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

487 Background: HD IL-2 is associated with an objective response rate of 16-20% with durability of response in select mRCC patients. HD IL-2 is also associated with significant toxicity including vascular leak syndrome and inflammatory side effects. Few predictive markers can identify patients likely to respond to HD IL-2. Methods: Patients treated with HD IL-2 at the University of Utah Huntsman Cancer Institute from 2000 to 2012 with clear cell mRCC were evaluated. Grade of toxicities during HD IL-2 treatment were collected based on provider documentation in the electronic health record. Rates of adverse events (AEs) and overall survival stratified grade 3 AEs were evaluated by Kaplan-Meier survival estimates and Cox proportional hazards models. All AEs were graded per common terminology criteria version 4. Grade 3 rigors were defined as severe rigors requiring opioids. Results: A total of 85 patients were included with a median age of 56 years (range 32-76 years) and 79% (n = 67) were male. Patients belonged to the following MSKCC risk categories: 11 (13%) good, 70 (82%) intermediate, and 4 (5%) poor risk. The mean total dose received was 1097 MIU (range: 160 – 3048 MIU). The prevalence of grade 3 AEs is presented in the table. Median survival of patients with ≥grade 3 rigors after HD IL-2 administration was 1501 days vs 533 days for those without (p = 0.0005, HR 2.54). Presence of rigors was also associated with a significant improvement in progression free survival, time to next treatment and response rates. No other AEs predicted response to HD IL-2. Conclusions: Presence of grade 3 rigors predicts improved survival during HD IL-2 therapy. Notably, grade 3 fever was rarely observed because of our institutional protocol of routinely using scheduled antipyretics to diminish fevers. [Table: see text]
A phase I, open label, dose escalation and cohort expansion study to evaluate the safety and immune response to autologous dendritic cells (DC) transduced with AdGMCA9 (DC-AdGMCAIX) in patients with mRCC.
Authors: Kabbinavar Fairooz F. , Zomorodian Nazy , Belldegrun Arie S. , Wong Steven G. , Bot Adrian , Chodon Thinle , Comin-Anduix Begonya , Nguyen Phuong , Khan Faraz , Rettig Matthew , Pantuck Allan J. 
Published: February 2017

490 Background: Carbonic anhydrase IX (CAIX) is an attractive target for the development of a RCC specific vaccine. We developed a fusion gene construct, GM-CSF + CAIX, transduced by a replication deficient adenovirus into autologous dendritic cells (DC) that are injected in patients with mRCC. This is a ph1 study of cancer vaccine against CAIX gene expressed on RCC tumors. Methods: A recombinant adenovirus encoding the GMCSF-CAIX fusion gene (AdGMCAIX) was produced per GMP in collaboration with the NCI RAID program. The final product is produced in an in-house GMP cell processing facility using DCs cultured ex vivo from patients’ PBMC's and engineered with AdGMCAIX prior to intradermal injection. The transduced DCs are expected to stimulate an antigen specific immune response against CAIX expressing RCC, leading to a potential anti-tumor effect. Dose escalation in 3 dose cohorts (5 X 106, 15 X 106, and 50 X 106 cells/administration) follows the std 3+3 ph1 design with an expansion cohort. DC-AdGMCAIX is given intradermally Q 2 weeks X 3 doses. The primary aim is safety of DC-AdGMCAIX injections. Secondary aims are to evaluate immune responses & the antitumor effects per RECIST 1.1. Pts with clear cell mRCC with ECOG 0-1 & measurable disease & adequate organ function were enrolled. Results: Six pts with clear cell mRCC are enrolled. Four pts received all 3 planned vaccine doses and the fifth pt only the 1st dose. No SAE’s were seen to date. One pt had chills that lasted several minutes and transient Gr1 leucopenia. One pt has worsening of pre-existing proteinuria, though unclear if related to the vaccine. One pt has PD & the other two have SD on D85 scans. Tumor bx shows intra-tumoral infiltration by T cells. Conclusions: These early data show that autologous DC transduced by Ad-GMCAIX vector can be safely given to mRCC patients without any acute SAE’s noted at the doses tested so far. The study will complete its 3rd cohort & expansion cohort enrollment. This data support the further development of Ad-GMCAIX vaccine strategies either alone or in combination with approved therapies. Funding: Supported by NCI RAID Initiative NSC 740833 and Kite Pharma.
Perioperative outcomes following surgical resection of renal cell carcinoma with upper level IVC thrombus: A contemporary multicenter experience.
Authors: Abel Edwin Jason , Thompson R. Houston , Margulis Vitaly , Heckman Jennifer E. , Merrill Megan M. , Darwish Oussama M. , Krabbe Laura-Maria , Boorjian Stephen A. , Leibovich Bradley C. , Wood Christopher G. 
Published: February 2017

