bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial and ethnic disparities in clinical presentation and prognosis of conjunctival cancer.
Authors: Zhang Yang , Aurit Sarah J , Kosoko-Lasaki Omofolasade
Published: May 2019

e13086

Background: To investigate racial and epidemiological disparities in presentation and prognosis of conjunctival cancer in a retrospective population-based study. Methods: Non-Hispanic white (NHW) and African American patients with squamous cell carcinoma or melanoma of the conjunctiva or cornea with known age, insurance, gender, zip code-level income and education, and tumor size were selected from the National Cancer Database (NCDB). Patients were stratified based on race and ethnicity into two mutually exclusive groups, and unadjusted comparisons were made with the Chi-square or Mann-Whitney tests. Survival was examined with the Kaplan-Meier method and a Cox regression model was employed after checking that the proportional hazards assumption was met for all pertinent variables. SAS version 9.4 was used for all analyses and p< 0.05 was considered significant. Results: Of the 2,192 identified patients from 2004 to 2014, 104 were African American. Unadjusted differences were found between groups in regard to age, histology, insurance, income, and education. African American patients in comparison to NHW were younger (median age: 61 years vs. 71 years; p< 0.001), had a higher proportion of Medicaid (10.6% vs. 3.4%) or no insurance (11.5% vs. 2.7%), and resided in areas with lower levels of education (36.5% of African American patients vs. 17.0% of NHW patients were from areas with greater than 21% of the population with no high school degree). It was also found that African Americans had higher proportion of squamous cell carcinoma than NHW (69.9% vs. 81.7%; p= 0.007). In general, risk of death was higher for older African American males with no private insurance, and for those from areas of lowest level of income. Conclusions: Disparities in socioeconomic factors were observed in the African American population. In addition, the overall incidence of conjunctival and corneal cancer occurs at a younger age in African Americans, who also face poorer prognoses. This association between social inequality and poor outcome warrant further investigation.
Angiotensin converting enzyme inhibitors use and development of lung cancer: A systematic review and meta-analysis.
Authors: Bahaj Waled , Albawaliz Anas , Qureini Aref , Abughanimeh Omar Khaled Mahmoud , Younis Moustafa , Tahboub Mohammad , Noman Anas , Bin Abdulhak Aref A
Published: May 2019

e13093

Background: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly prescribed medications for hypertension and heart failure. Generally, ACEIs are well-tolerated medications with reasonable safety profile making them a favorable choice by many clinicians. However, several studies with conflicting results have signaled an association between ACEIs use and the development of lung cancer. We sought to systematically review the literature and perform the first meta-analysis to study the risk of lung cancer among ACEI users. Methods: We performed a literature review by searching multiple databases. A random effect meta-analysis approach was used to pool the data and relative risk was used to calculate the overall effect estimate. Results: A total of 423 articles were identified but only 6 observational studies were included with a total of 872,220 patients (634,672. ACEIs users). The relative risk of lung cancer development among ACEIs users was 1.02 (CI 0.89-1.16) compared to non-ACEIs users. Conclusions: Current systematic review and meta-analysis show no significant association between ACEIs use and the development of lung cancer. The result of our meta-analysis provides further assurance to the health care providers regarding ACEIs use.
Association of atrial fibrillation with colorectal and breast cancer: A systematic review and meta-analysis.
Authors: Farooq Muhammad Zain , Mukthinuthalapati V V Pavan Kedar , Lateef Noman , Siddiqi Tariq Jamal , Asmi Nisar , Malik Saad , Patlolla Sri Harsha , Riaz Irbaz Bin , Murad M. Hassan , Babiker Hani M.
Published: May 2019

e13096

Background: Several studies have reported the association between atrial fibrillation (AF) and malignant cancer. Recently, results from a large cohort within the Women’s Health Study showed increased incident risk of breast, colon and lung cancer in patients with AF. Therefore, we performed a systematic review to assess the available evidence and a meta-analysis to define the strength of this association. Methods: MEDLINE, Cochrane and Scopus databases were searched for all prospective studies that reported the association between AF and presence of cancer. The HR for incident risk of common cancers was recorded (Breast, Lung, Colorectal) in patients with and without AF. Lung cancer was excluded because the data required for the analysis was not consistently reported. The DerSimonian-Laird random effects meta-analysis was performed to derive pooled Hazard Ratio (HR) estimates for incident risk of colorectal and breast cancer in patients with AF. Q-test was used to assess between-study heterogeneity; I2 statistic was computed to expresses the percentage of the total observed variability due to study heterogeneity. Results: A total of 390,479 participants in 3 prospective studies were included in the analysis. Mean age of participants was 66.3 ± 6.5 with mean follow up for 12.6 years. Patients with atrial fibrillation had 27% more risk of developing colorectal cancer [HR 1.27 (1.07-1.51) p < 0.005, I2= 73%] and 14% more risk of developing breast cancer [HR 1.14 (1.03-1.26) p = 0.01, I2= 37%] as compared to those without atrial fibrillation. Applying these hazard ratios to age adjusted yearly incidence ratios from 2000-2015, one in 5824 new onset AF cases will develop CRC and one in 7474 new onset AF cases will develop breast cancer. Conclusions: There is small but statistically significant increase in risk of subsequent diagnosis of colorectal or breast cancer diagnosis in patients with AF. Shared risk factors such as old age or systemic disease processes may explain this association. While the results of this analysis raise interesting questions for future search, these results should not be used as basis to initiate cancer screening for an occult cancer in a patient with AF.
Time to cancer diagnosis in young women presenting to surgeons with breast-related symptoms: A population-based cohort study.
Authors: Menes Tehillah S , Sella Tal , Chodick Gabriel
Published: May 2019

