bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rare tumor with matched germline whole exome sequencing to identify somatic and inherited variants of clinical significance.
Authors: Perkins Bryce , Sprissler Ryan , Babiker Hani M. , Chalasani Pavani , Johnstone Laurel , Lau Brandon , Ramos Kenneth , Placencia Crystal , Gutenkunst Ryan , Hammer Michael , Mahadevan Daruka 
Published: May 2019

1523 Background: Rare cancer incidence is defined as <6/100,000 cases. These cases are challenging due to delays in diagnosis, late stage at diagnosis, lack of standard of care and poor outcomes. We present molecular profiling of 28 rare tumor cases analyzed by whole exome sequencing (WES) seen in the Early Phase Therapeutics Program. Methods: We performed WES on 15 rare tumors with matched germline DNA, as well as tumor only on 2 additional cases. We sequenced a panel of 500 candidate cancer genes in 6 tumor/normal and 6 tumor only cases. Copy number alterations (CNAs) were assessed for the tumor-normal WES cases with SNVs and small indels for all cases. Caris (AZ) (tumor only) and liquid biopsy (Gaurdant360, CA) were also conducted in these patients for comparison. Results: Rare tumors affected 18 different tissues of the body with 1 case affecting tissue typical of common cancers. The rare tumor group contained 25% pathogenic or likely pathogenic germline variants compared to 7.1% for common tumors. This increased rate of inherited pathogenic variants met statistical significance: Fisher exact test (p = 0.0118). A total of 69 sequence variants and 8 CNAs were identified, 37 were actionable. For all but 3 patients, there was at least one variant associated with an actionable outcome given off-label use or clinical trial participation. There was excellent concordance with results from commercial sequencing; however, our tumor/germline sequencing identified additional germline variants of clinical significance, all were loss-of-function variants in tumor suppressors. Tumor vs. normal analysis showed that the majority of the commercially reported VUS were in fact germline VUS. In one case, a reported pathogenic variant we found to be an inherited pathogenic germline variant. 15 patients received at least 1 line of therapy indicated by genomic sequencing. For these patients the PFS ratio when compared to the most recent line of therapy prior to targeted therapy was 2.02, with 10/15 (67%) patients having a PFS ratio of >1.0, and 6/15 (40%) of patients having PFS ratio >1.3. Conclusions: We demonstrate the importance of tumor-normal analysis, especially in the context of rare tumors. Rare tumor patients may disproportionately benefit from tumor vs. normal WES at diagnosis to improve PFS within targeted therapy trials, guided by genomics.
Safety and efficacy of aspirin for primary prevention of cancer: A meta-analysis of randomized controlled trials.
Authors: Haykal Tarek , Barbarawi Mahmoud , Zayed Yazan , Kheiri Babikir , Yelangi Anitha , Dhillon Harsukh , Goranta Sowmya , Chahine Adam , Samji Varun , Bachuwa Ghassan , Katato Khalil 
Published: May 2019

1533 Background: In the United States, cancer is the second leading cause of mortality, and millions more battle cancer worldwide. As such, primary prevention of cancer is a major interest globally. Aspirin has been studied as a primary prevention method for multiple diseases, mainly cardiovascular disease and various forms of cancer. The role of aspirin as a primary prevention of cancer is still controversial and may be more beneficial in certain cancers over others. With rapidly surfacing large randomized controlled trials (RCTs) studying this subject, we aimed to evaluate the efficacy and safety of aspirin as a primary prophylaxis for cancer. Methods: A comprehensive electronic database search was conducted for all RCTs that compared aspirin versus placebo for the prevention of any type of disease, and where cancer incidence or mortality was reported. The primary outcome was cancer-related mortality. Secondary outcomes were cancer incidence, all-cause mortality, major bleeding, any bleeding and gastrointestinal (GI) bleeding. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest follow-up period. Results: We included 16 RCTs with 104,018total patients, mean age of 60.51 years, mean follow-up of 5.48 years, and a male percentage of 38.72%. We found that aspirin was not associated with a significant reduction of cancer-related mortality compared with placebo (RR 0.99; 95% CI: 0.87-1.12; P = 0.85: I2= 41%). Compared with placebo, aspirin was not associated with significant reduction of all-cause mortality (RR 0.97; 95% CI: 0.92-1.02; P = 0.19; I2= 13%) or cancer incidence (RR: 0.98; 95% CI: 0.92-1.04; P = 0.43; I2= 16%). However, aspirin treatment was associated with significantly increased risks of any bleeding (RR 1.63; 95% CI: 1.31-2.03; P < 0.01), major bleeding (RR 1.41; 95% CI: 1.26-1.57; P < 0.01), and GI bleeding (RR 1.85; 95% CI: 1.38-2.48; P < 0.01) compared with placebo. Conclusions: Our study did not find any significant reductions in cancer-related mortality or cancer incidence when compared with placebo. Our study also highlights the dangers of aspirin for primary prevention of cancer as aspirin was found to cause higher rates of bleeding (any bleeding, major bleeding, and GI bleeding) compared to placebo at the longest follow-up period with no significant benefit in cancer primary prevention.
Role of vitamin D supplementation for primary prevention of cancer: Meta-analysis of randomized controlled trials.
Authors: Samji Varun , Haykal Tarek , Zayed Yazan , Gakhal Inderdeep , Veerapaneni Vijay , Obeid Michelle , Kheiri Babikir , Badami Sunil , Bachuwa Ghassan , Danish Rizwan 
Published: May 2019

