bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of CCP assay in an updated series of biopsy samples obtained from commercial testing.
Authors: Crawford E. David , Shore Neal , Scardino Peter T. , Davis John W. , Tward Jonathan D. , Harrison Lowndes , Evans Brent , Fitzgerald Lisa , Stone Steven , Brawer Michael K. 
Published: February 2017

64 Background: The cell cycle progression (CCP) score is an RNA-based expression assay which has improved the prediction of prostate cancer aggressiveness in nine separate retrospective cohorts. In this analysis, we characterized the patient population and CCP score performance in commercial testing. Methods: Formalin-fixed prostate biopsy samples from 4,261 patients were submitted by 930 physicians to Myriad Genetic Laboratories for CCP test analysis. Patient clinicopathologic data was obtained from the test request form. The CCP score was calculated based on RNA expression of 31 cell cycle progression genes normalized to 15 housekeeping genes. Patients were sorted in to AUA risk categories and assigned a relative classification of cancer aggressiveness based on the CCP score. Results: Of the 4,261 samples that contained sufficient carcinoma (>0.5mm linear extent), 4,218 (99.0%) provided quality RNA for analysis. The CCP score distribution ranged from -2.9 to 3.4. Correlation with Gleason score was r=0.35 and the correlation with PSA was r=0.16. Based on the CCP score, 36.8% of men had a less aggressive cancer and 21.2% of patients had a more aggressive cancer than expected based on clinicopathologic prediction. Conclusions: The CCP test can improve risk stratification for men with prostate adenocarcinoma independent of other clinicopathologic variables. Fifty-eight percent of men tested in the commercial assay were assigned to a different risk category than predicted by their clinicopathologic features.
Biochemical failure after treatment for localized prostate cancer: Does original therapeutic modality affect long-term survival?
Authors: Reichard Chad A. , Kovac Evan , Ciezki Jay P. , Tendulkar Rahul D. , Klein Eric A. , Stephenson Andrew J. 
Published: February 2017

65 Background: Mortality among men with biochemical failure (BF) after treatment is variable. We examined the long-term survival of men with BF to determine if differences exist, depending on original treatment modality. Methods: Between 1995 and 2008, 6,084 patients underwent treatment for clinically localized prostate cancer at our institution (4,276 underwent radical prostatectomy (RP); 1,808 underwent EBRT). Clinical information and follow up data was obtained from prospectively maintained databases. Survival was assessed using log rank test. Results: 526 (12%) patients had BF defined by PSA > 0.4 after RP. 326 (18%) patients had BF after EBRT, defined as PSA nadir +2. 197 (60%) of EBRT patients received ADT as neoadjuvant/concurrent/adjuvant therapy. Median overall survival was 154 months (95%CI 148-157) versus 129 months (95%CI 123-135) for RP and EBRT respectively (p<.0001). Median prostate cancer specific survival was 125 months (95%CI 93-148) versus 107 months (95%CI 92-123) for RP and EBRT respectively (p=0.17). There was no difference in prostate cancer specific survival between treatments among patients in D’Amico intermediate and high risk groups. Conclusions: In patients with biochemical recurrence after definitive treatment, patients treated with RP have improved overall survival compared to patients treated with EBRT. However, there is no difference among treatment groups in prostate cancer specific survival.
Effect of neoadjuvant systemic therapy prior to radical prostatectomy in high-risk prostate cancer on surgical morbidity: Contemporary results utilizing the Clavien System.
Authors: Williams Stephen Bentley , Davis John W. , Achim Mary F. , Zurita Amado J. , Matin Surena F. , Pisters Louis L. , Ward John Francis , Pettaway Curtis Alvin , Chapin Brian Francis 
Published: February 2017

