bluuebunny/crossref_metadata_2025 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.
Precision prevention of TMPRSS2:ERG prostate cancer.
Authors: Mucci Lorelei A. , Ahearn Thomas , Penney Kathryn , Pettersson Andreas , Graff Rebecca E , Kantoff Philip W. , Finn Stephen , Loda Massimo ,   Transdisciplinary Prostate Cancer Partnership
Published: February 2017

78

Background: Increased integration of tumor biomarker data into prostate cancer epidemiology studies is needed to identify molecular subtypes that underlie its etiology and progression. We hypothesize that the TMPRSS2:ERG gene fusion is a unique prostate cancer subtype that is etiologically distinct from cancers lacking TMPRSS2:ERG. Methods: We leveraged the Physicians’ Health Study and Health Professionals Follow-up Study cohort data on pre- and post-diagnostic lifestyle factors, inherited genetic variants, circulating biomarkers, and clinical data and follow-up for 30 years. We have a tumor repository of men with prostate cancer and tumor tissue microarrays. Using immunohistochemistry, we characterized TMPRSS2:ERG status for 1,491 incident prostate cancer cases in these cohorts, and also have biomarker data on a range of additional markers from immunohistochemistry and mRNA expression profiling. Results: Fifty percent of prostate cancer cases were ERG-positive. ERG-positive cancers show much higher expression of insulin/IGF signaling, PTEN loss, higher VDR expression, as well as expression of mismatch repair genes. In contrast, ERG-negative prostate cancer is characterized by increased presence of chronic inflammation and atrophy. We found higher pre-diagnostic free testosterone levels, but not other sex hormones, were associated with increased risk of ERG-positive (OR = 1.4, 95% CI = 1.0-1.8) but not ERG-negative disease (OR = 0.9, 95% CI = 0.7-1.2). Of 39 known genetic risk loci, six were significantly associated (p < 0.05) with ERG+ versus ERG- cancer (2 expected by chance). Prostate cancer risk factors such as taller height (an indicator of growth factors in puberty) are uniquely associated with ERG-positive prostate cancer. Moreover, we observe a complex interaction of components of insulin/IGF and ERG-status on prostate cancer mortality. Conclusions: TMPRSS2:ERG is a highly prevalent somatic event in prostate cancer that likely defines a unique molecular subtype of this common disease. Understanding the differences between these two prostate cancer subtypes may enhance opportunities for prevention.
Impact of therapy on gene expression in high-risk prostate cancer (PCA) treated with neoadjuvant docetaxel and androgen deprivation therapy.
Authors: Beltran Himisha , Wyatt Alexander , Chedgy Edmund , Fazli Ladan , Sboner Andrea , Halabi Susan , Gleave Martin
Published: February 2017

8

Background: Molecular analyses of neoadjuvant post-treatment radical prostatectomy (RP) specimens has been challenging as often times only microscopic foci remain present at time of RP precluding RNA-seq. DNA analysis alone in the absence of expression may be suboptimal in elucidating complex mechanisms of resistance and/or prognostic risk stratification. We therefore set out to develop an assay that could quantify mRNA expression in treated and untreated PCA using formalin fixed paraffin embedded (FFPE) tissues. Methods: We evaluated 40 untreated and post-treatment FFPE specimens as well as patient-matched pre-treated needle biopsies and baseline clinical data from patients enrolled on CALGB 90203: a randomized phase 3 trial comparing noeadjuvant docetaxel and ADT followed by RP vs RP alone for men with high risk localized PCA. High-density tumor areas were selected for RNA extraction (min 50ng RNA). We used NanoString nCounter to quantify gene expression of a custom panel of 75 genes including AR and androgen regulated, neural/neuroendocrine (NE), EMT, cell cycle, hormone receptors, TMPRSS-ERG, ARv7 splice variant, and housekeeper genes. mRNA data was integrated with matched whole exome sequencing data. Frozen specimens and RNA-Seq (n = 7) were used for QC and comparative analysis. Results: Quantitative expression using Nanostring showed high correlation with RNA-seq of patient-matched frozen tissue (Spearman coefficient 0.9). There was significant upregulation of AR and the ARv7 expression following treatment, as well as a subset of NE and EMT genes; three high chromogranin A outlier cases were identified in the treatment arm. There was an overall higher AR score in treated cases (based on expression of 30 AR signaling genes) compared to untreated, along the spectrum of CRPC. Conclusions: These data support the feasibility of quantifying gene expression in neoadjuvant-treated PCA cases with limited FFPE tissue requirement. Extensive characterization of AR status and NE/EMT genes identifies molecular outliers that can arise post-treatment and provides new insight into the heterogeneity of treatment response and potential early markers of resistance. Clinical trial information: NCT00430183.
MRI-US fusion targeted biopsy results in men with a history of prior cancer.
Authors: Nawaf Cayce , Rosoff James , Lu Amanda , Weinreb Jeffrey , Humphrey Peter , Levi Angelique , Schulam Peter , Sprenkle Preston
Published: February 2017

