bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examination of genomic copy number alterations in renal cell carcinoma with sarcomatoid features.
Authors: Ito Timothy , Pei Jianming , Dulaimi Essel , Menges Craig , Abbosh Philip , Chen David Y. T. , Greenberg Richard E. , Viterbo Rosalia , Kutikov Alexander , Smaldone Marc C. , Uzzo Robert G. , Testa Joseph R. 
Published: February 2017

478 Background: Sarcomatoid differentiation is an uncommon histological finding in renal cell carcinoma (RCC) that may develop from any RCC subtype and is associated with a very poor prognosis. The identification of genetic alterations that drive this aggressive phenotype could aid in the development of more effective targeted therapies. In this study, we aimed to identify unique copy number alterations (CNAs) in patients with sarcomatoid RCC when compared to those with other RCC subtypes. Methods: Genomic copy number analysis was performed using single nucleotide polymorphism (SNP)-based microarrays on tissue extracted from the tumors of 80 patients (9 with sarcomatoid features (sRCC), 39 clear cell (ccRCC), 26 papillary (pRCC) and 6 chromophobe RCC (chRCC)) who underwent renal mass excision between 2010 - 2014. Statistical analysis was performed using Kaplan Meier (KM) survival analysis, t-tests and Fisher exact tests where appropriate. Results: sRCC tumors exhibited significantly higher numbers of CNAs when compared to ccRCC, pRCC and chRCC (mean 20.1 vs. 6.6 vs. 7.0 vs. 6.3, respectively; p <0.0001). The most common copy number losses occurred in chromosome arms 1p, 3p, 9q, 15q, 18q, 21q, and 22q, with losses of 9q (88%), 15q (77%), 18q (66%), and 22 (77%) being unique among sRCC tumors when compared to the other 3 histologies. The most common copy number gains were in chromosome arms 1q, 8q, 17q, and 20p/q, with 1q (55%) and 8q (66%) gains unique when compared to the other 3 histologies. Of the sRCC tumors, 3 arose from ccRCC, 2 from pRCC and 4 from unclassified RCC. sRCC was associated with worse survival compared to ccRCC, pRCC and chRCC on KM analysis (p=0.0006), and higher rates of lymph node positivity (77% vs. 3% vs. 12% vs. 0%, respectively; p<0.0001) and metastases (100% vs. 13% vs. 4% vs. 0%, respectively; p<0.0001) on presentation were observed with sRCC. Conclusions: Sarcomatoid differentiation in RCC is associated with a high rate of chromosomal changes with unique copy number alterations including losses of 9q, 15q, 18q and 22q and gains of 1q and 8q. Identification and validation of candidate driver genes or tumor suppressor loci within these chromosomal regions may help identify targets for future therapies.
Circulating cytokines and angiogenic factors (CAFs) in patients with advanced non-clear cell renal cell carcinoma treated with sunitinib: Results from a phase II clinical trial.
Authors: Bilen Mehmet Asim , Zurita Amado J. , Ilias-Khan Nasreen A. , Chen Hsiang-Chun , Wang Xuemei , Hodges Sherie , Lim Zita D. , Jonasch Eric , Khakoo Aarif Yusuf , Tannir Nizar M. 
Published: February 2017

483 Background: Development of hypertension (HTN) during VEGF-directed therapies is associated with improved overall survival (OS) in patients (pts) with clear-cell renal cell carcinoma. There is paucity of data about the molecular determinants of response and survival outcomes in non-clear cell renal cell carcinoma (nccRCC) pts treated with targeted therapies. We investigated CAFs and correlated them and HTN with outcomes of nccRCC pts treated with sunitinib in a phase II trial. Methods: Using a bead-based multiplex assay (Luminex), levels of 30 CAFs (including mediators of inflammation, angiogenesis, immunity, and metastasis) were measured prior to start of sunitinib therapy (baseline) and at 4 weeks after completion of cycle 1. Sunitinib benefit was defined as having partial response (PR) or stable disease (SD) by RECIST lasting ≥4 months. Cox proportional hazards regression models were used to assess the association between CAFs, HTN, and survival outcomes. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and OS. Results: Fifty-seven pts [papillary (27), chromophobe (5), unclassified (8), collecting duct/medullary carcinoma (6), sarcomatoid (7), others (4)] were evaluable. Median follow up was 59.1 months (range, 30.6-82.6); 43 pts (75%) have died and 14 (25%) were alive at last follow up. Sunitinib benefit was seen in 21 pts (8 papillary, 4 chromophobe, 3 unclassified, 3 others, 2 collecting duct/medullary carcinoma, 1 sarcomatoid); 2 pts were not evaluable for response. Median PFS was 2.9 months (95% CI, 1.4-5.5) and median OS 16.8 months (95% CI, 10.7-27.4). 29 pts developed HTN during the first cycle, but there was no significant association between HTN and OS, PFS or sunitinib benefit. Elevated baseline levels of GRO, TGFα, sTNF-RI, sVEGF-R2 and IL-8 were correlated with higher risk of death. Conclusions: In this phase II trial in pts with advanced nccRCC, we found no significant association between HTN and PFS, OS, or sunitinib benefit. Candidate CAFs were identified that could be incorporated into prognostic and predictive models for validation in future studies in nccRCC.
Prognosis and outcome of patients with pancreatic metastases from renal cell carcinoma: When the site matters.
Authors: Grassi Paolo , Doucet Ludovic S. , Grünwald Viktor , Melichar Bohuslav , Galli Luca , De Giorgi Ugo , Guida Annalisa , Ortega Cinzia , Santoni Matteo , Bamias Aristotelis , Verzoni Elena , Iacovelli Roberto , Derosa Lisa , Studentova Hana , Pacifici Monica , De Braud Filippo G. , Escudier Bernard J. , Procopio Giuseppe 
Published: February 2017