66 Background: There is limited evidence definingthe morbidity of radical prostatectomy (RP) with curative intent for patients with high risk prostate cancer. Multimodality treatment for men with high risk prostate cancer using neoadjuvant systemic therapy followed by surgery is being increasingly explored. Methods: We analyzed 215 consecutive patients with high risk and very high risk prostate cancer who underwent robotic or open RP with extended pelvic lymph node dissection previously untreated or received neoadjuvant systemic therapy between 2006 and 2010 at a single tertiary care academic center. Univariable and multivariable logistic regression analyses were used to identify predictors of complications. Results: Baseline characteristics were similar between patients who underwent neoadjuvant systemic therapy followed by RP versus RP alone except for PSA (PSA< or equal to 4 ng/ml: 75.4% vs. 15.5%, p<0.001) and preoperative hemoglobin (13.8 g/dl vs. 14.4 g/dl, p=0.003), respectively. Twenty nine percent of patients (63 of 215 patients) experienced a complication of any grade ≤90 d after surgery 6% experienced Grade ≥3, with no significant difference between either cohort (p=0.50). On multivariate analysis, estimated blood loss [Odds Ratio (OR) 1.10; 95% CI, 1.0 to 1.2, p=0.03), length of stay (OR 1.75; 95% CI, 1.3 to 2.4, p=0.001) and preoperative hemoglobin (OR 0.71; 95% CI, 0.53 to 0.94, p=0.02) were independent predictors of the occurrence of any grade complication. Considering grade 3 or 4 complications, procedure time (OR 2.20; 95% CI 1.0 to 4.8, p=0.05) and estimated blood loss (OR 1.39; 95% CI, 0.98 to 1.96, p=0.06) were significant predictors of major complications. Conclusions: Postoperative morbidity in patients with high risk prostate cancer following RP with or without the use of neoadjuvant systemic therapy is comparable to contemporary RP series of low to intermediate risk disease reporting outcomes in a similar fashion. Use of neoadjuvant systemic therapy prior to RP was safe and did not appear to increase the risk of having a perioperative complication.
Association between a 17-gene genomic prostate score and multiparametric prostate MRI in men with low- and intermediate-risk prostate cancer (PCa).
Authors: Leapman Michael S. , Westphalen Antonio C. , Ameli Niloufar , Lawrence H. Jeffrey , Febbo Phillip G. , Cooperberg Matthew R. , Carroll Peter 
Published: February 2017

83 Background: A biopsy-based RT-PCR assay (Oncotype DX Prostate Assay) providing a Genomic Prostate Score (GPS) as a measure of tumor aggressiveness and multi-parametric prostate MRI (mpMRI) are clinically utilized predictors of adverse pathology at prostatectomy. These tests have not been directly compared and it remains to be determined whether they provide independent information. Methods: We evaluated the association between GPS results (scale 0-100) and baseline endorectal mpMRI in men with clinically localized PCa. MR studies were reviewed to a five-tier scale of increasing suspicion of malignancy. Mean apparent diffusion coefficient (ADC) was calculated from a single dominant lesion. Mean rank of the GPS (0-100) and GPS-predicted likelihood of favorable pathology among MRI strata were compared with the Kruskal-Wallis test. Regression analysis was performed between mean ADC and scaled GPS within CAPRA risk groups. Results: Of 332 patients who received GPS testing at a single institution, 94 were identified with low (n=59) and intermediate (n=35) CAPRA risk prostate cancer who received mpMRI within a two-year interval of prostate biopsy. A broad distribution of GPS was observed across categories defined by mpMRI criteria. Among intermediate risk patients both GPS and the GPS-predicted likelihood of favorable pathology were associated with MR score (p=0.01 and p<0.01, respectively). For low risk patients, neither GPS nor likelihood of favorable pathology were significantly different across MR findings (p=0.12 and p=0.21, respectively). Mean ADC was not significantly associated with GPS or likelihood of favorable pathology for either low (p=0.24) or intermediate (p=0.91) risk categories. Conclusions: While a broad distribution of GPS was observed across mpMRI criteria, increasing GPS was associated with highly suspicious MRI findings in men with intermediate risk PCa. No significant associations were observed between MRI categories and either GPS or likelihood of adverse pathology in low risk patients.
Evaluation of early clinical experience of a novel prognostic proteomics prostate cancer biopsy test.
Authors: Choudhury Sibgat , Trock Bruce J. , Benson Skone Rene , Nardone Julie , Dunyak James , Shipitsin Michail , Epstein Jonathan I 
Published: February 2017

