bluuebunny/crossref_metadata_2025_split huggingface dataset:
Landscape of genetic alterations in oropharyngeal squamous cell carcinoma (OPSCC) based on RNA-seq and WES analysis of FFPE samples and correlation with data from TCGA.
Authors: Seby Sandra , Rossi Michael R. , Magliocca Kelly R. , Patel Mihir , Griffith Christopher C , Steuer Conor Ernst , Wang Xu , El-Deiry Mark , Shin Dong Moon , Kowalski Jeanne , Chen Zhuo Georgia , Saba Nabil F. 
Published: September 2018

e17527 Background: Whole human exome sequencing (WES) has identified well characterized somatic mutations (such as TP53, CDKN2A, PIK3CA and HRAS) in patients with squamous cell carcinoma of the head and neck (SCCHN). We sought to optimize a combined RNA-seq and WES approach for identifying actionable mutations and gene expression signatures in p16 + versus - OPSCC. Methods: Relying on formalin fixed and paraffin embedded (FFPE) samples we applied a minimal mutation and copy number content (151 genes) on DNA and an extensive RNA panel on a total of 27 OPSCC (22 p16 +, and 5 p16 -). SAMSeq was used to identify the differentially expressed genes. Unsupervised hierarchical clustering of the TCGA OPSCC samples with available p16 status (n = 31) was performed for external validation of the results. Statistical significance was further tested by Fisher’s exact test. Results: We identified a gene signature differentially expressed in p16+ and p16- OPSCC. External validation showed a significant association between gene expression and p16 status (P = 0.00033). We did not however find an association with mutation burden and smoking history. A number of pathways associated with this gene signature such as NCAM1 may have relevant biologic implications in OPSCC. Conclusions: Our results underscore the reliability of integrating data from FFPE samples in distinguishing gene signatures characteristic of p16 + versus p16- OPSCC; these signatures need to be further explored for their biologic relevance in OPSCC (This research was supported by a grant NCI R21 CA182661-01A1to NFS and GZC).
Treatment response and prognosis according to pre and post treatment Ebstein-Barr virus DNA level in nasopharyngeal carcinoma patients.
Authors: Ahmedova Aysel , Ozkaya Kubra , Tambas Makbule , Gezer Ugur , Ozgur Emre , Sahin Dilek , Sanli Yasemin , Altun Musa 
Published: September 2018

e17544 Background: To evaluate pre and post-treatment Epstein-Barr virus (EBV) DNA copy numbers, to investigate changes with treatment and the possibility of using it as a follow-up marker in nasopharyngeal carcinoma (NPC) patients. Methods: Blood samples were obtained before (0-3 weeks) and after treatment (mean 6 weeks) and number of EBV DNA copies were determined by PCR . Treatment was administered as concomittant chemoradiotherapy ± induction chemotherapy. MRI and PET-CT were performed prior (0-4 weeks) and after (6-16 weeks) treatment. Mann Whitney test was used for 2 group comparisons of parameters with no normal distribution and comparison of quantitative data. Fisher-Freeman-Halton and Wilcoxon Signed Ranks tests were used for comparison of qualitative data and intra-group comparison of parameters with non-normal distribution. Kaplan Meier Survival analysis was used to assess survival. Results: The study included 50 NPC patients treated between 2011 and 2015. Median follow-up is 25.3 (27.5 ± 14) months. 12 patients had residual-recurrent or metastatic (3 patients initially had distant metastasis) disease. Mean survival is 49.77 ± 2.4 months. Median posttreatment EBV DNA level is lower than pretreatment EBV DNA level (p = 0.001). Pretreatment EBV DNA copy numbers are higher in patients with residual-recurrent or metastatic disease (RRM) than those without RRM (p=0.05). Mortal patients had higher pre (p = 0.015) and post (p = 0.043) treatment EBV DNA levels than those who survived. Overall survival (OS) is higher in patients with undetectable (n:41) than those with detectable (n:9) EBV DNA levels after treatment (p = 0.02). Conclusions: The OS is lower in patients with higher pretreatment and detectable posttreatment EBV DNA levels. This study implies that pre and post treatment serum EBV DNA levels can be used as prognostic indicators and also be beneficial as a follow up marker in NPC patients. [Table: see text]
Acute kidney injury in head and neck cancer patients treated with chemoradiation with cisplatin: A single-center cohort study.
Authors: Meerten Esther Van , Owusuaa Catherine , Hoorn Ewout , De Hoop Esther Oomen 
Published: September 2018

