bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the Living With Cancer (LWC) PRO tool for identifying patients (pts) with cancer appropriate for end-of-life care consultations.
Authors: Paramanathan Dhakshila , Pecora Andrew , Schultz Eric , Noh Hyun gi , DeMarco Katherine , Contreras Jose , Choi Kelly , Goldberg Stuart L. 
Published: February 2017

85 Background: End-of-life care (EOLC) discussions for pts with advanced malignancies are often delayed resulting in unwanted, wasteful treatment. COTA Inc has developed a 7-item PRO instrument (LWC) to facilitate identification of pts in distress. A pilot study of 433 pts at a single institution was able to determine a threshold distress score (> 28) correlating with physician assessment of appropriateness for EOLC consultation (2015 ASCO Palliative Care Symposium). Methods: LWC explores 4 personhood and clinical domains (performance status, pain, burden, and depression). Each question presents a 5-level Likert scale supplemented by a pt derived weighting of importance. The PRO was completed by 700 pts at Regional Cancer Care Associates throughout NJ between Sept 2015 and Apr 2016. The primary oncologists separately/independently classified 611 pts as appropriate to continue therapy (Group 1) and 89 pts as appropriate to curtail therapy (Group 2). Results: A score of 29 on LWC (range 0-112) was the threshold achieving optimal sensitivity (51%) and specificity (78%) in identifying pts in Group 2 (51% of pts whose oncologists felt appropriate to curtail therapy scored > 29; 78% of pts whose oncologists felt appropriate to continue therapy scored < 29). The threshold had positive predictive value 25% and 8% false omission rate (1 - negative predictive value) (25% pts scoring > 29 should be in Group 2; 8% scoring < 29 should be in group 2). A score 29 was 2.3 times more likely in pts belonging to Group 2 (likelihood ratio), and was a predictor of physician category (logistic regression p < 0.0001). LWC had a Cronbach’s alpha coefficient 0.85, indicating internal consistency and ability to measure a single latent construct. 3 questions (Performance Status, Wants, and Lack of Pleasure) contained the most information (estimate the latent trait with precision) and had high discrimination parameters (discriminate between pts lacking latent trait and displaying latent trait). Conclusions: The LWC instrument is able to identify cancer pts for whom EOLC discussions may be appropriate. A study to determine the correlation between the threshold score, EOLC consultation rate and overall survival is underway.
Psychosocial distress screening in the health care safety net.
Authors: Albert Margot , Cimino Theora , Kinderman Anne , Safier Leslie , Harris Heather A. 
Published: February 2017

91 Background: Recognizing that psychosocial distress (PSD) is underestimated in patients with cancer, the Commission on Cancer mandated screening using a validated tool. Studies of PSD screening exist, but none to date in a diverse, multicultural safety net setting where patients face challenges such as homelessness, mental illness, and substance abuse, which may augment PSD. Methods: We performed a retrospective cohort study of patients with cancer offered PSD screening during 2015. Overall distress scores and problems in each domain were analyzed. Chart review identified potential predictors of distress including age, gender, race, language, housing, psychiatric illness, substance abuse, and cancer stage. Results: Of 177 eligible patients, 113 (64%) completed screening. The most common reasons patients were not screened were refusal, too symptomatic (physically or emotionally), or language barriers. Of screened patients, 40.7% were female, 57.5% male, and 1.7% transgender. 31% were Caucasian, 27% Asian/Pacific Islander, 25% Hispanic, and 17% African American. 35% were non-English speaking. 29% had history of mental illness and 34% of substance abuse. 23% were marginally housed or homeless. 63% reported moderate to severe levels of PSD as defined by the NCCN as ≥ 4. Patients with mental illness were nearly twice as likely to report PSD ≥ 4 (p = 0.012) and had higher mean PSD scores (5.78 vs. 4.03, p = 0.002). English speaking patients had a mean PSD score of 5.01 compared to 3.6 and 3.2 for Spanish and Chinese speaking patients, respectively (p = 0.02 for English v. Chinese) and more domains causing PSD (p = 0.028 for English v. Chinese). Lack of stable housing also correlated with more domains causing PSD (p = 0.05). Conclusions: This proved to be an ethnically diverse cohort with high rates of mental illness, substance abuse, and homelessness, with the majority reporting moderate to severe distress. Even with a small cohort, English language and mental illness were significant predictors of PSD, and housing status correlated with more domains contributing to PSD. Several other variables trended toward significance, suggesting a larger cohort may be needed to determine if additional characteristics predict higher levels of PSD.
Patient-specific meta-analysis (MA) of two validation studies to predict pathologic outcomes in prostate cancer (PCa) using a 17-gene genomic prostate score (GPS).
Authors: Cooperberg Matthew R. , Brand Timothy C. , Simko Jeff , Sesterhenn Isabell , Zhang Nan , Crager Michael , Maddala Tara , Lawrence H. Jeffrey , Febbo Phillip G. , Srivastava Shiv , Chan June M. , Cullen Jennifer , Carroll Peter 
Published: February 2017

