bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular tumor burden as a new quantitative CT imaging biomarker for predicting metastatic RCC response to antiangiogenic therapy.
Authors: Smith Andrew Dennis , Zhang Xu , Souza Frederico , Roda Manohar , Zhang Haowei , Bryan Jason 
Published: February 2017

595 Background: Anti-angiogenic (AAG) therapy is designed to devascularize tumors, so we developed methods for measuring the vascular tumor burden (VTB) on CT images. This study was designed to validate initial changes in the VTB as a quantitative CT imaging biomarker for predicting progression-free survival (PFS) in patients with metastatic RCC treated with AAG therapy. Methods: As part of a multi-institutional prospective phase III trial by Motzer et al. NEJM 2009, adult patients with metastatic clear cell RCC were treated with sunitinib (N=375). In this post hoc secondary analysis, quantitative CT imaging software was used to measure the VTB in cm2on baseline and initial post-therapy CT images (N=275 with digital images). Enhancing MASS (eMASS) Criteria response groups included Favorable Risk (FR; 30% decrease in VTB), Intermediate Risk (IR; not FR or UR), or Unfavorable Risk (UR; 20% increase in VTB or new metastases). Initial post-therapy CT images were evaluated by eMASS Criteria, RECIST, Choi Criteria and MASS Criteria. Comparison of PFS among response groups was evaluated using log-rank test and Cox-proportional hazards ratio. Results: Median PFS of the cohort was 1.1 years. Median PFS of the response groups from the criteria are depicted in Table 1. The median difference in PFS (MD) and hazard ratio (HR) for eMASS Criteria IR vs FR (MD=1.2, p<0.001; HR=5.24, 95%CI=3.71-7.41, p<0.001) were substantially higher than for RECIST SD vs PR (MD=0.3, p=0.237; HR=1.42, 95%CI=0.79-2.57, p=0.241), Choi Criteria SD vs PR (MD=0.4, p=0.003; HR=1.86, 95%CI=1.22-2.83, p=0.004), or MASS Criteria IR vs FR (MD=0.2, p=0.051; HR=1.37, 95%CI=1.00-1.89, p=0.052), indicating that patients with eMASS IR were 5 times more likely to progress than patients with FR. Conclusions: A quantitative CT imaging biomarker designed to measure initial changes in the vascular tumor burden is highly predictive of PFS in patients with metastatic RCC treated with AAG therapy. [Table: see text]
The incidence of adverse pathologic characteristics in small renal masses as size increases.
Authors: Nawaf Cayce , Rosoff James , Adeniran Adebowale , Humphrey Peter , Shuch Brian M. 
Published: February 2017

596 Background: The AUA guidelines include active surveillance (AS) as an option for patients with the cT1a renal mass (≤4 cm). We evaluate how increasing tumor size (≤4 cm) correlates to the incidence of adverse pathologic features (APF) found on nephrectomy. Methods: We queried a single institution database of nephrectomy specimens from subjects undergoing surgery for renal cell carcinoma (RCC). From a total of 898 consecutive cases, 389 patients had primary tumors that were ≤4 cm and N0, M0. All cases were centrally reviewed for the following adverse pathologic features: high nuclear grade (Fuhrman grade 3 or 4), lymphovascular invasion (LVI), histologic tumor necrosis, sarcomatoid features, rhabdoid features, papillary type II histology and advanced stage (≥pT3). Tumor size categories were compared in 1 cm increments. Relationships between the variables were analyzed by chi-square, Fisher’s exact, and ANOVA tests. Results: There was a significant increase in tumor grade (p=0.006) and stage (p=0.04) seen as size increased. APF were found in 157 (40.4%) of tumors ranging from 22.2% for tumors ≤1 cm to 50.8% of tumors >3 to ≤4. There was a significant increase in the presence of one or more of any APF as size increased (p=0.013). Conclusions: Tumors ≤4 cm that could be considered for AS still show frequent aggressive characteristics at nephrectomy. As over half of tumors 3-4 cm have APF, caution is advised when placing patients with larger tumors on AS. Renal tumor biopsy may identify several aggressive histologic characteristics and could be considered to aid the selection of patients considering AS. [Table: see text]
Baseline subject characteristics to predict compliance with study-mandated prostate biopsy in men at risk of prostate cancer: Results from REDUCE.
Authors: Fischer Sean , Sun Xizi , Howard Lauren E. , Moreira Daniel , Castro Ramiro , Andriole Gerald L. , Vidal Adriana , Freedland Stephen J. 
Published: February 2017

