bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly accurate NGS-based multi-gene testing in the diagnosis of thyroid nodules with indeterminate cytology.
Authors: Song Yuntao , Zhang Bin , Ma Tonghui
Published: May 2020

e13579

Background: Thyroid nodules are highly prevalent, Fine-needle aspiration (FNA) is the standard pre-operative tool for diagnosis. However, some of the samples are classified as indeterminate, which leads to unnecessary surgery. BRAF V600E mutation is often used as a diagnostic marker for thyroid cancer, and it is highly specific for papillary thyroid carcinoma (PTC). But BRAF mutation is rarely occurred in thyroid nodules with indeterminate cytology. To diagnose the indeterminate thyroid nodules precisely, some NGS-based multi-gene testing panel has been developed and clinically used in America and Europe, but rare research was reported in China. In this study, we evaluated the value of a next-generation sequencing (NGS) panel to cancer diagnosis in indeterminate thyroid nodules. Methods: From February 2018 to September 2018, 360 patients with thyroid nodules who underwent FNA at Peking University Cancer Hospital were enrolled. And the FNA samples with indeterminate cytology were evaluated using a next-generation sequencing (NGS) assay, including 16 genes analyzed for point mutations and 26 types of gene fusions. Diagnostic performance of this multi-gene testing panel was compared with BRAF V600E single gene mutation analysis. Results: 141 nodules were cytologically indeterminate among 360 patients on FNA biopsy, 72 of which were resected and analyzed by NGS successfully. Histologic analysis after surgery revealed 41 (56.9%) cancers in these 72 patients. The multi-gene testing assay could classify 30/41 cancers correctly, showing a sensitivity of 73.2%, specificity of 96.8%, positive predictive value of 96.8%, and negative predictive value of 73.2%. The diagnostic accuracy of the multi-gene testing was significantly higher than the BRAF V600E mutation analysis (83.3% vs 73.6%, x2= 31.588, p < 0.01). Conclusions: Our study demonstrated that the multi-gene testing provided both high sensitivity and high specificity for cancer detection in thyroid nodules with indeterminate cytology, and its accuracy was much higher than BRAF V600E mutation test.
Overview of obesity and breast cancer in Brazil: 24 year of follow up.
Authors: Pereira Andrea Z , Pitito Bianca de Almeida , do Prado Rogério Ruscitto , Mattar Andre , Hegg Roberto , Shida Jorge Yoshinori , Gebrim Luiz Henrique
Published: May 2020

e13580

Background: Obesity is one of the major public health challenges of the 21st century. The prevalence of obesity is growing exponentially across all age groups and on all continents and it is associated with morbidities such as cardiovascular disease, diabetes mellitus type 2, dyslipidemia, hypertension and cancer. There is a higher risk of developing breast cancer in postmenopausal obese women, and with worse outcome for women of all ages. Objectives: To evaluate obesity prevalence in breast cancer patients and its association with recovering, survival, death, age, Human Epidermal Growth Factor Receptor 2 (HER2) and anti-human KI67 antibody(KI67). Methods: A retrospective cohort study was performed between 1994 and 2018 at the Breast Cancer Department, São Paulo State Government Women's Health Reference Center (Perola Byington Hospital), São Paulo, Brazil with 8824 breast cancer patients. From those, 2899 patients were excluded because they did not have description of weight and/or Body Mass Index (BMI). Survival analysis was performed according to BMI groups. Results: The participants had mean (SD) age of 54 (12.0) years and weight of 70 (15.0) kg. There were 769 (13%) deaths and the mean survival was 20 (2.0) years. 1787 (30%) participants were stratified in obese (BMI≥30Kg/m2) and 4138 (70%) non-obese Obese were older (p < 0,001) and had a higher frequency of HER2 negative (p < 0,04) than non-obese women. There were not a significant difference in frequencies of KI67, recovering and survival between groups. The prevalence of obesity was not different over 24 years. Conclusions: There was a relevant prevalence of obesity in breast cancer patients, which was associated with HER2 negative and age, but not with recovering or survival.
A nomogram to predict the probability of breast intraductal tumors in patients with nipple discharge: A report based on our 13-year clinical experience.
Authors: Jiang Siyuan , Wang Bin , Zhu Lizhe , Yu Shibo , Ren Yu
Published: May 2020

