survival (OS) between AAM and CM. A multivariable model was developed to determine significant predictors of OS. Results: Of the 653 men with penile SCC, 198 [38 (19%) AAM and 160 (81%) CM] had locally advanced and/or metastatic disease. Median follow up for the entire cohort was 12.5 mos. For all stages, AAM demonstrated a significantly decreased median OS compared to CM (26 vs. 37 mos, p=0.03). For locally advanced and metastatic disease, there was a persistent, but non−significant, trend toward disparity in median OS between AAM and CM (17 vs. 23 mos, p=0.06). Fewer AAM compared to CM received surgery plus additional therapy for locally advanced and/or metastatic disease [8 (21%) vs. 42 (26%)], but this difference was not statistically significant. After adjusting for age, stage, and treatment type, AAM had increased likelihood of death from penile SCC (HR 1.63, p=0.015). Conclusions: Mortality rates from penile SCC remain high in contemporary series. For AAM in Florida, advanced stage at presentation, along with treatment disparity, may partially explain decreased survival rates. Further studies are needed to determine the additional socioeconomic, as well as potential biologic, factors that may predict the relatively poor outcome observed in AA men with penile SCC.
Incidence and severity of prostate cancer in 360 hypogonadal men treated with testosterone undecanoate injections (TU) for up to 8 years and 296 untreated hypogonadal controls.
Authors: Haider Ahmad , Haider Karim Sultan 
Published: February 2017

50 Background: Testosterone therapy (TTh) in middle-aged and elderly men is still associated with concerns regarding prostate cancer (PCa). In this registry study, we investigated the incidence of PCa in hypogonadal patients on long-term treatment with TU in comparison to an untreated hypogonadal control group (CTRL). Methods: In a cumulative registry study, 360 men (mean age: 57.37±7.29 years, range: 33-70) with testosterone (T) ≤12.1 nmol/L received TU 1000 mg every 12 weeks following an initial interval of 6 weeks for up to 8 years. 296 hypogonadal men (mean age: 64.79±4.28 years, range: 57-74) decided against TTh, mainly due to financial reasons. Prostate volume (PV) and PSA were measured and digital rectal examination (DRE)/ transrectal ultrasound (TRUS) performed before treatment initiation and then regularly every 3-6 months. Biopsies were performed when indicated according to EAU guidelines. Results: From baseline to 8 years, PV increased from 29.24±10.38 to 31.13±11.45 ml in the T group and remained stable from 34.45±5.89 to 33.51±12 in CTRL. PSA increased slightly from 1.74 ± 0.93 to 1.83±0.93 ng/ml in the T group and remained stable from 2.25±1.34 to 2.19±1.17 in CTRL. In T-treated patients, 7 men (1.9%) were diagnosed with PCa. In the control group, 12 (4.1%) were diagnosed with PCa. The incidence per 10,000 years was 30.05 in the T group and 63.54 in CTRL. The mean age of PCa patients was 64 years in the T group and 65 years in CTRL. All patients underwent radical prostatectomy. The predominant Gleason score was 3 in all patients in the T group, lymph nodes and surgical margins were negative. In CTRL, three men had a predominant Gleason score of 3, 8 had 4, and 1 had 5. 7 patients had positive lymph nodes and no patient had a positive surgical margin. Conclusions: Long-term treatment with TU in hypogonadal men undergoing regular monitoring according to EAU guidelines does not increase the incidence of PCa in comparison to an untreated hypogonadal CTRL group. PCa was more severe in the CTRL group.
T-cell receptor (TCR) repertoire in metastatic renal cell carcinoma (RCC) patients treated with first-line vascular endothelial growth factor receptor blockade.
Authors: Ho Thai Huu , Gagnon Robert Charles , Liu Yuan , Hodi F. Stephen , Signoretti Sabina , Choueiri Toni K. 
Published: February 2017