100 Background: We validated a biopsy-based assay as a predictor of PCa aggressiveness in two independent patient cohorts. Using GPS with NCCN risk group, the test provides an estimate of likelihood of favorable pathology (LFP) in low-intermediate risk PCa based on data from the first validation study. The second study re-confirmed the association between GPS and LFP. We combined information from both studies to provide more precise estimates of LFP, and examined predictive models using GPS with other clinical risk tools. Methods: Patient-specific MA provides precision-weighted predictions for individual patients using data from multiple studies (Crager and Tang, J. Appl. Stat. 2014). MA was performed on the two validation studies (732 patients total) using GPS (scale 0-100) with CAPRA score, NCCN risk group, or AUA/EAU risk group as predictors of LFP (Gleason score 3+3 or 3+4, organ-confined disease). Decision curves were calculated using the MA risk estimates. Results: MA provided more precise estimates of LFP with narrower confidence intervals (CIs) than either study alone (median width 24% narrower than the smaller of the two individual study CIs). GPS added significant predictive value for LFP to each of the 3 clinical classifiers. A model utilizing GPS and CAPRA provided the most risk discrimination. In decision-curve analysis, greater net benefit was shown when combining GPS with each clinical classifier compared with the clinical classifier alone. Over a wide range of threshold probabilities, incorporation of GPS would be expected to lead to fewer treatments of patients with favorable pathology without increasing the number of patients with adverse pathology left untreated. The proportion of men with MA-estimated LFP > 80% was 31% with GPS and CAPRA, and 23% with GPS and NCCN risk group; 11% were identified with LFP > 80% using NCCN risk group alone. Conclusions: Patient-specific MA of two independent studies provided more precise risk estimates reflecting the complete body of evidence. GPS adds predictive value to three clinical risk tools. The MA-estimated LFP identified more patients with an LFP > 80% than identified by clinical classifiers alone.
Intraductal carcinoma and cribriform architecture as novel prognostic factors in patients with prostate cancer treated with dose-escalated radiotherapy.
Authors: Murgic Jure , Berlin Alejandro , Chua Melvin , Pintilie Melania , Bristow Robert G. , van der Kwast Theodorus 
Published: February 2017

101 Background: Intraductal carcinoma (IDC) and cribriform architecture (CA) represent distinct pathohistological variants of high-grade prostate cancer associated with aggressive disease and poor clinical outcome. We evaluated impact of IDC and/or CA (IDC/CA) as a prognostic marker in patients with prostate cancer who underwent contemporary image-guided, dose-escalated, intensity-modulated radiotherapy (IMRT). Methods: Radiotherapy and clinical records of 379 patients with localized prostate cancer treated from 2005 to 2012 with prostate IMRT with 78 Gy in 39 fractions were retrospectively reviewed. Original diagnostic prostate biopsy slides were centrally reviewed by an expert genitourinary pathologist and scored for presence of IDC/CA. The impact of IDC/CA and other pre-treatment and treatment-related factors on biochemical relapse-free survival (BRFS) was evaluated. Results: IDC/CA was present in 19.3% of patients. After median follow-up of 56 months, 39 (10.3%) and 10 (3.6%) patients experienced biochemical failure and distant metastasis, respectively. On univariate analysis, the presence of IDC/CA was associated with decreased BRFS (HR 4.1 (95% CI: 2.2-7.8), p < 0.0001) and metastasis-free survival (HR = 4.7 (95% CI: 1.4-15.6), p = 0.013). On multivariate analysis, IDC/CA was associated with decreased BRFS (HR = 2.3 (95% CI: 1.2-4.7), p = 0.02) together with NCCN risk group (overall p = 0.0004), Gleason score (overall p = 0.016) and percent of positive biopsy cores (HR = 5.78 (95% CI: 1.4-23.9), p = 0.015). Within intermediate risk patients, presence of IDC/CA was associated with decreased BRFS (HR = 3.3 (95%CI: 1.5-7.1), p = 0.031) and was able to further stratify GS 4+3 patients (HR = 4.5, (95% CI: 1.6-13.0), p = 0.0045). Conclusions: The presence of IDC/CA in the prostate biopsy has negative prognostic impact in patients treated with dose-escalated radiotherapy. Furthermore, the prognostic significance of IDC/CA, even among unfavorable intermediate-risk patients, suggests that these pathological features should be considered in existing risk stratification tools for this patient group.
Focal HIFU (high intensity focused ultrasound) treatment of unilateral localized prostate cancer: Hemiablation strategy—A prospective French multicentric study with 111 patients.
Authors: Pasticier Gilles , Crouzet Sebastien , Rouviere Olivier , Mege-Lechevallier Florence , Tonoli-Catez Helene , Chapelon Jean-Yves , Rischmann Pascal , Gelet Albert 
Published: February 2017