e13099

Background: Reports on delay to diagnosis of cancer in young women are based on retrospective studies and conflicting. The purpose of this study was to investigate time to cancer diagnosis in women presenting to a surgeon with breast-related complaints; and particularly, the role of age. Methods: A population-based cohort study including all women aged 18 to 44 presenting to a surgeon with a breast-related complaint between 2005 and 2015 in a large Israeli healthcare plan (N = 157,264). We collected data including demographics, diagnosis codes, breast imaging and biopsies. Breast cancer diagnosis within one year of the visit was ascertained from the national cancer registry. Time to breast imaging and biopsy was compared between the different age groups. Logistic regression analysis was used to determine the association between age and delay to biopsy while adjusting for possible confounders. Results: During the first year after the visit, 45,434 (29%) women had a breast imaging study; 5,767 (3.7%) women had a breast biopsy; and 676 (0.43%) were diagnosed with breast cancer. Overall, time to first breast imaging (mean, 53 days) and biopsy (mean, 68 days) did not differ significantly between the age groups. Non-specific visit codes (other than breast mass) were associated with delays to imaging and biopsy. This was more pronounced in the women ultimately diagnosed with breast cancer. Among women diagnosed with breast cancer, age under 40 (OR 2.3, 95% CI 1.4; 3.9), being post-partum (OR 2.6, 95% CI 1.1; 5.9) and a non-specific visit code (OR-8.3, 95% CI 4.9; 14.2) were associated with delay to biopsy. Conclusions: Symptomatic women with lower a-priori likelihood of breast malignancy (younger age, post-partum, or non-specific visit code) are at a significantly greater risk of delayed diagnosis of cancer. Physicians should be aware of the challenging diagnosis in young women with non-specific symptoms.
Global burden of HPV-related cancers in men: A systematic literature review.
Authors: Varga Stefan , Wang Xuan , Luttropp Karin , Morais Edith , Walia Anuj , Pimpin Laura , Eriksson Jennifer , Kothari Smita
Published: May 2019

e13108

Background: Human papillomavirus (HPV) causes about 5% of all cancer cases worldwide. Global male-specific incidence of HPV-related cancers, including anal (AC), penile (PC) and head and neck (HNC) cancer, is largely unknown. This study aims to summarize global incidence and HPV prevalence of these cancers in men. Methods: The systematic literature review was conducted following PRISMA guidelines. MEDLINE and EMBASE were searched for studies published in English between Jan 2008-Mar 2018 containing male-specific AC/PC/HNC incidence data, or HPV prevalence in AC/PC/HNC adult patients. Results: Fifty-six studies reported AC incidence in men between 1962-2014. The rate ranged between 0-1.5/100,000 persons in the general population. Globally, AC incidence increased over time. In the US, AC incidence in HIV-positive men increased from 10.5 to 20.7/100,000 person-years (PYs) from 1980-1989 to 1990-1995, and from 47 to 270/100,000 PYs between 1984 and 2013 in HIV-positive men who have sex with men (MSM). Prevalence of any HPV among men with AC ranged between 20-96%, HPV-16 and -18 being the most prevalent (14-100% vs 8-24%). PC incidence among men was reported in 14 studies between 1962-2015. The rate ranged between 0-10.2/100,000 persons (0-12.8/100,000 PY), with higher incidence rates in older men. Prevalence of any HPV among men with PC ranged between 6.3-100%, HPV-11 and -16 being the most prevalent (0.7-80% vs 18.1-79.2%). HNC incidence among men was reported in 66 studies between 1973-2014. Global cancer registry data reported a range of HNC incidence from 1.4-42.2/100,000, declining over time depending on the geographical location. The corresponding incidence range for oropharyngeal cancer (OPC) was 0.4-17.8/100,000, with higher incidence rates for men aged 55 and above and a rapid increase during the past decade in well-developed regions. Prevalence of any HPV ranged between 0-93.8%, HPV-16 and -18 being the most prevalent (1.2-86% vs 2.5-46.9%). Conclusions: This review demonstrates the existing burden of HPV-related cancers globally. Overall, the incidence of HPV-related AC and OPC appears to have increased among men between 1962 and 2015, highlighting a growing unmet medical need and the importance of preventing HPV infection.
Influenza and mortality for non-small cell lung cancer.
Authors: Kinslow Connor J , Wang Yuankun , Liu Yi , Zuev Konstantin M. , Wang Tony J. C. , Donalek Ciro M. , Amori Michael , Cheng Simon
Published: May 2019

e13114

Background: Lung cancer is the leading cause of cancer deaths in the United States and worldwide. While influenza illness is known to be particularly dangerous for frail and elderly patients, the relationship between influenza illness and outcomes in cancer patients remains largely unknown. Methods: Monthly mortality rates for all patients at risk, as well as newly diagnosed patients, with non-small cell lung cancer (NSCLC) diagnosed between 2009 and 2015 were compared during high and low flu months using data from the Surveillance, Epidemiology, and End Results (SEER) Program and the Center for Disease Control and Prevention (CDC) website. Influenza severity was determined by the percentage of outpatient visits to healthcare providers for influenza-like illness (ILI). CDC ILI activity levels were matched with SEER data by month and state. State-months with an ILI activity level of 8 or higher were considered to be high flu months, as defined by the CDC. Results: 195,038 patients with NSCLC from 13 states were included in the analysis. 52 out of 1,081 state-months (5.1%) had high flu activity. Monthly mortality rates for low and high flu months were 4.9 and 5.7%, respectively (p = .001). The monthly mortality rate for newly diagnosed patients was also significantly higher during high flu months (9.4 vs. 10.2%, p = .01). When the analysis was limited to winter months only, monthly mortality rates for low and high flu months were 4.7 and 5.3%, respectively (p = .02). The relationship between flu severity and mortality was also observed at the individual state level. Conclusions: Increased influenza severity is associated with higher mortality rates for NSCLC patients. Future research should elucidate the relationship between vaccination and survival in lung cancer patients.
Analysis of nationwide lung, breast, and prostate cancer incidence in relation to provider availability and training programs in oncology.
Authors: Mehta Smit , Krikorian Armand A
Published: May 2019

