bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of clinical parameters and overall survival (OS) in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with high-dose interleukin-2 (HD IL-2).
Authors: Stenehjem David D. , Parikh Kinjal , Batten Julia Anne , Van Atta Joan , Crispin Hilda , Sageser Daniel S. , Grossmann Kenneth F. , Wang Junfeng , Tantravahi Srinivas Kiran , Samlowski Wolfram E. , Agarwal Neeraj 
Published: February 2017

476 Background: HD IL-2 immunotherapy can provide durable responses in mRCC, but has a high incidence of severe adverse events (AEs). Therefore, determining pts most likely to achieve response before and during HD-IL2 treatment will help clinicians and pts best utilize HD IL-2 for the treatment of mRCC. Methods: Sequential clear cell mRCC pts treated with HD IL-2 at the University of Utah Huntsman Cancer Institute from 2000 to 2012 were included. The following clinical parameters were assessed: AE incidence, type and severity; total dose of IL-2 received and use of a 40 MIU dose cap; baseline weight, age, gender and MSKCC prognostic risk; and systemic therapy pre- or post-HD IL-2. Univariate and multivariate analyses were constructed using COX Proportional Hazard model. Results: 85 pts with clear cell mRCC treated with HD IL-2 were included with a median age of 56 years (range 32-76). Pts belonged to the following MSKCC categories: 11 (13%) good, 70 (82%) intermediate, and 4 (5%) poor risk. The median OS was 817 days. Multivariate analysis identified 6 factors associated with OS including: MSKCC prognostic group (intermediate vs good HR = 4.31, CI 1.41-16.04), grade 3 rigors (no vs yes HR = 3.07, CI 1.49-6.47), baseline weight (<80 vs >80 kg HR = 2.18, CI 1.08-4.39), total dose of IL-2 administered (quartile 1 vs 2 HR 2.90, CI 1.06-8.57; quartile 1 vs 3 HR 7.37, CI 2.63-21.54; quartile 1 vs 4 HR 25.17, CI 7.34-102.01), composite of the number and severity of AEs (continuous, HR 5.11, CI 1.01-27.56), and gender (female vs male HR 2.84, CI 1.06-7.20). Factors not associated with an OS benefit in this model include age at metastatic disease, use of a 40 MIU IL-2 dose cap and systemic therapy pre- or post-HD IL2. Conclusions: The following parameters predicted an OS benefit with HD IL-2 when controlled for MSKCC prognostic risk and systemic therapy pre or post HD IL-2: fewer and less severe AEs; higher baseline weight; male gender; and the ability to tolerate a higher cumulative dose of IL-2. Notably increased age did not portend poor outcome, and should not be considered a contraindication to treatment with HD IL-2 in otherwise eligible patients.
Neutrophil to lymphocyte ratio and response to tyrosine kinase inhibitor therapy in metastatic renal cell carcinoma.
Authors: Templeton Arnoud J. , Amir Eitan , Aneja Priya , Vera-Badillo Francisco Emilio , Hermanns Thomas , McNamara Mairead Geraldine , Heng Daniel Yick Chin , Knox Jennifer J. 
Published: February 2017

477 Background: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are markers of host inflammation and have prognostic value in many solid tumors. Here we aimed to explore the association of NLR and PLR with response to tyrosine kinase inhibitor (TKI) treatment in metastatic renal cell carcinoma (mRCC). Methods: Data from patients with mRCC treated at the Princess Margaret Cancer Centrein Toronto with a TKI as first-line treatment were retrospectively collected. The association of several variables with response to treatment (complete response [CR] or partial response [PR] vs. stable disease > 3 months [SD] or progressive disease [PD]) was assessed by binary logistic regression. Significant variables were dichotomized and cut-offs selected by the area under the receiver operating characteristic (AUC) curve. Results: Data from 157 patients treated between 11/2004 and 09/2012 were analyzed. Median age at start of TKI treatment was 61 years and first-line treatment was sunitinib, sorafenib, and other in 49%, 43%, and 8% of patients, respectively. Best response was CR/PR, SD, and PD in 27%, 55%, and 18% patients. On multivariable analysis NLR > 2.5 and Karnofsky Performance Status (KPS) < 90% were associated with a lower likelihood of response and each allocated a score of 1 unit. Response rates for a score of 0, 1, or 2 were 45% (29-61%), 28% (17-38%), 10% (1-19%), respectively. PLR did not retain association with response in multivariable analysis. Conclusions: NLR and KPS are associated with response to TKI treatment in mRCC. Data from an external validation set will also be presented.
Suitability of clear cell renal cell carcinoma to heat shock proteins-inhibitors.
Authors: Brunelli Matteo , Massari Francesco , Ciccarese Chiara , Ferrero Stefano , Gazzano Giacomo , Modena Alessandra , Bria Emilio , Tortora Giampaolo , Bosari Silvano , Martignoni Guido 
Published: February 2017

