bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRCA carrier status as an independent prognostic factor associated with earlier biochemical relapse in local prostate cancer.
Authors: Castro Elena , Olmos David , Goh Chee Leng , Saunders Ed , Leongamornlert Daniel , Tymrakiewicz Malgorzata , Bancroft Elizabeth , Page Elizabeth , Dadaev Tokhir , Govindasami Koveela , Guy Michelle , Sawyer Emma , Wilkinson Rosemary , Ellis Steve , Frost Debra , Peock Susan , Antoniou Antonis C. , Easton Doug , Kote-Jarai Zsofia , Eeles Ros A. ,   UK Genetic Prostate Cancer Study and EMBRACE Collaborators
Published: March 2020

1545 Background: Biochemical relapse after local treatment for prostate cancer (PCa) indicates recurrent disease and is associated with shorter survival. Germline BRCA mutations are associated with worse PCa outcomes. BRCA carriers are currently treated with the same protocols used for non-carriers. We analyzed biochemical-progression free survival (bPFS) after conventional treatment for localized PCa in a cohort of BRCA patients (pts). Methods: In this retrospective case-control study, each BRCA carrier (9 BRCA1 and 34 BRCA2) treated with radical prostatectomy (RP) or external beam radiotherapy (RT) was matched with 3 non-carriers (NC) by age at diagnosis (±5 yrs), TNM stage, Gleason score, presenting PSA, local treatment , androgen-deprivation therapy (ADT) and year of treatment (±3 yrs). All NC were screened for BRCA1 and BRCA2 mutations. Biochemical failure was reviewed according to ASTRO and NCCN criteria. The Kaplan-Meier method and a multivariate Cox regression model adjusted by matching factors were employed. Results: 172 pts were included. Median follow-up was 76 months (ms). Median age at diagnosis was 58 yrs (43-75). Tumour stages were I 11%, IIA 19%, IIB 28%, III 28%, IV 14%. 80 pts received RT (18 BRCA2, 5 BRCA1, 57NC) and 85% also received ADT (70% for ≥6 months). 92 pts underwent RP (16 BRCA2, 4 BRCA1 and 72 NC), and 9% of them received ADT (<6months). Overall, median bPFS was 71ms. For those treated with RT, median bPFS was 65ms in NC vs 39ms in BRCA carriers (p=0.023). bPFS was not affected by ADT duration. Median bPFS after RP was 65ms in BRCA carriers. No difference was observed in 3yrs-bPFS between BRCA carriers and NC (73% vs 76%). The adjusted MVA confirmed the independent prognostic value of tumour stage (p=0.004) and BRCA status (p=0.032) for bPFS. Among BRCA carriers, the risk was greater when the analysis was limited to BRCA2 pts (p=0.013, HR 2.1,.95%CI 1.2-3.7). Conclusions: Our results suggest that BRCA carriers with PCa have worse local disease control than NC when treated with RT, regardless of ADT duration. No differences in bPFS were observed in pts treated with RP after >6 yrs median follow-up. These results may have implications for tailoring clinical management for these patients.
Public perception of cancer risk.
Authors: Burns Lisa , Kenny Ursula , Healy Laura , Cushen Samantha , O'Reilly Seamus , Ryan Aoife M , Power Derek Gerard 
Published: March 2020