501 Background: Reports have demonstrated an inverse relationship between suppression of immune surveillance mechanisms and activation of the vascular endothelial growth factor receptor (VEGFR) pathway suggesting that T cell repertoires may impact response to VEGFR blockade. We evaluated the association between clinical outcomes and T cell repertoire in metastatic RCC patients receiving a front-line anti-VEGFR, pazopanib. Methods: Pre-treatment RCC tumors were analyzed from VEG105192, a phase III study of mRCC patients randomized (2:1) to pazopanib (paz) 800 mg daily vs placebo (pbo) for TCR gamma (TCRG) and TCR beta (TCRB) CDR3 regions. Using the Adaptive Biotechnologies immunoSEQ Assay, we assessed TCR clonality, a measure of total repertoire represented by expanded clones, and entropy, a measure of evenness and diversity. PD-L1 was evaluated by immunohistochemistry (IHC) H-Scores. The goal of the study was to determine if the repertoire of T cell clones was associated with progression-free survival as a clinical endpoint. Results: In the cohort with available tissue, the median PFS was 10.8 and 5.5 months (mos) for paz and pbo, respectively. TCRB (n = 114) and TCRG (n = 43 pbo, 109 paz) clonality ranged from 0-0.31 and 0-0.98, and entropy from 1-12.1 and 0-10.37, respectively. TCRB and TCRG entropy were highly correlated (Spearman’s R = 0.92, n = 114). Samples from the pbo-treated group with higher TCRG entropy, defined as the top 25th percentile, were associated with an improved median PFS (12.8 months) when compared to the lower 75th percentile (3.1 months, P = 0.023); similar trends were seen for TCRB entropy. Neither entropy nor clonality was associated with maximal reduction in tumor volume in the paz-treated group. PD-L1 H-scores were not associated with entropy or clonality (P > 0.05). Conclusions: Our data suggests that RCC samples with higher entropy are associated with a favorable prognosis. Identification of tumors with restricted TCRB/G chain usage and less diverse repertoire, as represented by lower entropy and higher clonality, may impact responses to VEGFR blockade and requires further study. Clinical trial information: NCT00334282.
Combined DNA-methylation intensity and clinical risk score to stratify patients for high-grade disease.
Authors: Van Neste Leander , Stewart Grant , Gaston Sandra Marlene , Grizzle William E. , Adams George W. , Kearney Gary P , Epstein Jonathan I , Harrison David James , Partin Alan W. , Van Criekinge Wim 
Published: February 2017

51 Background: Prostate cancer (PCa) diagnostics remains challenging due to fear of over-diagnosis and overtreatment. Due to low accuracy of PSA too many men are biopsied that do not have a subsequent PCa diagnosis or that have indolent disease. Furthermore, persistent risk factors and fear of missed PCa leads to many unnecessary repeat biopsies. Most prostate tumors have epigenetic DNA-methylation aberrations, which display a field effect that can be observed in normal-appearing surrounding tissue, and that could help alleviate biopsy-sampling errors. Methods: A training cohort of methylation-positive men with a negative index biopsy followed by either a Gleason score (GS) ≥ 7 (n=43) or cancer-negative (n=226) repeat biopsy was evaluated. Using the initial negative biopsy, men were stratified for the likelihood of harboring high-grade PCa focusing on a methylation intensity algorithm involving GSTP1, RASSF1 and APC. This algorithm was validated in a cohort of 102 men, with either a PCa-free (n=20), GS6 (n=46), or GS≥7 (n=36) biopsies. Results: The methylation intensity-based algorithm was developed on PCa-negative index biopsies and optimized to predict the presence of GS≥7 cancer in a repeat biopsy. The methylation intensity was significantly higher in GS≥7 compared to PCa-free repeat biopsies (p<0.001). Men with GS6 PCa detected upon repeat biopsy exhibited intermediate intensities. When combined into one model with clinical risk factors (age, pathology, DRE, PSA), an area under the curve (AUC) of 0.762 was obtained, which was significantly higher than the AUC of PSA (0.574; p=0.004) or the AUC of the clinical risk as calculated by the PCPT risk calculator (0.618; p=0.029). In the validation set, an AUC of 0.818 was obtained, with higher intensities for men with GS≥7 disease compared to men with GS6 PCa (p=0.002). Conclusions: The risk score can identify clinically significant cancer in PCa-negative biopsies and is strongly correlated with the GS of PCa-positive biopsies. The risk score could better stratify men for the need for repeat biopsy and the risk of harboring occult clinically significant PCa. The same algorithm could be used to segregate likely under-graded men from active surveillance candidates.
Single-institutional analysis of patients with clear-cell papillary renal cell carcinoma.
Authors: Casuscelli Jozefina , Winer Andrew G. , Reznik Eduard , Xu Jianing , Manley Brandon , Chouhan Jyoti , Reuter Victor E. , Tickoo Satish , Russo Paul , Coleman Jonathan A. , Hsieh James , Hakimi A. Ari 
Published: February 2017