480 Background: Heat shock proteins (HSP) HSP27 and HSP90 are expressed in response to a wide variety of insults, thus allowing the cell to adapt to stress. In cancer cells, both HSP27 and HSP90 may participate to carcinogenesis, suggesting these chaperones as an appealing target for cancer therapeutics. The role of HSP in the development and progression of renal-cell carcinomas (RCCs) remains to be defined. We sought to evaluate a series of clear cell RCCs. Methods: 388 RCCs with clear cell histology available on 10 tissue microarrays were recruited. Each case was represented by 3 neoplastic cores. All these cases were stratified according to the Mayo Clinic SSIGN (Size, Staging, Grading, Necrosis) score into five prognostic groups with increasing worse prognosis (1 to 5). Immunostainings for HSP27 and 90 were performed. A mean score number from the three cores was set per case (percentage x intensity). Results were detailed per number of scorable cases per SSIGN category (1 to 5). Results: 117 and 122 RCCs were respectively available for HSP90 and HSP27 scoring. The remaining samples were lost due to the lack of tissue sections or to the absence of adequate neoplastic cells scorable. HSP90 scored 4,9 in 32 with SSIGN1, 3,5 in 41 SSIGN2, 4,8 in 11 SSIGN3, 4,2 in 22 SSIGN4 and 5 in 3 SSIGN5 patients. HSP27 scored 4,6 in 33 with SSIGN1, 3,1 in 43 SSIGN2, 2,6 in 11 SSIGN3, 3,6 in 24 SSIGN4 and 2,7 in 3 SSIGN5 patients. A significant trend of increasing value for HSP90 has been observed when comparing cases tabled SSIGN1-2 versus SSIGN3-5 (4,2 to 4,6 mean values) (p=0.05); a minor stratification has been observed for HSP27 (3,8 to 3,9) (p=0.08). Conclusions: In conclusion, HSP90 and HSP27 are variable immunoexpressed in a subset of clear cell RCCs, with a trend to higher prognostic SSIGN score. At light of new emerging targeted-therapies in kidney cancer, we report an increasing suitability of these patients to therapies that target the pathways of heat shock protein molecules. Additional learning of the HSP role in clear cell RCCs carcinogenesis is required to guide future therapeutic developments.
Immunohistochemical evaluation of aldose reductase expression in collecting duct carcinoma for differential diagnosis from other renal malignancy.
Authors: Hashimoto Yasuhiro , Yamamoto Hayato , Okamoto Akiko , Imai Atsushi , Hatakeyama Shingo , Yoneyama Takahiro , Koie Takuya , Ohyama Chikara , Mimata Hiromitsu 
Published: February 2017

483 Background: Collecting duct carcinoma (CDC) is a rare tumor but its recognition is important for the prediction of prognosis and decision making of the treatment. However, its diagnosis is challenging because of versatility of pathological features. We explored the possibility whether aldose reductase (AR), osmoregulatory protein and abundant in renal medulla, can be used as a marker for the pathologic diagnosis of CDC. Methods: We prepared anti-AR monoclonal antibodies, examined expression of AR protein in the human normal kidney. Immunohistochemical expressions of AR, 34bE12, a-methyl CoA racemase (AMACR) and expressions of lectins (Ulex europaeus agglutinin 1; UEA-1 and peanut agglutinin; PNA) were examined on normal kidney, 12 cases of CDC, 10 cases of papillary renal cell carcinoma (pRCC), and 10 cases of invasive urothelial carcinoma (iUC). Results: AR 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, AR was strongly positive in 9 of 12 CDC cases. AR was negative in cases of either iUC or pRCC. In contrast, although lectins were positive in all cases of CDC, they were also found in all types of malignancy. iUC was positive for 34bE12 in all cases but also so in some cases of CDC and pRCC. AMACR was positive for all the cases of pRCC but also positive for other tumors. Conclusions: Compared with other markers, AR may be a more specific and potentially useful marker for CDC. [Table: see text]
Association of partial nephrectomy and presence of robotic surgery for kidney cancer in the United States.
Authors: Kardos Steven V. , Shuch Brian , Schulam Peter , Trinh Quoc-Dien , Sun Maxine , Shippee Nathan D. , Sammon Jesse D. , Kim Simon P. 
Published: February 2017