484 Background: Pancreatic metastases from renal cell carcinoma (PmRCC) are uncommon and their prognostic value in the era of targeted terapies (TTs) is not well defined. We evaluated the outcome of a cohort of PmRCC patients (pts) who were treated with either surgery and TTs. Methods: PmRCC pts treated between 1993 and 2014 were identified from the databases of 10 European centers. Clinical records were retrospectively reviewed and pts characteristics, including demographics and clinical outcome, were analyzed. Kaplan-Meier methods and log-rank test were used to evaluate progression-free survival (PFS) and overall survival (OS). Cox’s proportional hazard models were used for OS analysis. Results: A total of 232pts were evaluated. Median age was 61 years, sex ratio M/F was 147/85, and PmRCC were synchronous in 69 pts (30%). Pts treated with pancreatic surgery (including radiosurgery) were 67 (29%), while patients receiving systemic treatment were 210 (91%). Pts with only PmRCC were 23 (11%), whereas in the other 201 cases: lung (25%), lymphnodes (16%), and liver (13%) were the most common metastatic sites. The majority of pts (94%) received nephrectomy (Nx). Median time from Nx to PmRCC occurrence was 92 months (IQR 50-143). First-line TTs included: sunitinib (42%), sorafenib (12%), pazopanib (9%), interferon+bevacizumab (8%), and temsirolimus (1%), 30% of pts received cytokines and 65% of pts received subsequent lines of TTs. Best response to first-line treatment were complete response (5%), partial response (41%), and stable disease (36%) with a disease control rate (DCR) of 82% and a median PFS of 12 months (IQR 9-13). Median OS (calculated from the time of PmRCC occurrence to death) was 73 months (IQR 61-90) with a 5-yr OS of 59%. Median OS for pts treated with surgical resection was 114 months (IQR 90-204) with a 5-year OS of 81%. At univariate analysis only Motzer/Heng prognostic score were significantly associated with OS (p=0.006). Conclusions: PmRCC are associated with long-term survival, usually occur many years after Nx and seem to lead to a less aggressive disease. Surgery should be considered in oligometastatic disease as it can be associated with prolonged survival. TTs are active in these pts and achieve high DCR.
Adrenalectomy for malignant disease: Utilization and outcomes by surgeon specialty and surgical approach.
Authors: Faiena Izak , Tabakin Alexandra , Leow Jeffrey , Patel Neal , Modi Parth K , Salmasi Amirali H. , Chung Benjamin I. , Chang Steven L. , Singer Eric A. 
Published: February 2017