e17559 Background: Patients with advanced head and neck cancer (HNC) are commonly treated with chemoradiation with concomitant cisplatin. Acute kidney injury (AKI) is considered a dose-limiting toxicity of cisplatin. We aim to describe the incidence and risk factors of AKI. Methods: In our tertiary center, we retrospectively identified 261 patients with advanced HNC and adequate renal function who were treated curatively from 2008 to 2015 using radiotherapy and concurrent three-weekly cisplatin. Outcome was the first AKI episode, defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines as a ≥50% rise in serum creatinine compared to baseline. Several potential predictors were investigated by means of logistic regression analyses. Results: In our cohort (mean age 58 ± 8 years, 74.3% male), a total of 102 (39.1%) patients developed AKI. Factors significantly associated with AKI in the univariate analysis were: age, alcohol consumption, excessive smoking, diabetes, hypertension, diuretic use, renin-angiotensin-aldosterone-system blockers, and administration of furosemide when indicated during first cisplatin cycle. In the multivariable model smoking 6-25 and > 25 cigarettes per day (OR 1.85; 95% CI 1.01-3.39 and OR 3.22; 95% CI 1.34-7.70, respectively), diabetes (OR 2.58; 95% CI, 1.01-6.61), furosemide (OR 2.39; 95% CI, 1.36-4.18) , and hypertension (OR 2.79; 95% CI, 1.52-5.12) remained independent risk factors for AKI. Conclusions: The identified risk factors smoking, diabetes, and hypertension may have caused pre-existing kidney damage and therefore have predisposed to AKI. Co-administration of furosemide with cisplatin is a potentially reversible risk factor for AKI.
Change of surgical procedure for thyroid tumor after collaboration with Nagasaki (Japan) and Semipalatinsk (Kazakhstan).
Authors: Maeda Shigeto , Adylkhanov Tasbolat 
Published: September 2018

e17590 Background: From 1949 to 1989, 456 nuclear tests were conducted by the former Soviet Union at the Semipalatinsk Nuclear Test Site (SNTS) in Kazakhstan. It is very important to assess the clinical behavior of thyroid cancer which may be affected by SNTS in the control of an accurate diagnosis and standardized surgery. We have collaborated with the Semipalatinsk Oncology Center since 1999, in order to establish an optimal method to diagnose and perform a thyroidectomy and a lymph node dissection for the patients with papillary thyroid cancer that is better suited for the Semipalatinsk environmental effects. Methods: To assess the change of diagnostic accuracy and thyroid surgery from 1999 to 2010 in Semipalatinsk Oncology Center in collaboration with Nagasaki University and Nagasaki Medical Center. Material: A total of 200 patients with thyroid cancer who underwent thyroid surgery at the Semipalatinsk Oncology Center were evaluated. From the 200 patients, 145 patients with papillary thyroid cancer were assessed for surgical procedure. This was a cross-sectional observational study. Results: 1) Before 2001, there were few preoperatively diagnosed thyroid cancers and from 2002, preoperatively diagnosed papillary cancers increased. 2) The partial lobectomies were mainly performed until 2001. From 2002 to 2010, total lobectomies were chosen for the majority of the patients, but total thyroidectomies were rarely performed. 3) Up to 2014, there are no local and distant metastasis were seen in those patients with papillaty cancer. Conclusions: An accurate diagnosis and standardized surgery for thyroid cancer helped to evaluate the biological characteristics of thyroid cancer which may be affected by SNTS in next decade.
Evaluation of the quality of cancer treatment in a population of patients (pts) with metastatic colorectal cancer (mCRC) in routine clinical practice in different regions of Russia.
Authors: Fedyanin Mikhail , Aliyeva Shamai , Vladimirova Liubov Yu , Erdniev Sanal , Ivanov Alexander , Katkov Alexey , Kulik Valeriy , Kuzmina Evgeniya , Matyushina Elena , Nikitina Larisa , Orlova Rashida , Povyshev Anton Yurievich , Pshevlotskiy Eduard , Ramazanova Madina , Shalofast Olga , Smirnova Elena , Tkachuk Alexandra , Ulanova Natalya , Tjulandin Sergei 
Published: September 2018

