bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of CEP72 rs924607 with vincristine-induced peripheral neuropathy (PN) in patients with diffuse large B-cell lymphoma on CALGB 50303 (Alliance).
Authors: Hertz Daniel Louis , Larson Nicholas Bradley , Pierpont Timothy , Bartlett Nancy L. , Zelenetz Andrew David , Wilson Wyndham Hopkins , Leonard John Paul , Jung Sin-Ho , Riska Shaun M. , Richards Kristy L. 
Published: May 2020

e13535 Background: Pediatric patients (pts) receiving long-term vincristine treatment for acute lymphoblastic leukemia (ALL) who carry two variant alleles of CEP72 rs924607 experience more severe peripheral neuropathy (PN) at lower cumulative vincristine doses. The objective of this retrospective pharmacogenetic analysis was to determine if pts homozygous for rs924607 have increased PN risk when receiving short-term vincristine treatment for diffuse large B-cell lymphoma (DLBCL). Methods: Caucasian pts with DLBCL randomized to either of two vincristine-containing regimens (R-CHOP or DA-EPOCH-R) on the CALGB 50303 (Alliance) trial were genotyped for germline rs924607 via TaqMan. Vincristine was administered intravenously 1.4 mg/m2 (2 mg cap) on day 1 of each R-CHOP cycle (1.4 mg/m2/cycle) or 0.4 mg/m2/day (no cap) on days 1-4 of each DA-EPOCH-R cycle (1.6 mg/m2/cycle). Dosing was repeated every 21 days for 6 treatment cycles, for a maximum cumulative vincristine dose of 8.4 (R-CHOP) or 9.6 (DA-EPOCH-R) mg/m2 over 18 weeks. The primary analysis compared risk of NCI CTCAE grade 3 or higher PN in rs924607 homozygous variant pts versus wild-type allele carriers using multivariable Cox proportional hazards regression adjusted for treatment received (R-CHOP vs. DA-EPOCH-R), age (continuous), and sex (male vs. female). A secondary analysis was conducted only in pts assigned to the DA-EPOCH-R arm. Results: Of 307 pts included in the analysis, 32 (10.4%) experienced grade 3+ PN. PN occurrence was nominally lower in homozygous pts (5/59 = 8.5%) than wild-type carriers (27/248 = 10.9%). In the primary analysis, homozygous pts did not experience PN earlier in treatment (Hazard ratio (HR) = 1.04, (95% confidence interval: 0.39-2.75), one-sided p-value = 0.47). There was no significant difference between groups in dose-at-PN occurrence (homozygous (n = 5): 8.81 mg/m2 vs. wild-type carrier (n = 27):6.74 mg/m2, p > 0.05). The secondary analysis in pts on the DA-EPOCH-R arm (n = 147), in which the majority of PN events occurred (n = 27/32 = 84%), homozygous pts (n = 26) did not have significantly increased PN risk (HR = 1.30, p = 0.56). Conclusions: This retrospective analysis of the prospective CALGB 50303 trial did not find that pts homozygous for CEP72 rs924607 had increased PN risk during short-term vincristine treatment for DLBCL. Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org . ClinicalTrials.gov Id: NCT00118209.
The prevalence of targetable genomic alterations is substantially high in rare tumors.
Authors: Wang Shuhang , Li Ning , Chen Rongrong , Yu Yue , Fang Yuan , Gu Dejian , Yi Xin , Huang Huiyao , Wu Dawei , Fang Hong , Bai Ying , Sun Chao , Qi Anqi , Fan Qi , Zhou Ying 
Published: May 2020