484 Background: While hospital and surgeon characteristics are associated with the type of nephrectomy performed for renal cell carcinoma (RCC), it is unknown whether hospital presence of robotic surgery increases the likelihood of patients receiving partial nephrectomy (PN). Therefore, we evaluate the relationship of PN and hospital presence of robotic surgery from a population-based cohort in the U.S. Methods: After merging the Nationwide Inpatient Sample (NIS) and the American Hospital Association (AHA) survey from 2006 to 2008, we identified 21,999 patients who underwent either PN or radical nephrectomy (RN) for RCC. The primary outcome of this study was the type of nephrectomy performed. Multivariable logistic regression was used to identify hospital characteristics associated with receipt of PN, after adjusting for patient case mix. Results: Overall, we identified 4,832 (22.0%) and 16,347 (88.0%) patients who were surgically treated for RCC with PN and RN, respectively. On multivariable analysis, patients undergoing surgery were more likely to receive PN at academic (OR: 2.77;p<0.001), urban (OR: 3.66; p<0.001), and American College of Surgeon (ACOS) designated cancer centers (OR: 1.10; p<0.05) compared to non-academic, rural, and non-designated hospitals, respectively. After adjusting for patient and hospital characteristics, patients undergoing surgery at hospitals with presence of robotic surgery were also associated with higher adjusted odds ratios for receipt of PN compared to those treated at hospitals without the presence of this advanced treatment technology (OR: 1.28; p<0.001). Conclusions: While academic status and urban locations are established characteristics influencing the type of nephrectomy performed for RCC, ACOS cancer center designation and hospital presence of robotic surgery were also associated with higher use of PN. Our results are informative in identifying key hospital characteristics which may facilitate greater adoption of PN.
Potential impact of prior high-dose IL-2 on the outcomes of sunitinib (Su) treatment (tx) in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Rosenbaum Eli , Gottfried Maya , Hammers Hans J. , Eisenberger Mario A. , Carducci Michael Anthony , Sinibaldi Victoria J. , Neiman Victoria , Sarid David , Gez Eliahu , Hayat Henry , Peer Avivit , Sella Avishay , Mermershtain Wilmosh , Rouvinov Keren , Berger Raanan , Kejzman Daniel 
Published: February 2017

494 Background: Targeted txs are the tx of choice in most mRCC pts. However, HDIL2 which may produce durable responses in a small percentage of cases, is still an option in carefully selected pts. While the effect of prior HDIL2 on the outcome of targeted txs in mRCC pts is poorly defined, a recent single center report (Birkhäuser FD, Cancer J 2013) revealed an improved disease-specific survival in pts treated with prior HDIL2. We aimed to study the effect of prior HDIL2 tx on outcome of mRCC pts treated with sunitinib. Methods: Records from 302 mRCC pts treated with Su from 2004 to 2013 in 9 centers across 2 countries were retrospectively reviewed. We compared the response rate, progression free survival (PFS), and overall survival (OS), between post HDIL2 pts (n=27) and individually matched tx naïve pts (n=27). Progression free survival and overall survival were determined by Cox regression. Results: All pts had prior nephrectomy and clear cell histology. The groups were matched by age (median 61), gender (male 74%), Heng risk (favorable 37%, intermediate 59%, poor 4%), sunitinib induced hypertension (67%), sunitinib dose reduction/treatment interruption (41%), smoking status (active 7%), use of angiotensin system inhibitors (41%), the presence of more than one metastases site (96%), and pre-tx neutrophil to lymphocyte ratio (> 3 in 22%). Furthermore, they were balanced regarding the presence of lung (68%), liver (31%), and bone (43%) metastases, and the use of bisphosphonates (32%). In prior HDIL2 versus tx naïve pts, objective response was partial response/stable disease 89% (n=24) versus 74% (n=20), and progressive disease at first imaging evaluation within the first 3 months (mos) 11% (n=3) versus 26% (n=7) (p=0.29, OR 2.4). Median progression free survival was 21 versus 12 mos (HR 2.3, p=0.005), and median overall survival 25 versus 20 mos (HR 2.2, p=0.013). Conclusions: In metastatic renal cell carcinoma patients treated with sunitinib, prior high dose IL-2 therapy may improve the outcome.
Safety and efficacy of targeted therapy for renal cell carcinoma (RCC) with brain metastasis.
Authors: Bastos Diogo Assed , Molina Ana M. , Jia Xiaoyu , Velasco Susanne , Patil Sujata , Voss Martin Henner , Feldman Darren Richard , Motzer Robert John 
Published: February 2017