498 Background: Surgery for RCC patients with IVC thrombus above the hepatic veins is complex and associated with an increased risk of perioperative morbidity and mortality. However, minimal data exist that describe contemporary perioperative outcomes at major referral centers or the prognostic factors associated with adverse surgical outcomes. The objective of this study is to determine the preoperative predictors of major complications and 90 day mortality after surgery in RCC patients with IVC thrombus above the hepatic veins. Methods: Records were reviewed of all RCC patients with IVC tumor thrombus above hepatic veins who had surgery from 1/2000 to 12/2012 at Mayo Clinic, MD Anderson, UT Southwestern and the University of Wisconsin. Major complications were recorded were defined as 3A or greater according to the Clavien- Dindo system within 90 days of surgery. Univariate and multivariate (MV) analyses were used to evaluate associations of preoperative clinical, pathological or laboratory variables with risk of major complications or 90-day mortality. Results: A total of 162 patients were identified for study (thrombus level 3,4 in 69 and 93 patients, respectively, according to Neves classification). Cardiopulmonary bypass was used in 60/162 (37.5%), while 40 (24.7%) patients underwent pre-operative angioembolization. Major complications were reported in 55 (34.0%) patients, with the most common being respiratory (12.4%), hematologic (9.2%) and cardiac (8.6%). On MV analysis, preoperative systemic symptoms and level 4 thrombus were independently associated with an increased risk of major complications. Mortality was reported in 17 (10.5%) patients within 90 days after surgery. On MV analysis, ECOG performance status and low serum albumin were independently associated with increased risk of 90 day mortality. Conclusions: Contemporary perioperative mortality and major complication rates for RCC patients with upper level thrombus are 10 and 34%, respectively. ECOG PS >1 and low serum albumin are associated with an increased risk of perioperative mortality, and should be considered when selecting patients for neoadjuvant systemic therapy trials.
Temporal trends and factors associated with receipt of systemic therapy among patients undergoing cytoreductive nephrectomy.
Authors: Smaldone Marc C. , Handorf Elizabeth , Kim Simon , Thompson Robert Houston , Costello Brian Addis , Corcoran Anthony , Wong Yu-Ning , Uzzo Robert G. , Leibovich Bradley C. , Kutikov Alexander , Boorjian Stephen A. 
Published: February 2017

503 Background: We evaluated temporal patterns in the utilization of systemic therapy among patients undergoing cytoreductive nephrectomy (CN) for metastatic Renal Cell Carcinoma (mRCC) from a large national cancer registry and assessed patient characteristics associated with receipt of systemic treatment. Methods: We reviewed the National Cancer Database to identify patients with stage IV RCC who underwent CN between 1998-2010. Systemic therapy was defined as any treatment with immunotherapy and/or chemotherapy (including targeted agents). We evaluated the association between clinicopathologic features and receipt of systemic therapy using multivariable logistic regression with generalized estimating equations, and assessed the interaction of treatment with time, stratified as immunotherapy (1998-2004) versus targeted-therapy (2005-2010) eras. Results: Of 22,409 patients with mRCC undergoing CN, 8,830 (39%) received systemic therapy. Receipt of systemic therapy increased from 32% in 1998 to 49% in 2010 (p<0.001), largely due to increased utilization of chemotherapy (13.9% vs. 46.7%; p<0.001). Following adjustment, increasing patient age (51-60 years: OR 0.82 [CI 0.73-0.92]; 61-70 years: OR 0.67 [CI 0.59-0.76]; ≥71 years: OR 0.36 [CI 0.31-0.43]), as well as coverage with Medicaid (OR 0.61 [CI 0.5-0.74]), Medicare (OR 0.70 [CI 0.62-0.79]), or no insurance (OR 0.75 [CI 0.63-0.91]) were associated with decreased utilization of systemic therapy. Although use of systemic therapy in the elderly (≥71 years) and in patients with Medicare/Medicaid remained lower throughout the study period, each of these cohorts was significantly more likely to receive systemic treatment in the targeted versus immunotherapy era (all p values <0.05). Conclusions: Utilization of systemic therapy among patients undergoing CN has increased over time, coinciding with the introduction of targeted therapies. Nevertheless, still less than half of such patients receive systemic treatment. While the etiology for lack of treatment is likely multifactorial, the potential health policy implications of continued disparities in care warrant further investigation.
Temporal changes in the survival of metastatic renal cell cancer patients and the impact of targeted agents: Single center experience.
Authors: Erman Mustafa , Arik Zafer , Kilickap Saadettin , Bilen Cenk Yucel , Yazici Sertac , Akdogan Bulent , Ozen Haluk 
Published: February 2017

