bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of cardiovascular events with degarelix versus leuprolide after biochemical relapse of prostate cancer: Exploratory analysis of a randomized controlled trial.
Authors: Higano Celestia S. , Crawford E. David , Shore Neal D. , Bosnyak Zsolt , Malmberg Anders , Neijber Anders , Klotz Laurence 
Published: February 2017

151 Background: Androgen deprivation therapy (ADT) has been associated with increased cardiovascular (CV) risk in men. A pooled analysis of phase 3 trials comparing LHRH agonists with degarelix in PCa patients indicated a lower risk of CV events or death in those treated with degarelix. We now report the incidence of non-fatal CV events in men with PCa and pre-existing CV disease (CVD) treated with degarelix or leuprolide in the CS37 trial. Methods: CS37 was a prospective, randomized trial comparing intermittent (n=175) and continuous (n=50) degarelix with continuous leuprolide (n=178) in patients with biochemical relapse of PCa in the United States. CV events were retrospectively analyzed up to Month 12 (intermittent arm events censored at Month 7). Cox regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: 143 men (35%) had pre-existing CVD at baseline; 88 treated with degarelix and 55 treated with leuprolide. For degarelix and leuprolide treatment arms, median age (range) was 75 (51–88) and 73 (53–89) years and median BMI (range) 28.0 (17.7–40.7) and 30.1 (23.5–48.3) kg/m2, respectively. A slightly higher proportion of men treated with leuprolide than degarelix had a Gleason score of 7–10 (35 [64%] vs 46 [52%]) and slightly more men treated with degarelix vs leuprolide had hypertension (31 [35%] vs 15 [27%]), diabetes (70 [80%] vs 39 [71%]) and used statin medication (67 [76%] vs 36 [65%]) at baseline. The proportion of men who smoked or had hypercholesterolemia at baseline was similar between treatment arms. During the observation period, a subsequent CV event occurred in 3 (3.4%) men treated with degarelix and 8 (14.5%) treated with leuprolide (HR=0.22; 95% CI 0.05–1.03, p=0.054). Conclusions: Retrospective analysis of men with pre−existing CVD in CS37 identified a lower risk for subsequent CV events in men treated with degarelix vs leuprolide. The difference in CV event risk was seen within 12 months of treatment initiation. Our analysis adds to previous data on CV risk with ADT and supports consideration of CV risk factors when choosing a drug for androgen deprivation.
Weekly cabazitaxel in "unfit" metastatic castration-resistant prostate cancer patients (mCRPC) progressing after docetaxel (D) treatment: Preliminary results of CABASEM-SOGUG phase II trial.
Authors: Fernandez Calvo Ovidio , Fernandez Parra Eva , Perez-Valderrama Begoña , Mellado Begoña , Ochoa de Olza Maria , Castellano Daniel E. , Domenech Montserrat , Hernando Polo Susana , Anido Urbano , Arranz Arija Jose Angel , Caballero Cristina , Juan M Jose , Duran Ignacio , Campayo Marc , Serrano Monica , Climent Miguel Angel ,   SOGUG: Spanish Oncology Genitourinary Group
Published: February 2017