88 Background: Standard clinical and pathological parameters derived from diagnostic biopsy are insufficient to accurately assess final prostate tumor pathology of patients with biopsy Gleason grades 3+3 or 3+4. We developed a novel assay (ProMark) that performs quantitative measurements of 8 protein markers from prostate biopsy FFPE sections. In the validation study, assay risk scores were strongly predictive of final prostate tumor pathology with a C-stat of 0.69 (95%CI = 0.63 – 0.76) (p<0.0001). By design, the train-test (N=381) and validation (N=274) studies were enrichment studies, with a higher % of aggressive disease than in the intended use population. Here we study 293 needle biopsy cases that have come to our CLIA lab for ProMark testing over a four month period. The objective of this study is to establish the ProMark score distribution for these ‘real world’ clinical use patients, and to confirm that this distribution matches our clinical validation study. Methods: To establish prevalence of aggressive disease in the intended use population, we used the Institutional Urology Prostate Cancer Database at Johns Hopkins. Among 9,305 men with biopsy Gleason 3+3 or 3+4 and prostatectomy from 2004-2014 the distribution of favorable (GS<4+3 & organ confined) and unfavorable (GS≥4+3 or non-organ confined) based on surgical pathology is 73.1% vs. 26.9%. The adjusted risk score distribution from the validation trial (N=274) is then compared to the CLIA lab samples (N=293), based on cumulative distributions and binomial confidence intervals. Results: Comparison of the risk score distribution of early clinical data with the population-adjusted validation score distribution shows good agreement based on 95% CIs. Table shows expected and measured frequencies in Low, Intermediate and High risk categories. The K-S test for comparison of distributions has p-value=0.44, supporting equivalence of distribution. Conclusions: The results of our study show that early clinical practice closely matches expectations from controlled clinical studies. [Table: see text]
Association of ERG-PTEN expression profile of prostate biopsy with PSA velocity.
Authors: Algotar Amit , Cress Anne , Nagle Ray , Sokoloff Mitchell , Singh Parminder , Behnejad Roxanna , Stratton Steven 
Published: February 2017

92 Background: Although ERG and PTEN expression has demonstrated to have a role in prostate carcinogenesis, its association with important clinical markers such as PSA velocity (rate of prostate specific antigen [PSA] change over time) is currently unknown. This novel pilot study presents the results of the above association with the aim of understanding its clinical utility. Methods: Data for this study was obtained from men enrolled in a phase 2 clinical trial conducted to determine the effect of selenium supplementation on prostate cancer progression. All men in this trial were diagnosed with prostate cancer and opted for watchful waiting as their treatment modality. Biopsy tissue collected at randomization was stained for ERG and PTEN using immunohistochemistry techniques. PSA was measured at baseline and at each follow-up visit (every three months). PSA velocity was calculated using mixed effects regression models and the study group was divided into three tertiles. Results: Data from 77 subjects indicates ERG and PTEN expression is independently associated with lower PSA velocity (p = 0.02 and 0.037 respectively). Joint effect of ERG and PTEN expression on PSA velocity was also analyzed using logistic regression. As compared to the wild type (ERG+/PTEN-), ERG-/PTEN- and ERG-/PTEN+ subjects demonstrated increased risk for high PSA velocity. Odds ratios (95% confidence intervals) are: 4.05 (0.68, 24.1) and 1.71 (0.12, 23.1), respectively. These models were adjusted for age, race and Gleason score. Conclusions: This is the first study to report on an association between ERG-PTEN expression and PSA velocity, an important clinical marker of aggressive prostate cancer. Results of this study are counterintuitive to the current understanding of ERG-PTEN mechanism in prostate carcinogenesis indicating presence of yet undiscovered molecular pathways. Hence further research is needed to delineate these pathways and determine clinical utility of ERG and PTEN expression in prostate cancer.
The effect of connexin 36 deletion on chemotherapy-induced peripheral neuropathy (CIPN).
Authors: Sterman Adam , Hanstein Regina , Spray David C. 
Published: February 2017