1534 Background: In the United States cancer is the second leading cause of mortality, as such, primary prevention of cancer is a major public health concern. Vitamin D supplementation has been studied as a primary prevention method for multiple diseases including cardiovascular disease, osteoporosis, diabetes mellitus and cancer. The role of aspirin as primary prevention of cancer is still controversial. With fast emergence of large randomized controlled trials (RCTs) in that regards, we aimed to evaluate the efficacy of Vitamin D supplementation as primary prophylaxis for cancer. Methods: A comprehensive electronic database search was conducted for all RCTs where comparison of Vitamin D supplementation versus placebo for the prevention of any type of disease with at least 3 years of Vitamin D supplementation was used and where cancer incidence or mortality was reported. The primary outcome was cancer-related mortality and cancer incidence. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest follow-up. Results: We included 10 RCTs with 79,055 total patients, mean age of 68.07 years, a female percentage of 78.02% and a minimum follow-up of 4 years and more. Vitamin D was associated with significant reduction of cancer-related mortality compared with placebo (RR 0.87; 95% CI: 0.79-0.96; P = 0.05: I2= 0%). Compared with placebo, Vitamin D was not associated with significant reduction of cancer incidence (RR: 0.96; 95% CI: 0.86-1.07; P = 0.46; I2= 31%). Conclusions: Our study highlights that the use of Vitamin D supplementation for primary prevention of cancer is important as it does decrease cancer-related mortality once cancer is diagnosed, however it has no role or effect on cancer incidence.
Opportunistic off-target cancer screening in organized programs: The EDIFICE 6 survey.
Authors: Morere Jean F. , Couraud Sebastien , Roupret Morgan , Touboul Chantal , Lhomel Christine , Eisinger Francois , Viguier Jerome , Greillier Laurent , De La Motte Rouge Thibault 
Published: May 2019