88

Background: Appropriate risk stratification of men on active surveillance for prostate cancer is essential to identify men in whom it is safe to take this deferred treatment approach. This study evaluates upstaging rates using MRI-US fusion targeted biopsy in men who have had a prior positive standard 12-core biopsy. Methods: Between 12/2012 and 06/2015, 374 men with an indication for prostate biopsy underwent pre-biopsy mpMRI followed by 12-core standard trans-rectal mapping biopsy (Mbx) and MRI-Ultrasound fusion targeted biopsy (Tbx) of lesions identified on mpMRI. The combination of Mbx and Tbx, when both occurred, constitutes a fusion biopsy (Fbx). Men who underwent both Mbx with or without Tbx using the Artemis/Pro-Fuse system with a previous non-MRI-guided biopsy and a diagnosis of prior Gleason 6 prostate cancer were included. Patients without a lesion on MRI underwent Mbx only. Maximum Gleason scores (GS) were assigned on a per patient basis with Mbx GS available for all patients in the cohort and Tbx GS available only for patients with a lesion visible on MP-MRI. Clinically significant (CS) cancer was defined as GS ≥ 3+4. GS per patient was compared by chi-square and McNemar’s test. Results: 118 patients met inclusion criteria (Mean PSA = 6.9, Mean age = 62.5). 40 patients (34%) were upstaged by Fbx to Gleason ≥ 7. Of those upstaged, 17 men (14%) would have been missed by Mbx alone, in comparison to 7 (6%) that were missed by Tbx alone. Total number of prior biopsies (p = 0.28) and number of years on Active Surveillance (p = 0.22) were not related to upgrade on Fbx. Older men (65.3 vs. 60.9, p = 0.033) and those with higher PSA (8.7 vs 5.8, p = 0.002) were more likely to be upgraded on Fbx. Tbx was more likely to identify CS cancer than Mbx (85% vs 56%; p < 0.012). Conclusions: MP-MRI Fusion biopsy more accurately stratifies men with a previous prostate biopsy than those receiving a template mapping 12-core biopsy alone. Tbx should be strongly considered before enrolling a patient in active surveillance since up 14% of clinically significant cancer would have been missed with a 12-core biopsy alone. [Table: see text]
Does the choice of hormone therapy affect medium-term outcomes following radical external beam radiotherapy for localized prostate cancer?
Authors: Lyons Ciara , Blayney Jaine K. , Mitchell Darren M. , Harney Jacqueline A. , McAleese Jonathan , Shum Lin , Stewart David P. , Jain Suneil , O'Sullivan Joe M.
Published: February 2017

97

Background: Multiple randomized controlled trials (RCTs) have demonstrated the benefit of the addition of androgen deprivation therapy (ADT) to external beam radiotherapy (EBRT) in the treatment of men with localized prostate cancer (PC). Anti-androgens (AA) may have a better toxicity profile than luteinizing hormone-releasing hormone agonists (LHRHa). However, no RCT has directly compared these agents in combination with radical EBRT. We evaluated outcomes for men with localized PC treated with EBRT in conjunction with either LHRHa or AA therapy. Methods: Data from 409 consecutive patients treated in NI with radical EBRT (70-74 Gy/2Gy #) between 2005 and 2009 were reviewed. Baseline and treatment characteristics analysed comprised age at diagnosis, T stage, initial PSA (iPSA), Gleason score, age-adjusted Charlson comorbidity index (aCCI), ADT type and radiation dose. Outcomes included biochemical progression-free survival (bPFS; Phoenix), prostate cancer-specific survival (PCSS) and overall survival (OS). Cox Proportional Hazards model was used for multivariate analysis (MVA). Results: Men receiving LHRHa were significantly more likely to be older and have a higher iPSA. On MVA, factors independently associated with biochemical failure were T stage ≥ 3 and use of AA (p < 0.004 and p < 0.02 respectively). On MVA, the single independent factor for poorer OS was higher aCCI (p < 0.000015). There was a trend towards poorer OS in the LHRHa group (p = 0.087). Conclusions: An aCCI > 4 was the only independent factor for poorer OS. While there was a significantly increased rate of biochemical failure in the AA group, there was a trend towards poorer OS in the LHRHa group. This study suggests that AA may be a reasonable alternative to LHRHa therapy in men with localized PC treated with radical EBRT and ADT. [Table: see text]
The frequency of druggable targets in localized prostate cancer: Initial analysis from the Decipher GRID.
Authors: Erho Nicholas , Alshalalfa Mohammed , Wood Penelope J. , Takhar Mandeep , Ashab Hussam Al-Deen , Davicioni Elai
Published: February 2017