e13539 Background: Comprehensive Genomic Profiling may be informative for novel treatment strategies and to improve outcome for patients with rare solid tumors. This study aims to discover opportunities for use of targeted therapies currently in routine practice in patients with rare tumors. Methods: Solid tumors with an incidence lower than 2.5/100,000 per year was defined as rare tumors in China after comprehensive analysis based on epidemiology data and current availability of standardized treatment. Genomic data of rare tumors from the public database cBioPortal was compared with that of Chinese population for targetable genomic alterations (TGAs). TGAs was defined as mutations of ALK, ATM, BRAF, BRCA1, BRCA2, CDKN2A, EGFR, ERBB2, FGFR1,2,3, KIT, MET, NF1, NTRK1,2,3, PIK3CA, PTEN, RET, and ROS1 with level 1 to 4 of evidence according to OncoKB knowledge database. Results: Genomic data of 4901 patients covering 63 subtypes of rare tumor from cBioportal was obtained as the western cohort. Data of next generation sequencing (NGS) of 1312 patients from across China covering 67 subtypes was summarized as the Chinese cohort. Forty-one subtypes were overlapped between the two cohorts. The accumulative prevalence of TGAs was 20.40% (1000/4901) in cBioportal cohort, and 53.43% (701/1312) in Chinese cohort (p < 0.001). Among those 41 overlapping subtypes, it was still significantly higher in Chinese cohort compared with cBioportal cohort (54.1%% vs. 26.1%, p < 0.001). Generally, targetable mutations in BRAF, BRCA2, CDKN2A, EGFR, ERBB2, KIT, MET, NF1, ROS1 were ≥3 times more frequent in Chinese cohort compared with that of cBioportal cohort. Cancer of unknown primary tumor type, gastrointestinal stromal tumor, gallbladder cancer, intrahepatic cholangiocarcinoma, and sarcomatoid carcinoma of the lung were the top 5 tumor types with highest TGAs. Conclusions: The incidence of TGAs in rare tumors was substantially high worldwide and was even higher in Chinese rare tumor population. Comprehensive genomic profiling may offer novel treatment paradigms to address the limited options for patients with rare tumors.
Family cancer patterns and variation by race and ethnicity among individuals with pathogenic variants in multi-gene cancer predisposition panels at a large urban comprehensive cancer center.
Authors: Tatineni Sushma , Purrington Kristen , Assad Hadeel , Abdallah Nadine , Tarockoff Meri , Surapaneni Malini , Petrucelli Nancie , Reagle Rachel , Simon Michael S. 
Published: May 2020

e13540 Background: The identification of pathogenic variants and variants of unknown significance (VUS) in multi-gene cancer predisposition testing raises new questions regarding cancer risk and management. We evaluated the personal and family cancer patterns and variation by race and ethnicity, among individuals positive for pathogenic variants in non-BRCA1/ 2 cancer predisposing genes. Methods: The Karmanos Cancer Institute (KCI) Cancer Genetics database was queried from May 13, 2013 through December 31, 2018. There were 3,544 unrelated individuals evaluated for hereditary cancer predisposition of whom 1,868 had 18-gene panel testing at 6 sites across Michigan. Data was collected on personal and family cancer history including ages at diagnosis utilizing a 3-generation pedigree, self-identified race and ethnicity and results of genetic testing. We describe the prevalence of pathogenic variants by proband cancer diagnosis, family history, race, and ethnicity. Results: The race/ethnic distribution of the tested cohort included 67.5% non-Hispanic White (NHW), 24.4% African American (AA), 2.1% Arab, 1.8% Ashkenazi Jewish (AJ), 1.0% Hispanic, and 3.4% other. The distribution of cancer diagnoses included 40.6% breast, 5.5% ovarian, 4.1% colon, 3.5% endometrial, 2.0% pancreas and 39.7% unaffected. Pathogenic variants were seen in 151 (8.1%) individuals and VUS in 309 (16.5%). The five most common pathogenic variants were CHEK2 (40), MUTYH (22), ATM (20), and PALB2 (18). The most common pathogenic variants by race and ethnicity were CHEK2 (NHW), RAD51C (AA), PALB2 (Arab), CHEK2, MSH6 (AJ), and none in Hispanics. Variants associated with the four most common cancer types were breast ( CHEK2 ), ovarian ( CHEK2, MUTYH, BRIP1), colon ( ATM), and endometrial ( MSH6, PALB2). Of 40 individuals with CHEK2 variants, 92.5% were NHW, and 34 (85%), 31 (78%), 10 (25%), 1 (2.5%) had family history of breast cancer, breast cancer before age 50, ovarian, and colon cancer, respectively. Of 20 with ATM variants, 95% were NHW, 13 had family history data and 10 (76.9%), 8 (61.5%), 2 (15.4%), 1 (7.7%) had family history of breast, breast cancer before age 50, ovarian, and colon cancer, respectively. Conclusions: Pathogenic variants seen using multigene panel testing differ by race, ethnicity and personal/family history of cancer. This data will inform genetic counseling strategies in regards to cancer risk and management. Data on additional genes updated through 2019 will be presented.
Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) for advanced breast cancer patients with high risk for Hereditary Breast and Ovarian Cancer Syndrome (HBOC).
Authors: Sant'Ana Rosane Oliveira , Silva-Fernandes Isabelle Joyce de Lima , Luciano Maria Claudia dos Santos , Silva Paulo Goberlanio de Barros , Lima Marcos Venício Alves 
Published: May 2020

