bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of metastatic renal cancer with high-dose interleukin-2 after targeted therapy.
Authors: Hawkins Robert E. , Galvis Victoria , Shanks Jonathan , Dalal Neha , Thistlethwaite Fiona , Spencer-Shaw Andrea 
Published: February 2017

439 Background: High-Dose Interleukin-2 (HD IL2) remains a good option for treatment of metastatic renal cancer. As a first-line treatment, in carefully selected patients, it can produce high rates of response ( OR 50%; CR 25%) (Shablak A et al., J Immunotherapy 2011, 34(1):107-122). Its use after targeted therapies is controversial and there are reports of increased toxicity, particularly an increased incidence of cardiovascular toxicity (and possibly a reduced response rate (Cho DC et al., J Immunotherapy 2009, 32(2):181-520). However, there is potential to use it either in patients who have failed treatment with targeted therapy or as a consolidation therapy after successful treatment with a targeted agent. Methods: Here we present the outcomes of 16 patients treated with first-line immunotherapy with HD-IL2 after targeted therapy: of these 8 had been treated after failure of 1-3 lines of targeted therapy and 8 have been treated as consolidation after initial response to sunitinib. The histological characteristics of the tumours all fitted into the “favourable” group as defined previously by us and all had high levels of expression of CAIX (> 80%). All had ECOG PS 0/1, a satisfactory baseline stress echo, an interval of at least 8 weeks from last dose of targeted agent to start of HD-IL2 and at most 2 organs of disease. Results: Toxicity is indistinguishable from that of patients without prior treatment and no patient needed inotropic support or admission to intensive care. The number of doses given per cycle was also similar to that in unpretreated patients. Overall the response rates are excellent – with 9/13 evaluable patients having RECIST defined response and 6/13 having a complete remission. To date none of the patients in complete remission have realpsed but follow up is relatively short with the longest being 24 months. The responses have been particularly striking following treatment with mTor inhibitors. Conclusions: Overall, HD IL2 can be given safely in carefully selected patients after targeted therapies. It appears to be effective as a salvage therapy and potentially as a consolidation therapy. Updated results will be presented.
A phase I study of S-1 in combination with sorafenib in metastatic renal cell carcinoma (mRCC).
Authors: Ozono Seiichiro , Takayama Tatsuya , Fujisawa Masato , Miyake Hideaki , Hashine Katsuyoshi , Ninomiya Iku , Tatsugami Katsunori , Sakai Hideki , Ohba Kojiro , Akaza Hideyuki , Tsukamoto Taiji , Naito Seiji 
Published: February 2017

447 Background: S-1 is an oral anticancer agent combining tegafur, a prodrug of 5-fluorouracil, with 5-chloro-2,4-dihydroxypyridine and potassium oxonate. The purpose of this study was to confirm the recommended dose (RD) and maximum tolerated dose (MTD) of S-1 in combination with sorafenib, a small molecular inhibitor of several tyrosine protein kinase, in Japanese patients with mRCC. We assessed dose-limiting toxicities (DLTs) and pharmacokinetic interactions during the first cycle of treatment. Methods: Eligible patients had a histologically confirmed diagnosis of clear cell or papillary mRCC, measurable lesions, a history of no previous treatment or not more than 1 regimen of cytokine treatment, an ECOG performance status of 0 or 1, prior nephrectomy, and adequate organ functions. In this study, four dose levels were prepared, and the starting dose was set at Level 1B. S-1 was administered on days 1 to 28, and sorafenib was given on days 1 to 42 as one cycle. The MTD was assessed using a “3 + 3” dose escalation design and was defined as the highest dose level for which the incidence of DLTs was less than 33%. Results: Between August 2009 and March 2010, 9 patients were enrolled. Two DLTs occurred in patients assigned to level 2, which was the full therapeutic dose of each agent. Therefore, the MTD was not confirmed, but the RD was determined to be level 2. Although renal clearance affected the pharmacokinetics of S-1, there were no obvious drug interactions between S-1 and sorafenib. Details are shown in the Table. Conclusions: This combination therapy can be administered with acceptable tolerability, no overlapping toxicity, and no drug interactions. The RD for phase II studies was fixed at level 2, and a phase II study is ongoing. [Table: see text]
Use of Fuhrman grading system for Japanese patients with renal cell carcinoma.
Authors: Miyaji Yoshiyuki , Kanomata Naoki , Ohira Shin , Ohbatake Aya , Fujita Masaichiro , Fukumoto Kazuhiko , Fujii Tomohiro , Jo Yoshimasa , Yokoyama Teruhiko , Nagai Atsushi 
Published: February 2017