6 Background: Study compliance is crucial when the study outcome is determined by an invasive procedure, such as prostate biopsy. To investigate predictors of compliance in study-mandated prostate biopsies, we analyzed demographic, clinical and reported lifestyle data from the REDUCE trial. Methods: We retrospectively identified 8,062 men from REDUCE with at least 2-years of follow-up, and used multivariable logistic regression to test the association between baseline demographic and clinical characteristics and undergoing the study-mandated prostate biopsy at 2 years. We then examined whether missing any of these data was associated with undergoing a biopsy. Results: In REDUCE, 20% of men did not undergo a 2-year biopsy.On multivariable analysis, non-North American region was predictive of 35-55% increased likelihood of undergoing a 2-year biopsy (p ≤ 0.001). Being enrolled at a center that enrolled >10 subjects (2nd and 3rd tertile) was associated with a 40-49% increased likelihood of undergoing a 2-year biopsy (p < 0.001). Missing one or more baseline variables was associated with a 25% decreased likelihood of undergoing a 2-year biopsy (OR = 0.75; p = 0.002). Conclusions: In REDUCE, men outside North America, those at higher volume centers, and those with complete baseline data were more likely to undergo study mandated 2-year biopsies. Given prostate biopsy is becoming increasingly utilized as an endpoint in trials that are often multi-national, regional differences in compliance should be considered when designing future trials. Likewise, efforts are needed to ensure compliance in low-volume centers or among subjects missing baseline data.
Analytic morphometrics: Assessing the role of sarcopenia and abdominal fat measurements in predicting survival for mRCC patients undergoing cytoreductive nephrectomy.
Authors: Waingankar Nikhil , Uzzo Robert G. , Handorf Elizabeth , Haseebuddin Mohammed , Corcoran Anthony , Piotrowski Zack , Smaldone Marc C. , Kutikov Alexander 
Published: February 2017

603 Background: Analytic morphomics have emerged as promising biomarkers of post-surgical outcomes. Decision-making in patients with mRCC is nuanced, as benefits of cytoreductive nephrectomy (CN) must be balanced against risks of delaying or forgoing systemic therapy. We sought to identify if pre-operative morphometrics predict survival in patients undergoing CN. Methods: We reviewed clinical, histopathologic, and radiographic data for patients who underwent CN at our institution from 2006-2012. Pre-operative cross-sectional images of T12 to L4 were assessed. Subcutaneous fat content (average distance from skin to fascia in midline); visceral fat (average distance from fascia to anterior vertebral body); and total body fat (visceral + subcutaneous fat) were quantitated. Psoas muscle area and density at L4 were indexed. Primary outcomes were OS and DSS. Results: 62 patients had complete data for review. Median age at surgery was 60 years (range 40-77), Charlson score was 1 (0-5), and ECOG PS was 0 (0-2). There were 42 patients with lung , 26 with bone, 8 with liver, and 5 with brain metastases (average metastatic sites per patient = 1.8). 46 patients (75.4%) received adjuvant systemic therapy. At 16 months follow-up, 23 patients (37.1%) died from disease, while 17 (27.4%) died of other causes. Median survival following surgery was 13 months (range 1-75). Morphomic metrics did not correlate with survival (Table). Conclusions: Pre-operative morphometrics did not correlate with survival outcomes in a cohort of patients undergoing cytoreductive nephrectomy. Perhaps acuity of mRCC onset and speed of progression reduce prognostic value of morphometrics in this population. [Table: see text]
Accuracy of kidney cancer diagnosis and histological subtype within cancer registry data.
Authors: Wood Lori , Himmelman Jeff , Thompson Kara , Merrimen Jennifer 
Published: February 2017