e13549 Background: Local Advanced Breast Cancer (LABC) is associated with high risk of death. NAC is a safe and effective approach for these populations. pCR is a proven prognostic factor in several studies of NAC. HBOC is associated to high risk of breast cancer usually in young age and especially for BRCA1 mutations with a basal phenotype. The aim of this study was to evaluate the influence of BRCA mutational status on frequence of pCR. Methods: this is part of a retrospective, observational study of prevalence of HBOC among patients admitted for cancer therapy in our institution. Since August, 2018 over 300 pte suspected for HBOC (by NCCN criteria) have been screened for NGS with a 31-gene painel. Statistical analysis performed Person X2/Fisher and logistic regression ( p< 0.05; SPSS 20.0). Results: Most pte were women (80%), with median age of 38y (22-72y), most tumors were (80%) stage III, Luminal B (23%) and TNBC (36%). Pathogenic mutations were identified in 34%(n = 28) of the sample ( BRCA1 50%, BRCA2 16.7%, PALB2 16.7%, follow by TP53, PMS2, XRCC2, MUTYH, BARD1 and ATM with 2.8% each).The majority of patients had more than 1 NCCN criteria: age < 45y (83%), family member with BC < 50y (24%) or TNBC (33%) the most common. TNBC tumors had stronger association with germline mutation ( p< 0.001). Regarding response rate there were 13 stable disease (SD), 5 progressive disease (PD), 43 pCR and 39 pathological partial response (pPR). There were no differences in pRC among mutated or no mutated pte, p= 0,170. However, among mutated TNBC there were strong correlation with more pCR, p< 0,006. There was no difference on pCR rate related to mutation status (BRCA vs Non-BRCA), p = 0,84. Conclusions: the present study corroborates other data about the impact of germline mutation status over pCR after NAC for LABC, except for mutated TNBC population, whose seems to be more NAC sensitive.
Outcome of mammography examination among asymptomatic women.
Authors: Kolade-Yunusa Hadijat Oluseyi 
Published: May 2020

e13558 Background: Early detection of breast cancer is important in reducing mortality, morbidity and high socio-economic burden associated with it. Mammography is currently the primary imaging modality used as a screening tool to detect early breast cancer in women experiencing no symptoms as they are most curable in the early stage. The aim of the study is to determine the mammographic outcome in asymptomatic women who presented for mammographic breast examination in Abuja,Nigeria. Methods: This descriptive cross-sectional study comprises of 113 asymptomatic women who presented for mammographic examination at the Radiology department of University of Abuja Teaching Hospital, Gwagwalada from March 2015 to December 2018. Two basic views (craniocaudal and mediolateral views) of the breast were obtained using EXR-650 machine.Additional views were obtained when necessary. Images of the breast were review by radiologist. Results: The mean age of study population was 40.72 ±10.45years with age range of 35 and 65 years. The mammographic outcome among asymptomatic women who had mammographic examination was negative in 69(61.1%) women and positive in 44(38.9%). The differences observed between the positive and negative mammographic outcome was statistically significant p = 0.01. The positive outcome noted in mammograms of women examined were: benign mass in 18(15.9%) women; 9(8.0%) had benign calcification; 7(6.2%) showed architectural distortion; 5(4.4%) was inconclusive; focal asymmetry in 3(2.6%); and suspicious mass in 2(1.8%). Conclusions: Mammogram is an important tool for screening and diagnoses of breast pathologies. In this study, screening of women reveals various benign and malignant breast changes which necessitate early interventions. Early detection of breast cancer save lives. [Table: see text]
Relationship between nutritional status and length of hospital stay in oncological surgery.
Authors: Meissner Carl , Otto Ronny , Fahlke Joerg , Mueller Mathias , Ridwelski Karsten 
Published: May 2020