519 Background: Though targeted agents have dramatically changed the outcome of metastatic renal cell cancer (mRCC) patients, it has not been possible to show any survival advantage, probably due to substantial cross-over in randomized trials. The change in survival times following the introduction of targeted agents may yield indirect evidence of an improvement in overall survival (OS). Methods: First targeted agents were available in Turkey in 2007. Data from the hospital charts of adult mRCC patients treated between January 2003 and December 2012 were included. Demographic and clinical findings along with patient, tumor, and treatment-related prognostic factors and their correlation with progression-free survival (PFS), and OS were analyzed. Results: One hundred and seventy six patients had metastatic disease. Of these, 107 patients received at least one dose of interferon-α and 74 patients received at least one targeted therapy. Median follow-up was 19.1 months (range 1-97 months) and median OS was 24.6 months (95% CI, 20.4-28.9). Median OS of patients who received any targeted therapy was significantly better than those who did not (29.1 mths [95% CI, 21.4-36.8] vs 19.4 mths [95% CI, 14.2-24.6]; p=0.036). The study period of 2003-2012 was subdivided into 4 consecutive groups. Although not statistically significant, a trend toward better survival was observed with advancing years and increasing targeted therapy use (p=0.09). For example, median OS of patients diagnosed in 2006 and 2007 was 14.1 months (95% CI, 10.4-17.8) while median OS of those diagnosed in 2010 or later was 30.8 months (95% CI, 18.3-43.3). Patients in intermediate and poor Memorial Sloan-Kettering Cancer Center risk groups benefited more from targeted therapies (p=0.001). Conclusions: Patients who received any targeted therapy lived longer than those who did not. Trend toward better survival was associated with advancing years and increasing targeted therapy use. The introduction of targeted agents appear to benefit mRCC patients in terms of OS as well.
High preoperative monocyte-lymphocyte ratio (MLR) as a prognostic factor in nonmetastatic clear cell renal cell carcinoma.
Authors: Hutterer Georg C. , Stoeckigt Caroline , Stojakovic Tatjana , Martin Hernandez Jessica M. , Eberhard Katharina , Mannweiler Sebastian , Gerger Armin , Pummer Karl , Pichler Martin , Zigeuner Richard 
Published: February 2017