e13116

Background: Lung, Breast, and Prostate cancer are the leading causes of cancer incidences and mortality across all ages, races, and genders. These accumulate to 1.2 million deaths from 2011-2015. We hypothesize that the regional provider availability should match the local patterns of cancer incidences due to resource scarcity. This analysis examines the nationwide incidence of the most common cancers in relation to provider availability and conducts a further analysis of the location of training programs in relation to cancer incidence. Methods: Lung, Breast, and Prostate cancer incidences in the U.S. between ages 19-85 was assessed using data from the CDC and NCI. Oncology fellowships were found through the ERAS portal and the databases of the AMA. Oncologists’ practicing locations were found using Doximity data. These datasets were mapped using Google Maps software and a gap analysis was conducted. Results: In 2015, approximately 6.2% of the population were diagnosed with lung cancer, 12.4% of women with breast cancer, and 11.2% of men with prostate cancer. The highest incidences were seen in Kentucky, Connecticut, and New Jersey. Above average incidences were seen in New Hampshire, West Virginia, Mississippi, Louisiana, and Massachusetts. Roughly 25% of the 16,215 registered oncologists were concentrated in Florida, Texas, and California. A total of 132 oncology fellowships were identified, with only eight located within a 50-mile radius of the areas of most need. Conclusions: We found a significant disparity in the distribution of cancer incidences versus location in oncologists and fellowship programs. This data, along with data from the 2018 National Oncologists Workforce suggests that Florida, California, Michigan, Illinois, and New York have the highest percentage of oncologists near or above retirement age; indicating that the gap is likely to widen. It also showed a 12-fold variation in oncologist retention compared to where they completed their fellowship, with metropolitan areas in California rounding out the top 10 highest percentages of trained oncologists1. This highlights the need to match the workforce with areas of highest need, such as the Appalachian states; which have some of the highest cancer incidences and largest discrepancies of training programs and oncologists.
Vitamin D deficiency in patients with newly diagnosed cancer.
Authors: Shaikh Hira , Bakalov Veli , Mao Shifeng
Published: May 2019

e13117

Background: Vitamin D deficiency (VDD) is pandemic in modern society. There has been increasing interest in vitamin D and its impact on cancer. A number of studies have been published on a possible link between VDD and cancer. However, because of inconsistent results, controversy remains in various aspects of vitamin D. In this study, we assessed the association of VDD with various cancers. Methods: A retrospective study was conducted in a tertiary care hospital network in western Pennsylvania. Electronic health record database was used to extract the data from patients seen in outpatient office with newly diagnosed cancer who had a measured 25-hydroxy vitamin D level at diagnosis between 02/2016 and 02/2018. VDD was defined as level less than 30 ng/dl. Patient demographics, smoking, and vitamin D status were used for multivariate logistic regression analysis in order to determine odds ratio (OR) of certain cancer type in our cohort. We used SPSS version 23 for statistical analysis. Results: A total of 934 patients (59.2% female) with cancer were included. Most patients, 86.4%, were Caucasian, and 10.8% African American (AA). VDD was found in 433 patients (46.4%) and more prevalent in men (n = 203, 53.3%), and AA (n = 65, 64.4%) in our cohort. The most common cancer type was breast cancer (30.9%), followed by prostate cancer (11.3%), lymphoma (11.1%), and lung cancer (7.8%). After adjusting to demographic characteristics and smoking status, VDD was significantly associated with pancreatic cancer (OR = 2.28, p = 0.02), and reversely associated with breast cancer (OR = 0.56, p = 0.001). VDD was also prevalent in colorectal cancer, but not statistically significant, (OR = 1.71, p = 0.064). Conclusions: Our study demonstrated that VDD is prevalent among cancer patients, especially in men and AA patients. There is a strong association between VDD and the malignancies of digestive system, particularly pancreatic cancer. Further studies are needed to assess the effect of VDD on disease-specific risk and cancer mortality as well as the impact of vitamin D supplement.
Determination of plasma EGFR mutations from non-small cell lung cancer patients at Bach Mai Hospital.
Authors: Pham Cam Phuong , Mai Khoa Trong , Loi Nguyen Thuan , Hien NGO Thi Thu , Vo Quynh Thi Thuy , Tran Ha Dinh
Published: May 2019