e13591 Background: In Germany, a serious illness is the main cause of malnutrition. Various studies have already shown that the length of time in hospital for various diseases and operations in malnourished patients increases. This leads to a deterioration in the quality of life of the patient and results in considerable costs for the health care system. Methods: In order to investigate the relationship between nutritional status and length of hospital stay, a patient group of 363 patients who had a tumor with the primary tumor in the gastrointestinal tract was first identified. All patients had an NRS score of 3 or greater and a meaningful laboratory with regard to protein and albumin levels and / or results of a bioelectrical impedance analysis. The average length of stay for these patients was determined depending on the various parameters. Results: The present study shows that malnourished patients have to stay in the hospital for between 2 and 11.1 days longer. When evaluating the NRS score, the protein and albumin level as well as the BCM and the ECM / BCM index, a longer hospital stay of malnourished patients compared to those who were not malnourished was demonstrated. The BMI is an insufficient parameter to describe the nutritional status. An extension of the length of hospital stay cannot be demonstrated only on the basis of the BMI. Conclusions: Since an inadequate nutritional status obviously affects the length of hospital stay in oncological patients, they should be examined early for malnutrition. The length of stay can be shortened through nutritional therapy measures, which also leads to a significant reduction in costs.
Role of CD8+ T-cell infiltration in breast tumors of Black women compared to White women.
Authors: Abdou Yara , Attwood Kristopher , Yao Song , Cheng Ting-Yuan David , Bandera Elisa , Zirpoli Gary , Payne Ondracek Rochelle , Stein Leighton , Bshara Wiam , Khoury Thaer , Ambrosone Christine B. , Omilian Angela 
Published: May 2020

e13608 Background: Literature regarding racial differences in tumor immune responses in breast cancer remains sparse. To address this research gap, we assessed CD8+ T-cells in breast tumor samples from the Women’s Circle of Health Study (WCHS) population of predominantly Black breast cancer patients. We characterized and compared the density of CD8+ T cells, their prognostic value and their association with pharmacologic beta-blockers. Prior studies suggest that reducing adrenergic signaling through beta blockers can stimulate CD8+ T-cells. Methods: Tumor-infiltrating CD8+ T-cells were assessed by IHC staining of tissue microarray cores from 688 breast cancer patients, including 550 Blacks and 138 Whites. CD8+ T cells were scored with digital image analysis. Comparisons of demographic and clinical variables (including CD8+ T cell density) were made using the Mann-Whitney U or Kruskal-Wallis and Fisher’s exact tests. Associations with overall survival (OS) and disease-specific (DSS) survival were evaluated using the log-rank test of Cox regression. Analyses were performed in the overall sample and by disease sub-type. Results: Higher CD8+ T cell density was seen in Black women compared to White, with mean values of 756.2/mm2 and 292.4/mm2 respectively (p < 0.001). Within the overall population and in black women, CD8+ T cell density was significantly higher in younger patients, patients with high grade, and ER negative tumors. No significant associations were observed between CD8+ T cell density and OS or DSS. However, when stratified by subtype, Black patients with triple negative breast cancer and high CD8+ T cell density showed a trend towards improved OS in comparison to patients with low CD8+ T cell density (p = 0.065). 170 patients with information on beta blocker usage were analyzed. No significant associations were noted between CD8+ T cell density and beta blocker use. Conclusions: We observe a significantly higher CD8+ T cell density in Blacks compared to Whites, but this does not confer a survival advantage. Additionally, beta-blockers did not seem to enhance CD8+ T cell infiltration in tumors from Black patients. Our data raise the possibility that distinct mechanisms of immune cell action may occur in different racial groups. Future studies are needed to determine the functional properties of CD8+ T cells in Black women and to characterize additional immune cell subtypes that may also play a role.
Trends in gender-based disparity in incidence, mortality and survival for major digestive disease cancers in the U.S. (2000-2016).
Authors: Sada Yvonne , Zafeiropoulou Efthalia , Richardson Peter , Kramer Jennifer , Christie Israel , Jiao Li , Liu Yanhong , Chiao Elizabeth , White Donna 
Published: May 2020

e13621 Background: Males have excess risk of most digestive cancers; whether cancer mainly due to virus (stomach), lifestyle including obesity/alcohol (colon/esophagus), or both (liver). We evaluated for secular trends in gender-specific incidence, mortality and survival for these cancers in the U.S. Methods: We used official U.S. Cancer Statistics [USCS] data (2000-2016) to calculate annual age-adjusted incidence and mortality rates (IR/MR). It covers >98% population/all states (vs. SEER-10 statewide registries, covers <1/3rd African-Americans/Whites). We calculated mortality-to-incidence rate ratios (MIR), an established 5-year survival proxy. We used Joinpoint to assess trends in average annual percentage change (AAPC). Results: Table shows age-adjusted IRs and MRs for colon, esophagus and stomach cancer decreased for men and women (all AAPCs negative, all significant but stomach IR women), with both liver IR/MR significantly increasing in both genders. Gender differences in relative burden were seen (e.g., MRs in colon>esophagus>liver>stomach in men vs. colon>stomach>liver>esophagus in women), with greatest male excess in esophagus (e.g., 4.4-fold IR). MIRs suggested less favorable survival (higher=worse) for men for esophagus/colon. Conclusion: Substantial gender disparity persists in digestive cancers, with male excess gap decreasing for colon and increasing for liver. [Table: see text]
Breast cancer frequency and survival by molecular subtype in central Illinois.
Authors: Sahib Hamsa , Abedrabo Sabree , Niaz Zurain , Koester Cameron , Maini Ruby , Lara Garcia Odalys Estefania , Tandan Nitin , Parajuli Priyanka , Regmi Manjari Rani , Cheema Asad , Mirihagalle Noupama , Ibrahim Abdisamad M. , Bhandari Bishal , Johnson Alexander , Delfino Kristin , Robinson Kathy , Desai Meghna R. , Kulkarni Abhishek 
Published: May 2020