534 Background: The ratio of peripheral blood absolute monocyte count to absolute lymphocyte count (MLR) has been proposed as a negative impact for patient’s survival in haematological cancers. However, findings about MLR’s potential prognostic significance in non-metastatic renal cell carcinoma (RCC) patients have not been reported yet. Methods: We retrospectively evaluated the prognostic significance of the MLR in a cohort comprising of 678 consecutive non-metastatic clear cell RCC patients, operated between 2000 and 2010 with curative radical or partial nephrectomy at a single tertiary academic centre. Pre-treatment MLR was calculated one day before surgical intervention. Patients were categorised using an MLR cut-off of 0.35. Cancer-specific- (CSS), metastasis-free- (MFS), as well as overall survival (OS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of the MLR, multivariate Cox regression models were applied for all three endpoints. Additionally, the influence of the MLR on the predictive accuracy of the Leibovich prognosis score was determined by Harrell’s concordance index (c-index) and decision curve analysis (DCA). Results: An increased MLR was statistically significantly associated with poor outcomes for all three endpoints in univariable analyses (all p≤0.006). Multivariable analyses identified an increased MLR as an independent prognostic factor for patients’ CSS [HR=2.33, 95%CI=1.10-4.94, p=0.027], but not for MFS [HR=1.59, 95%CI=0.94-2.69, p=0.087], nor for OS [HR=1.37, 95%CI=0.93-2.03, p=0.112]. The estimated c-index was 0.83 using the Leibovich prognosis score and 0.86 when MLR was added. Conclusions: Regarding RCC patients’ CSS, an increased MLR represented an independent prognostic factor. Adding the MLR to well-established prognostic models such as the Leibovich prognosis score might improve their predictive ability.
Clinical outcomes and survival of patients (pts) with sarcomatoid metastatic renal cell carcinoma (smRCC).
Authors: Tantravahi Srinivas Kiran , Stenehjem David D. , Agarwal Archana , Kollepara Sri Lakshmi S. , Batten Julia Anne , Ward Michael , Albertson Dan , Wang Junfeng , Liu Ting , Agarwal Neeraj 
Published: February 2017

535 Background: SmRCC is a rare variant of RCC associated with poor outcome. No definitive therapeutic recommendations exist. We present survival outcomes in pts with smRCC treated with systemic therapy. Methods: From a single institutional database (years 2000-2012), we identified 21 pts with documented sarcomatoid features who received systemic therapy. Survival was assessed in the overall cohort and in subgroups divided by clinicopathologic characteristics, including the extent of sarcomatoid features, and Memorial Sloan-Kettering Cancer Center (MSKCC) risk criteria. Sarcomatoid component of the tumor was classified by predominant (≥20%) and non-predominant (<20%). Immunohistochemistry (IHC) analysis was performed for mammalian target of rapamycin (mTOR) signaling, phosphorylated ribosomal protein S6, proviral integration site proteins (PIM 1,2,3), Beta-catenin, E-cadherin, phosphatase and tensin homolog (PTEN), U3 small nucleolar ribonucleoprotein (IMP-3), p53, and epithelial membrane antigen (EMA) on tumor samples, where available. Results: 21 pts were included with a median age of 62 years (range 39-74) and 13 pts were male (62%). One pt received first line cytotoxic chemotherapy, 3 pts received first line immunotherapy, and 17 pts received targeted therapy. Pts belonged to the following MSKCC risk categories: 1 (5%) favorable, 13 (62%) intermediate and 7 (33%) poor risk. Median overall survival (OS) of the entire cohort was 249 days (95% CI 161-519 days). Median OS in pts stratified as MSKCC poor, intermediate, and good risk was 2556, 430, and 137 days respectively (Poor vs Intermediate HR 4.38, p = 0.0159, CI 1.30-19.90). There was no significant difference in OS in pts with sarcomatoid predominant disease vs. non-predominant disease (234 vs 286 days, p = 0.744, HR 0.85, CI 0.31-2.39). Conclusions: Overall OS in pts with smRCC is inferior compared to that reported in clear cell variant mRCC. Although MSKCC risk scores may be useful in determining prognosis, further studies are needed to identify relevant biomarkers and define the optimal therapeutic strategy for this disease. Correlation of survival outcomes with the IHC profile of tumors will be presented.
Population pharmacokinetic analysis of abiraterone acetate in healthy volunteers and chemotherapy-naive and chemotherapy-pretreated metastatic castration-resistant prostate cancer patients.
Authors: Stuyckens Kim , Saad Fred , Xu Steven , Ryan Charles J. , Smith Matthew R. , Griffin Thomas W. , Yu Margaret K. , Vermeulen An , Nandy Partha , Poggesi Italo 
Published: February 2017

