bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term response in metastatic renal cell carcinoma patients receiving first-line therapy with VEGF TKIs.
Authors: Tantravahi Srinivas Kiran , Patel Shiven B. , Ravulapati Sowmya , Batten Julia A. , Merriman Joseph , Stenehjem David D. , Agarwal Neeraj 
Published: February 2017

436 Background: A subset of metatstatic renal cell carcincoma (mRCC) patients (pts) on first-line (1st) vascular endothelial growth factor inhibitors (VEGF TKIs) will have a long-term response (LTR) defined as a progression free survival (PFS) of >18 months (mos) on continuous therapy, and may be candidates for intermittent VEGF TKI therapy. Methods: From our institutional dataset of mRCC pts, we identified pts receiving 1st VEGF TKIs and who achieved a LTR. Data on clinical characteristics and survival outcomes were compared between those with LTRs and rest of the patients (control). Continuous and categorical variables were assessed by Wilcoxon rank sum and chi-square, respectively; and survival outcomes were compared by log-rank tests. Results: Of 89 pts, 24 (33%) had LTRs, of whom 5 pts have discontinued treatment (range 1-5 years) without subsequent disease progression, and 4 pts took treatment breaks for 3-9 mos. Baseline pts or disease characteristics were not predictive of LTRs (Table). Conclusions: A subset of mRCC pts receiving 1st VEGF TKIs achieve a LTR, and are not currently identifiable by baseline clinical characteristics including prognostic risk categorization. Identification of biomarkers predictive of LTR may allow intermittent or even deferred therapy with VEGF TKIs minimizing toxicity and cost. [Table: see text]
Management and outcomes of patients with renal medullary carcinoma (RMC): A multicenter retrospective study of 39 patients.
Authors: Shah Amishi Yogesh , Karam Jose A. , Rao Priya , Jonasch Eric , Rathmell Kimryn , Matin Surena F. , Vaishampayan Ulka N. , Heng Daniel , Plimack Elizabeth R. , Guancial Elizabeth A. , Fung Chunkit , Lowas Stefanie Rose , Lim Zita D. , Wood Christopher G. , Tannir Nizar M. 
Published: February 2017

438 Background: RMC is a rare and aggressive neoplasm that afflicts primarily young black patients with sickle cell trait. Our primary objective is to report the outcomes of RMC patients through a collaborative initiative. Methods: After IRB approval, we retrospectively reviewed records of RMC patients treated from 2000-2013 at 7 academic institutions. Overall survival (OS) was calculated from RMC diagnosis to date of death. Descriptive statistics were used. Results: A total of 39 patients were included. Median age was 27.8 years and 29 (74%) were males. 38 (97%) had sickle cell trait. Median renal tumor size at presentation was 5.8 cm (range 3.4-11.4 cm). 3 patients presented with stage I disease, 13 with stage III disease, and 23 with stage IV disease. 22 patients had ECOG PS 0-1 and 17 had ECOG PS 2-3. The most common metastatic sites at diagnosis were lymph nodes in 27 and lung in 13. 26 patients (66.7%) had a nephrectomy. Pathologic stage was pT1-2 in 6 and pT3-4 in 20. 23 of these patients (88.5%) had positive lymph nodes at RPLND. 7 patients received preoperative systemic therapy. Median duration of pre-op therapy was 16 weeks (range 12-27 weeks). 1 patient had CR, 3 had PR and 3 had SD as best response to pre-op therapy. All patients received at least 1 line of systemic therapy. Median OS was 12.2 months. One patient had clinical CR with preoperative chemotherapy, near path CR on nephrectomy, and is currently NED at 27.4 mos. 5 patients are alive to date, though no patients have survived past 37 months. Conclusions: Patients withRMC have a grave prognosis. Nephrectomy (upfront or delayed) was associated with improved OS, even in patients with poor PS, though poor PS patients should be considered for upfront chemo. More effective therapies are desperately needed to improve patient outcomes. [Table: see text]
Cost analysis of an initial observation approach in metastatic renal cell carcinoma from a prospective study.
Authors: Parekh Hiral D. 
Published: February 2017