e13631 Background: Breast cancer is the most common female malignancy. In 2019, it is estimated that there were 268,000 new cases of female breast cancer. The most common subtype was HR+/HER2 based on 2012-2016 cases, a much higher rate than triple negative breast cancer. Best survival rates are found among women with HR+/HER2- subtype followed by HR+/HER2+ and HR-/HER+ subtypes. Triple negative subtype comparatively had a poorer survival.Our objective was to determine breast cancer rate and survival by molecular subtype in the central Illinois population. Methods: A cohort of 478 patients diagnosed with breast cancer between January 2014 and December 2017 was identified by using ICD codes. Eligibility criteria included pathology confirmed breast cancer.Categorical variables were summarized as frequencies and percentages. Predictors of survival were assessed with Cox proportional hazards regression analyses.All significance was assumed at the p < 0.05 level. Results: Luminal A breast cancer was the most common type in our population. In the cohort of 478 patients, 208 patients (74%) were found to have Luminal A. whereas, 37 patients (13.21%) had Basal subtype, 20 patients (7.14%) had Luminal B and 13 patients (5.36%) had Her2 enriched subtype. However, there was no statistical difference in survival between the subtypes. Conclusions: Although the frequency of cancer subtypes in our population is comparable to the national epidemiology data,we observed that there is no statistical difference in survival as compared to NCI SEERS data. This could be due to optimum care and patient’s adherence to chemo-radiation or due to small sample size. This could be an important area of future research to investigate if we can increase survival of poor prognosis subtypes (as triple negative) by following the same measures. Long term follow up for the patients in the study might also be necessary.
Mutation spectrum of EGFR in 21,324 patients with non-small cell lung cancer successfully tested by multiple platforms in a CAP-accredited laboratory.
Authors: Mao Linlin , Zhao Weiwei , Li Xiaoxia , Zhang Shangfei , Zhou Changhong , Zhou Danyan , Ou Xiaohua , Xu Yanyan , Tang Yuanxiao , Hu Changming , Luo Pifu , Yu Shihui 
Published: May 2020

e13637 Background: Genotyping epidermal growth factor receptor ( EGFR) gene in patients with advanced non-small cell lung cancers (NSCLC) is essential to identify those patients who may benefit from targeted treatments. However, the testing methodology is still a puzzle for many clinicians. This study retrospectively reviewed the EGFR data from testing patients with NSCLC in our laboratory in 10 years. Methods: A total of 21,324 NSCLC cases successfully underwent EGFR genotyping in our laboratory for clinical therapeutic purpose, including 5,244 cases tested by Sanger sequencing, 13,329 cases tested by real-time PCR, and 2,751 tested by next generation sequencing-NGS. Results: 54.6%, 20% and 2.3% samples were recorded with tumor cell content (TCC) of < 40%, < 20% and 1% respectively. The average EGFR mutation rate was 45.1%, with 40.3% identified by Sanger sequencing, 46.5% by real-time PCR and 47.5% by NGS. Comparable EGFR mutation rates were observed in cases with 1%-20% TCC from real-time PCR and NGS platforms. In these cases with EGFR mutations, 93.3% of them carried a single EGFR mutation (92.1% with a classical mutation as 19del or L858R, and 7.9% with an uncommon mutation) and 6.7% harbored complex EGFR mutations. 65.3% of the cases carrying EGFR mutations identified by NGS also have tumor related variants in other genes. 26.5% more cases were found to have oncogenic driver mutations with therapeutic significance beyond EGFR by NGS. Conclusions: NGS may be the most optimal methodology to detect EGFR mutations in patients with NSCLC compared with Sanger sequencing and real-time PCR platforms from accuracy and comprehensiveness aspects, but some other issues, such as Turn Around Time (TAT), still should be considered in clinical practice.