e13121

Background: Lung cancer patients with mutations in the epidermal growth factor receptor (EGFR) are primary candidates for EGFR-targeted therapy. Reliable analyses of such mutations have previously been possible only in tumor tissue. Here, we demonstrate that mutations can be detected in plasma samples of non-small cell lung cancer patients at Bach Mai Hospital and relation of different variables to the frequency of EGFR mutations. Methods: 193 patients with non-small cell lung cancer were identified with EGFR mutation by cobas EGFR Mutation Test v2 kit (Roche Diagnostics, USA), evaluating the EGFR mutation status with different variables. Results: The EGFR mutation rate was 43%, common in patients with adenocarcinoma, female, non-smoking, late stage disease. The rate of EGFR T790M mutation was 36.1%. Among 78 patients who was previous treated TKIs, EGFR mutation rate was 73.1% and the rate of EGFR T790M mutation was 50.8% at the time of progression. The concordance of EGFR mutation from plasma sample with tissue sample was 81%. Conclusions: EGFR mutation in plasma sample results was not different from those in tissue samples and similar with result of studies in Vietnam and worldwide.
Molecular characterization of NSCLC-like and SCLC-like subsets in Chinese pulmonary large cell neuroendocrine carcinoma (LCNEC).
Authors: Wu Lin , Cao Liming , Chen Likun , Zhu Bo , HU Xiaohua , Gen Lin , Lin Yingcheng , Zhang Sheng , Huang Cheng , Peng Wenying , Jiang Meilin , Mao Xinru , Zhang Tengfei , Ye Junyi , Zhang Lu
Published: May 2019

e13125

Background: LCNEC is an aggressive, biologically heterogenous carcinoma which can be molecularly characterized as SCLC-like and NSCLC-like. Accurate distinction of molecular subset is of major clinical relevance since it may guide treatment choices in LCNEC. Here we determined the genomic characteristics of the two LCNEC subsets in a Chinese cohort to clarify their correlations with traditional lung cancer histologies. Methods: FFPE samples from 31 LCNECs were sequenced using a 520-cancer-related gene panel, with an average sequencing depth of 1353X. Comparative mutational analysis was conducted between NSCLC-like LCNECs from our cohort and adenocarcinomas from TCGA dataset. Results: Despite similar clinical features in terms of stage and age at diagnosis, NSCLC-like (42%, 13/31) and SCLC-like (32%, 10/31) subsets from LCNEC displayed distinct molecular characteristics. NSCLC-like subset harbored significant higher mutation frequencies of STK11, KEAP1 and FAT3 (53.8%, 38.5% and 38.5%, p = .007, .046 and .046), while SCLC-like subset was characterized by highly mutated RB1 (100%, p < .001) and PTEN (50%, p = .007). Compared with TCGA adenocarcinomas, NSCLC-like LCNEC displayed more frequent mutations in TP53, STK11, APC, KMT2D and SMARCA4 (76.9%, 53.8%, 30.8%, 30.8% and 23.1%; p = .043, .004, .045, .005 and .049). In addition, potential targetable alterations were present in 46.2% (6/13) pts of NSCLC-like subset. For those advanced stage pts, 2/5 NSCLC-like and 5/5 SCLC-like pts received relevant chemotherapy according to their molecular characteristics. The clinical outcomes of these pts are still under follow-up. Conclusions: This study demonstrates the distinct molecular features between NSCLC-like and SCLC-like subsets, and highlights the predominant genomic similarity and separate entities between NSCLC-like LCNEC with adenocarcinoma. Given the evidence that genomic profiling may aid in informing treatment decisions for pts with LCNEC, our study indicates that, based on accurate molecular typing, 46.2% NSCLC-like pts may benefit from potential targeted therapy and the rest of them may be more suitable to receive NSCLC-chemotherapy.
Clinical significance of pathogenic variants in germline BRCA wild type patients at risk for hereditary breast cancer.
Authors: Kuang Xiaying , Lin Ying , Shao Nan , Yu Liang , Shan Zhen , Chen Shuyin , Shi Xinyi , Liu Hao , Liu Jing
Published: May 2019

e13127

Background: Approximately, 10% of breast cancer (BC) are related to inherited germline mutations. BRCA1/2, the most recognized and tested genes, are responsible for 50% of hereditary BC. Genetic testing for hereditary BC has changed significantly. Increasing evidence suggests parallel multigene testing. Methods: NGS-based germline BRCA status assessment was performed on 209 high risk BC patients with at least one of the following risk factors: triple negative BC, early onset ( < -45), with a family history of BC, bilateral BC and male BC. Multigene-panel testing was subsequently offered to patients with at least 2 of the risk factors and WT germline BRCA. Capture-base targeted sequencing was performed on white blood cells using a panel consisting of 53 hereditary cancer-related genes, spanning 229kb of human genome. Results: Among the 209 patients screened, only 12 patients had pathogenic BRCA1/2 mutation. Next, we investigated the prevalence of non- BRCA pathogenic germline pathogenic mutations in patients with at least 2 risk factors. Thirty-seven patients met the criteria and only 23 patients had sufficient WBC DNA for sequencing. This cohort had a median age of 42, with a majority carrying infiltrating ductal carcinoma. Except for one bilateral BC patient who had stage IV disease, all other patients had early stage disease. We identified 5 pathogenic mutations from 5 patients spanning 4 genes: PALB2, PTEN, ATM and WRN, resulting in a prevalence rate of 20% for pathogenic germline mutations in high risk germline BRCA WT BC patients. Two patients carried mutations in PALB2, one with a frameshift and another with a splice mutation. Mutation types for PTEN, ATM and WRN were splice mutation, stop gain mutation and frameshift mutation, respectively. All 5 patients were diagnosed with BC before the age of 40. Three of them had bilateral BC; one had triple negative BC and another patient had a family history of BC. Conclusions: Our study confirms the clinical significance of testing non- BRCA genes, and suggests multigene panel testing for patients at risk for hereditary BC. Such approach increases the identification of hereditary BC, thus impacting clinical decision-making.
Genomic alteration features of six cancers and their correlation with clinical characters using the next generation sequencing.
Authors: Dong Qian , Yang Haiying , Jiang Da
Published: May 2019