439 Background: A prospective observational study of metastatic renal cell carcinoma (mRCC) prior to initiation of systemic therapy has been conducted. (Rini et al., ASCO 2014, abst 4520). A direct cost analysis was undertaken in mRCC patients from this trial matched to historical control mRCC patients treated with immediate systemic therapy. Methods: Histologically-confirmed, asymptomatic mRCC patients without prior systemic treatment were enrolled and followed until starting initial systemic treatment on a prospective trial. Patients underwent clinic visits and radiographic evaluation every 3 months for year 1, every 4 months for year 2, then every 6 months until treatment was initiated per physician discretion. Control mRCC patients who received immediate systemic therapy were matched for age, gender, Heng risk criteria and length of follow up. After clinical review, non mRCC-related encounters were excluded from final analysis. The direct cost of inpatient and outpatient visits plus associated laboratory analysis and imaging studies were compared between the 2 groups using the Wilcoxon signed rank test. Results: Seventeen matched pairs were included in the final analysis. The median (range) number of hospital admissions was 1 (range, 0-6) for the observation group and 1 (range, 0-5) for the immediate therapy group (p=1.0). The median (range) number of outpatient visits in the observation group was 17 (range, 6-39) and 19 (range, 4-59) in the immediate therapy group (p=0.47). In aggregate, the direct costs for the observation group were 30.6% less for outpatient visits and 21.9% less in total (outpatient plus inpatient visits) as compared to the immediate therapy group (p=0.19 for both). Conclusions: Initial observation as a management strategy for a subset of mRCC patients is associated with a non-significant aggregate decrease in direct costs compared to patients requiring immediate treatment. Further study is required to evaluate costs associated with different management strategies over the lifetime of mRCC patients.
MRI/US fusion-guided biopsy to detect clinically significant prostate cancer in the central gland correlating with index lesion.
Authors: Fascelli Michele , Frye Thomas P , George Arvin Koruthu , Abboud Steven , Chelluri Raju , Ho Richard , Sankineni Sandeep , Merino Maria J , Turkbey Baris , Choyke Peter L. , Wood Bradford J. , Pinto Peter A. 
Published: February 2017

44 Background: Central gland (CG) prostate cancers (CaP) are reported with lesser incidence and smaller tumor volume compared to the peripheral zone (PZ). Index tumor lesions defined by highest grade may be missed when in the CG. MRI/US fusion-guided biopsy allows targeting of lesions, potentially identifying cancer outside the traditional TRUS biopsy template. Methods: Retrospective review of 1,003 patients who underwent multiparametric MRI (mpMRI) found 2,119 suspicious lesions. Targets were biopsied and stratified by zonal distribution, CG or PZ. Cancer detection rates (CDR) were tabulated by location and correlated with PSA, Gleason score, prostate volume and MRI suspicion. Results: Fusion-guided biopsy targeted lesions in the central (711, 34%) or peripheral (1408, 66%) prostatic zones. CDR was similar between zones: 35.2% CG compared to 33.6% PZ (Table). CDR of clinically significant disease (Gleason >4+3) was similar in the CG and PZ despite higher prostate volume in those with CG lesions. In contrast to TRUS biopsy, upgrading occurred in 18.5% of CG patients versus 13.3% PZ (p=0.024). 36.6% (77/210) of CG lesions represented the highest risk lesion on MRI, translating to 13% (77/592) of the biopsy-proven CaP cohort. Conclusions: CG cancers occur at a similar frequency as PZ CaP. CG lesions were more likely to be upgraded from TRUS biopsy, frequently representing the index lesion. In upgraded patients, CG targets constituted the index lesion in a third of all males. MRI/US fusion-guided biopsy identifies clinically significant disease of the CG not captured on traditional biopsy. [Table: see text]
Overall survival (OS) in renal cell carcinoma (RCC) before and after the introduction of targeted therapies (TTs): A Norwegian population-based study (2000–2011).
Authors: Klepp Olbjorn Harald , Johannesen Tom Børge , Oldenburg Jan , Torgersen Knut Martin , Kowalski Jan , Solli Oddvar , Sandin Rickard , Beisland Christian 
Published: February 2017