452 Background: In Japan, the 3-tiered system compared with the size of nuclei of normal tubule cell was adopted as the histologic criteria for tumor grading of renal cell carcinoma (RCC) in “General Rule for Clinical and Pathological Studies on Renal Cell Carcinoma”. Fuhrman grading system is first adopted in the 4th edition (April, 2011). We evaluated the impact of these pathological features on RCC survival and recurrence in Japanese patients. Methods: We identified 187 consecutive patients who underwent partial or radical nephrectomy at our institution from 1996 to 2009 for RCC. Specimens were re-reviewed by a single pathologist (NK) blinded to clinical outcome data. The data captured were histological type according to the 2004 WHO classification and conventional Fuhrman grading system. Results: Median followup was 57 months (range 5 to 181). Median age at diagnosis was 65 years. The TNM stage (7th UICC) was I in 127 cases, II in 21, III in 20 and IV in 19. A total of 24 partial and 163 radical nephrectomies were performed. Of the specimens 144 (77.0%) were clear cell carcinoma. The metastasis-free survival rates in stage I, II and III at 5 years were 89.7% ,79.8% and 52.1%, respectively (p<0.001). Univariate analysis revealed that there were significant risk factors in T stage, in Furhman grade, in microscopic venous invasion, in capsular invasion and in tumor size more than 4.1cm diameter. On multivariate analysis Furhman grade (grade I and II vs. III, vs. IV) was the only significant risk factor (HR 4.35 (III vs. I and II), HR 3.33 (IV vs. I and II), p=0.037). The overall survival rates in stage I, II , III and IV at 5 years were 83.0%, 90.0%, 76.8% and 41.8%, respectively (p<0.001). On multivariate analysis T stage, capsular invasion and Furhman grade (p=0.003) were the significant risk factor. Conclusions: Even Japanese patients with renal cell carcinoma undergoing nephrectomy, Fuhrman grading system is the most important predictive factor for survival and disease-free survival.
Non–clear cell histology in patients with metastatic RCC as a prognostic indicator in the targeted therapy era.
Authors: Rampersaud Edward N. , Birkhauser Frederic , Logan Joshua E , Sonn Geoffrey , Chan Yvonne , Anterasian Christine , Li David , Pouliot Frederic , Kabbinavar Fairooz F. , Pantuck Allan J. , Belldegrun Arie S. 
Published: February 2017

454 Background: The role of targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) having non-clear cell histology (non-ccRCC) is still being defined. We sought to examine the factors associated with survival outcomes in patients presenting with various histological subtypes in the TT era. Methods: The UCLA Kidney Cancer Program database containing records of over 2000 patients was queried. The clinicopathologic factors between patients with clear cell subtype (ccRCC) and those with non-clear cell histology were compared using the Student’s T-test and the chi-square test for continuous and categorical variables, where appropriate. Survival outcomes were estimated using Kaplan-Meier (log rank). Univariate and multivariate Cox regression models were used to identify independent associations with survival. Results: Of 157 patients treated with FDA-approved TT, 132 (84%) had ccRCC while 25 (16%) had non-ccRCC. The two groups were balanced for baseline demographic variables, including gender, race, BMI, pack-years of smoking, T-stage, Fuhrman grade, performance status and UCLA Integrated Staging System (UISS) risk category. Median survival of patients with ccRCC and non-ccRCC was 41.6 and 18.1 months (p<0.001). In univariate analysis, non-ccRCC was associated with a 2.7-fold risk of cancer specific death compared to ccRCC patients. Among patients receiving TT-only, median survival of patients with ccRCC and non-ccRCC was 35 and 15.4 months (p=0.007). A subset of ccRCC patients treated sequentially with IMT followed by TT had a median survival of 73 months. Worsening UISS risk class and non-ccRCC histology, but not age, gender, race, tobacco exposure history, or tumor size, were independently associated with the risk of cancer death. Conclusions: Non-clear cell histology remains a significant and independent risk factor for cancer specific death for mRCC patients treated by TT even after controlling for UISS risk category. [Table: see text]
Lymphopenia as a prognostic factor in renal cell carcinoma.
Authors: Mozayen Mohammad , Tesfaye Anteneh , Katato Khalil 
Published: February 2017