e13582

Background: Nipple discharge is a common symptom of breast disease. Our aim was to perform a descriptive statistical analysis of the cases we collected and to establish a model to predict intraductal tumors. Methods: We conducted a retrospective study of patients from 2007 to 2019. The variables were analyzed by the c2 test. Univariate binary logistic regression was used to analyze the relationship between clinical features of patients. Receiver operating characteristics (ROC) were used to assess the sensitivity and specificity of the predictive ability of the model. Results: Patients with spontaneous, single duct, bloody discharge and smooth ductal wall were more likely to diagnose with tumor by ductoscopy. A model was established based on seven variables: age, side of discharge, spontaneous or not, duration of discharge, ductal wall and characteristics of discharge. It was subsequently validated in 178 patients with complete data on variables in the validation cohort. The area under ROC curve (AUC) were calculated to be 0.7024 indicating a good predictive ability. Conclusions: Patients with clinical characteristics of unilateral, bloody, single duct, spontaneous discharge and smooth ductal wall were more likely to have intraductal tumors by ductoscopy. Our nomogram can effectively predict intraductal tumors in patients with nipple discharge.
Statin use is associated with a lower risk of diffuse large B-cell lymphoma: A systematic review and meta-analysis.
Authors: Ponvilawan Ben , Charoenngam Nipith , Ungprasert Patompong
Published: May 2020

e13585

Background: Statin use is associated with decreased risk of several types of cancer such as hepatocellular carcinoma, colorectal cancer and hematologic malignancy, although the data on diffuse large B-cell lymphoma (DLBCL) is still inconclusive. The current systematic review and meta-analysis was conducted to summarize all available data on this association. Methods: A systematic review was performed using EMBASE and MEDLINE database from inception to October 2019 with search strategy that included terms for “statin” and “DLBCL”. Eligible studies could be either cohort or case-control studies that reported the association between statin use and risk of DLBCL. Eligible cohort studies must include patients with history of statin use and comparators with no history of statin use, then follow them for incident DLBCL and report the relative risk, hazard risk ratio, or standardized incidence ratio and associated 95% confidence intervals (CI) comparing the incidence of DLBCL between the two groups. Eligible case-control studies must include cases with DLBCL and controls without DLBCL, then search for prior statin use and report the odds ratio and associated 95% CI for this association. Point estimates along with standard errors were extracted and combined together for the calculation of the pooled effect estimate using the random effect, generic inverse variance method. Results: A total of 1,139 articles were identified using the search strategy. Six studies satisfied the inclusion criteria and were included into the meta-analysis. Statin use was associated with a significantly reduced risk of DLBCL with the pooled relative risk of 0.70 (95% CI, 0.56 – 0.88; I2 = 70%). Funnel plot was fairly symmetric and was not suggestive of presence of publication bias. Conclusions: This systematic review and meta-analysis found that patients with history of statin use had a significantly lower risk of DLBCL compared to individuals without history of statin use.
The contribution of hereditary cancer-related germline mutations to lung cancer susceptibility.
Authors: Song Lele , Liu Mengyuan , Liu Xinyi , Peisu Suo , Huang Tanxiao , Chen Yaru , Zhou Yanqing , Liu Guifeng , Yao Jianfei , Chen Shifu , Xu Mingyan
Published: May 2020