167 Background: Cabazitaxel (C), a novel taxane developed to overcome D resistance, showed an overall survival improvement after D in metastatic castration-resistant prostate cancer (mCRPC) in a three-weekly schedule. Its main toxicity is hematological, especially in unfit patients. We aimed to evaluate efficacy and safety of weekly C/prednisone (P) schedule in "unfit" mCRPC previously treated with D. Methods: Unfit pts defined as ECOG 2, dose reduction due to febrile neutropenia during D treatment or radiation therapy affecting more than 25% of bone marrow reserve, with mCRPC progressing after D treatment with adequate bone marrow, liver and kidney functions were included. C 10 mg/m2 was administered on days 1, 8, 15 and 22 of 5-week cycles with P (5 mg b.i.d.). Radiological and PSA response were evaluated according to the PCWG2 (Scher H, 2008) criteria and toxicity according NCI-CTC AE. Results: To date 70 pts have been enrolled and data are available for 66. Median age was 73 y (range 54-84), 67% pts had ECOG 2, 87% had bone, 14% liver and 11% lung metastases. Half of pts had Gleason >7. Treatment: 271 cycles (median: 3; range: 1-12); 1002 weekly infusions (median 11; range 1-48). Median dose intensity was 93%. Eighteen of 55 pts (32.7%) achieve ≥50% PSA response and 5 (9.1%) ≥80% PSA response. Radiological response was evaluable in 56 pts. PR was observed in 4 pt (7.1%) and SD in 29 pts (51.8%). Median PFS was 3.9 months. Median OS was 14.2 months. Most frequent toxicities of all grades as % of pts were: anemia (71.2%), asthenia (43.9%), thrombocytopenia (15.1%), leukopenia (24.2%), diarrhea (27.3%), nauseas (18.2%), neutropenia (12.1%), peripheral neuropathy (7.6%), and anorexia (18.2%). Grade 3-4: thrombocytopenia (4.5%), anemia (6%), neutropenia (3.0%), asthenia (10.6%), diarrhea (1.5%), anorexia (1.5%), No grade IV diarrhea nor febrile neutropenia were observed. Conclusions: Weekly cabazitaxel (10 mg/m2) plus prednisone administered to unfit pts seems a highly effective treatment and safe, with no grade 4 neutropenia, diarrhea or febrile neutropenia reported. Clinical trial information: NCT01518283.
Evaluation of basal and luminal subtypes of urothelial carcinoma in African American and non-African American patients.
Authors: Kardos Jordan , Melquist Jonathan J , Chism David D. , Choi Woonyoung , Cockerill Katherine , Paluri Ravi Kumar , Moses Kelvin A , Sonpavde Guru , McConkey David James , Kim William Y. , Dinney Colin P. N. , Milowsky Matthew I. 
Published: February 2017

305 Background: African American (AA) patients with urothelial carcinoma (UC) have been known to have a worse prognosis even when corrected for variables such as tumor stage and grade. Analysis of gene expression of several malignancies has resulted in the discovery of molecular subtypes with well-defined intrinsic biology. Recent studies in high grade (HG), muscle-invasive UC have led to the identification of two intrinsic, molecular subsets termed “luminal” and “basal” with characteristics of stages of urothelial differentiation, and that remarkably reflect the luminal and basal-like molecular subtypes of breast cancer. Patients with basal-like UC have a significantly worse overall survival. Methods: A total of 215 HG muscle-invasive UC tumors from the MDACC (n=75) and TCGA (n=140) were used to make intrinsic subtype calls using gene expression profiling (MDACC: DASL [cDNA-mediated Annealing, Selection, extension, and Ligation] and TCGA: RNA seq). Basal and luminal subtype calls were derived using previously published subtype classifiers (Damrauer et. al. PNAS, 2014 and Choi et. al. Cancer Cell, 2014). Patients were classified into AA and non-AA (white, Hispanic, or Asian) based upon self-reported race. Results: In total there were 16 and 199 tumors from AA and non-AA patients respectively. In non-AA patients, the proportion of tumors that were classified as basal and luminal were approximately equal (93 and 106 respectively), while in AA patients, there was enrichment of basal tumors (12 basal and 4 luminal) (p=0.03735, Fisher’s exact test). Conclusions: AA patients are enriched in the basal molecular subtype of UC. Similar findings have been previously documented in AA women with breast cancer. The enrichment of basal UC in AAs suggests that a biological explanation may in part underlie the poor outcomes seen in AA patients. Future studies will explore the prognostic and predictive implications of basal subtype in AA patients with UC.
Charting DNA methylation of long non-coding RNA in clear-cell renal cell carcinoma.
Authors: Malouf Gabriel , Zhang Jianping , Tannir Nizar M. , Thompson Erika , Spano Jean-Philippe , Khayat David , Su Xiaoping 
Published: February 2017