470 Background: Lymphopenia is known to be a negative prognostic marker for NHL and hematological malignancies, recent observational studies evaluated the presence of lymphopenia and its impact in solid tumor like colon, lung and pancreatic cancer. We aim to assess the effect of Lymphopenia at the renal cell carcinoma (RCC) survival. Methods: A retrospective review of 207 patients diagnosed with RCC between 1995 and 2008 in a community hospital setting was done. Patients with additional malignancies, lymphoma of the kidneys, with no follow up data or no preoperative complete blood count test were excluded. Demographics, preoperative complete blood count, pathology, disease stage, operative note, and subsequent follow up data were reviewed. Lymphopenia was defined as absolute lymphocytic count < 1200/µl. Last follow up date was used to calculate the 3 year overall survival. The primary outcome was 3 year overall survival. Results: A total of 207 patients were included in the study. Caucasians were 176(85.9%), African Americans were 13.7% and Asians were 1(0.5%). Males (M) were 127 (62.3%) and females (F) were 77(37.7%). The median age of the study population was 65 (22-91. Clear cell histology was seen in 79%. Stage I was seen in 53.9%, II in 23.5%, III in 13.7% and IV in 8.8% of the study population. Lymphopenia was seen in 81 (40%) patients (95 CI 34-48). Lymphopenia was seen in 31.8% of stage I; 50% of stage II, 41.4% of stage III, and 65% of stage IV patients (p=0.017). Lymphopenia was seen in 28.6% of African Americans and 42.7% of Caucasians (p=0.11). Lymphopenia was seen in 32.1% of females and 45.7% of males (p=0.03). The 3 year overall survival for the study population was 67.3% (95% CI: 60.4-73.7). The 3-year overall survival for patients with lymphopenia was 60.5%, compared to 73.6% in non-lymphopenic patients (p=0.04). Conclusions: Lymphopenia was seen to be higher among males and Caucasians, more frequently at advanced stage at diagnosis. Patients with lymphopenia were observed to have significantly worse survival when compared to patients with normal lymphocytic count in RCC. We conclude that lymphopenia is considered as a negative prognostic factor for RCC, and needed to be studied in the correlation of other known prognostic factors.
Association of metabolic syndrome with reduced survival among men receiving androgen deprivation therapy for nonmetastatic prostate cancer.
Authors: Rudman Sarah Maria , Gray Kathryn P. , Kasperzyk Julie , Pitt Michael , Giovannucci Edward , Loda Massimo , Mucci Lorelei , Sweeney Christopher 
Published: February 2017

56 Background: The metabolic syndrome (MS) is a set of risk factors implicated in both the development of prostate cancer (PC) and as a recognized complication of androgen deprivation therapy (ADT). In our previous study of a Veterans’ Administration (VA) cohort of relapsed PC patients (pts) on ADT, MS was associated with a shorter duration of PC control. Methods: We studied 347 patients (72 from VA and 275 from Health Professionals Follow up Study) treated with ADT for non-metastatic PC. 88% for biochemical relapse post definitive local therapy and 12% treated with primary ADT. MS was assessed by the modified Adult Treatment Panel III criteria prior to the commencement of ADT. Cox models tested for association between MS status and time to overall survival (OS) or time to PC specific survival, stratified by cohorts (VA vs. HPFS). Cumulative incidence of PC specific death (accounting for competing risk of death from other causes and co-morbidities) by MS status was estimated. Results: 96 patients (28%) had MS. 62 patients (18%) died of PC during a median follow-up of 9.5 years. The median OS for patients with and without MS was 7.5 and 10.6 years respectively. A multivariate Cox model adjusted for age at start of ADT, diagnosis, stage, Gleason score and primary treatment showed MS was associated with a significant 53% increased risk of death from any cause (HR(95%CI) 1.53(1.05-2.22); p=0.03). MS patients tended to have increased risk of PC specific death (HR(95%CI) 1.6 (0.9-2.84); p=0.11). Individual MS components hypertension, dyslipidemia, obesity and diabetes were not associated with an increased risk of death from any cause or PC. The cumulative incidence of PC specific death did not differ by MS status. Conclusions In men receiving ADT for androgen dependent PC without metastases, the presence of MS at the commencement of ADT is associated with an increased risk of death compared to those pts without MS. The shorter time to death appears to be at least in part due to shorter time to dying from PC.
Inhibition of Src and insulin/insulin-like growth factor-1 receptor (IR/IGF-1R) on tumors and bone turnover in prostate cancer (PCa) models in vivo compared with inhibition of either kinase alone.
Authors: Dayyani Farshid , Parikh Nila , Song Jian H. , Araujo John C. , Carboni Joan M. , Gottardis Marco M. , Trudel Geralyn C. , Logothetis Christopher , Gallick Gary E. 
Published: February 2017