e13594

Background: Germline variations may contribute to lung cancer susceptibility besides environmental factors. The susceptibility of germline mutations and their correlation with somatic mutations has not been systematically investigated in lung cancer patients. Methods: Germline mutations from 1090 lung cancer patients were analyzed with a 58-gene NGS panel containing known hereditary cancer-related genes, and were categorized based on ACMG guidelines in pathogenicity, and the corresponding somatic mutations were analyzed using a 605-gene NGS panel containing known cancer-related genes. Results: Genetic susceptibility was found in 4.5% of lung cancer patients, in which 14 patients with pathogenic mutations and 35 patients with likely-pathogenic mutations were identified. Significantly stronger family history was found with the pathogenic group than other groups. Pathogenic mutations fell most commonly in BRCA2 (6/14), followed by CHEK2 (3/14) and ATM (2/14). Likely-pathogenic mutations fell most commonly in NTRK1 mutations (4/35) and EXT2 mutations (4/35), followed by BRIP1 (3/35) and PALB2 (3/35). These genes are involved in DNA repair (BRCA1 and BRCA2, BLM, RAD50, BRIP1, MLH3), cell cycle regulation (such as CHEK2, ATM, NTRK1 and EPCAM) and tumor suppressor (such as PALB2). The overall odds ratio (OR) value of the pathogenic group was 17.93 (95% CI: 9.74 to 33.01), and was 15.86 (95% CI: 5.999 to 133.2) for the likely-pathogenic group, suggesting that the pathogenic or the likely-pathogenic germline mutations as a whole were risk factors for lung cancer. Somatic mutation analysis revealed no significant difference in TMB among the groups, although a trend of lower TMB in the pathogenic group was found. The SNV/INDEL mutation rate of TP53 in the pathogenic group was significantly lower. Pathway enrichment analysis found no significant difference in aberrant pathways among the groups. Conclusions: 4.5% of patients carrying germline variants may be linked to increased susceptibility to lung cancer. The susceptibility is mainly reflected in family history and morbidity risk without significant influence on aberrant pathways.
Marital status and survival analysis of patients with pure mucinous breast carcinoma: A SEER population-based retrospective study.
Authors: Tang Fan , Wei Xiaoqing , Dian Li ping , Zhou Qu zhi , Xu Rui , Ren Liping , Zhang Yuzhu , Chen Qianjun
Published: May 2020

e13598

Background: The present study was conducted to investigate the influence of marital status on survival of pure mucinous breast carcinoma(PMBC) based on surveillance, epidemiology, and end results (SEER) databases. Methods: Data were extracted from the SEER database on eligible patients diagnosed with pure mucinous breast carcinoma between 1998 and 2015. Patients were divided into married groups (including common law) and not married groups (including single[never married]/unmarried or domestic Partner、Divorced、Separated、Widowed). Survival curves were generated using the kaplan-meier method, and survival differences were estimated using the log-rank test. Multivariate Cox proportional risk models were used to assess independent risk factors for survival. Results: A total of 14972 eligible pure mucinous breast carcinoma patients were enrolled from the SEER database, including 7462(49.84%) married and 7510(50.16%) not married patients. The OS and CSS were significantly greater in married patients than not married patients (79.27 vs 62.49% for OS and 96.07 vs 93.34% for CSS, both P =0.000). Married patients were more likely to be more younger (aged≥75) (21.5% vs. 44.1%), cancer stage were even lower(stage I)(69.6% vs. 62.6%), (stage II)(28.6% vs. 33.9%), (stage III)(0.6% vs. 0.9%), (stage IV)(1.3% vs. 2.5%), more patients received breast conserving surgery(67.4% vs. 62.9%), chemotherapy(15.3% vs. 11.0%) and radiation therapy(54.3% vs. 43.1%), also no recurrent lymph node metastasis was observed(82.8% vs. 74.6%) compared to unmarried group(All P =0.000). The multivariate Cox proportional hazards model showed that marriage is an independent protective factor for OS (HR = 1.356, 95% CI: 1.271-1.446, P =0.000) and CSS (HR = 1.942, 95% CI: 1.681–2.644, P =0.000). Conclusions: Marital status was an independent prognostic indicator in PMBC patients. Research data showed that married pure mucinous breast carcinoma patients can obtain better OS and CSS than unmarried patients.
Hormone-replacement therapy may be associated with increased incidence of luminal breast cancer: Results from a large-scale health maintenance organization (HMO) analysis.
Authors: Siegelmann-Danieli Nava , Rosenberg Vered , Bareket-Samish Avital , Chodick Gabriel , Shalev Varda
Published: May 2020