1559 Background: The public’s knowledge of cancer risk factors has rarely been studied in Ireland. An understanding of this can help inform cancer prevention programs. Methods: An online surveywas used to assess the public’s perception of cancer risk. Results: 525 people completed the survey. Mean age was 40yrs (range:18-74), 82% were female and 36% had college degrees. 81% were concerned about developing cancer, however 20% believed if cancer was in their family there was nothing they could do about personal cancer risk. 20% did not know that cancer risk increased with age, 27% believed that >50% of cancers are inherited, and 54% believed 10-20% of cancers are inherited. The top 5 risk factors listed by respondents were: smoking 85%, diet 74%, alcohol 44%, genetics 38%, and environment 31%. Only 32% were aware that obesity is a risk factor for cancer and 33% did not think the location of fat was important for cancer prevention. When given a list of potential behaviours relevant to cancer risk 33% believed wearing a tight bra and 49% believed a blow to the breast could increase cancer risk. 87% believed genetics ‘strongly’ increased risk, 85% stress, and 86% believed cell phones increased risk. 12% believed ‘luck’ was important in avoiding cancer, 35% thought ‘detox’ diets and 61% believed organic food reduced risk. Only 33% agreed with the statement that ‘frozen vegetables/fruit are as good as fresh’, 40% were unaware of the link between red meat and cancer. The following foods were thought to increase risk: cheese (29%), soy (9%), milk chocolate (30%), red wine (25%), and eggs (11%). Aerosol use (71%), cleaning agents (73%), smoking (99%), cooking methods (68%), processed meat (86%), food irradiation (77%), and genetically modified foods (81%) were believed to increased risk. The majority were aware that berries, green tea, garlic, brassica vegetables and physical activity of 30 minutes a day can reduce cancer risk. Conclusions: There is a sizable portion of the population who are misinformed about cancer risk. Most are aware of classic risk factors (e.g. smoking, poor diet). Many overestimate risk attributable to genetics, environment, stress, and underestimate age, obesity and sunlight. One in 5 believes lifetime risk of cancer is non-modifiable.
On-line breath analysis of volatile organic compounds as a method for colorectal cancer detection.
Authors: Zambrana Tevar Francisco , Herrero Ana , Vidal-de-Miguel Guillermo , Bailador Gonzalo , Criado Ernesto , Marquina Isabel , Sanchez-Avila Carmen , Sereno Maria , Gomez Raposo Cesar , Lopez-Gomez Miriam , Merino Maria , Aguayo Cristina , Alvarez-Gallego Mario , Erdozain Jose Carlos , Comas Carmen , Mancenido Noemi , Feliu Jaime , Garcia Damian , Casado Enrique 
Published: March 2020

1570 Background: Analysis of exhaled volatile organic compounds (VOCs) in breath is an emerging approach for cancer diagnosis, but little is known about its potential use as a biomarker for colorectal cancer (CRC). We investigated whether a combination of VOCs could distinct CRC patients from healthy volunteers. Methods: In a pilot study, we prospectively analyzed breath exhalations of 38 CRC patient and 43 healthy controls all scheduled for colonoscopy, older than 50 in the average-risk category. The samples were ionized and analyzed using a Secondary ElectroSpray Ionization (SESI) coupled with a Time-of-Flight Mass Spectrometer (SESI-MS). After a minimum of 2 hours fasting, volunteers deeply exhaled into the system. Each test requires three soft exhalations and takes less than ten minutes. No breath condensate or collection are required and VOCs masses are detected in real time, also allowing for a spirometric profile to be analyzed along with the VOCs. A new sampling system precludes ambient air from entering the system, so background contamination is reduced by an overall factor of ten. Potential confounding variables from the patient or the environment that could interfere with results were analyzed. Results: 255 VOCs, with masses ranging from 30 to 431 Dalton have been identified in the exhaled breath. Using a classification technique based on the ROC curve for each VOC, a set of 9 biomarkers discriminating the presence of CRC from healthy volunteers was obtained, showing an average recognition rate of 81.94%, a sensitivity of 87.04% and specificity of 76.85%. Conclusions: A combination of cualitative and cuantitative analysis of VOCs in the exhaled breath could be a powerful diagnostic tool for average-risk CRC population. These results should be taken with precaution, as many endogenous or exogenous contaminants could interfere as confounding variables. On-line analysis with SESI-MS is less time-consuming and doesn’t need sample preparation. We are recruiting in a new pilot study including breath cleaning procedures and spirometric analysis incorporated into the postprocessing algorithms, to better control for confounding variables.
Study KBP-2010-CPHG: Characteristics and management of 7,051 new cases of lung cancer managed in French general hospitals in 2010.
Authors: Locher Chrystele , Herman Dominique , De Faverge Geoffroy , Barbieux Hubert , Lemonnier Christine , Hakim Khaldoun , Debieuvre Didier , Gury Jean-Pierre , Marcos Jean-Michel , D Arlhac Michel , Ferrer Lopez Pablo , Hauss Pierre-Alexandre , Raffy Olivier , Paganin Fabrice , Huchot Eric , Auliac Jean-Bernard , Martin Francis , Zureik Mahmoud , Blanchon Francois , Grivaux Michel 
Published: March 2020