e18022 Background: In Russia, there are no federal screening programs for detecting early stage of colon cancer; therefore we can assess the impact of various factors that could potentially affect the mortality of pts with mCRC Methods: We conducted a survey with 13 question according treatment of pts with CRC in 17 regional comprehensive cancer centers in 14 regions of Russia, with a total population of 26.347 billion. Results of the survey were conducted by methods of descriptive statistics. Effects of factors on mortality rate in regions were analyzed by a regression model Results: Only 34% pts with stage II-III received adjuvant chemotherapy. Mutation status of KRAS gene has been evaluated only in 33% pts with mCRC. In 2013, metastasectomy was performed only 13% of pts. Only 80% of pts who needed systemic treatment received chemotherapy (CT): doublets of CT (XELOX/FOLFOX/FLOX or FOLFIRI/XELIRI/IFL) - 49%, monotherapy of fluoropyrimidines - 39% of pts, bevacizumab – in 14% and anti-EGFR antibodies - 5% pts. Only 14% of pts with mCRC was placed central vein devices. Second line CT was performed in 47% pts: doublets – in 54%, monotherapy of fluoropyrimidines - in 24% pts, bevacizumab - 13% and anti-EGFR antibody - 8%. Third-line treatment was performed in 25% of pts: anti-EGFR antibodies - in 7.5%. According to regression analysis adjuvant chemotherapy (р = 0.01), bevacizumab only in the 1st line (р = 0.01), and installation of central venous devises (р = 0.07) and anti-EGFR antibody in the 1st line (р = 0.1) in wtKRAS pts had independent positive effect on the mortality rate in regions. We revealed a significant reverse connection between a high mortality rate in the region and administration of fluoropyrimidine monotherapy as 1st line treatment of metastatic disease (p = 0.01) Conclusions: The mortality with colorectal cancer is depended of complex factors that reflect the health care organization in the region, both at the stage of treatment of pts with early-stage and metastatic disease. We revealed that targeted agents are the most effective only in the 1st line settings.
Predictors of treatment attrition in patients with metastatic colorectal cancer (mCRC).
Authors: Bahrabadi Arvin , Ruan Jenny , Gresham Gillian , Cheung Winson Y. 
Published: September 2018

e18041 Background: Although the treatment landscape of cancer has evolved significantly with the introduction of novel and more efficacious drugs, the positive impact of these new therapies may be limited by attrition and ultimately non-exposure to later lines of therapy. Using a population-based cohort of mCRC, our aims were to characterize rates of attrition and determine factors associated with failure to receive each line of treatment. Methods: Medical records of patients who were diagnosed with mCRC from 2008-10 and referred to any 1 of 5 cancer centers in British Columbia were merged with systemic therapy data from the provincial pharmacy database. We classified patients into mutually exclusive treatment categories: a) receipt of all available lines of mCRC therapies; b) attrition directly attributable to disease, such as cancer progression or death; c) attrition attributable to other clinical factors, including toxicity, and d) attrition secondary to non-clinical factors, including personal/social circumstances. Multivariate logistic regression models were constructed to identify predictors. Results: We identified 525 eligible mCRC patients: median age 64 years, 57% men, 55% Caucasian, 68% ECOG 0/1, 41% and 35% never and ever smokers, respectively. The attrition rate was 40% (95% confidence interval [95% CI], 36%-44%) for first line treatment, 25% (95% CI, 19%-31%) for second line treatment and 14% (95% CI, 5.5%-22.5%) for third line. While cancer progression (31%) and chemo toxicity (30%) were the most common causes of attrition, other frequent reasons included death (20%) and patient preference (14%). On multivariable analysis, first-line treatment attrition was associated with worse baseline ECOG (odds ratio [OR], 1.92; p < 0.001) and older age at diagnosis of mCRC (OR, 1.04; p < 0.001). When we examined attrition over all lines, it was significantly correlated with worse ECOG (OR, 2.44; p < 0.001). Conclusions: Treatment attrition is a prevalent problem in mCRC and can hinder the benefits that would otherwise be possible with a sequential treatment algorithm. Some causes of attrition are potentially modifiable and may reflect opportunities for patients to maximize exposure to all lines of therapies.
The use of cardiovascular disease states as exclusion criteria in breast cancer trials: A 4-decade perspective.
Authors: Oren Michal , Oren Ohad , Mintzer David M. 
Published: September 2018