e13599

Background: Trends in breast cancer (BC) incidence may be impacted by potentially competing variables (e.g., mammography rates, hormone-replacement therapy [HRT] use). Methods: This observational retrospective study examined trends/associations between BC incidence, mammography rates, and HRT use among female members of the Maccabi Healthcare Services (the second largest HMO in Israel).BC subtypes were determined based on therapies received by patients diagnosed after 2006 (following trastuzumab approval in the adjuvant setting). Results: Between 2002 and 2014, 14,092 BC cases (88% invasive, 12% in-situ) were identified. The age-adjusted incidence rate of invasive BC peaked in 2005, consistent with increased mammography screening that year, and decreased thereafter. HRT use among all female members aged≥45 years decreased from 13.2% in 2002 to 4.6% in 2014, consistent with the global trend after the Women's Health Initiative publication. Analysis by BC subtype involved 6,218 invasive BC patients diagnosed between 2007 and 2014 (luminal A, 47.5%; luminal B1 without human epidermal growth factor receptor 2 [HER2] over-expression, 25.7%; luminal B2 with HER2 over-expression, 7.7%; estrogen receptor [ER]-negative/HER2+, 4.9%; triple negative, 8.3%; unknown, 6.0%). Overall, 75-86% of patients across all subtypes did not have any HRT exposure vs 14-25% who were current users (within 1 year before the BC diagnosis), recent users (within 2-5 years), or past users ( > 5 years). Current and recent use of HRT was statistically significantly higher in luminal BC vs ER-negative tumors: rates in luminal A/B1/B2, 15.3%/12.1%/11.1% vs ER-negative HER2+/triple-negative/unknown, 8.9%/9.7%/7.7% ( P< 0.001). In BC patients (≥45 years) with HRT exposure, the preparations used were estrogen plus progesterone (62%), estrogen alone (24%), and tibolone (14%). In non-BC cases (≥45 years), the respective values were similar: 61%, 26%, and 13%. Conclusions: HRT current/recent exposure may contribute to increased incidence of luminal BC tumors.
Prevalence of germline mutations in BRCA1/2 in patients from northeastern Brazil.
Authors: Picanço-Albuquerque Clarissa Gondim , Silva-Fernandes Isabelle Joyce de Lima , Bezerra Maria Júlia Barbosa , Luciano Maria Claudia dos Santos , Sant'Ana Rosane Oliveira , Silva Paulo Goberlanio de Barros , Lima Marcos Venício Alves
Published: May 2020

e13603

Background: Identifying carriers of hereditary cancer predisposition syndromes (HCPS) improves prevention and treatment. However, due to the elevated cost of genetic testing, information on the prevalence and incidence of HCPS is scarce, depriving patients of assertive treatment―a scenario observed worldwide, especially in regions like Northeastern Brazil. In this study, we determined the prevalence of hereditary breast and ovarian cancer (HBOC) in patients from Ceará (Brazil) based on NCCN criteria. Methods: The patients (n = 267) were evaluated using NGS gene panels, while retrospective data were analyzed statistically with the chi-squared test, Fisher’s test and multinomial logistic regressions ( p< 0.05; SPSS 20.0). Results: BRCA1/2 was detected in 21.3% (57/267) of the sample, but BRCA1 was more prevalent than BRCA2 (70%; 40/57 vs 30%; 17/57) ( p< 0.001). Having two or more primary tumors ( p= 0.031) or primary ovarian cancer ( p= 0.029) was associated with the pathogenic mutation BRCA1/2. The latter was detected in patients with bilateral tumors (40%) and male breast cancer (45%), and in patients under 45 years (67%), with familial breast cancer (27%) and familial ovarian cancer (41%). In the multivariate analysis, the triple-negative phenotype was strongly associated with mutated BRCA1/2 ( p= 0.003). Conclusions: The prevalence of HBOC in our sample is compatible with rates reported worldwide. The study variables (bilaterality, male sex, age < 45 years, family history of breast or ovarian cancer, and triple-negative phenotype) reinforce the diagnostic criteria published by the NCCN.
Lung cancer chemotherapy and radiotherapy toxicity in patients with HIV.
Authors: Mutetwa Tinaye , Marshall Deborah Catherine , Rehmani Sadiq , Polak Paz , Sigel Keith Magnus
Published: May 2020

