bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.