606 Background: Cancer registries are the mainstay for population-based cancer statistics including incidence and cancer type. In Canada, each province captures this data in provincial registries including the Nova Scotia Cancer Registry (NSCR).The goal of this study was to describe data from the NSCR about method of diagnosis and kidney cancer (KC) pathology and compare it to the actual pathology reports to determine the accuracy of diagnosis and histological subtype assignment. Methods: This retrospective analysis included patients with KC in the NSCR with an ICD-10-CM code C64.9 (malignant neoplasm of unspecified kidney, except renal pelvis) within the largest provincial metropolitan area from 2006-2010. Method of KC diagnosis (clinical, radiologic, histology, or autopsy) was recorded as was the pathological diagnosis based on WHO classification. All non-clear cell KC (nonccKC) diagnosis from the registry were compared to the actual pathology report (and pathology re-review when necessary) for comparison. Results: 733 pts make up the study cohort. 81.2% of patients were diagnosed based on nephrectomy, 11.5% on radiography, 6.5 % biopsy, and 0.8% autopsy. By registry data 53.1% had clear cell, 20.2% KC not otherwise specified (NOS), 12.7% papillary, 3.8% chromophobe, and many other nonccKC. By pathology reports, 62.2% had clear cell, 13.4% papillary, 4.4% chromophobe, only 2% KC NOS (because most radiological diagnosis were classified this way). A large number of pathological diagnoses make up the other nonccKC and discrepancies between registry data and pathology reports will be described and compared in detail. Conclusions: Registry data is commonly used to report cancer statistics. Registry data may not be accurate for the true incidence of KC since 11.5% were based on radiology alone. Clear cell KC made up 53% of registry diagnosis but 62% on pathology report review. Although papillary and chromophobe incidence did not vary a lot, other types of nonccKC did. This registry data did not differentiate between papillary type I and II. NonccKC should not be considered one entity. One must be aware of the gaps in registry data for KC statistics including overall diagnosis, clear cell and nonccKC subtypes.
Tumor contact length: A novel multiparametric MRI predictor of prostate cancer outcomes.
Authors: Kongnyuy Michael , George Arvin Koruthu , Iyer Amogh , Frye Thomas P , Kilchevsky Amichai , Sidana Abhinav , Krane Spencer , Kadakia Meet , Muthigi Akhil , Mertan Francesca , Chelluri Raju , Ho Richard , Su Daniel , Merino Maria J , Turkbey Baris , Choyke Peter L. , Wood Bradford J. , Pinto Peter A. 
Published: February 2017

61 Background: Multiparametric MRI (MP-MRI) can visualize prostate tumors. MP-MRI characteristics (extraprostatic extension (ECE), tumor volume, etc.) can be predictive of final pathologic findings such as lymph node (LN) involvement, pathological ECE (pECE), and biochemical recurrence (BCR). These are pivotal in the decision-making process regarding treatment. Tumor contact length (TCL) is defined as the length of cancer in contact with the prostatic capsule. We evaluated the ability of MP-MRI determined TCL in predicting pECE, BCR and LN in patients undergoing radical prostatectomy. Methods: All patients who underwent a 3T MP-MRI at the NCI from 2007 to 2015 were retrospectively classed into no ECE, suspicious ECE (sECE) and frank ECE (fECE) based on MP-MRI findings. sECE was defined as tumor with capsular bulge on MRI while fECE was clear capsular obliteration and tumor extension beyond the prostatic capsule. Demographic data was obtained on patients with fECE and sECE on MP-MRI with the presence of pECE, LN, and BCR status following radical prostatectomy from a single surgeon (PP) experience. Chi-Square and Wilcoxon rank sum test were used to compare proportions and continuous variables respectively. Logistic regression was used to determine the predictive ability of TCL. Statistical significance was defined as p-value ≤0.05. Results: Of all 1,260 patients who underwent MP-MRI, we focused on 146 who had sECE (68) or fECE (78) on MP-MRI. Mean age was 60 years and median prostate specific antigen was 11.7 ng/ml. Logistic regression analysis showed that MP-MRI determined TCL was predictive of ECE (p=0.01), LN status (p=0.0001) on final pathology and BCR (p=0.05) during follow up. Patients with pECE had a longer median MP-MRI TCL (2.8 cm) compared to those without pECE (2.4 cm), p=0.04. When analyzed individually, fECE correlated with pECE (p=0.05) while s ECE did not correlate with pECE (p=0.11). Although, not statistically significant, the median MP-MRI TCL for sECE with pECE was still longer than in sECE with no pECE in the sub-group analysis. Conclusions: Longer TCL on MP-MRI can indicate presence of ECE, LN involvement at final pathology as well as predict BCR on follow up.
Risk of hepatotoxicity with concurrent statin and tyrosine kinase inhibitor (TKI) or mTOR inhibitor (mTORi) in patients with metastatic renal cell carcinoma (mRCC).
Authors: Au Trang H. , Bailey Erin B. , Patel Shiven B. , Tantravahi Srinivas Kiran , Agarwal Neeraj , Stenehjem David D. 
Published: February 2017