1 Background: CIPN is a debilitating side effect and dose limiting toxicity of many chemotherapeutic agents. CIPN induces pathological changes in dorsal root ganglia (DRG), leading to increased cross-talk among the glia that surround sensory neurons (Satellite Glial Cells, SGC’s) and between sensory neurons and their adjacent SGCs via gap junctions. Since Connexin 36 (Cx36) is the main neuronal gap junction protein, we investigated CIPN in mice with deletion of Cx36. Methods: To induce CIPN, mice were given two i.p. oxaliplatin (oxa) injections 2 days apart. Controls received saline (sal). We used transgenic mice, which were either heterozygous for Cx36 or complete Cx36 knockouts (Cx36 Het or Cx36 KO), and littermate controls (Cx36 wildtype), 6-14 per group. Tactile sensitivity of the hindpaws was assessed prior to and every week after injections for 4 weeks using von Frey filaments. The number of paw withdrawals to 10 stimulations with each filament and pain thresholds (corresponding to filament that elicits 8/10 responses) were recorded. Results: Oxa-injected wildtype mice had higher response rates to filaments compared to sal-injected controls (p < 0.05), and lower tactile thresholds (at 9 days: sal 6.0±0.0g vs. oxa 1.9±0.5g, p < 0.0001), indicating hypersensitivity. Compared with wildtype, mice lacking Cx36 (Cx36 KO) displayed significantly less tactile hypersensitivity after oxa (tactile threshold at 9 days: WT 1.9±0.5g vs. KO 4.0±0.4g, p < 0.01), whereas oxa induced tactile hypersensitivity occurred in a similar fashion in Cx36 Het mice (tactile threshold at 9 days: WT 1.9±0.5g vs. Het 1.5±0.1g). At 9 days, there were fewer responses to filaments in oxa-injected Cx36 KO mice compared to oxa-injected wildtype mice (p < 0.05), but not in oxa-injected Cx36 Het mice. Conclusions: We found that oxaliplatin induces transient CIPN, represented by tactile hypersensitivity, in wildtype mice. Deletion of the gap junction protein Cx36, as displayed in the Cx36 KO mice, resulted in significantly less CIPN. This is the first report that a neuronal gap junction protein may modulate pain sensitivity, and points to a new molecule (Cx36) as a potential novel target for CIPN therapy.
Recovery of cancer patients' social lives upon referral to palliative care units.
Authors: Terui Takeshi , Hirayama Yasuo , Machino Takayuki , Kusakabe Toshiro , Nakamura Kenji , Mihara Hiroyoshi , Itoh Satoko , Ishitani Kunihiko 
Published: February 2017

107 Background: Our hospital is a cancer-specific facility that treats patients from diagnosis to terminal care. We evaluate the possibility of effective cancer chemotherapies for patients referred to our palliative care unit from other hospitals through case conferences in our institution. Even the patients referred to the palliative care unit of our institution are sometimes assessed as “very likely to be improved by standard or semi-standard treatment” by the palliative care and oncologic teams in our institution. We surveyed inappropriate cases that were mistakenly assessed as indicated for terminal care in their previous hospital. Methods: We reviewed 1535 patients referred to our palliative care unit from other hospitals because of anticancer chemotherapy contraindications over a 3-year period. We determined the number of the patients who were thought to actually have indications for cancer chemotherapy. Results: During the case conferences, 31 (2.0%) of the 1535 patients were thought to have indications for cancer chemotherapies. Standard chemotherapies were administered in our hospital to 6 patients. Four of the 6 patients were alive at one year and recovered their social life. Conclusions: Prudent assessment using updated guidelines are needed at the time of patient referral of a hospice. Ethical problems clearly exist with patients who were mistakenly assessed as indicated for terminal care in their previous hospital. There remains room for discussion of whether it is an ethical problem to overturn the will of a patient having chosen best supportive care (including those for whom it was presented as the only option by previous doctors or those who made positively the choice themselves) and proceed with cancer treatment.
Psychosocial distress in vulnerable patient populations: What happens after screening?
Authors: Cimino Theora , Albert Margot , Safier Leslie , Harris Heather A. , Kinderman Anne 
Published: February 2017

114 Background: The Commission on Cancer mandates psychosocial distress screening for patients with cancer, as well as documentation of referrals made to address sources of distress. Patients in safety net settings, who are vulnerable to significant economic and social stressors, may benefit from such screening; however, it is unclear if patients can access needed services and if their needs change over time. We examined the experience of cancer patients in an urban safety-net healthcare system to identify areas of improvement in the provision of support services. Methods: We performed a retrospective cohort analysis of patients screened for psychosocial distress during 2015. We reviewed medical records from initial oncology visits for results of screening and referrals made at that time. Those who reported a distress score of ≥ 4 were eligible for telephone follow up, which occurred 1-12 months after initial screening. Patients who agreed to participate completed a telephone survey that assessed current distress and referral status. Results: Of 113 patients who completed a psychosocial distress screen, 60% (n=68) reported a distress score of ≥ 4 and were called for follow up. Of these 68 patients, 17 (25%) had died or enrolled in hospice, 16 (25%) could not be reached after 3 attempts, 7 (10%) had transferred care, and 1 declined to participate. 26 patients (38%) completed telephone follow up. Patients reported an average distress score of 3.8, compared to 6.2 at their first visit. While “worry” was the most commonly reported problem at baseline, “pain” was the most common problem at follow up. For these 26 patients, a total of 69 referrals were made at their first visit, 59% of which were not accessed. 58% of the reasons given for not accessing referrals cited factors other than lack of interest, including requiring more information, not hearing back from the organization, and transportation issues. Conclusions: Significant barriers, such as difficulty with referrals and follow up, may interfere with providing care to a diverse, underserved population of patients who report high levels of distress at their first oncology visits. Alternative approaches, including primary or specialty palliative care, may be needed in this population.
Referral patterns and characteristics of uninsured versus insured patients referred to the outpatient supportive care center (SCC) at a comprehensive cancer center.
Authors: Azhar Ahsan , Yennu Sriram , Ramu Aashraya , Zhang Haibo , Haider Ali , Williams Janet L. , Bruera Eduardo 
Published: February 2017