432 Background: Long non-coding RNAs (lncRNA) play a key role in regulating cell physiology through different mechanisms including the recruitment of histone-modifying enzymes. Recently, lncRNA classification of clear-cell renal cell carcinomas (cc-RCC) established four subtypes with different clinico-pathological features. However, the interplay between those lncRNA and DNA methylation patterns remains unknown. Methods: We performed a genomic analysis of GENCODE lncRNAs in cc-RCC using The Cancer Genome Atlas (TCGA) molecular RNAseq profiles of 471 primary tumors. Furthermore, we reannotated data of DNA methylation combining 27K (n=173) and 450K (n=298) Infinium arrays. We described global correlations between lncRNA expression and DNA methylation and established lncRNA methylation subtypes based on distinct signatures. In addition, we identified lncRNA regulated by DNA methylation and associated with poor outcome. Results: We identified 2,138 lncRNAs which contain promoters located in CpG islands (CGI). Out of those, 59 (2.8%) lncRNAs showed DNA methylation in both normal and cancer as compared to 1,487 (69.5%) lncRNA which were unmethylated in both of them. Importantly, 592 (27.7%) lncRNAs gained DNA methylation in ccRCC and this was associated with the repression of the expression of 70 of them. Unsupervised clustering of lncRNA using the most variable DNA methylation probes revealed three robust subtypes associated with distinct outcome. Finally, by integrating cancer subtypes data with clinical information, we identified several lncRNAs which promoter methylation was associated with patient outcome. Conclusions: Our study represents the first integrative analysis of lncRNA and DNA methylation in ccRCC and provides new insights in the role of epigenetic alterations in kidney cancer. Furthermore, we identified a subset of lncRNA regulated epigenetically which may represent potential therapeutic targets.
Is RCC truly radioresistant? Local control rates of metastatic renal cell carcinoma (RCC) to the lung using stereotactic radiotherapy (SBRT).
Authors: Altoos Basel M , Amini Arya , Bourlon Maria Teresa , Fisher Christine M. , Bedrick Edward , Flaig Thomas W. , Lam Elaine Tat , Kessler Elizabeth Riley , Kavanagh Brian D. , Karam Sana D 
Published: February 2017

445 Background: The use of radiation therapy (RT) for renal cell carcinoma (RCC) is controversial because RCC has traditionally been considered to be “radioresistant”. Based on this concern, current studies have suggested the need for higher doses with conventional fractionation (CF) or the use of SBRT with RCC. The purpose of this study is to determine the efficacy of these modalities by comparing the radiographic and symptomatic local control (LC) rates in patients with metastatic RCC to the lung. Methods: We retrospectively analyzed the radiographic and symptomatic RT response in 27 consecutive RCC patients with 37 RCC lung lesions treated between 2005 to 2014. Twenty-six (70.2%) were treated with SBRT and eleven (29.8%) with CF. Only 9 patients (33.3%) had symptoms prior to RT. Median SBRT dose and fraction was 50 Gy (range 25-60) and 3 (range 1-6) versus CF 30 Gy (range 20-55) and 10 (range 5-22) respectively. Toxicity was evaluated by CTCAE 4.0. Results: Median follow up was 16 months (range 1-102). Rates of radiographic local control with SBRT and CF were 92.3% vs. 55.4% respectively (p=0.0016). Under univariate analysis, predictors for radiographic LR were gross tumor volume (GTV) > 20 cc (p < 0.0001), planned tumor volume (PTV) of > 100 cc (p < 0.0001), and biologic effective dose (BED) < 70 Gy (p=0.0001). Subanalysis of CF demonstrated that a BED < 54 Gy was also a strong predictor for LR (p=0.0012). Under multivariate analysis, PTV was a strong predictor for radiographic LR (odds ratio [OR] = 42.2, p=0.0492). For the 9 symptomatic patients, 3 of 4 (75%) patients in the CF arm and 4 of 5 (80%) in the SBRT arm experienced partial or complete symptomatic relief. The median time to relief of symptoms in the SBRT and CF arms were 0.5 and 2 months, respectively. All patients receiving CF had symptomatic LR compared to none in the SBRT arm (p=0.0124). One patient in the SBRT arm had grade 2 hiccups and one with grade 2 pneumonitis in the CF arm. There were no other grade 2 toxicities or higher. Conclusions: SBRT demonstrated an encouraging local control rate and was capable of safely providing symptomatic relief to patients. The traditional view of radioresistance in RCC may not apply in the era of SBRT.
Place of short-term androgen deprivation therapy in intermediate-risk prostate cancer treated with radiotherapy: A phase III trial.
Authors: Nabid Abdenour , Carrier Nathalie , Vigneault Eric , Souhami Luis , Lemaire Céline , Brassard Marc-André , Bahoric Boris , Archambault Robert , Vincent François , Nguyen-Huynh Thu-Van 
Published: February 2017