512 Background: Recently clear cell papillary renal cell carcinoma (cpRCC) has been recognized as new histologic subtype with immunohistochemical profiles that differentiate it from clear cell (ccRCC) and papillary (pRCC) RCC. Several previous studies highlighted the indolent behaviour of this entity in the reported cases. Our primary objective is to further elucidate the genomic and clinical characteristics of cpRCC. Methods: 44 patients with cpRCC were selected from the MSKCC database with surgery performed between 2007 and 2014. Only tumors with appropriate histological configuration and immunohistochemically confirmed CAIX and CK7 positivity and CD10 negativity were included. Whole exome sequencing (WES) was performed on 5 cpRCC tumor samples and one sample was analyzed by next-generation sequencing (MSK-IMPACT). A further comparison was made to 825 ccRCC and 219 pRCC tumors with initial pT1 diagnosis from our institutional database. Differences in the variables across groups were analyzed with the Chi-Square and the Kruskal–Wallis tests. To visualize and test the survival distribution differences, we used Kaplan–Meier plots and Log-rank tests. Results: Sequencing did not reveal VHL mutations or other known driver mutations commonly seen in ccRCC or pRCC and no recurrent mutations were identified. The median follow up period for cpRCC was 27 months, for ccRCC 59 months and for pRCC 63 months. cpRCC frequently co-occured with ccRCC or other RCC subtypes (17/44 cases). Female patients developed cpRCC significantly more frequently than ccRCC or pRCC (47.7% P<0.001) and Kruskal-Wallis test revealed differences in tumor size between the 3 groups (cpRCC median size 2.5 cm, P<0.001). Recurrence, metastatic development and death from kidney cancer was observed in ccRCC (3.7%, 2.3% and 0.8%) and in pRCC (4.5%, 1.8% and 2%), but not in the cpRCC cohort. Conclusions: cpRCC is genomically distinct from ccRCC and pRCC and lacks driver mutations commonly associated with aggressive disease. The tumors tend to present smaller than other RCC subtypes, commonly co-occur with other RCCs and disproportionately affect women. Extended follow-up of larger cohorts is necessary to confirm the true indolent nature of cpRCC.
Early tumor shrinkage under first-line tyrosine kinase inhibitor as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma.
Authors: Miyake Hideaki , Harada Ken-ichi , Fujisawa Masato 
Published: February 2017

523 Background: The objective of this study was to assess the prognostic impact of early tumor shrinkage induced by first-line tyrosine kinase inhibitors (TKIs) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Methods: This study included a total of 185 consecutive Japanese patients with mRCC, consisting of 120 and 65 who were treated with sunitinib and sorafenib, respectively, for at least 3 months as first-line therapy. Prognostic outcomes in these 185 patients were retrospectively assessed focusing on the significance of tumor shrinkage at 12 weeks after the introduction of TKIs as a predictive factor of OS. Results: As the best responses to TKIs, 3, 40, 105 and 37 were judged to show a complete response, partial response, stable disease and progressive disease, respectively. The median progression-free survival (PFS) and OS in the 185 patients was 7.3 and 33.6 months, respectively. At 12 weeks after the introduction of TKIs, 9 patients reached a tumor shrinkage from -100 to -50%, 42 patients from -49 to -25%, 59 patients from -24 to 0%, and the remaining 70 patients had a gain of tumor size or new metastatic lesions. The median OS stratified according to tumor shrinkage at 12 weeks after the introduction of TKIs as shown above was 59.2, 39.1, 27.8 and 19.1 months, respectively. Univariate analysis identified the Memorial Sloan-Kettering Cancer Center (MSKCC) classification, Heng risk classification, C-reactive protein (CRP) level, lymph node metastasis, bone metastasis, liver metastasis, number of metastatic organs, histological subtype, sarcomatoid feature, PS and tumor shrinkage as significant predictors of OS. Of these significant factors, only the MSKCC classification, CRP level, liver metastasis and tumor shrinkage were shown to be independently associated with OS by multivariate analysis. Conclusions: These findings suggest that tumor shrinkage at 12 weeks after the introduction of TKIs was shown to have a significant impact on the OS in mRCC patients; therefore, early tumor shrinkage could be used as a reliable surrogate endpoint of OS in patients with mRCC receiving TKI as first-line agent.
Impact of metformin on outcomes in patients (pts) with metastatic renal cell carcinoma (mRCC): Results from a pooled clinical trials database.
Authors: Hamieh Lana , McKay Rana R. , Mickey Suzanne S , Lin Xun , Simantov Ronit , Choueiri Toni K. 
Published: February 2017

