bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene-expression profiling of collecting duct carcinoma of the kidney.
Authors: Tessari Anna , Testa Isabella , Verzoni Elena , Nigita Giovanni , Colecchia Maurizio , Palmieri Dario , Grassi Paolo , Maggi Claudia , Martinetti Antonia , De Braud Filippo G. , Croce Carlo M , Procopio Giuseppe 
Published: February 2017

540 Background: Collecting duct carcinoma (CDC) of the kidney is a rare tumor, originating from renal medulla, characterized by younger age at diagnosis and poor prognosis. Since targeted therapies are currently not available for CDC, we aimed to identify the most deregulated pathways in this type of cancer to gain insights into new molecular targets. Methods: Total RNA was extracted from FFPE samples of primary CDC (n=9), clear cell carcinoma (CCC, n=7) and healthy normal (n=7) adjacent renal tissues (23 total samples). Gene expression profile was performed by GeneChip Human Transcriptome Array 2.0 (HTA 2.0 -Affymetrix). The One-Way between-subject ANOVA algorithm was used to calculate statistical significances of pairwise comparisons. Transcripts with a linear fold change (f.c.) of <-2/>2 (p-value<0.05) were included in the study. Functional enrichment analysis identified the most deregulated pathways in CDC. Results: A total of 1,079 genes (827 coding, 252 non-coding) were significantly deregulated comparing CDC, CCC and normal kidney (p<0.05). In CDC vs normal tissue comparison, 484 genes (339 coding, 145 non-coding) are significantly up-regulated, and 49 (40 coding, 9 non-coding) down regulated in tumors (p<0.05). The 4 most highly expressed transcripts in CDC are currently unknown, requiring further studies. Among the most altered known transcripts, we identified FN1 (f.c. 6.33), miR-21 (f.c. 4.01), KNG1 (f.c. -9.4) and AQP2 (f.c. -6.03), whose deregulation was previously associated with advanced disease and lower survival in renal cancer, supporting the quality of our analysis. Functional enrichment analysis indicated a strong downregulation of transcripts associated with histone modifications, function of cytoplasmic ribosomal proteins, senescence, autophagy and focal adhesion in CDC vs both CCC and normal tissues. Conclusions: Our analysis identifies several coding and non-coding transcripts differentially expressed in CDC vs CCC and normal kidney, resulting in alteration of a number of cellular pathways associated with cancer pathogenesis, progression and prognosis. These results pave the way to a deeper understanding of a rare tumor as CDC, driving the development of new, targeted therapies for this aggressive disease.
Very late relapse metastatic renal cell carcinoma: Characteristics and outcomes of patients with a disease-free interval of greater than 10 years.
Authors: Kucharczyk John Ross , Matrana Marc Ryan 
Published: February 2017

541 Background: Late relapse of renal cell carcinoma (RCC), or presentation with metastatic disease after a disease free interval of >5 years, is a known behavior of RCC. Recent studies have concluded that late relapse RCC is associated with favorable patient and tumor characteristics as well as an improved response to targeted therapy (TT) when compared to early relapse patients. Less studied are patients who relapse very late, with a disease free interval >10 years. We evaluated the clinical characteristics, response to TT and outcomes of this unique population. Methods: We collected data on consecutive patients with metastatic RCC who had disease recurrence >10 years after nephrectomy. Outcomes were tabulated using basic statistical techniques; adverse events were graded using CTCAE v4.0 and treatment response graded using RECIST 1.1. Results: Among 720 RCC patients treated with nephrectomy, we identified 8 who developed recurrent metastatic disease after a >10 year disease free interval (median: 16.7 years; range: 11.7-29.0). All patients presented with clear cell histology; 88% favorable IMDC and MSKCC risk subgroups. All patients presented with multiple metastases, with the most common sites being lung and bone, while unusual sites such as soft tissue, pancreas and adrenal were also detected. Median time on first-line TT was 20.1 months; 4, 3 and 1 patient received pazopanib (best response: PR), sunitinib (best response: SD) and cytokine (best response: PD) as first-line therapy, respectively. The median number of sequential TT received was 2 (range: 1-4). Four patients died, median OS was 46.6 months (range: 9.8-129), 3 year OS rate was 63%. Common adverse events to TT were fatigue (88%), anorexia (38%) and diarrhea (50%), 94% grade 1/2. Conclusions: Patients are at life-long risk of recurrence after resection of localized RCC as it is possible for metastases to present >10 years after resection. Patients in our study had relatively large metastatic burden and a wide distribution of metastatic sites, insights that may be useful clinically during surveillance. Our cohort demonstrated favorable prognostic features and outcomes when compared to historical controls.
Do pathological parameters of primary tumor correlate with overall survival (OS) of metastatic clear-cell renal cell carcinoma (ccRCC)?
Authors: Basso Umberto , Maruzzo Marco , Fraccon Anna Paola , Sava Teodoro , Massari Francesco , Sacco Cosimo , Valcamonico Francesca , Maines Francesca , Lo Re Giovanni , Donati Donatella , Baier Susanne , Durante Emilia , Soraru' Mariella , Nicodemo Maurizio , Bearz Alessandra , Sartori Donata , Fiduccia Pasquale , Zustovich Fable , Pasini Felice , Zagonel Vittorina 
Published: February 2017