98

Background: Prostate cancers patient management has been enhanced with commercially available genomic prognostic tests such as the Decipher prostate cancer classifier that are useful for making treatment decision-making. In addition to being the most validated predictor of metastasis in prostate cancer, Decipher is also a genome-wide assay that measures the expression of many druggable targets. Methods: Decipher GRID (Genomic Resource Information Database), was queried to assess the expression patterns of 14 genes from 5 biological pathways (Table) in 1,850 patients from previously published Decipher validation studies. The frequency of high (or low) expression of each gene was ascertained using a standard and more conservative thresholds based on the median absolute deviation (MAD) metric. For the standard threshold, genes whose high expression is of clinical relevance, patients with gene expression above the median + 1.48*MAD were annotated as high expression and for genes whose low expression is of clinical relevance, patients with gene expression below the median - 1.48*MAD were annotated as low expression. For the conservative threshold, median +/- 2*1.48*MAD was used. Results: See Table. Conclusions: Since every patient receiving the Decipher test also has a genome-wide expression profile, the Decipher GRID will allow researchers to evaluate on a systematic population-level the expression of genes that may be targeted with existing therapies. Such information may be useful for selection of optimal systemic therapy and inclusion into clinical trials of novel targeted agents. This rich genomic resource is being made available on a research use only basis to prostate cancer researchers and to clinicians seeking to uncover individualized genomic insights for patients to advance precision medicine. [Table: see text]
Utilization of 17-gene biopsy-based genomics scores in treatment decisions for low- to intermediate-risk patients with prostate cancer.
Authors: Katz Aaron , Mulcahy Megan , Rice Jacquelyn , Kosinski Kaitlin E.
Published: February 2017

e627

Background: Patients with prostate cancer are faced with many different treatment options for their disease. A biopsy-based 17-gene genomic analysis is clinically validated as a predictor of favorable pathology and is used in our practice to aid men considering Active Surveillance in lieu of definitive treatment for their low- to intermediate-risk prostate cancer. We analyzed the treatment decisions made after receiving the Genomic Prostate Score (GPS) results of this test. Methods: We identified 77 patients between 2013 to 2015 from our practice who received Genomic Prostate Score results. We characterized their demographics, NCCN criteria both before and after the test, their Genomic Prostate Score (GPS), chance of favorable pathology, and treatment decision after the test. Results: Average age of the group electing surveillance after the genomic test was 61 years versus 65 in the group electing treatment (p=0.04). Average GPS in the surveillance group was 20 versus 28 in the treatment group (p=0.03). Average percent chance of favorable pathology was 80% in the surveillance group versus 63% in the treatment group (p<0.001). Conclusions: Biopsy-based genomics analysis can be a helpful tool for patients and practitioners who are evaluating candidacy for an Active Surveillance regimen versus definitive treatment for low- to intermediate-risk prostate cancer. [Table: see text]
Changes in prostate volume during neo-adjuvant hormone therapy and definitive radiotherapy.
Authors: McPartlin Andrew , Hosni Ali , McWilliam Alan , Van Herk Marcel , Kershaw Lucy , Choudhury Ananya
Published: February 2017