531 Background: Metformin has been shown to confer anti-neoplastic properties in several tumor types. Its effect on outcomes in mRCC patients has not been completely characterized. In this study, we evaluated the role of metformin on survival outcomes in pts with mRCC. Methods: We conducted a retrospective study of pts with mRCC treated on several phase II and III clinical trials from 2003-2013. We analyzed overall survival (OS) in the metformin users versus non-users using the Cox regression model and the Kaplan-Meier method. Results: We identified 4,736 pts with mRCC including 486 diabetic pts of whom 218 (4.6%) were metformin users. The majority were <65 years of age (69%), male (71%), with clear-cell histology (89%) and prior nephrectomy (70%). With regard to IMDC risk groups, 14%, 42%, and 24% had favorable, intermediate, and poor-risk disease, respectively. Pts received treatment with sunitinib (n=1,059), sorafenib (n=772), axitinib (n=896), temsirolimus (TEM) (n=457), TEM + interferon (IFN)-α (n=208), bevacizumab (BEV) + TEM (n=393), BEV + IFN-α (n=391), or IFN-α (n=560); overall 3,044 (64%) received first-line therapy. In the total cohort, metformin use did not impact OS when compared to users of other anti-diabetic agents (p=0.17) or non-diabetics (p=0.69). In diabetic pts, metformin use did not confer a survival advantage when stratified by type of therapy and IMDC risk group. However, in the cohort of diabetic pts receiving sunitinib (n=128), metformin use was associated with an improvement in OS when compared to users of non-metformin anti-diabetic agents (29.3 versus 20.9 months, respectively, p=0.0008, HR 0.051, 95% CI 0.009, 0.292). Conclusions: This is the largest study to date investigating the role of metformin on outcomes in mRCC pts. In this analysis, we demonstrate that concomitant use of metformin may improve survival in diabetic pts with mRCC treated with sunitinib. Based on preclinical data, we hypothesize that the mechanism underlying this survival benefit may be related to synergistic inhibition of the MAPK pathway. However, the study is limited by the small number of diabetic patients. Larger prospective studies are warranted to validate these results.
Who could be appropriate candidates for partial nephrectomy in localized renal cell carcinoma? Selection by preoperative factors.
Authors: Nagao Kazuhiro , Sakano Shigeru , Fujii Nakanori , Kobayashi Keita , Inoue Ryo , Yamamoto Yoshiaki , Matsumoto Hiroaki , Matsuyama Hideyasu ,   Yamaguchi Uro-Oncology Group
Published: February 2017

542 Background: Chronic kidney disease (CKD) is a risk factor for the cardiovascular disease, which affect to the patients’ survival, while an EORTC randomized control trial did not show superiority of partial nephrectomy (PN) against localized renal cell carcinoma (RCC) in overall survival compared to radical nephrectomy (RN). We aimed to evaluate the role of operative methods affecting the survival and tried to estimate a predictive model for high risk CKD after surgery. Methods: We reviewed the data of 357 cases with clinical T1 RCC treated by RN (292 cases, RN group) or PN (65 cases, PN group) at Yamaguchi University Hospital or its related hospitals. We supposed the cases with CKD stage 3b or higher after surgery as high risk CKD. And we set the primary endpoints as the ratio of the cases with high risk CKD and overall survival after surgery. Results: Median follow-up period after surgery was 70 months (3-161). Statistically significant difference in performance status and clinical T stage were observed between the groups, but not in other patients’ characteristics. Mean values of preoperative eGFR were 69.2 and 65.5 ml/min/1.73m2 in RN and PN group, which decreased to 46.0 and 57.9 at 5 years after surgery, respectively. There was a significant difference in the incidence of high risk CKD between RN (39.3%) and PN group (2.2%) at 5 years after surgery. During follow up period, 17 cases (4.4%) were inducted to dialysis, there was no difference in the incidence between the RN and PN group. Multivariate analysis showed that eGFR ( < 72 ml/min/1.73m2; Odds ratio 15.3), proteinuria (Odds ratio 3.84), smoking (Odds ratio 2.76), BMI ( > 23; Odds ratio 2.66) and age ( > 67 years old; Odds ratio 2.47) could be significant predictive factors for high risk CKD at 5years after surgery. Our predicting model for high risk CKD showed 86.8% of sensitivity and 74.8% of specificity. But there was no significant difference in overall survival between the RN and PN group. Conclusions: Although there was a significant difference in the incidence of high risk CKD between RN and PN group, operative methods did not affect to the survival. Postoperative high risk CKD could be predictable by preoperative clinical factors.