489 Background: Adrenal cancers have traditionally been treated using an open surgical approach. With advances in minimally invasive surgery (MIS), adrenal tumors have become more amenable to MIS resection. We report a study on the utilization and outcomes of surgery for adrenal cancers on a national level. Methods: Data on patients who underwent open, laparoscopic, or robotic adrenalectomy for adrenal cancer (ICD-9 code 194.0) from 2003-2013 were extracted from the nationally representative Premier Hospital Database. Surgeon specialty, patient demographics, hospital characteristics, intraoperative and perioperative data, and complications were compared. Data were analyzed using univariate and multivariate logistic regression analyses. Results: 4,781 adrenalectomies were performed for malignant disease. Surgery was more commonly performed in patients >50 years of age (83%), men (64%), and white race (80%). There was no significant difference in rate of adrenalectomy with regards to comorbidities, insurance status, teaching vs. non-teaching hospital, hospital bed size, or geographic region. Adrenalectomy for malignant disease was more commonly performed by non-urologists (66 vs. 34%; p=0.011). Among non-urologists, open surgery was most common followed by laparoscopic and robotic approaches (56.3% vs. 37.4% vs. 6.4%, respectively) as compared to urologists (48.8% vs. 38.4% vs. 12.9%, respectively). There was no difference in complication rate or operative time between surgeon types. On multivariate regression analysis, the best predictor of major complication was a Charlson Comorbidity Index (CCI) >2 (OR 6.1, 95% CI 2.9-12.5; p<0.0001). Surgical approach and surgeon specialty were not predictors of complications. Conclusions: Adrenalectomy for malignant disease was more commonly performed by non-urologists via an open approach. Patient CCI >2 was associated with a higher rate of post-op complications, while surgical approach did not influence complication rate. These findings indicate that MIS can be performed safely for adrenal cancers. Prospective study of MIS for adrenal cancer is needed to evaluate its oncologic efficacy.
Effect of sunitinib treatment on mutations and methylation in metastatic renal cancer.
Authors: Stewart Grant , Van Neste Christophe , Meynert Alison , Semple Colin , O'Mahony Fiach , Laird Alexander , Mackay Alan , Trooskens Geert , Van Criekinge Wim , De Meyer Tim , Powles Thomas , Harrison David James 
Published: February 2017

492 Background: The effect of VEGF targeted agents on DNA mutations and epigenetic expression in metastatic clear cell renal cancer (mccRCC) has not been reported. We hypothesise that significant DNA mutations and methylation changes occur with treatment which may be associated with resistance. Methods: DNA was extracted from sequential frozen pairs of primary tumour tissue from 14 mccRCC patients, in the SuMR clinical trial (NCT01024205), at presentation (biopsy) and after 3-cycles of sunitinib (nephrectomy). Multiple biopsies were taken to assess for heterogeneity. Biopsy and nephrectomy samples were compared in untreated tumours as controls. Array CGH, Ion Torrent sequencing (48 key ccRCC genes were assessed [Table]), and methylCap-seq DNA methylation analysis were performed. Results: aCGH hierarchical clustering showed that samples from 2/14 patients clustered together (13%). There were no significant increase in copy number variations (CNVs) following treatment with sunitinib. For somatic mutations of the 48 key genes, there were no patients in whom all samples clustered together. Conversely, at methylation level, all samples for each patient clustered. Mean frequency of mutations in the key genes relative to normal kidney was identical for biopsy and nephrectomy samples (n=14 mutations). 12/48 genes had CNVs or mutations in ≥2 patients following treatment with sunitinib (table). VHL was the only gene with significant difference in methylation pre- and post-sunitinib therapy (FDR=0.077; logFC=-0.8734, hypermethylated following sunitinib therapy); there was no difference in VHL methylation pre- and post-renal artery clamping. Conclusions: Intratumoral heterogeneity was not apparent in DNA methylation, unlike DNA. This may facilitate in biomarker research. The significant increase in VHL methylation following sunitinib gives insight into possible mechanisms of resistance at an epigenetic level. [Table: see text]
Hospital re-admission patterns and outcomes following major urologic cancer surgery.
Authors: Nayak Jasmir G. , Holt Sarah , Gore John L. 
Published: February 2017

497 Background: Peri-operative morbidity and mortality varies considerably among hospitals. Given the highly complex surgery required for urologic cancer, post-operative adverse event management may be superior if treated in the same institution as the index surgery. Methods: We accessed the Washington State Comprehensive Hospital Abstract Reporting System from 2009-2013 to identified patients who underwent radical nephrectomy (RN), partial nephrectomy (PN), radical cystectomy (RC) or retroperitoneal lymph node dissection (RPLND) for malignant disease. Mortality rates were assessed in those with an adverse outcome requiring hospital re-admission within 90 days of surgery. The primary hospital (PH) was the institution where the main surgery took place. Secondary hospitals (SH) were all other hospitals. Relationships with mortality were examined using multi-variate modeling. Results: 4,542 patients were identified who underwent major urologic cancer surgery, of which 56% were RN, 26% PN, 15% RC and 2% RPLND. Overall, 795 (18%) experienced an adverse event following surgery requiring hospital admission. 64% of patients returned to their PH for management, but was dependent on the surgery performed (60% RN, 65% PN, 67% RC and 83% RPLND). When stratified by hospital volume, patients were more likely to present to their PH (p=0.0005), with more patients returning to their PH if it was a low vs. high volume center (72% vs 55%). Comorbidities and length of stay on index surgical admission did not affect whether patients chose to present to their PH or a SH for adverse event management. The overall mortality rate was 5%. On multi-variate analysis, patients who underwent surgery at a high-volume PH and presented to a SH for adverse event management had higher rates of mortality (p=0.03). Conclusions: Adverse events within 90 days of surgery of major urologic cancer surgery are associated with a low mortality rate, and most patients present to their PH for management. However, patients presenting to a SH experienced a higher mortality rate following an adverse event. These findings require further investigation and may aid in future quality improvement initiatives to reduce the morbidity associated with these complex surgeries.
Medical therapy for renal cell cancer with pancreatic metastases: Experience of the Gustave Roussy Institute.
Authors: Doucet Ludovic S. , Derosa Lisa , Albiges Laurence , Massard Christophe , Loriot Yohann , Fizazi Karim , Escudier Bernard J. 
Published: February 2017