e628

Background: Neo-adjuvant hormone therapy (NA-HT) produces profound changes in prostate vasculature and volume. There is little data available on how prostate volumes changes during radiotherapy (RT) after NA-HT. This is highly relevant in the context of adaptive RT and focal boosting. Methods: Eleven patients with intermediate- or high-risk prostate cancer, receiving 3 months NA-HT plus 60 Gy RT in 20 fractions, underwent four multiparametric MRI scans. These were performed before and after NA-HT, then during the third week of RT and 8 weeks after RT. The prostate was contoured on each scan by a radiation oncologist with experience in prostate MRI and reviewed by a second radiation oncologist. Statistical analysis was performed using Spearman correlation and the unpaired t-test with Welch’s correction. Results: One patient declined the post-treatment scan. NA-HT induced a dramatic mean volume reduction of 47%, range -27% to -64%. Volume changes during NA-HT inversely correlated with volume change during RT (r -0.755, p=0.01). Patients with ≥50% vs. <50% reduction during NA-HT experienced significantly different responses to RT with +29.4% vs. -9.1% (p=0.006) mean volume changes respectively from pre-RT size by week three. Absolute volume pre-NA-HT (p=0.64) or pre-RT (0.29) was not predictive for subsequent change. There was a small mean volume change post RT of -5%; range -20% to +15%. Conclusions: In this study a reduction in volume during RT is seen in patients with smaller than 50% prostate shrinkage due to NA-HT. Other patients experienced a mean volume increase of nearly one third by week three. This would be equivalent to an increase of around 4mm for an initial diameter of 40mm. In case of small treatment margins, the radiotherapy should be adjusted for these changes. [Table: see text]
Diagnosis and semiquantification of osteonecrosis of the jaw by bone scan index on bone scintigraphy.
Authors: Yaegashi Hiroshi , Mizokami Atsushi , Watanabe Satoru , Nakajima Kenichi , Noguchi Natsuyo , Kawashiri Shuichi , Namiki Mikio
Published: February 2017

e639

Background: Bone management is extremely important for maintaining QOL of prostate or renal cancer patients with bone metastasis. Physicians often administrate bone modifying agents (BMA), zoledronic acid or denosumab, to prevent skeletal-related event and bone pain for such patients. However, osteonecrosis of the jaw (ONJ) is one of sever adverse events of BMA (Medication-related ONJ; MRONJ). The early detection and follow-up of ONJ is extremely important issue. In order to achieve this issue, we utilized bone scintigraphy and a computer-aided diagnosis using a bone scan index (BSI). Methods: A total of 22 patients with either prostate cancer or renal cancer (27 lesions) diagnosed with MRONJ after treatment with BMA were investigated. Median age was 72.5 years (range 52-82 years). The primary disease was prostate cancer (81.8%), renal cancer (18.2%). Regarding the treatment, 86.4% of the patients were treated with bisphosphonate drugs, none in denosumab, and both in 13.6%, respectively. The median duration of medication was 33 months (range 7-70 months) by the time of MRONJ diagnosis. All patients underwent Tc-99m methylene diphosphonate bone scintigraphy. Bone uptake in the jaw was analyzed using BSI, which was calculated by BONENAVI (FUJIFILM RI Pharma, Japan; EXINIbone, EXINI Diagnostics, Sweden). Significant hot spots were manually selected according to both serial scintigraphic images and dental records, and the fraction of them to the entire skeleton was referred as BSI of the jaw (BSIJ). The level of BSIJ was evaluated in comparison with stage of ONJ and inflammation marker, C-reactive protein (CRP). Results: The median BSIJ of lesions was 0.14 (range 0.00-0.43) at the time of MRONJ diagnosis. If MRONJ is not treated appropriately, BSIJ tended to increase during treatment with BMA. When patients were classified according to their clinical stages of MRONJ, higher stage MRONJ lesions had significantly higher BSIJ (p < 0.01). In addition, BSIJ was correlated with CRP. Conclusions: Evaluation of BSIJ using BONENAVI on bone scintigraphy was helpful for early detection and follow-up of MRONJ. Furthermore, increased BSIJ on bone scintigraphy were related to CRP and stage of ONJ.
Improving quality of care and health outcomes for cancer survivors: Insights from the Patient-Centered Outcomes Research Institute’s (PCORI) cancer portfolio.
Authors: Arora Neeraj K. , Gayer Christopher , Lawrence William , Gershteyn Vadim , Parry Carly , Dunham Kelly , Clauser Steven
Published: February 2017