102 Background: Up to a third of patients with localized prostate cancer (LPCa) have unilateral disease that may be suitable for a treatment of one lobe. Our aim was to evaluate the ability of HIFU to achieve a local control of the tumor in patients with unilateral LPCa. Methods: The French Urological Association (AFU) conducted a multi-institutional study, to evaluate hemi-ablation with HIFU as a primary treatment for patients >50 years, T1C or T2A, PSA<10ng/ml, Gleason ≤7 (3+4), and unilateral disease. 111 patients were treated: mean age 64.8 ±6.18 years, mean PSA 6.23±2.5 ng/ml. Gleason sum was ≤6 in 73.9% and 7 in 26.1%.primary outcome was the negative biopsy rate. Secondary outcomes were genitourinary side effects measured using validated questionnaires. The tumor was localized using MRI followed by random and targeted transrectal biopsies. Only the pathological prostate lobe was treated using HIFU. Results: The PSA nadir value was 1.87±1.49 ng/ml and the PSA at 12 months was 2.49±2.1 ng/ml (median 1.89). Ninety patients out of 101 (89%) in whom control biopsies were performed, had histological absence of significant disease (Gleason 7 or presence of cancer core length >3mm): treated side 5%, untreated side 5.9%. However 32.6% of men had persistent cancer of any threshold. Additional therapies were proposed in 33 patients (29,7%): active surveillance (16 patients), Redo-HIFU (8 patients), external beam radiation therapy (3 patients), radical surgery (6 patients). The RTFS (radical treatment free survival rate defined as absence of whole gland therapy) at 2 Years was 89%. At 12 months pad free continence was preserved in 103/106 (97%) and erectile function (IIEF5 score ≥16) was preserved in 40 patients out of 51 patients (78%). Conclusions: HIFU hemi ablation strategy allows an encouraging local control of the cancer has minimal side effects compared with standard whole gland treatments and allows additional therapies if necessary. Clinical trial information: HIFU/AFU/08.06.
Utilization of radiotherapy for prostate cancer according to urologists’ practice patterns.
Authors: Williams Stephen Bentley , Huo Jinhai , Smith Benjamin D. , Hoffman Karen E. 
Published: February 2017

11 Background: Physician practices that offer ancillary medical services may refer their patients for such services, a process known as self-referral. Self-referral for radiation therapy according prostate cancer risk and cost of care is not known. We evaluated how utilization and cost of care differ for men diagnosed with prostate cancer in a self-referring urologic practice (SRP) compared to a traditional urologic practice. Methods: 17,982 men 66 years and older diagnosed with localized prostate cancer from 2006 to 2009 were identified from the Texas Cancer Registry. Disease was classified as favorable if low-grade and clinical T1 or T2. The diagnosing urologist was classified as being affiliated with a SRP if their practice owned a linear accelerator. Multilevel logistic regression models evaluated the odds of receiving a specific type of treatment adjusted for diagnosis year, age, comorbidities, race/ethnicity, income, education, clinical tumor stage, and tumor grade. Cost of care was calculated from Medicare expenditures within 12 months of diagnosis. Results: Diagnosis in a SRP increased from 2.2% of prostate cancers in 2004 to 24.5% in 2009 (p< 0.001). Men diagnosed in SRPs were more likely to receive upfront treatment (vs. watchful waiting/active surveillance) than men diagnosed by traditional practices (92.7% vs. 89%; AOR 1.61, p<0.001) and were more likely to be treated with external beam radiation (47.4% vs. 34.1%; AOR 1.59, P<0.001). This persisted for both favorable and unfavorable risk cancer. Men diagnosed in SRPs were more likely to receive upfront treatment (favorable: 92.9% vs. 87.1%; AOR 1.89, p<0.001; unfavorable: 97.9% vs. 95.0%; AOR 2.07, p=0.002) and more likely to be treated with EBRT (favorable: 41.2% vs. 31.1%; AOR 1.45, p=0.002; unfavorable: 49.0% vs. 38.1%; AOR 1.53, p<0.001). Median annual prostate cancer care cost was $2,460 (95% CI $1,663-$3,368) higher for men diagnosed by SRPs. Conclusions: Older men diagnosed with prostate cancer in SRPs are more likely to undergo upfront treatment and to receive radiation treatment. This may increase appropriate treatment of unfavorable disease but contribute to overtreatment of favorable disease.
Risk factors for disease progression after post-prostatectomy salvage radiation: Long-term results of a large institutional experience.
Authors: Rodin Danielle , Andersen Lars Wiuff , Buscariollo Daniela , Drumm Michael , Clayman Rebecca Helen , Galland Sigolene , Eidelman Alec , Feldman Adam S. , Lee Richard J. , Dahl Douglas M. , McGovern Francis J. , Olumi Aria F. , Niemierko Andrzej , Shipley William U. , Zietman Anthony L. , Efstathiou Jason A. 
Published: February 2017