e13130

Background: Next-generation sequencing (NGS) examination based on liquid biopsy has been agreed as a kind of routine diagnostic tool in cancer field and may provide new sights about oncogenesis mechanisms. This study aimed to observe the genomic alteration features of common cancers and their correlation with clinical characters. Methods: We enrolled 39 subjects (38 subjects with cancer and 1 healthy subject) and administrated mutation examination using a panel including 38 genes, which targeted 6 cancer types. For each subject, the genomic DNA was extracted and NGS was performed. Results: All patients were found to carry at least one alteration among the 38 genes. PSM2 showed a highest mutation rate, with 77% subjects carrying mutations in this gene. Besides, MSH2 and STK11, etc. exhibited a high mutation rate. Overall 17 genes were found to contain known pathogenic or outcome-unknown mutations, among which 15 had outcome-unknown mutations and 5 had recognized pathogenic mutations. RAD50 had a highest frequency of outcome-unknown mutations, and secondly MLH1 and MRE11A. The clinical characters including sex, metastasis/recurrence, and family cancer history had relationships with mutation types. Conclusions: Genomic DNA sequencing is a feasible and minimally invasive approach in cancer genetic analysis and a promising tool in prediction of cancer onset and prognosis. A large amount of variations are associated with sex, family history and cancer types, and may decide metastasis/recurrence outcomes. Those who have a family history of cancer are recommended to receive NGS examination.
Screening of colorectal cancer (CRC) patients for lynch syndrome (LS) emphasizes the need for public insurance coverage of genetic testing: Results of a national program by the Hellenic Society of Medical Oncology (HeSMO).
Authors: Saridaki Zacharenia , Saloustros Emmanouil S. , Tsoukalas Nikolaos , Makatsoris Thomas , Lypas Georgios , Kalofonos Haralabos , Christopoulou Athina , Bompolaki Iliada , Sougklakos Ioannis , Voulgaris Evangelos , Karampeazis Athanasios , Papandreou Christos , Anagnostopoulos Athanasios , Galani Eleni P. , Ballasis Konstantinos , Zagouri Flora , Rizos Georgios , Athanasiadis Athanasios , Varthalitis Ioannis I. , Boukovinas Ioannis
Published: May 2019

e13141

Background: Lynch Syndrome is associated with germline mutations in Mismatch Repair (MMR) genes ( MLH1, MSH2, MSH6, PMS2). CRC patients whose tumors exhibit high-level microsatellite instability (MSI-H) have an increased probability of LS. Although the diagnosis of LS has important implications for the patient and the family, germline genetic testing is not reimbursed by the Hellenic Public State Healthcare Services. To address this need HeSMO conducted a national program to screen and diagnose CRC patients with LS. Methods: All patients with CRC were eligible. Assessment for LS involved initially screening tumor tissue for the presence of MMR deficiency, either via molecular MSI testing or via immunohistochemistry (IHC) to detect the absence of one or more MMR proteins. Patients with an MMR-deficient tumor in the absence of a somatic cause (e.g. BRAF mutation or MLH1 promoter hypermethylation) underwent genetic counseling and germline testing to confirm a LS diagnosis. Results: From June 2017 to December 2018, 104 patients diagnosed with CRC were enrolled and tested. Median age of diagnosis was 58,5 years (range 32 - 89) and male-to-female ratio was 1.6:1. Fifty patients (48%) had tumors that exhibited the MSI-H phenotype. From the MSI-H tumors, 41 (82%) did not harbor the BRAF V600E mutation and 33 of them (80.5%) did not harbor an MLH1 promoter hypermethylation. Therefore, 33 patients were invited for genetic counseling and testing. Fifteen patients (45.45%) were diagnosed with LS: 6 ( 40 %) had a mutation in MLH1 (one of which had also a mutation in PMS2 gene), 4 (26.6%) in MSH6, 4 (26.6%) in MSH2 and 1 (6.6%) in PMS2. Conclusions: In our series, 30% of the CRC patients with MSI-H tumors were tested positive for LS. These results confirm the value of a universal screening program of CRC patients for LS. Hopefully, these results will convince the Hellenic Public State Healthcare Services to reimburse screening and germline genetic testing of CRC patients for LS.
Differences in MSI phenotype between cancer types using a new PCR-based pan-cancer biomarker panel.
Authors: Bacher Jeff , Udho Eshwar , Storts Doug , Halberg Richard , Galllinger Steven , Jenkins Mark A. , Lindor Noralane M.
Published: May 2019