1574 Background: An initial epidemiologic study was performed in 2000 by the French College of General Hospital Respiratory Physicians (Study KBP-2000-CPHG). Over the last 10 years, lung cancer management changed: new drugs such as targeted therapies appeared; new diagnostic techniques such as exploration for genetic mutations in the tumour have been developed; a new TNM classification has been drawn up. The aims of this study were to describe patient characteristics, first-line management, 1, 4 and 5-year survival rates and to compare the results with those of Study KBP-2000-CPHG. Methods: A prospective multi-centre study included all patients ≥18 years presenting with a new case of primary lung cancer, histologically or cytologically diagnosed between 1 January and 31 December 2010 and managed by one of the participating centers. A standardised form was completed for each patient. A steering committee checked the exhaustivity of data’s collection. Results: 7,610 patients from 119 general hospitals were included between 1 January and 31 December 2010. The main patient characteristics were: mean age 65.5 years (+/-11.3); 24.3% female; 10.9% non-smokers, 39.9% ex-smokers, 49.2% current smokers; 68.9% performance status 0 and 1; 9.1% of patients had lost >10 kg within the previous 3 months. The main tumour characteristics were: 13.7% small-cell lung cancer; 46.2% adenocarcinoma, 26.8% squamous-cell carcinoma; EGFR mutation, explored in 30.5% of cases, were found in 10.5% of cases; 16.4% stage IA to IIB, 13.4% stage IIIA, 10.2% stage IIIB and 60.0% stage IV. First-line treatments were: curative surgery, 16.6%; chemotherapy, 63.4%; radiotherapy alone, 17.8%; combined radio-chemotherapy, 8.8%; and supportive care, 11.1%. Targeted therapy was used in 6.6% of patients treated by chemotherapy. Conclusions: In 10 years, characteristics of lung cancer patients changed with an significantly increase of women, non-smokers, adenocarcinoma histology and stage IV at diagnosis.
The influence of prognostic factors on metastatic breast cancer survival over time.
Authors: Rosenzweig Margaret Quinn , Jung Su Yon , Brufsky Adam 
Published: March 2020

1589 Background: Recent evidence suggests that survival in metastatic breast cancer is slowly improving associated with the use of better adjuvant and metastatic chemotherapeutic and targeted agents. Patient and clinical factors such as age, estrogen status, non-white race, Her 2 status, disease free interval and sites of metastatic breast cancer involvement indicate worse clinical outcome after recurrence. This analysis focused on the influence of these factors on metastatic breast cancer survival over time. Methods: Subjects were women with metastatic breast cancer from one large urban practice, of the University of Pittsburgh Cancer Institute Breast Cancer Program followed from 1999 through December, 2008. Patients were dichotomized into two time categories: A) 1999 through 2004 and B) 2005 through 2008. Outliers of long term survivors (n =72) with survival extending beyond 6 years were excluded. Log rank tests were conducted for assessing the relationship between prognostic factors and survival. Results: Cohorts included patients diagnosed with metastatic breast cancer in 1999 through 2004, (n=284) and 2005 through 2008, (n=332). They were followed up to December, 2011. Median survival improved over time (p=0.053). Estrogen negativity remained significant for worse survival across both time periods (p<0.0001). Age, presence of brain metastasis and Her 2 status were not significant for influence on survival at either time interval. Shorter disease free interval (p= 0.02), higher number of metastatic sites (p=.001) and presence of visceral metastasis at diagnosis (p=0.003) became significant for worse survival in the 2005-2008 intervals but had not been in the earlier time period. African American race was highly significant (<0.001) for worse survival in 1999-2004 but lost significance in 2005 through 2008 with dramatic survival increase (median survival - 12.5 months to 35 months). Conclusions: It is important for clinicians to clarify the prognostic features associated with worse outcomes in metastatic breast cancer. With newly emergent therapies and sensitivity toward specific patient factors these features evolve over time.
Effect of sunlight exposure on survival in patients with lymphoma: Results from the prospective Singapore Lymphoma Study.
Authors: Lee Yin Leng , Tay Kevin , Lim Soon Thye , Tan Soo Yong , Tao Miriam , Quek Richard Hong Hui , Tan Leonard , Ha Tam Cam 
Published: March 2020