e13616

Background: Lung cancer is the leading cause of cancer death for people living with HIV (PWH), and this group experiences lung cancer outcome disparities for unclear reasons. To better understand these disparities, we explored potential differences in adverse events since the start of chemotherapy, or radiation therapy (RT), among PWH with stage I-IIIA non-small cell lung cancer (NSCLC). Methods: Our matched case-cohort study used data from SEER-Medicare data on stage I-IIIA NSCLC diagnosed between 2000 and 2013. We identified 809 early stage NSCLC patients with HIV; 40 were treated with chemotherapy and 60 with RT. For each therapy type, a PWH case was matched, by age, sex, and cancer stage to 10 controls with no evidence of HIV infection. Outcome Measures: Acute severe chemotherapy or RT toxicity ascertained by a relevant inpatient diagnosis within 6 months of chemotherapy initiation or chronic toxicities from outpatient diagnostic codes within 24 months. We also evaluated overall (all-cause) and lung cancer-specific survival. Results: Among hematologic toxicities, PWH treated with chemotherapy were more than twice as likely to develop severe anemia [odds ratio [OR] = 2.3 (95% confidence interval [95% CI]: 1.2-4.6)]; but not neutropenia or thrombocytopenia (both p > 0.06). Among patients receiving chemotherapy, HIV was not associated with any other severe acute toxicities including fever, infection, nausea, renal dysfunction, and septicemia. For chronic complications, PWH had increased risk of neuropathy (OR 4.2; 95% CI: 1.3-13.6). Overall, HIV was associated with an increased count of chemotherapy complications seen per patient [p = 0.02]. PWH receiving chemotherapy had worse all-cause mortality (hazard ratio (HR) = 1.7; 95% CI: 1.2-2.4) and higher lung cancer-specific mortality (HR 1.8; 95% CI: 1.2-2.7) compared to uninfected persons after adjusting for treatment with surgery. In contrast, HIV was not significantly associated with severe RT complications (esophagitis, pneumonitis or hemoptysis), although all-cause mortality (HR 1.5; 95% CI: 1.1-2.0) and lung-cancer specific mortality (HR 1.5; 95% CI: 1.1-2.0) were higher among PWH receiving RT after adjusting for treatment with surgery. Conclusions: Antiretroviral-era PWH with early stage lung cancer experienced more frequent complications after chemotherapy but not radiotherapy compared to matched uninfected persons. These toxicities may have led to treatment alterations potentially contributing to outcome disparities seen in this high-risk group.
Lipid levels and survival after obesity-related cancer in the Women’s Health Initiative CVD biomarker cohort.
Authors: Hovsepyan Gayane , Lehman Amy , Thomson Cynthia A. , Iyengar Neil M. , Beebe-Dimmer Jennifer Lynn , Barac Ana , Shadyab Aladdin H. , Brasky Theodore , Saquib Nazmus , Wild Robert , Desai Pinkal , Caan Bette Jane , Simon Michael S.
Published: May 2020