549 Background: T and N stage, Fuhrman grade, necrosis and sarcomatoid features in the primary tumor are key prognostic factors for relapse of ccRCC, but they are not part of Heng's algorithm applied to predict OS in the metastatic setting, which instead is based on 6 clinical/laboratory items. Methods: Retrospective analysis on correlation between pathological parameters and OS (from start of first-line targeted therapy) and Heng's prognostic factors in a multicenter cohort of pts with advanced ccRCC, all of whom had undergone surgery on the kidney. Results: From 2006 to 2012, data of 903 eligible metastatic pts were collected from 33 Italian Oncology Institutions, median age 66 years, 72.6% males, 36.4 metastatic at diagnosis. After a median observation of 42 mo, 70,5% of pts died, estimated OS is 28.5 mo. Heng good prognosis pts were 14.45%, intermediate 69.1% and poor 16.45%. Univariate analysis showed that all pathological parameters significantly correlated with OS: T stage 3-4 vs 1-2 (HR 1.3), N1 vs N0 (1.3), Fuhrman grade 3-4 vs 1-2 (1.7) presence of necrosis (1.5) and sarcomatoid features (1,6). All pathological parameters had a strong correlation with a time to metastases < 1 year, while only weak correlations were found with the other clinical prognostic items of Heng's model. At multivariate analysis only N stage showed an independent impact on OS (table). Conclusions: T3-4 stage, N1, Fuhrman grade 3-4, presence of necrosis and sarcomatoid features negatively affect OS of metastatic ccRCC, but clinical items of Heng's model confirm to have a more robust prognostic significance at multivariate analysis. [Table: see text]
Sunitinib scheduling in metastatic renal cell cancer: A single-center experience.
Authors: Picardo Sarah Louise , Collins Dearbhaile , Al Khamis Amnah , Mallett Victoria Teresa , Keegan Niamh M. , Ismail Irnani , Hennessy Bryan , Breathnach Oscar S. , Grogan William , Morris Patrick G. 
Published: February 2017

554 Background: Sunitinib is a receptor tyrosine kinase inhibitor that has proven activity as first line treatment for metastatic renal cell carcinoma (mRCC). The recommended dose is 50mg once daily in a 4 week on 2 week off schedule. However this regimen has a significant side effect profile and alternative schedules have been used to minimize dose reductions and maintain dose intensity. We sought to identify the incidence of dose modifications and assess toxicity in patients treated with two sunitinib schedules in a National Cancer Center. Methods: Patients with mRCC who had sunitinib as first line treatment were identified retrospectively and patient data reviewed. Two patient groups were identified: those who received sunitinib 50mg day 1-28 in 6 week cycles (cohort 1) and those who received sunitinib 50mg day 1-14 in 3 week cycles (cohort 2). Primary end point was incidence of dose modification. Secondary end points included incidence of common sunitinib-related side effects. Known prognostic variables, including prior nephrectomy, body mass index (BMI) and use of angiotensin system inhibitors (ASI) were correlated with time to disease progression (TTP). Results: Between 2009 and 2014, 28 patients were identified. Of those, 23 (83%) patients were treated in cohort 1, and 5 (17%) patients in cohort 2. Dose modifications were required in 13 (56.5%) patients in cohort 1, but only 2 (40%) patients in cohort 2. Common sunitinib-related side effects in cohort 1 included hypertension in 19 (79%), weight loss in 10 (41.6%), fatigue in 9 (37.5%) and nausea in 8 (33.3%) patients respectively. Overall, the use of ASIs correlated significantly with longer median TTP (10.5 months) compared to non-users (4 months) (p = 0.04). BMI ≥ 25 (TTP 9 vs. 3 months, p = 0.008) demonstrated a similar correlation. However, no difference in median TTP was noted between patients who had prior nephrectomy compared to those who had not (5 vs. 4 months) (p = 0.18). Conclusions: In this small retrospective study, standard sunitinib scheduling was associated with a high incidence of dose modifications and side-effects. Consistent with previous studies, we identified known prognostic variables. The use of sunitinib 50mg day 1-14 in 3 week cycles may be more tolerable for patients.
RECORD-4 phase 2 trial of second-line everolimus (EVE) in patients (pts) with metastatic renal cell carcinoma (mRCC): Final OS analysis.
Authors: Cosgriff Thomas , Yang Lin , Alyasova Anna , Ye Dingwei , Karpenko Andrey , Li Hanzhong , Alekseev Boris , Xie Li-ping , Kowalyszyn Ruben Dario , Karyakin Oleg , Neron Yeni Verónica , Collins LaTonya , Brechenmacher Thomas , Lin Chinjune , Morgan Liza , Motzer Robert J. 
Published: February 2017