1593 Background: Recently, several studies evaluating the effect of ultraviolet light exposure on the risk of developing lymphoma have yielded conflicting results, in part due to seasonal and latitude variation. Further, most of these studies also lack long term follow up and could not systemically address the influence of sunlight exposure on survival. In this prospective, epidemiological study, we explored the relationship between past sunlight exposure and survival in lymphoma patients in tropical Singapore, where sunlight exposure is constant throughout the year. Methods: Singapore Lymphoma Study was established in 2005. A total of 384 patients with histologically confirmed lymphoma were followed from date of diagnosis through November 2011. Interviewers were trained to conduct in-person interviews to collect detailed information, including every occupational period that lasted at least 1 year and number of hours worked outdoor from 9am to 5pm using a structured questionnaire. Descriptive, multivariate and survival analysis (Kaplan Meier; age, gender, race and education level adjusted) were performed. Results: Among all lymphoma subtypes, the most prevalent was diffuse large B cell lymphoma, 47.7%, followed by Hodgkin lymphoma, 14.6%, follicular lymphoma, 12.2% and T cell lymphoma, 6.5%. 97.1% had black or brown eye color and 49.6% had fair skin. Overall survival of lymphoma and NHL subtype decreased significantly with increasing lifetime occupational hours (ptrend=0.01 and 0.03). Chinese was associated with longer survival with increasing daily sunlight exposure during childhood and adolescent years, whether at school or outdoor leisure (ptrend=0.04) and there were no evidence for non-Chinese (Malays or Indians). Patients with lighter eye color results in shorter survival (HR=2.91, 95% CI: 1.15-7.34, p=0.02). Conclusions: We found leisure sunlight exposure during childhood and adolescent years to be beneficial to the survival of Chinese lymphoma patients and increasing lifetime cumulative occupational exposure is associated with increasing risk of death. This data contributes to the growing research on the effects of sunlight exposure on lymphoma patients.
The evolution of breast cancer screening in the Medicare population: Clinical and economic implications.
Authors: Killelea Brigid K. , Long Jessica B. , Ma Xiaomei , Wang Rong , Chagpar Anees B. , Ross Joseph , Gross Cary P. 
Published: March 2020

1595 Background: Breast screening has evolved as newer approaches to mammography, ultrasound, and MRI have diffused into clinical practice. The use of these technologies and their impact on screening-related costs and outcomes remain undefined, particularly among older women. Methods: Using the Surveillance Epidemiology and End Results – Medicare linked database, we identified women aged 66 and older without a diagnosis of breast cancer. We constructed two cohorts (2001 vs. 2006) and followed each for two years. We assessed changes in imaging technology, screening-related costs (defined as costs for screening and subsequent imaging and testing, adjusted to 2009 USD), and stage at diagnosis between the two cohorts. Results: There were 136,845 women in the 2001-2002 (earlier) cohort and 137,733 in the 2006-2007 (later) cohort. The mean age was 76.9 and 77.2 respectively, (p<.001). The proportion of women receiving any screening mammogram was 42.5% in the earlier cohort and 43.4% in the later cohort, (p<.001). The use of digital mammography for screening increased from 2.2% to 15.0%, (p<.001). The use of any computer aided detection (CAD) increased from 3.2% to 29.3% (p<.001). MRI use increased from 0.03% to 0.2%, and ultrasound use from 4.0% to 4.5% (p <.001 for both). Average screening-related cost increased 31%, from $101 to $132 (p<.001). There was no significant difference in early stage at diagnosis over time (58.1% of women were in situ/stage I in early period vs. 57.2% in later period, p=.65). Conclusions: The use of digital mammography and CAD increased substantially between 2001 and 2007, contributing to a 31% increase in screening-related costs for women in the Medicare program. The increased cost of screening and downstream testing must be evaluated in context of an absence of benefit in terms of stage at diagnosis.
A revised RTOG recursive partitioning analysis (RPA) model for glioblastoma based upon multiplatform biomarker profiles.
Authors: Chakravarti Arnab , Wang Meihua , Aldape Kenneth D. , Sulman Erik P. , Bredel Markus , Magliocco Anthony M. , Klimowicz Alexander C. , Hegi Monika , Stupp Roger , Gilbert Mark R. , Curran Walter J. , Werner-Wasik Maria , Mahajan Anita , Schultz Christopher J. , Mehta Minesh P. 
Published: March 2020