443 Background: The Renal Comparison study in Norway (RECON) is a retrospective non-interventional study of OS in all patients diagnosed with RCC and metastatic (m)RCC before and after the introduction of TTs. Methods: Using data from two national health registries, Cancer Registry of Norway (diagnosis and cause of death) and Norwegian Prescription Database (all dispensed drugs), we assessed OS in RCC and mRCC patients diagnosed during two periods after (2009–2011 and 2006–2008) and one period before (2000–2005 [RCC]; 2002–2005 [mRCC]) the introduction of TTs and factors influencing OS in mRCC. Multivariate analysis was performed using a Cox proportional hazards model, including estimation of adjusted HR. The regression model included the covariates age, gender, geographic region, nephrectomy status, diagnostic period and TT prescription. Results: In total, 2,176, 1,887, and 3,233 RCC patients were identified in 2009–2011, 2006–2008 and 2000–2005, respectively, of whom 2,160 (30%) had mRCC. From 2006 to 2011, TT use in mRCC patients significantly increased from 21% to 56% (p<0.01); sunitinib was the most frequent first-line treatment (93%). RCC patients diagnosed in 2009–2011 and 2006–2008 had a significant improvement in OS compared with patients diagnosed in 2000–2005 (median OS: not reached and 76 vs. 49 months, respectively; both p<0.001 [log-rank]). Similarly, a significant OS improvement was shown in mRCC patients diagnosed in 2009–2011 and 2006–2008 compared with 2002–2005 (median OS: 11.0 and 8.0 vs. 6.0 months, respectively; both p<0.001 [log-rank]; with adjusted HR [95% CI] of 0.77 [0.68–0.87] and 0.87 [0.78–0.98], respectively). Factors significantly associated with longer OS in mRCC were (HR, 95% CI): younger age (0.98, 0.98–0.99), female gender (0.88, 0.79–0.97), prior nephrectomy (0.49, 0.43–0.55) and TT prescription (0.58, 0.51–0.65). Significant regional variation was also shown. Conclusions: A significant OS improvement was shown in RCC and mRCC patients following the introduction of TTs. This advance has continued into the later TT era and, although multifactorial in origin, the contribution of TTs in mRCC is highly likely.
Association and prognostic impact of peripheral blood counts with tumor programmed death ligand one expression.
Authors: Lewis Daniel , Joseph Richard Wayne , Serie Daniel , Eckel-Passow Jeanette , Ho Thai Huu , Cheville John C. , Kwon Eugene D. , Thompson Robert Houston , Leibovich Bradley C. , Parker Alexander S. 
Published: February 2017

447 Background: Components of the peripheral blood counts (PBC) are associated with poor prognosis in patients diagnosed with non-metastatic clear cell renal cell carcinoma (ccRCC). Related to this, higher tumor expression of programmed death ligand one (PDL1) is also associated with poor ccRCC prognosis. Herein, we utilize a large cohort of patients undergoing nephrectomy for localized ccRCC to evaluate the association of PBC with tumor expression of PDL1. Secondarily, we examine the association of PBC and relapse free survival (RFS) after adjusting for age and PDL1 expression. Methods: Through chart review, we obtained PBC values at time of nephrectomy for patients enrolled in the Mayo Clinic Renal Registry from 1990-2009 who were treated for localized (M0) ccRCC including the following: hemoglobin (HGB), white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophil count (AEC), absolute monocyte count (AMC), and platelets (PLT). We determined tumor PDL1 expression as a continuous variable (% of positive PDL1 tumor cells) using the 5H1 antibody on archived tissues. We analyzed the correlation of PBC values with PDL1 expression as a continuous variable using a linear estimate. To evaluate the association of PBC values with RFS after adjusting for PDL1 expression, we employed multivariate Cox regression models. Results: A total of 706 ccRCC patients had available PDL1 expression and PBC. PDL1 expression was inversely associated with HGB (linear estimate of -0.02, p<0.001) and positively associated with platelets (linear estimate 1.73, p<0.001) whereas there was no association with PDL1 with WBC, ANC, AEC, or AMC. After adjusting for age and PDL1 expression, a higher HGB (HR=0.87, p<0.001), higher ALC (HR 0.68, p=0.003), and higher AEC (HR 0.12, p=0.002) were all associated with improved relapse free survival. Conversely, higher PLT was associated with decreased RFS (HR 1.002, p<0.001). Conclusions: PDL1 expression is associated with decreased HGB and increased PLT at the time of nephrectomy. After adjusting for PDL1 expression and age, higher HGB, ALC, and AEC are associated with improved RFS, while higher platelets are associated with decreased RFS.
Immune cell repertoire in patients with metastatic renal cell carcinoma: Data from prospective clinical trial.
Authors: Damarla Vijay , Elson Paul , Wood Laura S. , Sybor Sylvia , Rayman Pat A. , Wong Yu Ning , Plimack Elizabeth R. , Finke James , Rini Brian I. 
Published: February 2017