560 Background: The phase 2 RECORD-4 study assessed EVE in pts with mRCC who progressed after 1 prior anti-VEGF or cytokine (J Clin Oncol 2015;abstr 4518). At primary analysis, median progression-free survival (PFS, primary end point) in the overall population was 7.8 months (95% CI, 5.7-11.0). Here we present results of the final updated primary PFS and final overall survival (OS) analysis. Methods: RECORD-4 enrolled 134 pts with clear cell mRCC into 1 of 3 cohorts based on prior first-line therapy: sunitinib (cohort 1, n=58), other anti-VEGF (cohort 2, n=62: 23 sorafenib, 16 bevacizumab, 13 pazopanib, 10 other), or cytokines (cohort 3, n=14). Pts received EVE 10 mg/d until progression of disease (PD; RECIST, v1.0) or intolerance. Database lock for final analysis was June 26, 2015. Results: Demographics were balanced among cohorts; overall most pts were men (68%) and most had good/intermediate MSKCC prognosis (90%); median age was 59 yrs. Median duration of exposure was 5.8 mo. At the time of final analysis, study discontinuation was primarily due to disease progression (61%). In the overall population, median PFS (95% CI) was 7.4 (5.6-10.5) mo and median OS (95% CI) was 23.8 (17.0-not evaluable [NE]) mo (Table). Overall rate of grade 3 or 4 adverse events (AEs) was 56%. There were 13 on-treatment deaths; primary causes were disease progression, multi-organ failure, and respiratory failure (2.3% each). Conclusions: RECORD-4 final OS analysis supports EVE as a second-line option after sunitinib and other first-line therapies. EVE safety profile was consistent with previous experience. Clinical trial information: NCT01491672. [Table: see text]
Contemporary utilization of non-surgical management for stage I renal masses.
Authors: Ristau Benjamin T. , Handorf Elizabeth , Schaff Matthew , Kim Simon P. , Haseebuddin Mohammed , Waingankar Nikhil , Haifler Miki , Cahn David , Greenberg Richard Evan , Viterbo Rosalia , Chen David Y. T. , Kutikov Alexander , Uzzo Robert G. , Smaldone Marc C. 
Published: February 2017