e13618

Background: Previous investigations have demonstrated an inconclusive relationship between lipid biomarkers and mortality after cancer. Methods: We used data from 2,279 postmenopausal women diagnosed with 13 obesity-related cancers, who were part of the Women’s Health Initiative (WHI) lipid biomarkers cohort, to evaluate the relationship between lipid levels measured at study entry prior to cancer diagnosis, and mortality after cancer. Baseline lipid measurements consisted of HDL-Cholesterol, LDL-Cholesterol, and non-HDL-Cholesterol with ranges of measurement listed in the table. Obesity-related cancers included: meningioma, thyroid, adenocarcinoma of esophagus, breast, multiple myeloma, liver, kidney, gallbladder, stomach, uterus, pancreas, ovaries, and colorectal. The age adjusted relationship between baseline lipids and all-cause mortality as well as mortality due to cancer were estimated using Cox proportional hazards models and Fine-Gray models, respectively. Results: The majority of women in the cohort had either desirable or acceptable lipid levels (86% HDL-C, 30% LDL-C and 61% non-HDL-C. Low vs. desirable HDL-C levels were associated with higher risk of all-cause mortality (hazard ratio (HR) 1.54, 95% confidence interval [CI] [1.48, 1.60], p <.001) and higher cancer mortality (sub-distribution hazard ratio (SHR)1.9, 95% CI [1.51, 2.3], p <.001). High non-HDL-C vs desirable, was associated with higher all-cause mortality (HR 1.13, 95% CI [1.06, 1.21], p = .001) however no significant impact on cancer mortality (SHR 1.06, 95% CI [0.87, 1.30], p = 0.563). LDL-C levels demonstrated a more complex relationship with mortality, nevertheless, very high LDL-C levels were associated with higher risk of all-cause mortality (HR 1.63, 95% CI,1.21-2.2, p = ,0.001) and cancer-specific mortality (HR 1.78, 95% CI 1.22-2.63, p = 0.003). Conclusions: Elevated LDL-C and lower HDL-C may be associated with a lower risk of all-cause and cancer specific mortality in women diagnosed with obesity related cancers in the WHI. Results of multivariable adjustment for important predictors of mortality including race/ethnicity, medication use and other socio-demographic and clinical factors will be presented. [Table: see text]
Cancer site distribution in district hospital in central India.
Authors: Pendharkar Dinesh , Tripathi Chandramauli
Published: May 2020

e13627

Background: Many state governments have started district cancer care program to offer cancer services in district general hospitals. These places are most frequented by every level of population. The access is free, close to their residence and has an equitable atmosphere. The program created de-facto registry of local cancer patients. We, here analyze trends of various types of cancer in one such hospital of central India. Methods: All patients reporting to this unit for various support in cancer are registered with unique id. The registry takes their local residential details and details of the medical history related to cancer. They are offered support all through their journey of cancer from diagnostics to end of life care, palliative care. Data of 2014-2019 are analysed from District Ujjain in central India. Results: Total of 3562 patients were registered with proven diagnosis of cancer. There were 1805 male (50.7%) and 1757 females (49.3%.In female group age varied between 2to 97 years, with a mean of 51.41 and median age of 50 years. In male group,the age ranged between 1 to 92, with mean age of 53.46 and median of 55 years. The five commonest cancer amongst female included breast, head and neck, ovary, cervix and lung. In males the commonest five were-Head and neck, lung, prostate, oesophagus and colo-rectal (Table). The group of head and neck cancer include all sites of the head and neck area together. Conclusions: The pattern of cancer in districts is giving new geopathological information. It is clear that tobacco related cancer predominates in male and female both, but breast cancer is number one even in a relatively rural area. In female ovary is increasing and cervix is coming down compared to national data.In view of governments putting in extensive pressure on early detection schemes in India,this data is extremely important. Based on these realistic data, the strategy may be changed for the district. [Table: see text]
Identifying the most vulnerable areas for the occurrence of new cases and deaths related to cervical cancer in the city of Recife, Brazil: See to act.
Authors: Telles O Lima Jurema , Santos Candice Lima , Azevedo Carla Rameri Alexandre Silva De , Katz Leticia , Lopes Andréa , Pinto Rodrigo alves , Sales Mozart j t
Published: May 2020