503 Background: The prognosis of renal cell carcinoma (RCC) patients with pancreatic metastases has been reported to be better amongst patients with metastatic disease in several series. However, the benefit of medical treatments, especially antiangiogenic (AA) therapy, is still poorly reported. Methods: We retrospectively reviewed clinical outcomes of RCC patients with pancreatic metastases treated with systemic treatments between 2000 and 2014. Results: Eighty-four patients (pts) were recorded, among which 24 underwent local treatment of pancreatic metastases (83% surgery). Clear cell histology accounts for 92%. At the initiation of systemic treatment, prognostic score according to IMDC was good, intermediate, or unknown in 36%, 50%, and 13% respectively. Median overall survival (OS) was 83,2 months (mo) (55.6-29.4). Median OS was 127 mo (106.6-not reached [NR]) for patients who underwent a local treatment on the pancreas vs. 56.5 (39.8-NR) for those who did not (p=0.04). Cytokines used as first-line systemic therapy (n=27, 52% interleukin-2-based, 22% good prognostic group, 59% intermediate, 19% unknown) yielded an overall response rate (ORR) of 26%, a median treatment duration of 5.4 months (mo) (4.7-5.9) and a time to treatment failure (TTF) of 14.5 mo (12-32.2). Patients who received AA (n=77, previous cytokines 25%) showed, for the first use of AA, an ORR of 61%, with a median treatment duration of 11.5 mo (9-14.7) and a TTF of 18.2 mo (12.4-25.8). OS from the time of first systemic therapy was 107 mo (63.8-140.4) in patients who received AA vs. 30 mo (5.4-NR) in those who did not (p=3.10-5). Conclusions: This study confirms the more favorable prognosis of patients with pancreatic metastases from RCC. ORR to both cytokines and AA is higher than that observed in a general population of patients with metastatic RCC. The molecular basis for this observed better outcome deserves further investigation.
Phase II clinical trial of low-dose interleukin-2, interferon-alpha, and low-dose tegafur uracil therapy for advanced renal cell cancer.
Authors: Kato Tomoyuki , Iwamura Masatsugu , Fujita Tetsuo , Saito Seiichi , Ohshiro Yoshinori , Imai Tomoyuki , Kawata Nozomu , Tomita Yoshihiko , Sejima Takehiro , Kishida Takeshi , Tochigi Tatsuo , Kawamura Sadafumi 
Published: February 2017

508 Background: The objective of this trial was to evaluate the efficacy and safety of immunochemotherapy with very low-dose interleukin-2, interferon-alpha and tegafur uracil (IAT therapy) in treatment naïve metastatic renal cell carcinoma (RCC) patients with pulmonary metastasis only. Methods: Previously untreated metastatic renal cell cancer patients only with pulmonary metastasis were enrolled in this multicenter, open-label, single arm, phase II trial. Eligibility criteria included ECOG performance status (PS) 0-2, low or intermediate risk per MSKCC score, and adequate organ function. The primary endpoint was the overall response rate (ORR) per RECIST v1.1. Secondary endpoints were time to progression (TTP), response duration, overall survival (OS), ECOGPS and safety. Safety was assessed by CTCAE, v4.0. Low dose (0.7-2.1 MIU/ day) IL-2 was administered intravenously in the first five days of the first and third week. IFN-alpha (500 MIU/day) was administered 3 times per week in week 2. From 4th to 7th weeks, patients received IFN- alpha 3 times per week and 100 mg tegafur uracil t.i.d. Results: Twenty-eight eligible patients were enrolled from Apr 2009 through Dec 2013. Twenty-one patients were evaluable for ORR. Three patients had partial response (PR) 11 stable disease (SD), and 7 progressive disease (PD). ORR was 14.4% and median duration of PR was 18.0 months. TTP and OS were not reached to median and 3-year OS rate was 76.3%. Twenty-seven patients (96.4%) had an ECOGPS of 0 and 1 (3.6%) had PS of 1. Three patients experienced exacerbation in PS (PS 0 to 1). The most common adverse events (AEs) were elevation of ALT (35.7%) and fever (32.1%). AEs grade 3 included rash (14.3%), depression (3.2%), syncope (3.2%), fever (3.2%), elevation of ALT (3.2%). Four patients discontinued therapy at the time of ORR analysis due to AEs (3 rash, 1 depression). Conclusions: IAT therapy for RCC patients with only pulmonary metastasis is safe and appears to have clinical benefit as reflected by ORR rate and long OS. Clinical trial information: 00002222.
How reliable is a negative MRI/TRUS fusion biopsy? The predictive value of targeted biopsy for prostate cancer.
Authors: Fascelli Michele , Sussman Rachael , Frye Thomas P , George Arvin Koruthu , Abboud Steven , Chelluri Raju , Ho Richard , Brown Anna Mary , Sankineni Sandeep , Merino Maria J , Turkbey Baris , Choyke Peter L. , Wood Bradford J. , Pinto Peter A. 
Published: February 2017