5 Background: The place of short term androgen deprivation therapy (STADT) in combination with radiation therapy (RT) for patients with intermediate risk prostate cancer (IRPC) remains controversial. The purpose of this prospective, randomized trial was to compare outcomes between patients with IRPC treated with different doses of RT with or without STADT, (PCS III trial, Clinical Trials.gov, NCT00223145). Methods: From December 2000 to September 2010, 600 patients with IRPC were randomized to 6 months of STADT and two levels of prostate RT doses of 70 (arm 1) or 76 Gy (arm 2) versus prostate dose-escalated RT alone at 76 Gy (arm 3). STADT consisted of bicalutamide and gosereline for six months. RT (2 Gy per fraction) started four months after the beginning of STADT. Biochemical failure and disease-free survival (DFS) were primary end-points, with overall survival (OS) as secondary endpoint. DFS and OS rates were estimated with Kaplan-Meier and compared with log rank test and Cox regression. Results: Patient’s characteristics were well balanced among the 3 arms (median age 71 years, median PSA 10 ng/ml, median Gleason score 7). At a median follow-up of 75.4 months, biochemical failure occurred in 84 (14%) patients (arms 1 to 3: 12.5%, 8.0%, 21.5%) with statistical difference between arm 1 and 3 (p = 0.023) and arm 2 and 3 (p < 0.001). There was no significant difference between arm 1 and 2. A total of 113 (19%) patients had died with only 6 deaths (1%) attributed to prostate cancer. The 5-/10-year DFS rates were 93%, 97.5% and 86%, and 77%, 90% and 64.5%, respectively. Significant differences in DFS between the treatment arms were observed at 5 years but at 10 years it was observed only between arm 1 and 3 (p=0.01) and arm 2 and 3 (p<0.001). The 5-/10-year OS rates were 91%, 95% and 93%, and 64%, 70% and 78%, respectively. There was no statistical difference in OS between arms at 5 and 10 years. Conclusions: In patients with IRPC, the use of STADT in association with RT, even at lower doses, leads to a superior biochemical control and DFS as compared to dose-escalated RT alone. These outcomes did not translate into an improved OS. Source of Funding: AstraZeneca Pharmaceuticals Grant. Clinical trial information: NCT00223145.
Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype
Authors: Symmans W. Fraser , Wei Caimiao , Gould Rebekah , Yu Xian , Zhang Ya , Liu Mei , Walls Andrew , Bousamra Alex , Ramineni Maheshwari , Sinn Bruno , Hunt Kelly , Buchholz Thomas A. , Valero Vicente , Buzdar Aman U. , Yang Wei , Brewster Abenaa M. , Moulder Stacy , Pusztai Lajos , Hatzis Christos , Hortobagyi Gabriel N. 
Published: February 2017