564 Background: While active surveillance has gained traction as a primary treatment strategy for small renal masses in patients with significant competing risks, population level trends of non-surgical management (NSM) remain poorly characterized. Using a large national cancer registry, our objective was to assess temporal trends in utilization of NSM for stage I renal cell carcinoma (RCC). Methods: The National Cancer Database (NCDB) was queried for all patients with stage I RCC from 2003-2012. Patients were categorized as surgical intervention (partial [PN] or radical nephrectomy [RN]) or NSM, and patients undergoing ablative techniques were excluded from analyses. Temporal trends were assessed using Cochran-Armitage tests. Adjusting for patient, clinical, and tumor characteristics, multivariable logistic models were used to examine the association between clinicopathologic characteristics and receipt of NSM. Results: Of 176,975 patients identified, 89% underwent surgical intervention (PN 35.5%, RN 53.5%) and 11% underwent NSM respectively (Stage Ia: 13.1%, Stage Ib: 6.3%). From 2003-2012, utilization of NSM (6.1 vs. 13.1, p < 0.001) and PN (24.4 vs. 47.3%, p < 0.001) significantly increased, while performance of RN significantly declined (69.5 vs. 39.6, p < 0.001). Following adjustment, increased age (51-60 years: OR 1.70 [CI 1.6-1.8]; 61-70 years: OR 2.61 [CI 2.4-2.8]; 71+ years: OR 6.37 [CI 5.7-7.1]), African American race (OR 1.11 [CI 1.03-1.2]), Charlson score 2+ (OR 1.34 [CI 1.2-1.4]), and insurance status (uninsured: OR 1.71 [CI 1.5-2.0]; Medicaid: OR 1.92 [CI 1.7-2.1]; Medicare: OR 1.39 [CI 1.3-1.5]) were associated with receipt of NSM, while patients with tumors > 4cm (OR 0.42 [CI 0.40-0.45]) were less likely to undergo NSM. Conclusions: In hospitals reporting to the NCDB, utilization of NSM as a primary treatment strategy for stage I RCC has doubled from 2003-2012, most notably for tumors ≤ 4cm (Stage Ia). In absence of validated algorithms differentiating between active surveillance, watchful waiting, and those who lost access to care, racial and insurance disparities should be interpreted cautiously.
Expression of PD-1 and PD-L1 in patients with renal cell carcinoma with sarcomatoid dedifferentiation (sRCC).
Authors: Kawakami Fumi , Sircar Kanishka , Rodriguez-Canales Jaime , Tamboli Pheroze , Tannir Nizar M. , Jonasch Eric , Wistuba Ignacio Ivan , Wood Christopher G. , Karam Jose A. 
Published: February 2017

582 Background: sRCC is a very aggressive malignancy, with limited treatment options. Given the recent surge in novel immunotherapeutic agents targeting PD-1 and PD-L1, we decided to investigate the expression of these markers in patients with sRCC. Methods: PD-1 and PD-L1 immunohistochemistry was performed on whole sections from nephrectomy specimens in 118 patients with sRCC and 92 patients with clear cell RCC without sarcomatoid dedifferentiation(ccRCC). PD-1 staining was manually evaluated. PD-1 cell numbers ≥ 1/HPF was defined as positive. PD-L1 staining was evaluated with semiquantitative method (H-score = 0-300) with digital analysis. Results: Of the 118 patients with sRCC, 94 had clear cell epithelioid component and 24 had non-clear cell epithelioid component. In the cohort with ccRCC, 20 were grade 4, 58 were grade 3, and 14 were grade 2. 21 cases of sRCC that received neoadjuvant therapy and 2 sRCC and 1 ccRCC where digitally calculated H-score was at variance with manual evaluation were eliminated from the study. 98.6% (73/74) of clear cell sRCC were positive for PD-1. Similarly, 100% (20/20) of the non-clear cell sRCC, 95% (19/20) of the grade 4, and 55/58 (94.8%) of grade 3 ccRCC were positive for PD-1, whereas 9/14 (64.3%) of the grade 2 ccRCC expressed PD-1 (P= 0.0002). 43.2% (32/74) of clear cell sRCC and 55.0% (11/20) of the non-clear cell sRCC were positive for PD-L1, whereas only 10% of the grade 4 non-sarcomatoid ccRCC were positive for PD-L1 (P= 0.0047). None of the grade 2 and 3 ccRCC expressed PD-L1. All the PD-L1 positive cases except 1 clear cell sRCC case were also PD-1 positive. We found a threshold H-score ≥ 25 in sRCC to stratify patient groups with worse prognosis (P= 0.0435) with 29.3% of the cases showing H-score ≥ 25. High PD-L1 H-score was significantly associated with presence of metastatic disease (P= 0.0284). Conclusions: sRCC (both clear and non-clear cell) showed higher frequency and stronger expression of PD-L1 and higher PD-1 positive cell density compared to ccRCC without sarcomatoid component. High expression of PD-L1 is at significant risk of cancer related mortality for sRCC patients. These findings form a rationale to study PD-1 and PD-L1 targeting agents in patients with sRCC.
Role of non-neoplastic renal parenchyma abnormalities in the population with preoperative CKD.
Authors: Mir Maria Carmen , Pavan Nicola , Soodana-Prakash Nachiketh , Balise Raymond R , Venkatramani Vivek , Shabtaie Sam , Channagiri Varun , Fornoni Alessia , Thomas David B , Parekh Dipen 
Published: February 2017