1535 Background: The efficacy and benefit/risk ratio of organized nationwide cancer screening programs rely on the age range of eligible average-risk populations. We studied the characteristics of off-target populations who underwent opportunistic screening for colorectal (CRC), breast (BC) or cervical (CC) cancer, ≤5y prior to the recommended age. Methods: The French nationwide observational survey, EDIFICE 6, was conducted online (June 26-July 28, 2017) on a core sample of 12 046 individuals (18-69y). Representativeness was ensured by quota sampling on age, sex, profession, and stratification by geographical area/type of urban district. Opportunistic screening for BC (in 533 women, age 45-49y), CRC (in 1331 individuals, age 45-49y) or CC (in 633 women, age 20-24y) was assessed in terms of smoking status (current, former/never smoker), marital status (single, living with a partner), type of residential area (urban, rural), having a close relative with cancer, social vulnerability (EPICES score), and self-reporting own cancer risk (higher, identical/lower than average). Results: In the off-target populations, screening rates were 78% for BC (N = 418, mammogram), 13% for CRC (N = 172, fecal test or colonoscopy) and 42% for CC (N = 264, cervical Pap smear test). Premature BC screening rates were significantly higher (P < 0.05) in non-vulnerable than in vulnerable individuals (84% vs 69%), and among those self-reporting their own BC risk as higher than average (84% vs 76% reporting own BC risk as identical/lower than average). Premature CC screening rates were correlated with: smoking status (66% in current smokers vs 35% in former/never smokers), and marital status (63% in those living with a partner vs 34% single). Lastly, factors correlated with premature CRC screening were: type of residential area (urban, 15% vs rural, 8%), and believing own risk of CRC to be higher than average (27% vs 8% of those who self-reported their own CRC risk as identical/lower than average). Conclusions: This analysis reveals several factors related to premature screening for BC, CRC and CC, provides clear insight into off-target cancer screening uptake profiles, and hints at new strategies to ensure the optimal risk/benefit ratio of screening practices.
Low-fat dietary pattern and breast cancer mortality by metabolic syndrome degree: Secondary analyses of the Women’s Health Initiative (WHI) Dietary Modification randomized trial.
Authors: Pan Kathy , Aragaki Aaron K , Neuhouser Marian L , Simon Michael S. , Luo Juhua , Caan Bette , Linda Snetselaar , Mortimer Joanne E. , Manson JoAnn E , Kroenke Candyce , Lane Dorothy , Reding Kerryn , Rohan Thomas E , Chlebowski Rowan T. 
Published: May 2019

1539 Background: The WHI Diet Modification (DM) trial randomized 48,835 postmenopausal women with no prior breast cancer to a low-fat dietary intervention or comparison group. After 16.1 years follow-up, the intervention was associated with an 18% reduction in risk of death after breast cancer (P =0.01), with greater reduction (29%) in those with waist circumference≥88 cm (J Clin Oncol 2017). To extend these findings, we examined the influence of the dietary intervention on breast cancer mortality in subgroups defined by number of metabolic syndrome (MS) components with 19.6 years median cumulative follow-up. Methods: WHI DM has been previously described. Four MS components were determined at entry: 1) waist circumference≥ 88 cm, 2) high blood pressure or anti-hypertensive use, 3) high cholesterol history and 4) diabetes history, with women categorized as having 0 (n=10,639), 1-2 (n=30,948), or 3-4 (n=4,246) MS components. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomized group assignment and number of MS components. Results: Women with 3-4 MS components were more likely to be Black, be obese (BMI ≥30), and have diabetes (all P < 0.001). Breast cancers in women with 3-4 MS components were less likely to be local stage (P = 0.005) or well differentiated (P = 0.03). The magnitude of reduction in deaths from breast cancer in the dietary intervention vs comparison group increased as the number of MS components increased (interaction P = 0.01). Hazard ratios (HR) and 95% confidence intervals (CI) for death from breast cancer for intervention vs comparison groups for women with 0 MS components was 1.09 95% CI, 0.63-1.87, with risk low in both randomization groups (0.028% and 0.026%, respectively); for women with 1-2 MS components, HR 0.80 95% CI 0.62-1.02; and for women with 3-4 MS components, HR 0.31 95% CI, 0.14-0.69, with risk in the intervention group reduced to 0.026%. Conclusions: Adoption of a low-fat dietary pattern had a greater effect on reducing deaths from breast cancer in women with more MS components, suggesting that this is a high risk group more likely to benefit from the dietary intervention. Clinical trial information: NCT00000611.
Whole exome sequencing of germline DNA of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung adenocarcinoma (LUAD) according to KRAS status.
Authors: Perez-Gracia Jose Luis , Pita Guillermo , Segura Victor , Pajares Maria Jose , Fusco Juan Pablo , Andueza Maria Pilar , Sanchez-Bayona Rodrigo , Guruceaga Elisabet , Mora Maria Isabel , Gurpide Alfonso , de Torres Tajes Juan Pablo , Zulueta Javier , Pio Oses Ruben , Melero Bermejo Ignacio , Sanmamed Miguel F. , Rodriguez-Ruiz Maria E. , De Andrea Carlos E , Montuenga Luis M. , Gonzalez-Neira Anna , Patiño-García Ana 
Published: May 2019