610 Background: TKIs and statins alone can cause liver injury. When used together, there is additive risk for hepatotoxicity, as seen with pazopanib and simvastatin, and the potential for discontinuing TKI therapy. Liver enzyme abnormalities are also associated with mTORi. Hepatotoxicity from concurrent use of statins as a class with TKI or mTORi as a class in real world practice in mRCC has not been reported. Methods: This observational cohort study included adult patients treated with a TKI or mTORi for mRCC at the Huntsman Cancer Institute from 2004-2014. We performed a treatment line analysis. For each treatment line, CTCAE criteria were used to categorize maximum AST, ALT, and total bilirubin. Highest grade of any liver enzyme was compared between TKI with and without statin and between mTORi with and without statin (Fisher’s Exact test). Results: A total of 162 treatment lines were included. For TKI and statin, the three most common treatment line combinations were sunitinib and simvastatin (7), sunitinib and atorvastatin (4), and pazopanib and simvastatin (3). For mTORi and statin, the three most common treatment line combinations involved simvastatin with temsirolimus (7) and everolimus (3). Prevalence of hepatotoxicity is shown in the table. Conclusions: Our results show a trend toward significance in the prevalence of hepatotoxicity with concomitant mTORi and statin versus mTORi alone, perhaps explained by mTORi-mediated competitive inhibition of simvastatin (sensitive CYP 3A4 substrate). There was no difference in hepatotoxicity for TKI with or without statin, although there were few pazopanib and simvastatin combinations. Study limitations include the small sample size, limited number of TKI or mTORi and statin combinations, and retrospective study design. A larger study is needed to validate these findings. [Table: see text]
Assessment of metastasectomy complications in renal cell carcinoma.
Authors: Meyer Christian P , Sun Maxine , de Velasco Guillermo , Trinh Quoc-Dien , Choueiri Toni K. 
Published: February 2017

619 Background: Metastasectomy (MSx) is a viable option in patients with metastatic renal cell carcinoma (mRCC). Available information on perioperative outcomes is scarce. We assess complications of MSx in a large population-based US cohort. Methods: The Nationwide Inpatient Sample (2000-2011) was utilized to abstract all patients with a primary diagnosis of mRCC. MSx was defined as an organ-specific resection as a diagnosis of a metastasis to a corresponding site (liver; lung; brain; bones; lymph nodes; adrenal) during the same admission. All procedures concomitantly performed with radical or partial nephrectomies were excluded. Baseline characteristics and multivariable logistic regression analyzes described in-hospital complications, length of stay, and mortality following MSx. Results: Overall, 26,990 weighted patients had mRCC. Of those, 949 were treated with a MSx (3.5%). Common sites of MSx were liver (47.8%) and lung (33.2%). MSx patients were significantly younger than non-MSx patients (60 vs. 62 years, p=0.013). Overall in-hospital mortality rate was 2%. The most common in-hospital complications were prolonged length of stay, defined as ≥7 days (38.5%), respiratory complications (17.1%), vascular complications (14.8%), and blood transfusions (16.3%). In multivariable analyses neither patient nor hospital characteristics were significant predictors of overall complication rates. Conclusions: This study suggests that MSx is a sensible and safe approach for the treatment of mRCC. We did not find significant predictors of complications for MSx in mRCC patients. Nevertheless, postoperative care should be optimized to prevent unnecessary complications and prolonged length of stay.
Experience with IL-2 in metastatic renal cell carcinoma after treatment with one or more targeted therapies.
Authors: Mai Hanh P. , Vu Peter , Patel Arjune , Clark Joseph , Henry Elizabeth 
Published: February 2017