e13145

Background: A multiplexed biomarker panel was developed for detection of MSI that is more sensitive than currently available systems. Preliminary data showed an increased MSI sensitivity for colon polyps, endometrial (EC) and skin cancers. This study expands that finding to 14 different types of cancer. Methods: Selection of the best microsatellite markers was done using a cohort of 160 patients ≤55 years with ≥1 colon polyp and 100 EC patients ≤ 50 years. To validate the new panel, a cohort of 100 Lynch syndrome CRC, 100 sporadic MSI-High CRC, 100 sporadic MSI stable CRC and 219 extra-colonic cancers from the Colon Cancer Family Registry were tested for MSI. Samples were screened using a new 8-marker panel and Promega’s MSI Analysis System. Mismatch repair (MMR) gene mutation status and expression were determined. To compare the relative sensitivity of the 8-marker panel across all cancer types we developed a quantitative “MSI-score” for each cancer type. Results: Considerable differences in MSI phenotypes were observed between cancer types and a new approach to scoring MSI in extra-colonic cancers is proposed. Relative intensity of the MSI phenotype was characterized by MSI-Scores ranging from high of 66 (small intestine) to 6 (brain). The mutations in MSI samples were significantly more common and allele size shifts larger with the new biomarkers, making MSI classification more accurate and robost. MSI, IHC and MMR gene mutation status were highly correlated. Conclusions: The MSI sensitivity of the new biomarker panel for most cancer types was significantly higher than currently available PCR-based MSI systems. Development of the new pan-cancer PCR-based MSI system allows laboratories to leverage established equipment and known analysis techniques to keep turnaround time and costs, quick and affordable compared with emerging NGS-based technologies.
Towards a screening test for cancer by circulating DNA analysis.
Authors: Thierry Alain R. , Tanos Rita , Otandault Amaelle , Mollevi Caroline , Bauer Audrey , Tousch Geoffroy , Picque Lasorsa Laurence , El Messaoudi Safia , Colinge Jacques , Colombo Pierre-Emmanuel , Jacot William , Mazard Thibault , Sayagues Jose Maria , Gillet Brigitte , Pezet Denis , Ychou Marc
Published: May 2019

e13146

Background: Following works on the clinical potentials of circulating DNA (cfDNA), our group is now particularly focused on evaluating its potential for early detection of cancer. We recently developed a test (MNR: Multi Normalized Ratio), based on various cfDNA parameters determined by a specific q-PCR based method, targeting both nuclear and mitochondrial sequences. When applied to the supernatant of cell culture, the MNR had a discriminative potential of 100% between normal and cancer cell lines. Methods: We recently developed a screening test (MNR: Multi Normalized Ratio), based on various cfDNA parameters determined by a specific q-PCR based method, targeting both nuclear and mitochondrial sequences. When applied to the supernatant of cell culture, the MNR had a discriminative potential of 100% between normal and cancer cell lines. Results: We are currently carrying out an extensive evaluation of this test in plasma samples from diagnosed and healthy individuals. Preliminary results on the plasma of 289 healthy subjects and 1,200 patients with various types of cancer (colorectal, breast, lung, liver, pancreatic, ovarian) of all stages, revealed a high potential with an AUC of 0.82 (0.78-0.84, 95% confidence interval, CI) and 70% sens. with 78% spe.. In breast cancer (N = 169), an AUC of 0.82 (0.78-0.86, 95% CI) with 72% sens. and 80% spe. were observed. In all stages CRC patients (N = 887), the results showed an AUC of 0.81 (0.78-0.84, 95%, CI) and 68% sens. with 80% spe.; for CRC stages 0/I/II (N = 249), an AUC of 0.75 (0.71-0.80, 95% CI) and 60% sens. with 79% spe.; and for CRC stage IV (N = 101), a 0.86 AUC (0.82-0.91, 95% CI) with 81% sens. and 78% spe.. When combining the MNR test to a threshold value of the total concentration of cfDNA (AUC = 0.82 (0.79-0.84, 95% CI), 70% sens. and 80% spe. in all stage cancers (N = 1078)), in CRC stages 0/I/II (N = 249) vs Healthy Individuals (N = 289), we observed a 63% sens. with 84% spe. Conclusions: Furthermore we recently discovered that cfDNA fragmentation, as determined by Whole Genome Sequencing using either double or single strand library, is also a parameter enabling discrimination between healthy and cancer individuals. Data on a multi-parametric test combining total cfDNA quantification, MNR and fragmentation biomarkers with help of a ongoing decision tree algorithm in machine learning will be presented during the meeting. Our on-going data suggest that our strategy in targeting cfDNA quantitative/structural features might be powerful for cancer screening/early detection and appears as an alternative or a synergistic combination to searching mutations.
The effect of the Affordable Care Act on genetic testing patterns and outcomes for inheritable cancer syndromes: A single institution experience.
Authors: Zhou Zhen Ni , Frey Melissa Kristen , Fields Jessica , Gordhandas Sushmita , Ruiz Maria Paula , Caputo Thomas A. , Holcomb Kevin , Chapman-Davis Eloise
Published: May 2019

e13157

Background: National guidelines recommend genetic testing for women at increased risk for pathogenic mutations, however insurance coverage is a commonly cited barrier to test completion. The major provisions of the Affordable Care Act (ACA) became available in New York State (NYS) in January 2014. We sought to evaluate the effect of insurance status on genetic testing patterns following introduction of the ACA. Methods: Insurance status and genetic testing patterns at the hereditary breast and ovarian cancer center at a single institution were reviewed between 1/1/2013 and 12/31/2016. Insurance status and association with testing type and clinical outcomes were evaluated before and after January 2014. Results: During the study period, 1535 women underwent genetic counseling and genetic assessment. When comparing the cohort of women undergoing genetic testing prior to and following January 2014, significant increases in patients undergoing multigene panel testing were observed across all insurance types (6.3% vs. 40.6%, p < 0.001). While a significant increase in the number of patients with private insurance or Medicaid as primary coverage was seen, the increase in insured women was largely attributed to insurance polices through the ACA exchange (p < 0.001), with the majority being Medicaid ACA plans (80.3%). Conclusions: Since expansion of health insurance through the ACA in NYS, there has been a shift in the demographics of women undergoing genetic testing at a hereditary breast and ovarian cancer center with significantly more insured women and a rise in multigene panel testing. With insurance expansion and improved access to comprehensive genetic testing, insurance status should not be an obstacle for genetic testing.
Do genetic testing criteria identify individuals with Lynch syndrome prior to cancer diagnoses?
Authors: Reys Brian , Mauer Caitlin , Pirzadeh-Miller Sara , Ross Theodora S.
Published: May 2019