116 Background: Multiple barriers exist in providing quality palliative care to low-income patients with cancer. Such disparities may negatively influence effective management of symptoms including pain. Our objective was to compare referral patterns and characteristics (level of symptom distress) of uninsured vs insured patients. Methods: We reviewed randomly selected charts of 100 Indigent (IND) and 100 Medicaid (MC) patients and compared them with a random sample of 300 patients with insurance (INS) referred during the same time period (1/2010 to 12/2014) to our SCC. Data was collected for date of registration at the cancer center, diagnosis of Advanced Cancer (ACD), first visit to the SCC (PC1), symptom assessment (Edmonton Symptom Assessment Scale-ESAS) at PC1. We excluded self-pay patients. Results: Results for IND, MC and INS (n = 481) respectively are as follows: Mean (SD) Age in yrs. was 50 (12), 48 (11) and 63 (13); p < 0.001. Percentage of non-white was 44%, 51% and 19.5%; p < 0.001. Percentage of unmarried patients was 64%, 68% and 33%; p < 0.001. Mean (SD) ESAS score at PC1 for pain was 5.6 (3.2), 6.7 (2.5), 4.9 (3.2); p < 0.001. Percentage of patients on opioids upon referral was 86%, 62%, and 54%; p < 0.001. Mean (SD) for referral time in months from ACD to PC1 was 8.7 (SD 10.4), 12.3 (SD 18.1) and 12 (SD 19.9) p = 0.31; for no. of encounters with SC per month were 0.46 (0.45), 0.41 (0.46) and 0.3 (0.55); p = 0.01; for survival in months (PC1 to last contact) was 6.4 (5.8), 5.6 (6.4) & 6 (7.22) p = 0.77. Conclusions: Uninsured patients had significantly higher levels of pain, were more frequently on opioids, younger, non-white and not married. They also required a larger number of SCC encounters. Insurance status did not impact timing of SCC referral or SCC follow ups at our cancer center.
Palliative care consultation and advance care planning for adults with poor-risk leukemia admitted to an academic medical center.
Authors: Freeman Ashley , Wood William A , Fox Alexandra , Hanson Laura C. 
Published: February 2017

13 Background: Despite high mortality for certain patients with hematologic malignancies, integration of palliative care (PC) and documentation of advance care planning (ACP) is lacking. Our primary objective was to determine the frequency of PC consultation and ACP for inpatients with poor-risk leukemia at our institution. Our secondary objectives were to describe the content of goals of care (GOC) discussions and to characterize PC and end-of-life quality measures. Methods: Chart reviews were conducted for patients with poor risk leukemia (acute leukemia ≥ 65 years or relapsed leukemia > 18 years) admitted to the University of North Carolina from October 1, 2015 to March 31, 2016. The following was abstracted from the chart: demographic data, disease characteristics, presence of a PC consultation, frequency and content of ACP (written advance directive, documented GOC discussion, identified surrogate decision maker), PC quality measures (assessment of pain, dyspnea, nausea, constipation), and end-of-life quality measures (chemotherapy within 14 days of death, ICU stay within 30 days of death, hospice referral less than 3 days prior to death). Results: Thirty-eight subjects were identified. Fifty percent of patients were over age 65 with a new diagnosis of acute leukemia and 50% had relapsed leukemia. The majority of patients (66%) reported pain and 45% reported dyspnea on admission. Sixteen percent of patients died within 30 days of discharge. Eleven percent of patients received PC consultation and 16% had all elements of ACP documented in the chart. GOC discussions without a surrogate decision maker were documented for 37%; content included discussion of values (11%), prognosis (37%), treatment choices (21%), life sustaining preferences (16%), and hospice (21%). Conclusions: In this descriptive study of inpatients with poor-risk leukemia, we found that despite a poor prognosis and high symptom burden, only 11% of patients received PC consultation and 16% had all elements of ACP present in the chart. While our data are limited by documentation, we believe this represents missed opportunities for the delivery of high-quality care.