110 Background: Salvage radiotherapy (SRT) has been successfully used to treat recurrent prostate cancer following radical prostatectomy (RP). The objective of this study was to identify risk factors for disease progression post-SRT. Methods: Retrospective review of 719 consecutive patients who had RP and received post-operative radiation (adjuvant/SRT) for recurrent prostate cancer from 1992-2013. Disease progression was defined by a prostate specific antigen (PSA) ≥0.2 ng/ml, local recurrence, nodal failure, or distant metastases. Analysis was restricted to patients treated after 2000, when the PSA detectability threshold decreased to 0.2. Univariable and multivariable Cox regression analysis with backwards selection was performed with the following variables: demographics (age, race), pathological features (Gleason score, positive margins, pT-stage), surgery type, radiation details, hormone therapy, and pre-SRT PSA. Secondarily, we included PSA velocity and doubling-time as continuous variables in the model. Results: 384 patients received SRT after 2000, of which 152 had disease progression, with a median time to recurrence of 6.2 years (95% CI 4.1-7.6 years). Multivariable analysis results are reported in the Table. Gleason score, T-stage, seminal vesicle invasion, and pre-SRT PSA were associated with progression. Pre-SRT PSA ≤ 0.3 conferred the lowest rate of disease progression. In a secondary model, PSA kinetics was evaluated in which doubling-time was associated with progression (HR 0.98 per month increase, 95% CI 0.96-1.00; p=0.03). Conclusions: The lowest rate of disease progression was found amongst patients treated with a PSA ≤ 0.3. A shorter DT may also be a useful predictor of disease progression after SRT. [Table: see text]
Genomic predictors of biochemical failure following radical prostatectomy.
Authors: Aneja Sanjay , Yu James B. , Glazer Peter 
Published: February 2017

114 Background: Although clinical correlates can help predict biochemical failure (BF), genomic correlates have yet to be identified. We hypothesized there would exist genomic profiles in patients who experience BF after radical prostatectomy (RP), for whom aggressive regional therapy may be more appropriate. Methods: Genes of interest were identified using the 25 most commonly mutated genes from the COSMIC dataset. The Cancer Genome Atlas (TCGA) was used to study normalized microarray gene expression data for patients who underwent RP for treatment of Gleason 7-10, T1/T2 N0 prostate adenocarcinoma. BF was considered PSA > 0.1 following prostatectomy. Clinical data of interest included age, pre-treatment PSA, Gleason score, pathologic T stage, and country of origin. A multi-level hierarchical logistic regression model clustered with random effects by pathologic T stage and country of origin was built to identify predictors of BF. Variances were used to estimate how genomic differences explained differences in BF. Results: We identified 296 patients with T1/T2 N0 prostate adenocarcinoma who underwent RP. Median age was 60 with a median follow up of 2.3 years. 59% (n = 177) had Gleason 7 disease and 54% (n = 154) had T1 disease. 40.8% (n = 121) of patients had BF following RP. After adjusting for clinical covariates, 4 genes were associated with differences in BF. Specifically, increased RNA expression of E2F3 (OR 1.11 p < .001), CTNNB1 (OR 1.49, p = .002), and AR (OR 1.21, p < .001) were seen in patients who experienced BF. Expression of TP53 (OR 0.75, p < .001) and Gleason 7 disease (OR 0.62 vs. Gleason 8-10, p < .001) were associated with decreased likelihood of BF. Clustering by pathologic T stage accounted for 10% of variance in BF indicating that the 4 genes augment clinical patient characteristics. Conclusions: Genomic data augments pre-treatment clinical data in the stratification of patients undergoing RP. RNA expression of E2F3, CTNNB1, AR and TP53 is associated with differences in BF following RP. Clinically, these genes could aid in identifying patients who may benefit from more aggressive therapy. Further studies of the relationship between these genes and the development of prostate cancer could aid in future targeted therapies.
Phase II study of lovastatin to prevent rectal injury from radiation therapy for prostate cancer.
Authors: Anscher Mitchell Steven , Chang Michael G. , Moghanaki Drew , Rosu Mihaela , Mikkelsen Ross , Holdford Diane , Skinner Vicki , Grob B Mayer , Sanyal Arun J. , Mukhopadhyay Nitai 
Published: February 2017