622 Background: Over half of patients (pts) diagnosed with Renal Cell Carcinoma require systemic therapy for metastatic disease (mRCC). Approved first line treatment includes immunotherapy and targeted therapy (TT). TT is commonly used given its efficacy, favorable side effect profile, and convenience of oral administration. High dose IL-2 (HD-IL2) can induce durable long term remissions in a subset of pts. There is limited data on the efficacy of HD-IL2 after disease progression on TT. Methods: All pts treated with HD-IL2 for mRCC from 2008-2014 were reviewed. A focused analysis was performed on pts who received HD-IL2 after first-line TT. Three pts were excluded from analysis. Data regarding pt demographics, health status, disease related characteristics, prognostic factors, treatment history and toxicity were captured. Response to HD-IL2 was also classified using RECIST definition. Utilizing descriptive statistics, we examined response rates, toxicities, and outcomes in this subset of pts. Results: Eighteen pts received HD-IL2 after TT. Median age was 60 (range 48-72). Six pts had primary mRCC and 12 had recurrent mRCC. Twelve pts received HD-IL2 as a 2nd line of treatment. Six pts received HD-IL2 as a 3rd or higher line of treatment. Among pts treated with HD-IL2 as 2nd line, 8 pts (67%) had partial response and 1 (8%) had complete response; duration of response ranged from 5-20+ months and 3 pts remain in remission. All 6 pts treated as 3rd line or higher did not show objective response to HD-IL2. The 2nd line group received significantly more doses than pts treated as 3rd line or higher (mean doses, 37 vs. 18, p=0.01). Overall, adverse events were expected, with the exception of grade 4 cardiac toxicity in 2 pts who received HD-IL2 as 3rd line. Conclusions: The administration of HD-IL2 as 2nd line is tolerated without excess toxicity and can induce clinical response. In our sample, there was no response to HD-IL2 among pts who received two or more prior TT. More investigation is warranted to determine if 3rd line HD-IL2 is safe and retains clinical benefit.
Pathologic and biochemical outcomes among African American and Caucasian men with low-risk prostate cancer in the search database: Implications for active surveillance candidacy.
Authors: Leapman Michael S. , Freedland Stephen J. , Aaronson William J , Kane Christopher J. , Terris Martha K. , Amling Christopher L. , Carroll Peter , Cooperberg Matthew R. 
Published: February 2017

76 Background: Racial disparities in the incidence and risk profile of prostate cancer (PCa) at diagnosis among African American (AA) men are well reported, however it remains unclear whether AA race is independently associated with adverse pathological findings among men with clinical low risk disease. Methods: We conducted a retrospective analysis among 895 men, with clinical low risk (Gleason 3+3, clinical stage ≤T2a, PSA≤10 ng/mL) treated with immediate radical prostatectomy within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. We evaluated clinical and demographic characteristics by AA or Caucasian race. Associations between AA versus Caucasian race with pathologic Gleason upgrade (≥3+4), major upgrade (≥4+3), upstage (pT3a or higher), margin status and biochemical recurrence (BCR) were examined using chi-square, logistic regression, log-rank, and Cox proportional hazards analyses. Results: We identified 355 AA and 540 Caucasian men with low-risk tumors within the SEARCH cohort followed for a median of 6.3 (IQR 3.8-8.9). AA men were younger (mean 59.5vs. 62.0 years), and had higher median PSA (5.5 vs. 5.1). Following adjustment for relevant covariates, AA race was not significantly associated with pathological upgrade (OR 1.335, 95% CI 0.936-1.905, p=0.111), major upgrade (OR 0.561, 95% CI 0.300-1.049, p=0.070), upstaging (OR 1.111, 95% CI 0.670-1.844, p=0.683), or positive surgical margins (OR 1.046, 95% CI 0.732-1.494, p=0.806). The 5-year recurrence-free survival rates were 73.4% and 78.4% for AA and Caucasian men, respectively (log-rank p=0.178). After adjustment for clinical and pathological characteristics, AA race was not significantly associated with BCR (HR 1.1.054, 95% CI 0.814-1.501, p=0.521). Conclusions: In a cohort of low-risk men treated with prostatectomy within an equal access health system with a high representation of AA men, no significant differences were observed in the rates of pathologic upgrading, upstaging or biochemical recurrence. These data support continued use of AS in AA. Upgrading and upstaging remain concerning possibilities for all men regardless of race.