61 Background: The Src and IGF-1R axes are aberrantly activated in both PCa and the microenvironment of bone metastases. Dasatinib and BMS-754807 are clinically promising small molecule inhibitors with high potency against Src family kinases (SFK) and IR/IGF-1R, respectively. Based on a phase I/II clinical trial in which 9/19 pts treated with docetaxel + dasatinib were increased in serum IGF-1 levels after one cycle, the aim of this study was to establish potential antitumor cooperativity of inhibiting both IGF-1R and Src in experimental PCa models in vitro and in mice. Methods: Inhibition of Src and IGF-1R pathways was accomplished by pharmacologic agents (dasatinib against Src and BMS-754807 against IR/IGF-1R) as well as by shRNA, in PC3 and LNCaP cells. In vivo studies were done after orthotopic and intratibial injection of PC3 cells in nude mice. Results: SFK inhibition decreased proliferation and migration of PCa cells whereas IGF-1R blockade induced apoptosis. All anti-tumor effects were enhanced by dual blockade. IGF-1 induced phosphorylation of Akt1 and 2. Only Akt 1 phosphorylation was decreased by dasatinib; whereas Akt 1 and 2 phosphorylation were completely abrogated by the combination. Dasatinib and BMS-754807 inhibited orthotopic in vivo tumor growth of PC3 cells more potently than either inhibitor alone. Similarly, intratibial tumor growth and bone destruction was significantly reduced with the drug combination, accompanied by a decrease in serum bone turnover markers alkaline phosphatase and N-telopeptide. Conclusions: Dual inhibition of Src and IGF-1R has greater anti-tumor effect in PCa cells compared to inhibiting either alone. In the presence of IGF-1, dasatinib and BMS-754807 are necessary to inhibit IGF-1-induced phosphorylation of Akt1 and 2 in tumor cells in culture. In intratibial models, decreased bone turnover markers in serum support the concept of targeting both the epithelial and bone microenvironment. The combination of dasatinib and BMS-754807 may be a rational therapeutic approach in PCa by blocking complementary processes of tumor growth and progression.
Vitamin E and the risk of prostate cancer: Updated results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT).
Authors: Klein Eric A. , Thompson Ian , Tangen Catherine M. , Lucia M. Scott , Goodman Phyllis , Minasian Lori M. , Ford Leslie G. , Parnes Howard L. , Gaziano J. Michael , Karp Daniel D. , Lieber Michael M. , Walther Philip John , Parsons J Kellogg , Chin Joseph , Darke Amy K , Lippman Scott Michael , Goodman Gary E. , Meyskens Frank L. , Baker Laurence H. 
Published: February 2017