120 Background: Late radiation induced rectal injury remains an issue. Large population based studies indicate an incidence of at least 15%. Statins have been shown to reduce the risk of late radiation injury in animal models. The purpose of this study was to prospectively test lovastatin as a potential protector against radiation induced rectal injury, particularly bleeding. Methods: Eligible patients included men with adenocarcinoma of the prostate who were to be treated with radiation therapy with curative intent. Patients receiving primary radiation therapy (external beam alone, brachytherapy alone, or a combination of both) or post-prostatectomy radiation were eligible, as long as the minimum dose to the rectum was 60 Gy. Patients began lovastatin 20-80 mg/d on day 1 of radiation. Lovastatin was continued for 1 year and patients were followed for an additional year. Patients were seen at 1, 2, 4, 6, 9, 12, 18, 21 and 24 months after treatment. At each follow-up, they were assessed for GI, GU and erectile complications using both patient reported (IIEF, EPIC) and physician reported (CTCAE v3) instruments. The primary endpoint of the study was the incidence of rectal bleeding at 24 months (Grade 2 or higher). Results: From April 2007 through May 2013, 73 patients were enrolled. 21 patients either withdrew or were removed from the study due to noncompliance with the lovastatin regimen or toxicity from the drug. Patients who withdrew or were removed were replaced, in order to achieve the target number of 53 evaluable patients with complete 2-year follow-up. A total of 50 patients are evaluable. All but 2/50 evaluable patients achieved the 24-month follow-up goal. At 24 months, there were a total of 4 patients with rectal bleeding attributable to radiation; 3 were grade 2 and 1 was grade 3 (4/48=8%). Conclusions: The incidence of rectal bleeding at 2 years in this population of patients receiving lovastatin during and after radiation therapy for prostate cancer was less than expected based on historical controls. These data suggest that statins may be useful to protect patients from radiation induced rectal injury. Clinical trial information: NCT00580970.
Neurovascular bundle-sparing radiotherapy for prostate cancer using MRI-CT registration: A dosimetric feasibility study.
Authors: Cassidy Richard John , Yang Xiaofeng , Liu Tian , Nour Sherif , Jani Ashesh B. 
Published: February 2017

128 Background: Sexual dysfunction after radiotherapy for prostate cancer remains an important late adverse toxicity. The neurovascular bundles (NVB) that lie postero-laterally to the prostate are typically spared during prostatectomy, but in traditional radiotherapy planning they are not contoured as an organ-at-risk with dose constraints. Our goal was to determine the feasibility in sparing the NVB while still delivering adequate dose to the prostate. Methods: Twelve consecutive patients with intermediate- or high-risk prostate cancer (with no gross disease within 2mm of either NVB) who were treated with external beam radiotherapy, with the same primary PTV margins, to a dose of 79.2 Gy were evaluated. Pelvic MRI and simulation CT scans were registered using dedicated software to allow for bilateral NVB target delineation on T2-weighted MRI. A volumetric modulated arc therapy (VMAT) plan was generated using the NVB bilaterally with 2mm margin as an organ to spare (with goal of reducing V70Gy by 30%) and compared to the patient’s delivered plan. Dose-volume histogram (DVH) endpoints for NVB, rectum, bladder, and PTV79.2 were compared between the two plans using a 2-tailed paired t-test. Results: The V70 for the NVB was significantly lower on the NVB sparing plan (p <0.01), while rectum and bladder endpoints were similar. Target V100% was lower (but still > 95%), and V105 was higher for the NVB Sparing plans (p <0.01). The table summarizes the DVH comparisons between the two plans. Conclusions: “NVB-sparing” radiotherapy is dosimetrically feasible using VMAT technology; target coverage is acceptable without increased dose to other normal structures, but with higher target dose inhomogeneity. The clinical impact of “NVH-sparing” radiotherapy is currently under study at our institution. [Table: see text]