497 Background: Brain metastases (Bm) in RCC are associated with poor prognosis. The safety and efficacy of TT in this setting is not well established since patients (pts) with Bm were excluded from pivotal clinical trials. The primary objective was to assess safety and efficacy of TT in pts with Bm. Methods: Pts with mRCC treated with ≥ 28 days of TT after Bm diagnoses were retrospectively identified. Kaplan-Meier method and Cox proportional hazards model were used to analyze the association between clinical features and OS. Results: 65 pts were identified, including 52 (80%) treated with anti-angiogenic agents and 13 (20%) treated with mTOR inhibitors. Most pts had extracranial metastasis (98%) and 54% had ≥ 2 brain lesions. Fifty seven pts (88%) had local therapy for Bm before TT including surgery in 3 (5%), radiation therapy (RT) in 36 (55%) and both surgery and RT in 18 (28%). Median follow-up was 12.3 months (1.1 – 58.8). Median treatment duration was 3.4 months (0.3 – 31.9) for 1st line and 1.9 months (0.2 – 23.6) for 2nd line. Median OS was 12.2 months (95% CI 8.0 to 15.5). On univariate analysis using various clinical and treatment variables, MSKCC risk group (p = 0.001), histology subtype (clear vs other) (p < 0.0001), and number of Bm at diagnosis (p = 0.004) correlated with OS and retained statistical significance on multivariate analysis (Table). CNS complications were identified in only 5 pts (8%), including 2 with radiation necrosis and 3 with Bm hemorrhage. Conclusions: The use of targeted agents for pts with RCC and Bm appears safe with OS that compares favorably to historical results in the pre-TT era. Clear cell RCC, favorable MSKCC risk status, and solitary Bm are associated with better outcome. [Table: see text]
Overcoming mTOR resistance: Results of a phase I study of the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat.
Authors: Plimack Elizabeth R. , Wong Yu-Ning , Malizzia Lois , Corrigan Alycia , Olszanski Anthony J. , Denlinger Crystal Shereen , Roethke Susan , Tetzlaff Colleen H. , Hudes Gary R. 
Published: February 2017

501 Background: Elevation of pAKT levels has been shown to result from mTOR inhibition. We hypothesized that the HDAC inhibitor Vorinostat (Vori) would abrogate Ridaforolimus (Rida) resistance due to downregulation pAKT when used in combination in renal cell carcinoma (RCC). Methods: The primary objective was to determine the MTD most applicable to RCC patients (pts), thus while all solid tumors were allowed, prior cytotoxic chemotherapy was limited to 1 regimen. There was no limit to the number of prior targeted or immunotherapies. ECOG PS 0-1 and adequate organ and marrow function were required. A modified 3+3 dose escalation design tested 2 dose levels concurrently by escalating each drug in separate cohorts. Rida was dosed days 1-5 weekly, Vori days 1-3 weekly. Results: 15 pts (10 clear cell RCC, 3 papillary RCC, 1 esophageal, 1 carcinoid) were treated at one of 3 dose levels: 1) Rida 20mg QD + Vori 100mg BID, 2) Rida 20 mg QD + Vori 200 mg BID, 3) Rida 40 mg QD + Vori 100 mg BID. Inability to complete 80% of doses during cycle 1 due to thrombocytopenia resulted in DLTs in 2/6 pts in dose level 2. There were no other DLTs and no grade 4-5 toxicities. Related grade 3 toxicities were: hyperglycemia (1), anemia (2), fatigue (1), and mucositis (1). Grade 2 pneumonitis was seen in 2 pts. The MTD was Rida 20mg QD + Vori 100mg BID, however all 7 pts who received >2 cycles ultimately required dose reduction to Rida 10-20 mg QD + Vori 100 mg QD, for thrombocytopenia in 6/7 cases. Thus the recommended phase II dose to allow for chronic dosing is Rida 20mg QD + Vori 100mg QD. Four pts, all with RCC, maintained stable disease for 19, 21, 31+ and 59+ weeks. Of these, 3 had progressed on prior temsirolimus or everolimus including the 2 pts with ongoing disease control at the time of data cutoff (31+ and 59+ weeks), both of whom have papillary RCC. Conclusions: Rida 20mg QD + Vori 100 mg QD is the recommended phase II dose for this combination. Prolonged disease control was seen in 4/13 RCC pts, 3 of whom progressed on prior a prior mTOR inhibitor. Further study of combined mTOR and HDAC inhibition in RCC with tumor sampling to assess for pharmacodynamics and proof of concept is warranted to further define the toxicity, efficacy and mechanism of this combination. Clinical trial information: NCT01169532.
Utilizing percentage of sarcomatoid differentiation as a prognostic factor in renal cell carcinoma.
Authors: Kim Timothy , Lin Hui-Yi , Yue Binglin , Dhillon Jasreman , Fishman Mayer N. , Sverrisson Einar Freyr , Spiess Philippe E. , Gupta Shilpa , Pow-Sang Julio M. , Poch Michael Adam , Sexton Wade Jeffers 
Published: February 2017