Purpose To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)–targeted treatment. Methods We conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor–negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor–negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. Conclusion RCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated.
Barriers and facilitators of navigator-led advance care planning conversations in older patients with cancer.
Authors: Kvale Elizabeth Ann , Huang Chao-Hui , Niranjan Soumya J , Dionne-Odom J Nicholas , Kenzik Kelly , Bevis Kerri S. , Rocque Gabrielle Betty ,   The Patient Care Connect Group
Published: February 2017

17 Background: National guidelines and most individuals endorse advance care planning (ACP) as essential; however, few individuals engage in such planning. Little is known about the role of lay navigators in supporting ACP. We sought to understand facilitators and barriers of successful implementation of ACP conducted by lay cancer navigators. Methods: Semi-structured interviews were conducted with 26 lay navigators at 11 sites across the Southeast who were engaged in ACP implementation using Respecting Choices©. Interview topics included quality of ACP training, ACP conversation knowledge and comfort, barriers and facilitators, and perceived role in navigating patients with advanced cancer. Audio-recorded interviews were transcribed verbatim; thematic content analysis was conducted using NVivo 10 Software. Transcripts were reviewed for major themes and subthemes generated via line-by-line coding. Inter-rater agreement (2 primary coders) was assessed using Cohen’s Kappa ( = 0.81), indicating high agreement. Results: Navigators completed 672 ACP conversations across sites. Facilitators and barriers emerged across 3 domains: patient, navigator, and system domains. System facilitators included physician engagement and oncology-team consultation support while barriers included lack of time and space, lack of stakeholder support, and cultural suspicion. At the navigator level, established rapport was a necessary facilitator while personal discomfort and timing issues were barriers. At the patient level, prior experience with a family member was a facilitator while barriers included limited health literacy, fears, lack of readiness, and a “battle” mentality. Conclusions: Lay navigators can be trained to facilitate advance care planning conversations with cancer patients. Lay navigators identified several areas where additional training and infrastructure support might facilitate ACP in patients with advanced cancer. Future work should focus on designing and evaluating systems of healthcare delivery to support this activity.
Role of emergent palliative radiation therapy in the care of patients with cancer.
Authors: Singer Lisa , Zhang Michael , Braunstein Steve E. , Fogh Shannon E. 
Published: February 2017

201 Background: Radiation therapy (RT) provides an important role in the palliative care of patients with cancer. For patients with metastatic spinal cord compression not amenable to surgery, the value of timely palliative RT is well established; however, the value of the rapid application of RT for other chief complaints is less clear. The importance of palliative care service (PCS) involvement in patients treated with RT is becoming increasingly recognized and rapidly instituted RT could compromise this involvement. The purpose of this study was to assess the efficacy of emergent RT in alleviating symptoms in patients with cancer and to assess the extent of PCS in the management of patients treated with emergent RT. Methods: Patients treated with emergent RT were retrospectively identified through automated search of our institution’s radiation oncology electronic health record (EHR). Emergent RT was defined as treatment with RT in 48 hours or less from the time of simulation and flagged as emergent in the EHR by the radiotherapy team. Patients without a diagnosis of cancer were excluded from the study. For patients meeting inclusion criteria, data was collected regarding the chief complaint, completion of treatment, length of RT, and the primary outcomes of involvement of PCS and symptom relief. Results: From January to July 2015, 22 patients with cancer were treated with emergent RT. Prior to RT, 21 of 22 patients received other medical and/or procedural interventions. Sixty-four percent of patients were treated with 5 or fewer fractions and all but 2 patients completed RT. Symptoms improved in 73% of patients. PCS were involved in the care of 36% of patients. Conclusions: Emergent palliative RT provided symptom relief in the majority of patients; however, this study identified a lack of PCS involvement in the care of patients treated emergently. Study of long-term patient outcomes is needed. Future work should focus on developing clinical workflows that will better integrate involvement of PCS in the treatment of patients with palliative RT administered both emergently and non-emergently.