452 Background: Immune dysfunction is documented in renal cell carcinoma (RCC) patients and likely influences tumor progression. An ongoing prospective trial of observation in metastatic RCC patients prior to systemic therapy is investigating circulating immune cell populations. Methods: Asymptomatic patients with low volume metastatic disease were enrolled and followed until starting initial systemic treatment. Peripheral blood specimens were collected at baseline and again at 3, 6, 9, 12, 16, 20, and 24 months, and then every 6 months until initiating systemic therapy. Immune parameters measured included CD3+ and CD4+ INF-γ producing T cells (INF-γ+ T), CD4+CD25+FoxP3+ regulatory T-cells (Treg), CD33+HLADr-CD15+CD14- neutrophilic myeloid-derived suppressor cells (N-MDSC), monocytic M-MDSC, total MDSC, and lineage-negative MDSC. Similar immune parameters were recorded for treatment-naïve patients prior to immediate systemic therapy (sunitinib or pazopanib, n=34) and healthy volunteers (n=22) on separate IRB-approved protocols. The immune data was analyzed using Wilcoxon rank sum and signed rank tests and proportional hazards models. Results: Forty patients enrolled in the observation study had immunologic data. 25 patients (62%) started systemic therapy, and 15 (38%) continue observation. The observation group had lower baseline levels of MDSC, N-MDSC, M-MDSC, Tregs and higher levels of CD3+INF-γ+ T cells, CD4+ INF-γ+ T cells, and lineage negative MDSC compared to the immediate treatment group, although higher MDSCs and lower Tregs compared to healthy controls. The impact of baseline parameters on the duration of observation revealed that lower Tregs (p=0.003) were associated with a longer time on observation. There were no significant changes in immune parameters of observation patients over the length of observation. Conclusions: Metastatic RCC patients with indolent disease have low levels of Treg and MDSC, and a relatively preserved immune cell repertoire compared to patients requiring immediate therapy. Lower baseline Tregs may be associated with a longer length of observation.
Everolimus (EVE) versus temsirolimus (TEM) after first-line treatment with VEGF TKI in patients with metastatic renal cell carcinoma.
Authors: Patel Shiven B. , Agarwal Neeraj , Hsu JoAnn , Tantravahi Srinivas Kiran , Gill David , Vuong Winston , Batten Julia A. , Stenehjem David D. , Pal Sumanta Kumar 
Published: February 2017

460 Background: Given the lack of affordability with an oral drug like EVE and/or preference in some patients (pts), TEM has been used after disease progression on a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). However, efficacy of TEM and EVE in this setting has not been evaluated in a randomized trial. Methods: Pts who were treated with a first VEGF TKI for metastatic renal cell carcinoma (mRCC) and then treated with either EVE or TEM upon progression were identified from two institutional databases. Survival estimates of progression free (PFS) and overall survival (OS) were assessed from initiation of second-line (2nd) treatment by Kaplan-Meier methodology. Results: 90 pts were eligible that received either EVE (n=59; 66%) or TEM (n=31; 34%) in 2nd setting. Pts and disease characteristics were similar in both groups. Median PFS was not different, but OS was significantly improved with EVE (Table). Conclusions: After progression on a 1st VEGFTKI, 2nd EVE and TEM have similar efficacy in terms of PFS, but OS was significantly higher with EVE. Data need further validation in a larger cohort. [Table: see text]
Clinical features of metastatic renal cell carcinoma patients with intrinsic resistance to sunitinib: A Korean multicenter study.
Authors: Kim Jung Hoon , Won Young-Woong , Kim Seung Tae , Park Se Hoon , Lee Soonil , Lim Sung Hee , Hwang In Gyu , Oh Sung Yong , Ji Jun Ho , Lee Ji Yun 
Published: February 2017

462 Background: In a subset of patients with metastatic renal cell carcinoma (RCC), primary resistance to first VEGF targeted therapy is not fully understood, and the optimal treatment approach for these patients is still controversial. This study was aimed to characterize the primary sunitinib resistant patients and associated predicting factors. Methods: A total of 134 patients with recurrent or metastatic RCC, who were initially treated with sunitinib, consecutively selected from 4 centers in Korea, between January 2008 and March 2013. Patients in whom progressive disease (PD) was the best response during treatment with sunitinib were included in the primary sunitinib resistant group. Results: Among 134 patients, 33 (25%) patients primary resistant to sunitinib with a median age of 59 years (range, 28-78) were identified. Most patients had clear cell histology (94%) and good ECOG performance status (0, 1) (82%). According to MSKCC risk, 25% of patients were at favorable risk, 72% at intermediate risk, and 3% at poor risk. Univariate analysis revealed that poor performance status (ECOG≥2), elevated LDH, neutrophilia, and higher number of distant metastatic disease (≥3) and bone or hepatic metastasis were significant factors associated with intrinsic resistant disease. Neutrophilia (OR=7.4, p=0.015) and more than three distant metastatic disease (OR=3.6, p=0.031) were independently significant risk factors of predicting intrinsic resistant disease on multivariate analysis. There was statistically significant difference with regard to overall survival (median, 11.7 vs. 31.1 month; p=0.001) and progression free survival (median, 2.4 vs. 12.5 month; p<0.0001) between the patients with and without intrinsic resistance. Conclusions: Intrinsic resistance to sunitinib treatment is associated with a dismal prognosis in metastatic RCC patients. Along with above predicting clinical features, more understanding of the underlying mechanism and molecular biomarkers for detecting the intrinsic resistant disease are needed.
Identification of tumor biomarkers for sunitinib in advanced renal cell carcinoma (RCC).
Authors: Dai Hongyue , Fishman Mayer N. , Ching Keith A. , Williams James Andrew , Teer Jamie K. , English Patricia A. , Zhang Yonghong , Murray Brion W. , Kumar Naveen , Huntsman Shane , Berglund Anders E. , Dalton William S. , Matczak Ewa , Martini Jean-Francois 
Published: February 2017