10

Background: PCORI funds comparative effectiveness research (CER) which aims to produce evidence-based information to help people make informed health care decisions and improve outcomes that matter to patients. Cancer studies form one of the largest disease-specific PCORI-funded portfolios. Methods: We conducted a systematic analysis of PCORI’s cancer portfolio overall and of the subset of studies that focus on post-treatment survivorship. Results: As of June 2015, PCORI has funded 47 cancer projects totaling $125 million. Cancer studies account for 17% of PCORI’s dollar investment in CER research. These studies have focused on breast, lung, prostate, colorectal, cervical, ovarian, and pancreatic cancers as well as leukemia. A majority of PCORI-funded cancer studies are randomized trials (60% of studies, 72% of dollar investment). One-in-four studies address post-treatment survivorship (n = 12, $23 million). The 12 CER studies on post-treatment survivorship address a range of patient-centered issues. Four studies are evaluating different post-treatment surveillance approaches for breast (2 studies), colorectal, and lung cancer survivors respectively. Three studies are focusing on optimizing the care planning process for cancer survivors while another is evaluating the impact of an oncology medical home model on patient-centered outcomes. Four studies are addressing quality of life (QOL) issues, one is evaluating approaches for incorporating patient reported outcomes data in the clinical encounter, a second is evaluating a multi-component intervention to improve the QOL of cancer survivors, a third study is evaluating the comparative effectiveness of complementary therapies to treat symptoms, and another is addressing distress among caregivers of stem cell transplant survivors. Conclusions: PCORI-funded CER studies are rigorously evaluating the real world impact of a range of interventions aimed at optimizing the quality of care delivered to and outcomes experienced by cancer survivors. Our analysis of the cancer portfolio will inform future funding priorities aimed at improving patient-centered outcomes for cancer survivors.
Young adult female cancer survivors’ concerns about genetic cancer risk in offspring.
Authors: Raghunathan Nirupa Jaya , Thom Bridgette , Friedman Danielle Novetsky , Benedict Catherine , Kelvin Joanne Frankel
Published: February 2017

121

Background: More than 362,000 female cancer survivors under 40 years old live in the US. Research consistently shows no increased cancer risk among offspring of cancer survivors in the absence of a hereditary cancer. Still survivors voice concerns over the health of future children. This analysis explores young adult female cancer survivors’ (YAFCS) perceptions of genetic cancer risk and related reproductive concerns. Methods: Eligible females were aged 18-35, at least one year post-treatment. Participants were recruited using social media posts from 17 young adult cancer advocacy groups and directed to an anonymous web-based survey that included the Reproductive Concerns after Cancer Scale (RCACS), with a 3-item “Concerns about Future Child Health” subscale. Results: 346 YAFCS completed the full survey, and based on logic-based branching, 192 respondents could have completed the RCACS: 177 (92%) completed the entire scale and 187 (97%) completed the child’s health subscale. Mean RCACS score was 58.5 (sd = 11.6; range 22-86); mean child’s health score was 11.3 (sd = 3.3; range 3-15), with a negative skew. At the item-level, 65% of the sample worried about passing along cancer risk to offspring; 71% worried about family health history affecting future children; and 60% were afraid their children would have a high chance of getting cancer. RCACS and child’s health subscale scores did not vary by age, race, education, income, or diagnosis. Further, mean scores did not vary between survivors of family cancer syndromes (breast, ovarian, colorectal) and those with other diagnoses (RCACS: t = 1.4, df = 175, p = .14; child’s health: t = 0.02, df = 185, p = .99). Conclusions: Despite studies showing minimal genetic cancer risk in offspring of survivors, many YAFCS have concerns about the health of future children. This may be related to mistaken beliefs that genetic mutations within tumor cells are transmissible or unawareness of availability of pre-implantation genetic diagnosis for embryo selection in those with transmissible genetic mutations. There is a need to educate patients about these issues to enable them to make family building choices based on accurate information about genetic risk.
Timing of the survivorship visit and symptom prevalence in breast cancer survivors.
Authors: Moore Halle C. F. , Mustafa Ali Moaath Khader , Moeller Machelle , Rybicki Lisa A.
Published: February 2017

125

Background: Since 2009, breast cancer patients at the Cleveland Clinic have been offered Survivorship Visits during which treatment summaries and follow-up care plans are provided following a detailed assessment of patient reported concerns. Timing of the initial Survivorship Visit varied from within 6 months of to more than 5 years from completing initial therapy. It is hypothesized that survivorship needs will differ between early, middle and late survivorship periods. Methods: Through an IRB approved data base, we evaluated symptom prevalence among women treated for stage 0 to III breast cancer according to treatment received and by time interval between completion of initial treatment and the first formal Survivorship Visit. Time intervals were divided into early (within 6 months), middle (more than 6 months but less than 5 years) or late (5 years or more) survivorship periods with respect to completion date of local therapy and any chemotherapy. Symptom prevalence was compared among the three time intervals using the Chi-square test. Results: Between April 2009 and August 2015, 1257 patients received formal initial Survivorship Visits with completion of a survivorship questionnaire. Detailed results of patient reported rates of fatigue, pain, numbness, concentration difficulty, anxiety, depression, hot flashes, insomnia and sexual problems will be described during the three different survivorship periods (early, middle , and late). Conclusions: Understanding of patient reported concerns at various time points during cancer survivorship should allow for better tailoring of survivorship needs and services.