507 Background: Sarcomatoid renal cell carcinoma (sRCC) is a histologic feature that denotes an aggressive variant of kidney cancer and worse overall outcomes. Our aim was to determine if the percentage of sarcomatoid differentiation (% Sarc) could be used for prognostic risk stratification. Methods: We performed a retrospective analysis of patients who underwent surgery at our center and found to have sRCC. A single genitourinary pathologist reviewed each specimen for %Sarc and other pathologic variables of interest. %Sarc was analyzed as a continuous variable and as a binary variable using cut-points of 5%, 10%, and 25%. Potential prognostic factors associated with overall survival (OS) were determined using the Cox regression model. OS curves were generated with Kaplan-Meier methods and survival differences compared using the log-rank test. Results: Between 1998 and 2012, 1,307 consecutive cases of RCC were identified, of which 59 patients were confirmed to have sRCC (4.5%). As a continuous variable %Sarc was associated with OS (p=0.023). Predictors of survival on multivariable analysis included pT stage, tumor size, cM stage and % Sarc at the 25% binary level. OS was most dependent on the presence or absence of metastatic disease (4 months vs. 21.2 months, p=0.001). However, in a subgroup analysis of cM0 patients with locally advanced (≥ pT3) tumors, OS was significantly diminished in patients with >25% Sarc compared to ≤25% Sarc (p=0.045). OS relative to %Sarc was no different in subgroup analyses of patients with early stage disease (pT1-T2, M0) or in patients with clinical metastatic disease. Conclusions: Patients with sRCC have a poor overall outcome as evidenced by high rates of recurrence and death. Patients without clinical metastatic disease and >25% Sarc have a higher risk of relapse and worse OS. More effective understanding of the biological basis for the aggressive behavior of sarcomatoid RCC is needed, and nomograms to predict recurrence or survival following nephrectomy could incorporate this pathologic feature for added risk stratification.
Clinicopathologic factors associated with the development of sunitinib induced hypertension (HTN) in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Neiman Victoria , Gottfried Maya , Hammers Hans J. , Eisenberger Mario A. , Carducci Michael Anthony , Sinibaldi Victoria J. , Rosenbaum Eli , Sarid David , Gez Eliahu , Peer Avivit , Neumann Avivit , Kovel Svetlana , Sella Avishay , Mermershtain Wilmosh , Rouvinov Keren , Berger Raanan , Kejzman Daniel 
Published: February 2017

508 Background: The VEGFR inhibitor sunitinib is a standard treatment for metastatic renal cell carcinoma (mRCC). HTN, an on-target class effect of VEGF signaling-pathway inhibitors, has been shown to correlate with clinical outcome. Studies have shown the association between genetic polymorphisms in several genes, and the development of HTN in patients treated with targeted therapies. We aimed to study the association between readily available clinicopathologic factors and the development of sunitinib induced HTN in mRCC patients. Methods: Records from mRCC patients treated with sunitinib in 9 centers across 2 countries were retrospectively reviewed. Sunitinib induced HTN was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Analysis of the association between clinicopathologic factors and the development of HTN was performed using logistic regression. Results: Between 2004-2013, 302 patients with mRCC were treated with sunitinib. The incidence of sunitinib induced HTN was 50% (n=152). Clinicopathologic factors included in the analysis were age (median 63), gender (67% male), HENG risk (good 22%, intermediate 59%, poor 19%), smoking status (active 21%), BMI (obese=BMI ≥30, 28%; overweight=BMI 25-29.9, 37%; normal weight= BMI <25, 35%), pre-treatment HTN (58%), past nephrectomy (83%), histology (73% clear cell), > 1 metastatic site (82%), metastatic site (lung 72%, liver 25%, bones 40%), pre-treatment neutrophil to lymphocyte ratio (>3 in 45%), treatment line (first vs advanced), sunitinib dose reduction/treatment interruption (45%). Absence of liver metastases (OR 3.5, p=0.02), pre-treatment neutrophil to lymphocyte ratio ≤ 3 (OR 5.5, p=0.001), and BMI (overweight and normal weight vs obese, OR 2.2 and 2.3 respectively, p=0.01 both) were independently associated with the development of HTN. Conclusions: In metastatic renal cell carcinoma patients treated with sunitinib, readily available clinicopathologic factors may be used to identify patients who are prone to the development of HTN.