e13158

Background: Screening colonoscopies every 1-2 years are estimated to decrease the risk for colorectal cancer (CRC) development in individuals with Lynch syndrome (LS) by 62-72%. However, in order for risk reduction to be effective, genetic testing guidelines must identify individuals with LS before they develop CRC. Current NCCN indications for LS evaluation focus on individuals who have already developed cancer. This study aims to identify the effectiveness of NCCN criteria in identifying LS patients before a cancer develops. Methods: A retrospective chart review was performed for 173 patients with a personal history of a LS-associated cancer seen at UT Southwestern and affiliate hospitals between 2009-2018. All patients tested positive (pathogenic or likely pathogenic) for a LS-associated mutation. Review determined if patients met NCCN (v1.2018) criteria for the evaluation of LS before and after their personal diagnosis of cancer. The study controlled for known mutations in families, past iterations of NCCN guidelines and instances of limited family history. Results: Of patients with LS, 31.8% (55/173) met NCCN testing criteria only after their personal diagnosis of cancer. Data per gene reveals 13.3% (8/60) MLH1, 25.4% (16/63) MSH2, 44.8% (13/29) MSH6 and 85.7% (18/21) PMS2 mutation carriers in the cohort were missed by current guidelines . Conclusions: 31.8% of patients with LS mutations would not have met NCCN LS evaluation criteria prior to their diagnosis of cancer. Criteria disproportionately missed individuals with lower penetrant MSH6/PMS2 mutations. These findings highlight a need for the field to develop criteria that support the detection of LS in individuals with and without cancer. As the field debates the merits of population based testing, this study suggests the current criteria for LS germline testing are not sufficient for identification of LS prior to cancer diagnosis for many patients with LS.
Pulmonary F-18 FDG uptake of non-tumor area in lung cancer patients to provide risk stratification in postoperative acute exacerbation of interstitial lung disease.
Authors: Yamamichi Takashi , Shimada Yoshihisa , Makino Yojiro , Kakihana Masatoshi , Kajiwara Naohiro , Ohira Tatsuo , Ikeda Norihiko
Published: May 2019

e13165

Background: The incidence of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) is higher than the general population. In IPF patients with lung cancer, postoperative acute exacerbation (AE) is considered a fatal comorbidity. This study aimed to investigate whether FDG-PET/CT can be used to assess the risk of postoperative AE of IPF and severe respiratory adverse events (SRAE),which are defined as grade 3a or more severe respiratory complications such as AE, bacterial pneumonia, empyema, and bronchial fistula based upon Clavian-Dindo classification. Methods: We identified 822 patients with lung cancer who had preoperative FDG-PET/CT and subsequent pulmonary resection from July 2012 to July 2018. We reviewed the patients’ clinical records and transferredthe preoperative FDG-PET/CT images of each patient to SynapseVincent system (Fujifilm Corporation, Tokyo, Japan) for measuring SUV value of the lung.Inevery case, both SUVmax of main tumor (tumor-SUVmax) and non-lung tumor part (NLT-SUVmax) were measured. Univariate and multivariate analyses were performed for exploring significant parameters associated with AE and SRAE. Results: The cohort in this study consisted of 460 men and 362 women (mean age 67.9 ± 10.1 years; range 23–87). SRAE was observed in 35 (4.2%) patients including those with AE (n = 16, 1.9%). NLT-SUVmax and presence of IPF on CT were the independent predictive factors for both AE and SRAE. The receiver operating characteristic (ROC) area under the curve (AUC) of significant factors associated with AE and SRAE was measured, and cut-off levels on ROC curves for significant parameters associated with AE and SRAE were 1.69 and 1.55, respectively. The risk rates for the incidence of AE and SRAE according to NLT-SUVmax and chest CT findings were 19.0 % and 30.2% of the patients with positive IPF on CT and NLT-SUV max ≥1.69. Conclusions: NLT-SUVmax was the independent predictor of the incidence of AE and SRAE for patients who underwent pulmonary resection. FDG/PET-CT can be used in routine clinical practice to identify high-risk individuals for AE who require careful and intensive observation after pulmonary resection and that can facilitate clinical decision-making.
Risk factors associated with a second primary lung cancer (SPLC) in patients (pts) with a previous initial primary lung cancer (IPLC).
Authors: Nagasaka Misako , Farhat Dina , Belzer Kimberly , Kim Seongho , Mamdani Hirva , Sukari Ammar , Milczuk Mary Ann , Schwartz Ann G. , Wozniak Antoinette J.
Published: May 2019