1540 Background: Individual susceptibility to carcinogens may depend on the genetic background. We characterized the constitutional exome of individuals presenting extreme phenotypes of high sensitivity and resistance to develop tobacco induced LUAD, correlating the results to KRAS status. Methods: From an identification cohort (n=3,631) we selected 100 caucasian heavy smokers that either developed LUAD at early age (cancer cohort, n=50) or did not develop LUAD or other tumors at advanced age (cancer free cohort, n=50). We sequenced their germline DNA with the Agilent Human Exome Capture v5 (21,522 genes, 357,999 exons). Using logistic regression we selected the most significant variants between both cohorts and correlated them with KRAS mutation status of LUAD patients. Results: mean ages for the cancer and cancer free cohorts were 50 (range 34-55) and 78 years (72-90). Mean tobacco consumptions were 44 (range 6-72) and 55 pack-years (20-124). Median coverage was 96% at >10X; median depth was 97X. Table shows the most significant variants. rs7240666 ( ALPK2) achieved top significance (p=8.14x10-5, OR 0.18). rs78898229 ( ANKRD36C) and rs74866537 ( PTPN4) were predominantly represented in patients with KRAS+ tumors, OR: 16 (3.3-78) and 11.9 (3.3-43); and rs12426243 (CCDC41) in KRAS- tumors (OR: 13 (3-53). Conclusions: Our study characterizes for the first time the genotype of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced LUAD according to KRAS status. Our results warrants further study to assess their value to screen these clinically relevant phenotypes; and to identify mechanisms of high susceptibility and resistance to carcinogens. [Table: see text]
Prognostic significance of blood-based cancer detection in plasma cell-free DNA (cfDNA): Evaluating risk of overdiagnosis.
Authors: Oxnard Geoffrey R. , Chen Xiaoji , Fung Eric T. , Ma Ting , Lipson Jafi , Hubbell Earl , Kurtzman Kathryn N. , Patel Shilpen , Shaknovich Rita , Dong Zhao , Liu Hai , Brooks Jacqueline D. , Spigel David R. , Seiden Michael , Aravanis Alex , Klein Eric A. , Hartman Anne-Renee , Liu Minetta C. 
Published: May 2019

1545 Background: Screening tests for early cancer detection are often criticized due to risk of overdiagnosis—detection of good prognosis cancers which may not require immediate treatment. We recently reported development of cfDNA sequencing approaches for cancer detection; longitudinal follow-up (F/U) data were utilized here to evaluate prognostic significance of cancer detection using cfDNA. Methods: Plasma cfDNA samples were subjected to whole-genome bisulfite sequencing (WGBS, 30X) as part of a previously-reported Circulating Cell-free Genome Atlas (CCGA; NCT02889978) substudy. This exploratory analysis evaluated the overall survival (OS) of training and test set participants (pts) with cancer (20 cancer types, any stage I-IV). Combining train and test set pts, univariate and multivariate analyses (Cox proportional hazards) assessed OS association with WGBS result (cancer detected vs not detected, set at 98% specificity), clinical stage (IV vs I-III), diagnostic method (symptom- vs screen-detected), sex, age, and histologic grade. Results: Of 827 pts from the training set with F/U (median 12.2 mo), 334 (40.4%) had WGBS-detected cancer. Among 127 (15.4%) pts with cancer that died during F/U, cancer was detected in 104 (81.9%). Results were similar in the test set. In univariate analyses all variables were associated with prognosis, including WGBS result (HR 7.7 p<0.001). In multivariate analyses accounting for other covariates, the three variables that most significantly remained prognostic were WGBS (HR 3.0, p<0.001), clinical stage (HR 3.3, p<0.001), and diagnostic method (HR 3.0, p<0.001). Validation of these findings is ongoing in an independent cohort of ~5,000 cancer pts from CCGA using an optimized assay; updated performance results will be reported. Conclusions: Cancers detected using WGBS of cfDNA had a worse prognosis than cancers not detected. WGBS cancer detection carried comparable prognostic significance as clinical stage. By preferentially detecting higher risk cancers, cancer detection using plasma cfDNA may avoid some of the overdiagnosis that has been seen with some existing cancer screening methods. Clinical trial information: NCT02889978.
Characteristics of cancer patients with a history of solid organ transplantation: Analysis of a patient cohort reporting to a large cancer center.
Authors: Burock Susen , Nicklich Stefanie , Hartmann Leonie , Ulrich Claas , Keilholz Ulrich 
Published: May 2019