51 Background: Multiparametric MRI (mpMRI) has been shown to improve clinically significant prostate cancer (CaP) detection. Targeted biopsy using MRI/transrectal ultrasonography (TRUS) fusion is a novel diagnostic tool. The negative predictive value (NPV) of an MRI/TRUS fusion targeted biopsy of a suspicious lesion on mpMRI was determined. Methods: 30 of 181 men who underwent prostatectomy from 2008-2014 were retrospectively identified and had at least one lesion on mpMRI negative for cancer on MRI/TRUS fusion biopsy. Whole mount pathology specimens, gold standard for CaP detection, were aligned with MRI to assess true histopathology of all identified targets. Lesions negative for CaP on biopsy and not identified as cancer on pathology were considered true negatives (TN). Lesions biopsied negative but later found to possess foci of CaP on whole mount were considered false negatives (FN). Calculations of NPV were then made per biopsy year, MRI suspicion score, and lesion size on MRI. Results: 48 lesions of a total 81 identified on mpMRI were reported negative for CaP in the 30 patients who underwent fusion biopsy. Of these, 37 lesions were found to be truly negative on histopathology, while 11 lesions had CaP foci on whole mount specimen. Overall NPV was 77% (37/48). The NPV increased over time (Table 1), and was as high as 85.7% most recently. Conclusions: This series demonstrated a NPV of 77% for targeted MRI/TRUS fusion biopsy of lesions seen on mpMRI. The increasing NPV trend noted over time may have further applications to assess the learning curve for this diagnostic method. Not surprisingly, NPV is higher for low and moderately suspicious lesions than for highly suspicious lesions. This data may help physicians interpret the clinical implications of a negative fusion biopsy. [Table: see text]
Inferior vena cava thrombus recurrence after radical nephrectomy in renal cell carcinoma.
Authors: Kauffmann Caroline , Pfister David A. , Porres Daniel , Heidenreich Axel 
Published: February 2017

511 Background: Local recurrence after radical nephrectomy in renal cell carcinoma occurs in about 2-4% of the patients. An isolated intracaval thrombus is described in only very few cases. We report about our experience in the diagnosis and theapy of this random entity. Methods: 5 patients (2f, 3m) were referred to our institution with the diagnosis of an IVC thrombus recurrence. All patients had underwent a radical nephrectomy 1-9 years before the relapse. In 3 patients, the thrombus was diagnosed within the routine follow up, another 2 presented with swelling/deep vein thrombosis. The staging showed no other metastases. Results: The mean patient age at time of diagnosis was 73.8 (70-81) years. 2 patients presented with a level II thrombus, 2 with level III and one with a level IV thrombus. We could resect the thrombus completely in 4 cases and close the cava with a running suture. In one case we had to resect the inferior vena cava completely and replace it with a gortex prosthesis. The mean blood loss was 1.7 (0-8) liters at an operating time of 5.5 (4.3-7.6) hours. The mean follow up was 3.5 (0.5-8) years, until today occured one case of pulmonal metastatic disease. Significant perioperative complications classified after Clavien-Dindo occured in one case with an intraoperative bleeding and rupture oft he spleen that required a mass-transfusion. Conclusions: Although it is a technical demanding procedure, the surgical resection of a recurrent vena cava thrombus is the method of choice with only a little perioperative morbidity and high oncological effectivity. This random type of recurrent disease illustrates the importance of an adequate primary therapy as well as a regularly follow up after cava-involvement.