e18053 Background: At the time of diagnosis, patients with breast cancer have a higher prevalence of cardiovascular risk factors than the general population. It is likely that the prevalence of actual cardiac disease is also increased, although no published data is available to support this claim. Individuals with breast cancer who also have heart disease are typically disqualified from clinical trials. We attempted to define the evolution of cardiovascular exclusion criteria in clinical trials of breast cancer over the decades. Methods: We searched the NEJM for original research in “breast cancer” published from 01/1980 to 12/2016. We reviewed the nature of cardiovascular disease as exclusion parameters as well as trends over time. Results: 20 RCTs were analysed, 5 from each decade (total # of patients 21,231). Mean number of cardiac exclusion criteria per study increased over the decades (1980s: 0; 1990s: 0.2; 2000s: 1; 2010s: 7). The most common cardiac exclusion criteria were CHF and recent MI (35% and 25% of studies, respectively). Factors associated with a higher likelihood of having a cardiac exclusion criteria were source of funding (industry vs. university: 77.7% vs. 18.1%, P-value 0.005) and study’s country of origin (U.S versus non-U.S: 57.1% versus 16.6%, P-value 0.02). Prior to 2010, the complete list of exclusion criteria was available with the manuscript. From 2010, it became embedded within the study’s protocol file (and not printed). Cardiovascular AEs were infrequent (1980s: 0.02%; 1990s: 0%, 2000s: 0.08%; 2010: 0.29%). Before 2000, studies described the significant cardiac toxicity in the manuscript. After 2000, a comprehensive registry of AEs contained within supplementary files became the norm. Conclusions: The use of cardiovascular exclusion criteria in clinical trials in breast cancer has become common over the past decades. Currently, it is almost impossible for a woman to enter a trial with even a single cardiac condition. Given that a sizeable fraction of breast cancer patients has cardiac disease, consideration should be given to narrowing the scope of cardiac exclusion criteria to allow more patients to participate, while making the results of those trials more broadly generalisable.
Treatment, outcomes, and impact of racial disparities on young adults with pancreatic cancer.
Authors: Alese Olatunji Boladale , Jiang Renjian , Shaib Walid Labib , Wu Christina Sing-Ying , Behera Madhusmita , El-Rayes Bassel F. 
Published: September 2018

e18069 Background: Pancreatic cancer is a disease of the elderly. The treatment and outcomes of young adults with pancreatic cancer has not been well studied. The aim of this study is to describe the treatment, outcomes, and impact of race in young adults with pancreatic cancer. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2013. Univariate and multivariate testing was done to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between patient characteristics, time intervals and survival. Results: A total of 9,657 patients between 18 and 50 years of age were identified. The mean age was 45.4 years (SD±4.6), with a male preponderance (58.3%). Distribution across stages I-IV was 6.1%, 31.1%, 13.9% and 48.8% consecutively, and was similar across all racial groups. About 30.9% of patients underwent resection of the primary pancreatic tumor. Univariate analysis showed survival difference between ages 18-34 vs. 35-50 years old (HR 0.81; 0.71-0.92; p<0.001). On multivariable analysis, Hispanics had significantly higher survival rates than non-Hispanic Whites (NHW) (HR 0.7; 0.64-0.76; p<0.001). Compared to Blacks, Hispanics were more likely to benefit from surgical resection (HR 0.76; 0.61-0.94; p=0.011) and chemotherapy administration (HR 0.78; 0.69-0.88; p<0.001). Overall, patients treated between 2009 and 2013 had higher survival rates compared to 2004-2008 (HR 0.86; 0.82-0.91; p<0.001). The improvement in 5-year overall survival rates over time was highest in American Indians and Asian/Pacific Islanders (16.6% vs. 6.5%); Blacks (10.6% vs. 8.5%) and Hispanics (14.5% vs. 12.6%). NHWs marginally improved from 8.4% to 9.8%. Conclusions: Survival in pancreatic cancer patients younger than 50 years has improved over time, with major gains in minority populations. [Table: see text]
Surgeon influence on receipt of contralateral prophylactic mastectomy for breast cancer.
Authors: Katz Steven J. , Morrow Monica , Hawley Sarah T. , Jagsi Reshma 
Published: September 2018