58 Background: Abiraterone acetate (AA) is an effective therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). AA is metabolized to abiraterone, an androgen biosynthesis inhibitor. We performed population pharmacokinetic (PK) analyses to estimate PK parameters after a 1,000 mg/d oral dose of AA in patients with mCRPC with and without prior chemotherapy and after a one-time 1,000 mg dose in healthy volunteers, to determine consistency between groups. Methods: Studies included in analysis: COU-AA-302 (pre-chemotherapy mCRPC); COU-AA-301 and COU-AA-006 (post-docetaxel mCRPC); and COU-AA-008, COU-AA-009, and COU-AA-014 (healthy subjects). A total of 4,627 plasma concentrations from 360 subjects were analyzed using nonlinear mixed-effects modeling. Results: A two-compartment model with three-transit compartments following sequential zero-first order kinetics was used to characterize the systemic absorption of abiraterone. Absorption-related parameters were affected by food intake. Abiraterone PK was characterized by an extensive apparent clearance, which was lower in patients with mCRPC (1505 L/h) compared with healthy subjects (2240 L/h), and by large apparent central (5630 L) and peripheral volumes of distribution (17,400 L). PK of abiraterone was similar in chemotherapy-naïve and chemotherapy-pretreated patients and was characterized by a relatively high between- and within-subject variability (eg, between-subject coefficient of variation [CV%] for relative bioavailability in the clinical studies was 61.1% and the CV% for within-subject variability was 71.3%). No factors other than food intake and patient-healthy volunteer status impacted PK. Conclusions: Based on this population PK model, the recommended 1,000 mg/d dose of AA results in similar abiraterone exposure for patients with mCRPC regardless of prior chemotherapy status. The food effect on absorption-related parameters in this analysis confirms current dosing instructions for AA. Clinical trial information: NCT00638690, NCT00887198.
Rectal toxicity after permanent iodine-125 seed implantation: Nationwide cohort study in Japan (J-POPS).
Authors: Katayama Norihisa , Yorozu Atsunori , Maruo Shinichiro , Kojima Shinsuke , Ohashi Toshio , Tanaka Nobumichi , Saito Shiro , Dokiya Takushi , Fukushima Masanori , Yamanaka Hidetoshi 
Published: February 2017

73 Background: The purpose of this report is to describe acute and late rectal toxicities and to evaluate factors associated with rectal toxicity in permanent seed implantation (PI) patients enrolled in a nationwide cohort study in Japan. Methods: A total of 2,339 patients in 46 institutes were evaluated. They were treated in the nationwide cohort study entitled Japanese Prostate Cancer Outcome Study of Permanent I-125 Seed Implantation (J-POPS) during the first two years, until June 2007. Rectal toxicities were evaluated using the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, which were obtained at 3, 12, 24, and 36 months after completion of radiotherapy. The odds ratios (OR) of factors associated with greater than or equal to grade 2 rectal toxicity were calculated using a logistic regression model, and the 95% confidence intervals (CI) were estimated. Results: Greater than or equal to grade 2 rectal toxicities were seen in 2.8% of all patients (1.7% in the PI monotherapy group and 6.4% in the external beam radiation therapy [EBRT] combination therapy group). On multivariate analysis, among all patients, greater than or equal to grade 2 rectal toxicity was associated with rectal volumes receiving 100% of the prescribed dose (R100) (OR, 1.93; 95% CI, 1.39–2.68) and EBRT addition (OR, 3.00; 95% CI, 1.39–6.32). R100 in the PI monotherapy group (OR, 1.67; 95% CI, 1.06–2.64), and R100 (OR, 2.07; 95% CI, 1.30–3.30) and interactive planning (OR, 0.46; 95% CI, 0.23–0.92) in the EBRT combination therapy group were also associated with greater than or equal to grade 2 toxicity. Greater than or equal to grade 2 toxicity was seen in 3.7% and 1.4% of patients with R100 greater than or equal to 1 ml and R100 less than 1 ml, respectively, in the PI monotherapy group (OR, 2.78; 95% CI, 1.28–6.05) and in 14.1% and 5.4% of patients with R100 greater than or equal to 1 ml and R100 less than 1 ml, respectively, in the EBRT combination therapy group (OR, 2.88; 95% CI, 1.28–6.45). Conclusions: Rectal toxicity was relatively limited compared to other reports. For Japanese PI patients, R100 should be less than 1 ml, both in PI monotherapy and in EBRT combination therapy, and interactive planning should be performed for EBRT combination therapy.