7 Background: The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a non-statistically significant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer. Methods: SELECT randomized 35,533 men from 427 study sites in the United States, Canada and Puerto Rico in a double-blind manner between August 22, 2001 and June 24, 2004. Eligible men were 50 years or older (African Americans) or 55 years or older (all others) with a PSA <4.0 ng/mL and a digital rectal examination not suspicious for prostate cancer. Included in the analysis are 34,887 men randomly assigned to one of four treatment groups: selenium (n=8752), vitamin E (n=8737), both agents (n=8702), or placebo (n=8696). Data reflect the final data collected by the study sites on their participants through July 5, 2011. Results: This report includes 54,464 additional person-years of follow-up since the primary report. Hazard ratios (99% confidence intervals [CI]) and numbers of prostate cancers were 1.17 (99% CI 1.004-1.36, p=.008, n=620) for vitamin E, 1.09 (99% CI 0.93-1.27, p=.18, n=575) for selenium, 1.05 (99%CI 0.89-1.22, p=.46, n=555) for selenium + vitamin E vs. 1.00 (n=529) for placebo. The absolute increase in risk compared with placebo for vitamin E, selenium and the combination were 1.6, 0.9 and 0.4 cases of prostate cancer per 1,000 person-years. Conclusions: Dietary supplementation with Vitamin E significantly increases the risk of prostate cancer among healthy men.
High-dose-rate (HDR) brachytherapy with external beam radiotherapy for localized high-risk prostate cancer: Five-year results in 122 patients.
Authors: Yamamoto Toshihiro , Kido Masahito , Sasaki Hiroshi , Miki Jun , Kimura Takahiro , Miki Kenta , Yamada Hiroki , Aoki Manabu , Egawa Shin 
Published: February 2017

91 Background: To present outcome and morbidity of high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) for localized high risk prostate cancer. Methods: Between May 2005 and April 2009, 122 patients underwent Ir-192 HDR brachytherapy with EBRT and passed after HDR bachytherapy more than one year. The median follow-up was 46 months (range 2-76 months). All patients were high risk and localized prostate cancer. Median PSA was 40.2ng/ml (range 4.1-366ng/ml). Median Gleason Score was 8 (range 6-10). All patients were treated over six months neo-adjuvant hormonal therapy and over twenty-four months adjuvant hormonal therapy. Results: Only one patient had died of lung small cell carcinoma. 14 patients had revealed biochemical failure(BCF) by Phoenix definition. 5-year biochemical free rate was 78%. Clinical T3 group is significant worse than clinical T1-T2 group(5-y BCF 73% vs 81%, p<0.05). Of the 122 patients, only one patient displayed Grade 3 late GI toxicity. There were no other acute nor late severe toxicity. Conclusions: HDR brachytherapy for localized high risk prostate cancer resulted in good outcomes and had comparatively minor toxicity. Clinical T3 patients was poor outcome than clinical T1-2.
Analysis of 45 patients treated with sipuleucel-T (SIP-T) in a community practice.
Authors: Shah Tushar , Vogelzang Nicholas J. 
Published: February 2017

94 Background: We reviewed our toxicity experience with Sip-T since its FDA approval in May 2010. 340 pts were screened and 100 satisfied the general eligibility criteria for Sip-T; metastatic castrate resistant prostate cancer (mCRPC), minimally or asymptomatic status, limited or no visceral mets and not on chemotherapy. Methods: 45 were and 55 were not treated with Sip-T. As expected the characteristics of the 2 groups differed in that the untreated pts tended to be older, have higher ECOG scores, higher PSA, lower Hgb, fewer radical prostatectomies, more local radiation and TURPs, and more co-morbidities (HTN/diabetes/DVTor PE/TIA or CVA/CAD/AF/obesity/lipids). Prior systemic Rx to the Sip T pts included anti-androgens 93%, estrogens 33%, chemotherapy 31% and abiraterone 20%. Results: Central lines were placed in 32 pts. 10 of the first 17 had tunneled lines (TLs). One pt had a 10 day hospitalization for MRSA infection, 2 pts were delayed due to TL technical issues and all 10 pts complained about the complexity of TL care ( ∼1000 hrs of carer for the line to be used for ∼ 9 hours) 22 subsequent pts with central lines had external jugular lines (EJs) placed by interventional radiology before leukapheresis and removed the same day. No line complications have subsequently occurred. One pt pre-treated with samarium and ERT had too few cells for Rx. Two pts underwent a 4th pheresis for technical issues. One pt (no pre-meds) had marked rigors post-infusion #2. No other >grade 1 adverse reactions were noted during or after Sip T. 18% could not be weaned off low dose steroids before Sip T. No vascular events occurred. Median follow up is ∼ 10 months. 6 SipT pts (13%) and 11 untreated pts (18%) died of progressive disease. 3 of the 6 Sip T pts died within 30 days, all of progressive disease. Conclusions: Sipuleucel T administration in a community setting is generally uncomplicated. For pts requiring central lines, EJs are preferred. Pts with rapidly progressive disease should not receive Sip T.