586 Background: Renal cancer is associated with chronic kidney disease. Several studies have shown a 20% rate of preoperative CKD in the population undergoing partial nephrectomy. The non-neoplastic abnormalities (NNA) surrounding a tumor have been suggested as surrogates for long term renal failure. We have endeavored to describe the most relevant features within the above mentioned kidney area in patients with and without preoperative CKD. Methods: We retrospectively reviewed 201 patients who underwent nephrectomy between 2012 and 2014 with available histological assessment of NNA. Additional factors were included in the analysis such as demographic characteristics (age, sex, BMI) and comorbidities (hypertension, diabetes, Charlson comorbidity index). Pathological features were grouped as follows: glomerular (GA), interstitial (IA) or vascular abnormalities (VA). Univariate and multivariate logistic regression analyses were used to determine the associations between NNA and the presence of preoperative CKD stage III. Results: CKD stage III patients were older (68 vs. 56 years, P < .004) and presented a higher rate of DM with end-organ damage (n = 10, 13% vs N = 2 2%). Otherwise, people with and without CKD showed similar demographics. Overall, 56% of patients showed GA, 86% showed IA and 98% of patients presented with VA. In the multivariate analysis adjusted for comorbidities, the most relevant GAs were diabetic glomerulosclerosis (OR 7.32; p = 0.01), segmental sclerosis (OR 4.54; p = 0.0006) and glomerular adhesion (OR 2.80; p = 0.04). In the IA group, interstitial fibrosis (OR 7.36; p < 0.001), tubular atrophy (OR 2.75; p = 0.02) and acute interstitial inflammation (OR 12.47; p = 0.02) were significantly associated with decreased eGFR. Hyperplastic arteriolosclerosis (OR 2.30; p = 0.025) was an independent predictor of baseline eGFR < 60. Conclusions: NNA assessment from surgical specimen is feasible. Patients with baseline CKD present with several abnormalities related to inflammation and healing within the three nephron areas. The further investigation of these abnormalities might have a role in the evaluation of ultimate renal deterioration.
Analgesic use and risk of renal cell cancer: Results from two prospective cohort studies.
Authors: Preston Mark A , Zhang Xuehong , Graff Rebecca E , Sanchez Alejandro , Chang Steven L , Stampfer Meir J. , Choueiri Toni K. , Wilson Kathryn M , Cho Eunyoung 
Published: February 2017

588 Background: The relationship between the widely used analgesics (i.e., aspirin, other nonsteroidal anti-inflammatory drugs (NSAID), and acetaminophen) and risk of total and lethal renal cell cancer remains unclear. Methods: We examined the associations between analgesic use and risk of renal cell cancer overall and by subtypes, in the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). We collected information on aspirin, other non-aspirin NSAIDs, and acetaminophen in 1990 in the NHS and in 1986 in the HPFS, and every 2 years thereafter. We used Cox proportional hazards models, controlling for other known and suspected risk factors, to examine the associations between baseline and duration of use of each analgesic and risk of total renal cell cancer, lethal renal cell cancer (resulted in death due to disease), as well as clear cell renal cell cancer. We pooled results using a random-effects model. Results: During follow-up of 22 years among 77,527 women and 26 years among 45,913 men, we documented 438 cases of renal cell cancer (230 in women and 208 in men), of which 106 were fatal (56 in women and 40 in men) and 300 were clear cell (165 in women and 135 in men). The pooled multivariable relative risks (RRs) for total renal cell cancer were 1.13 (95% CI: 0.91-1.39) for aspirin use, 1.34 (95% CI: 1.03-1.75) for non-aspirin NSAID use, and 1.07 (95% CI: 0.80-1.44) for acetaminophen use. Similar results were observed for lethal renal cell cancer and clear cell renal cell cancer. Importantly, longer duration of non-aspirin NSAID use was associated with an increased risk of renal cell cancer. The pooled (all p-heterogeneity > 0.05) multivariable RRs for total renal cell cancer were 1.23 (95% CI: 0.94-1.62) for non-aspirin NSAID users of 4-10 years and 1.81 (95% CI: 1.21-2.72) for over 10 years. The corresponding RRs were 1.91 (95% CI: 1.04-3.49) and 3.97 (95% CI: 1.46-10.83) for lethal renal cell cancer, and 1.36 (95% CI: 0.99-1.88) and 1.58 (95% CI: 0.94-2.63) for clear cell renal cell cancer. Conclusions: Our findings support a significant positive association between non-aspirin NSAID use and risk of developing renal cell cancer, especially the lethal form.