e18145 Background: Rates of contralateral prophylactic mastectomy (CPM) have markedly increased but virtually nothing is known about the influence of surgeons on variability of the procedure in the community. We quantified the influence of attending surgeon on rates of CPM and clinician attitudes that explained it. Methods: Population-based sample of 7810 patients newly diagnosed with curable breast cancer (BC) in Georgia and Los Angeles County treated in 2013-15 were surveyed (response rate 70%, n = 5018) and responses were linked to 488 attending surgeons through patient report. Surveys were sent to surgeons towards the end of the patient data collection period and 377 completed them (response 77%). We linked 3718 respondent patients with unilateral disease to 365 respondent surgeons. Two surgeon attitudes scales were developed based on a scenario of a patient with early stage BC at average risk of a 2nd primary cancer: 1) favors initial breast conservation and, 2) reluctance to perform CPM if patient asks. We did multilevel analyses using information from patient and surgeon reports merged to SEER data. Results: A model including patient clinical factors and surgeon id predicted CPM extremely well as it explained 37% of the variability in the likelihood of CPM. Patient factors explained 16% of the variability but the surgeon identifier alone explained even more (21%). The odds of a patient receiving CPM increased 3-fold (95% CI 1.9, 4.7) if she saw a surgeon with a practice approach one standard deviation above a surgeon with the average CPM rate (15%). One quarter (24%) of the surgeon influence was explained by attending attitudes about initial recommendations for surgery and responses to patient requests for CPM. The rate of CPM was 34% for surgeons who least favored initial breast conservation and were least reluctant to perform CPM. By contrast, the estimated rate was 5% for surgeons who most favored initial breast conservation and were most reluctant to perform CPM if asked. Conclusions: Attending surgeons exert strong influence on the likelihood of receipt of CPM for breast cancer. Variations in surgeon attitudes about recommendation for surgery and response to patients request for CPM explain a substantial amount of this influence.
The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) in daily practice: A real-life feasibility analysis at the Medical University Vienna.
Authors: Kiesewetter Barbara , Raderer Markus , Steger Guenther G. , Bartsch Rupert , Pirker Robert , Zochbauer-Muller Sabine , Prager Gerald W. , Krainer Michael , Preusser Matthias , Schmidinger Manuela , Fuereder Thorsten , Marosi Christine , Locker Gottfried J. , Brodowicz Thomas , Zielinski Christoph 
Published: September 2018

e18151 Background: The ESMO-MCBS constitutes a new tool to quantify the clinical benefit that may be anticipated from a novel anticancer treatment based on original data from randomized or controlled trials. In contrast to comparable concepts, this score appears somehow unique as it concentrates on the clinical benefit for the individual patient irrespective of socioeconomic factors. Being introduced 2015; the MCBS has excited great public interest in Europe in the last year. We present here the first feasibility analysis of the MCBS under real-life conditions at the Medical University Vienna (MUV), one of Europe’s largest centers. Methods: This study evaluated systematically the practicability of the MCBS for advanced/metastatic malignant diseases treated at the MUV ( > 15 tumor entities). A 3-step approach including data analysis of regimens in regular use, assessment of scores (1 = not recommended to 5 = highly recommended) and evaluation of results with a focus on clinical feasibility was applied. Results: In the majority of tumor entities and clinical settings the assessed MCBS scores were consistent with our daily practice and particularly with our 1st line standards for common tumors like metastatic breast-, colorectal- or lung cancer. However, there were certain limitations including orphan diseases with a lack of randomized data (e.g. rare sarcoma subtypes) or tumor entities with cascade like treatment settings (e.g. colorectal cancer). Interestingly, new immunomodulatory approaches and checkpoint inhibitors in particular, scored strikingly high in comparison to conventional chemo due to a favorable toxicity profile, positive influence on quality of life and strong efficacy data in many cases. A broad selection of data will be presented at the meeting. Conclusions: Our analysis encompasses a wide range of tumor entities and clinical settings and reflects the daily experience of a university clinic. Mostly, the MCBS scores supported treatment decisions based on the clinical benefit to be expected from a novel therapy and might also support socioeconomic questions exemplified by high scoring of immunomodulatory approaches.