e13166

Background: The risk for development of a SPLC after treatment of an IPLC is around 1% to 2% per pt per year. The aim of this study was to characterize the risk factors associated with the development of a SPLC. Methods: Pts registered in the Karmanos Cancer Institute Tumor Registry diagnosed with an IPLC between 2000 and 2017 were included in this study. Pts with an IPLC who later developed a SPLC were matched for age, histology and stage to pts with an IPLC who did not develop a SPLC. SPLC was defined as a second lung cancer with a different pathology or if the same pathology, anatomically, molecularly, or chronologically distinct. Six variables including: stage at IPLC, histology, family history, surgery as a primary treatment for IPLC, and smoking history (determined by pack years, and continued tobacco use after first diagnosis) were reviewed. Logistic and Cox regression analyses were performed to determine the relationship of these characteristics with the development of a SPLC, and their association with overall survival (OS). Results: 121 pts with IPLC who later developed an SPLC were identified and compared to 120 pts with IPLC who did not develop a SPLC. Logistic analyses did not show that stage at first diagnosis, histology, family history, smoking history, and continued tobacco use after first diagnosis to be relevant for increased risk of SPLC. Pts who were primarily treated with surgical resection had a significantly higher probability of developing a SPLC (Odds Ratio: 0.24, 95% CI: 0.12 to 0.48, p < 0.001). Pts who did not have surgical resection as their primary mode of treatment for IPLC had a significantly higher risk of death than those who received surgical resection (HR 3.02, 95% CI: 1.99 to 4.57; p < 0.001). Conclusions: Based on our findings, pts who had surgical resection for an IPLC were found to have improved OS and a higher possibility of developing a SPLC. Stage at first diagnosis of IPLC, histology, family history, smoking history and continued use of tobacco after first diagnosis did not correlate with increased risk for SPLC. These results warrant further investigation and if confirmed could have an impact on surveillance recommendations post resection of initial lung cancers.
The clinical characteristic and prognostic factors of leptomeningeal metastasis in patients with non-small-cell lung cancer: A retrospective study from one single cancer institute.
Authors: Yan Weiwei , Yu Jinming
Published: May 2019

e13502

Background: Leptomeningeal metastasis (LM) is a detrimental complication of advanced NSCLC, and the optimal therapeutic approach for LM patients is in shortage. The retrospective study was to investigate clinical features and prognostic factors of NSCLC patients with LM. Methods: We retrospectively reviewed the records of NSCLC patients with LM at the Shandong Cancer Hospital and Institute between July 2014 and March 2018. Identified cases had pathology-proven NSCLC with either positive CSF cytology or LM enhancement by MRI. Results: One hundred and thirty-six NSCLC patients (58 men, 78 women) with LM were enrolled in the retrospective study, median age was 55 years (range, 29–89 years). Fifty-one patients harbored EGFR mutations and ALK rearrangement was detected in six patients. Treatment for LM consisted of EGFR-TKIs alone in 11 patients, WBRT alone in 19 patients, Chemotherapy (ChT) alone in 12 patients, EGFR-TKIs plus WBRT in 30 patients, WBRT plus ChT in 25 patients, and EGFR-TKIs plus ChT in 24 patients. The median progression free survival (PFSLM) was 3.9 months (95% CI, 3.178-4.622) and the median overall survival (OSLM) was 9.8 months (95% CI,7.5-12.1). A multivariate analysis indicated that KPS ≥ 80 (HR = 0.592, 95% CI:0.369-0.95; p = 0.03) and EGFR-TKIs (HR = 0.507, 95% CI:0.283-0.908; p = 0.022) after LM diagnosis were independent favourable predictors of survival, whereas smoking (HR = 1.181, 95 % CI:1.009-3.246; p = 0.047) was an independent predictor of poor survival. Conclusions: Patients with good performance status, non-smokers and the administration of EGFR-TKIs might improve clinical outcomes in NSCLC patients with LM.
Lethality and mitotic activity of T98G glioblastoma cells under the influence of pulsed magnetic fields and ionizing radiation.
Authors: Popov Ivan A. , Shikhlyarova Alla I. , Kit Oleg I. , Rostorguev Eduard Evgenevich , Gusareva Marina A. , Timoshkina Natalya N. , Potemkin Dmitrii S. , Atmachidi Dmitriy P. , Rozenko Ludmila Ya. , Zinkovich Mikhail S. , Zhukova Galina V.
Published: May 2019

e13511

Background: Development of alternative methods of non-invasive therapy in neurooncology is determined by the need to prevent the continued growth of glioblastoma and radiation-induced complications. Usage of electromagnetic influence for these reasons is determined by the oscillatory nature of intracellular processes and results of previous studies on the effect of weak electromagnetic radiation in tumor growth. The purpose of the study was to reveal the effect of a pulsed magnetic field (PMF) and ionizing radiation (IR) on human T98G glioblastoma cells. Methods: Human T98G glioblastoma cells were cultured in the RPMI-1640 medium (Biolot, Russia) supplemented with 10% fetal bovine serum (Thermo Scientific HyClone, USA). The culture was seeded in the Biofil plates (at least 8x105 cells per 3 mL of the medium), incubated (CB 150 Binder, Germany) and exposed to IR 10 Gy (TheratronEquinox-BestTheratronics) for 11.7 min. and/or PMF 15 mT or 300 mT with a sequence of frequencies 0.3-3.0-9.0 Hz for 7 min. (Neiro-MS/D by Neirosoft, Russia). The efficiency criteria were lethality and the mitotic activity of human T98G glioblastoma cells. Results: The highest cellular lethality was registered 3 hours (18.7 vs. 5.2% in controls, p≤0.05) and a day after IR exposure. PMF 15 or 300 mT alone increased lethality by 2.5-2.8 times compared to controls (p < 0.05). IR plus PMF (15 mT) did not caused increased lethality. At the same time, the most pronounced decrease in the mitotic activity a day after exposure (by 4.7 times, p < 0.05) was registered in PMF alone (15 mT). Conclusions: The inhibitory effect of PMF on the viability of human glioblastoma cells indicates the prospects for its use as an accompanying treatment in neurooncology.