2001 Background: The Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) model, which relies on clinical variables, has been used worldwide to establish distinct prognostic classes of patients (pts) with malignant glioma as well as eligibility criteria for clinical trials. In the present study, we have updated the RPA to include additional molecular variables, specifically for glioblastoma (GBM) patients treated in the temozolomide (TMZ)-era, to make the model more relevant, contemporary, and discriminatory. Methods: The dataset utilized was from RTOG 0525, a phase III study examining radiation (RT) with concurrent TMZ, followed by adjuvant standard dose vs. dose-dense TMZ in pts with newly-diagnosed GBM. 162 pts from RTOG 0525 had available tissues for profiling of key signaling molecules using the AQUA platform. Results: pAKT, c-met, and MGMT protein were each found to be significantly associated with adverse outcome on multivariate analysis. These variables were combined with clinical and genetic biomarkers (e.g., MGMT promoter methylation, IDH1 mutation, mRNA profiling) previously found to be of significance (MCP model, ASCO, 2011) to generate an even more robust, discriminatory RTOG RPA model. The explained variation for these three classification models was found to be 41.7 (Current RPA), 19 (MCP), and 14.9% (Clinical RPA), respectively, with higher values indicating better separation of prognostic groups (see table). Conclusions: The current RTOG RPA classification model, based upon incorporation of multi-platform biomarker analysis, holds promise for RT+TMZ-treated GBM patients; further validation of this model is planned. Financial Support: NCI grants U10 CA21661, U10 CA37422, U24 CA114734, 1RC2CA148190, 1RC2CA148190, RO1CA108633, and BTFC grant. [Table: see text]
The NFκB pathway as a key mediator of the glioblastoma mesenchymal subtype in glioblastoma stem cells and human tumors.
Authors: Vaillant Brian D. , Bhat Krishna , Sulman Erik P. , Balasubramaniyan Veerakumar , Ezhilarasan Ravesanker , Aldape Kenneth D. , Colman Howard 
Published: March 2020

2002 Background: The mesenchymal (MES) subtype of glioblastoma (GBM) is associated with worse prognosis and increased treatment resistance. Several transcription factors driving the MES phenotype have been identified, including STAT3, CEBP-β, and WWTR1/TAZ. However, the key signaling pathways driving this transcriptional program remain unknown. Methods: Expression profiling analyses was performed on multiple GBM stem cell (GSC) lines derived from individual human tumors. Three large GBM tumor gene expression datasets (TCGA, Rembrandt, Erasmus) were also used in the analyses to identify pathways activated in MES tumors and GSCs. Intracranial GSC xenograft models were used for in vivo validation. Results: We found that GSCs with a MES phenotype also demonstrated upregulation of a gene cassette associated with NFκB activation. Analysis of multiple large expression data sets also demonstrated a tight correlation between the MES phenotype and NFκB activation in human tumors. To determine the effect of NFκB activation in GSCs, we stimulated NFκB by addition of the inflammatory cytokine TNFα. This was accompanied by increased expression of the MES transcription factors (STAT3, CEBP-β, TAZ), and MES markers including CD44. Conversely, blockade of NFκB signaling in GSCs by IκB-α was sufficient to prevent TNF-induced MES transition. Investigation of potential source of NFκB activation suggested a role of microglia. Indeed, addition of supernatant from activated microglia was sufficient to activate NFκB and MES transition in GSCs that could be blocked by IκB-α. To test the role of microglia and NFκB activation on treatment resistance in vivo, treatment with minocycline, an inhibitor of microglia activation, led to a reduction of tumor grade and down-regulation of MES markers in intracranial GSC xenografts. Conclusions: NFκB appears to play an important role in induction of the MES phenotype in GBM and GSCs. Furthermore, activation of microglia is a potential source of NFκB activation in these tumors. These data suggest that blockade of NFκB and/or inhibition of microglia activation may be attractive therapeutic approaches for downregulating MES transition and overcoming treatment resistance in GBM.