1558 Background: Solid organ transplant recipients have a 2-4-fold elevated risk of developing cancer compared to the general population due to immunosuppressive therapy. Cancer patients with a history of organ transplantation (TPx) may or may not have a cancer attributed to immunosuppression. Here we report on a cohort of cancer patients of the Charité, diagnosed with the first occurrence of a solid cancer in 2010-2014 and a history of TPx. Methods: The cancer registry database of the Charité Comprehensive Cancer Center was queried for patients diagnosed with the first occurrence of solid cancer between 2010 and 2014 and a previous solid organ transplantation. General tumor and patient characteristics as well as outcome were analyzed. Results: A total of 226 patients (151 male, 75 female) were identified and included in the analysis. Transplanted organs included kidney in 148 patients, liver in 63, and heart, lung or a combination of both in 15. The median age at transplantation and initial tumor diagnosis was 54.7 years and 63.4 years respectively. Median interval between organ transplantation and diagnosis of the cancer was 8.1 years, range 0 - 39 years. 60.6% of cancers developed > 10 years after TPx. The interval between TPx and development of cancer inversely correlated to patient age at TPx, with a median of 17.9 years (age group 18-34), 13.0 years (35-49), 6.7 years, (50-64), and 5.3 years, (65+ years). The majority of cancers occurred within the first 10 years after TPx, however especially for the age group 35-49 cancer diagnoses peaked 20-25 years after transplantation. The most common cancer types where non-melanoma skin cancer (34%), followed by kidney (15%), lung (13%) prostate (8.61% of all male patients) and colorectal (4.87%). Median survival of all patients after tumor diagnosis was 4.6 years, with 1.0 years for lung cancer, 4.6 years for colorectal cancer, 5.7 years for prostate cancer respectively. The median OS was not yet reached for non-melanoma skin cancer and kidney cancer. Conclusions: Our data support the necessity of long- term follow up and cancer screening in patients after organ transplantation beyond the commonly practiced 10 years post transplantation screening.
Health insurance literacy, financial hardship and financial sacrifices among cancer survivors in the United States.
Authors: Zhao Jingxuan , Han Xuesong , Zheng Zhiyuan , Banegas Matthew P. , Ekwueme Donatus U. , Yabroff K. Robin 
Published: May 2019

1560 Background: Rising costs of cancer care have imposed substantial financial burden on cancer survivors. To date, little is known about the associations between potentially modifiable patient characteristics, including health insurance literacy (HIL), on financial burden among cancer survivors. This study aimed to evaluate the associations between HIL and financial hardship and financial sacrifices among adult cancer survivors in the United States. Methods: We identified 914 adult cancer survivors from the 2016 Medical Expenditure Panel Survey Experiences with Cancer Questionnaire. HIL was measured based on the question “Did you ever have a problem understanding health insurance or medical bills related to your cancer, its treatment, or the lasting effects of that treatment?” Medical financial hardship was measured in three domains—1) material (e.g. problems paying medical bills); 2) psychological (e.g. worry about large medical bills); and 3) behavioral (e.g. delay or forego healthcare because of cost). Financial sacrifices were based on questions related to changes in spending on vacation or leisure activities. We used multivariable logistic regression modeling to separately evaluate the associations between HIL problems and 1) financial hardship and 2) financial sacrifices. Results: 18.9% cancer survivors aged 18-64 years and 14.6% survivors ≥65 years reported HIL problems. Regardless of age groups, cancer survivors with HIL problems were more likely to report any material (OR =3.2; 95% CI:1.9-5.2) or psychological (OR=7.2; 95% CI: 4.1-12.7) financial hardship than those without the problems, as well as more likely to delay or forgo multiple medical care due to cost, including prescription medicine (OR=3.6; 95% CI: 1.8-7.1), specialist visit (OR=2.6; 95% CI: 1.2-5.8), and follow-up care (OR=2.1, 95% CI 1.2-4.0). Higher likelihood of reporting all measures of financial sacrifices were observed among those with HIL problems in both age groups (all p<0.05). Conclusions: Cancer survivors with HIL problems were more likely to report financial hardship and financial sacrifices than those without the problems. Improving HIL may help mitigate financial hardship.