470 Background: Sunitinib is a standard of care for advanced RCC. Despite efforts to identify predictive molecular markers for patient selection, none are available, likely due to multiple resistance mechanisms. Using the Total Cancer Care (TCC) database, which integrates patient clinical, molecular, and biospecimen data, we devised a tumor genomics and transcriptomics experiment to identify differences between RCC patients who derive prolonged clinical benefit from sunitinib versus those who are resistant. Methods: A discovery set of 34 RCC patients treated with sunitinib at the approved regimen were identified in the TCC database (n=16 treated for ≤6 months, having primarily discontinued for reasons other than tolerability; n=18 treated for ≥18 months). Tumor samples were analyzed by whole exome sequencing (WES) and by parallel 400-gene expression profiling. Following gene mutation identification and supervised gene expression analysis, molecular differences between the two groups were identified and tested for potential association with treatment duration. Results: Of the 34 cases identified, 24 remained for analysis following sample QC failure and clinical review (n=10 and 14 treated for ≤6 and ≥18 months, respectively). Gene expression analysis revealed a 37-gene signature associated with treatment duration: MAPK8 (JNK1) was a leading candidate biomarker (Pearson correlation with log [treatment duration]=–0.70; p=0.06 after Bonferroni multiplicity correction). Pathway-based WES analyses identified 25 potential variants of interest, none remaining statistically significant after correction. However, following genome-wide analysis, a single variant in an intronic region of ING3 was statistically associated with treatment duration (p=0.02). Conclusions: Activation of the PI3K/AKT pathway was a marker of resistance to sunitinib. In contrast, activation of the angiogenic, NOTCH, or JAK-STAT pathways was, to some degree, associated with sensitivity to therapy. However, neither VHL alteration nor lack of expression, nor alteration in chromatin-rearrangement genes, was associated with sunitinib treatment duration. These findings require further validation in a larger and independent cohort.
Association of chronic co-morbidities with long term survival with metastatic renal cell carcinoma (mRCC).
Authors: Campbell Matthew T. , Shah Amishi Yogesh , Nautiyal Kirtan Das , Hashemi Neda , Corn Paul Gettys , Pagliaro Lance C. , Jonasch Eric , Tannir Nizar M. 
Published: February 2017

472 Background: Since the introduction of targeted therapy, patients (pts) with mRCC are living longer. Cumulative toxicities of sequential targeted therapies remain an area largely unexplored. Methods: A retrospective review of consecutive mRCC pts evaluated at MDACC from 1/1/2001 to 12/31/2008 was conducted. We characterized pts who lived >4 yrs with metastatic disease. In the table below, de novo hypertension (HTN) refers to new onset HTN on VEGF or mTOR targeted therapy (TT), HTN exacerbation refers to HTN in pts with already documented HTN on TT, HTN exacerbation after de novo HTN refers to pts who had exacerbations during subsequent TT after de novo HTN on TT. Descriptive statistics were used. Results: 205 pts with evaluable initial data were characterized for baseline co-morbidities listed in the table below; 37 pts did not have adequate follow up. Of the remaining 168 pts, 12 were managed with surgical resections only and did not receive any systemic therapy, 12 pts received systemic therapy (Tx), but not TT, and 144 received TT: 142 pts (84.5%) received at least 1 VEGF-directed agent, 115 pts (68.5%) received multiple VEGF-directed agents, 75 pts (44.6%) received mTOR inhibitors. Conclusions: Development of HTN and HTN exacerbations are markers of treatment efficacy. The long-term survivors identified in our series had high rates of HTN, hyperlipidemia, hypothyroidism, and VTE. Toxicity cost is an important aspect of long-term survivorship and warrants continued study. [Table: see text]