e13628

Background: Cervical cancer (CC) is the second most incident and the most deadly among women from the Northeast’S Brazil and RECIFE-Pernambuco and the third most incident in Brazil. The occurrence of CC expresses a reality of inequality and inequity and should be understood not only as an oncological indicator, but essentially as an indicator of social vulnerability and health care needs. Its distribution occurs heterogeneously. Methods: Determine the geolocation of areas of greatest risk of occurrence of SC from the social and health determinants Considering the high incidence and mortality related to cervical cancer between 2006-2015, in the city of Recife, we used the spatialization technique to identify the most vulnerable territories for our intervention in the city of Recife. Results: 3,844 Cervical Cancer notifications AND 276 OBITUATIONS registered in the period 2006-2015 and the number of deaths in the period from 2009 to 2018, as a result, there are five areas of high influence. from spatialization, the heat zone generated by the 47 deaths that occurred in the north of the city of Recife WAS DETERMANED. Regarding the cytopathological supply, the ratio in 2018 was 0.37, being below the state average, which is 0.41. With a deficit of 45,041 screening cytopathological exams in the age group 25-64 years.the III Health Region was identified, based on the analysis of information from the State Health Secretary, which shows to be one of the areas of great social vulnerability, since 63% of the 22 municipalities that make up this health region and its population is in extreme poverty, according to IBGE (2010). Conclusions: The occurrence of deaths and new cases of cervical cancer in the city of Recife occurs geographically unequally and is associated with indicators of social vulnerability. IS IT POSSIBLE to identify a priority region to intensify public actions for prevention and early diagnosis. A challenging scenario has been found and must be actively addressed.
The spectrum of cancer in adolescents and young adults (AYAs): An observational study in a single institution from 2015-2019.
Authors: Goh Wei Lin , Hong Jiancheng , Wong Evelyn , Wong Victoria , Quah Daniel , Tan Yee Pin , Tan Yung Ying , Chan Selene , Chan Jason Yongsheng , Somasundaram Nagavalli , Harunal Rashid Mohamad Farid Rin , Poon Eileen Yi Ling
Published: May 2020

e13629

Background: Cancer in adolescents and young adults (AYAOs) refers to patients diagnosed with a malignancy between 16 and 39 years old. This is thought to be 5% in the Western population. The exact incidence and distribution in Asia is uncertain although the WHO estimated 650 000 AYAs to be newly diagnosed in this part of the world in 2018. There is limited data on the incidence and epidemiology on AYAs in Asia, but it is known from the western literature that the distribution of cancer types, clinico-pathological features and outcomes in this population is very different. We therefore, sought to evaluate the pattern of cancer types among the different age groups of the AYA population seen in a high-volume single Asian tertiary cancer centre. Methods: We undertook a retrospective observational study of all patients diagnosed with cancer between 16 and 39 years old who presented to the National Cancer Centre Singapore (NCCS) from 1 January 2015 to 31 December 2019. Results: A total of 2583 cases was observed during the 5-year period. The male: female ratio was 1:1.75. The majority of the patients were between of 35-39 years (y) ( n= 1128, 44.0%). The most common cancer across the different age groups in females were sarcoma (16-19 y), hematologic malignancies (20-24 y) and breast cancer (25-29 y, 30-34 y and 35-39 y). The most common cancer across the different age groups in males were hematologic malignancies (16-19 y), germ cell tumours (20-24 y), germ cell tumours, hematologic malignancies and sarcoma (25-29 y), hematologic malignancies (30-34 y) and colorectal cancers (35-39 y). The majority of the patients presented were localized disease (38.3%), while 19.4% presented with lymphatic involvement. Amongst 507 (19.6%) patients presenting with metastatic disease, 126 patients have deceased. Conclusions: This population has unique characteristics compared to their geriatric and pediatric counterparts. With an increased incidence and expected longer survivals, more efforts are needed to better understand the clinicopathological features of the AYA population. This will enable us to better survival rates and long-term treatment outcomes.
Landscape of IDH mutations in patients with solid tumors: A pan-cancer analysis.
Authors: Guan Xiaoxiang , Zhu Hong , Zhang Junling , Yuan Kai , Shen Dong , Zhao Jing , Zhao Zhengyi , Cui Longgang , Zhang Yuzi , Wang Guoqiang , Cai Shangli , Bai Yuezong
Published: May 2020

e13638

Background: Isocitrate dehydrogenase (IDH) is an enzyme family involved in cell aerobic metabolism of tricarboxylic acid cycle, including IDH1-3. Mutations in IDH family are common in glioma and hematologic malignancies. IDH inhibitors have shown promising efficacy not only in hematologic malignancies but also cholangiocarcinoma patients harboring IDH1 mutations. However, the landscape of IDH mutations in pan-cancer has not been fully characterized. Methods: Tissue or blood samples were subjected to NGS in a College of American Pathologists-certified and Clinical Laboratory Improvement Amendments-accredited lab for detection the IDH mutation. Results: A total of 12,372 patients from more than 20 solid tumor species were analyzed, including biliary carcinoma (960 cases), liver cancer (1433 cases), lung cancer (3557 cases) and colorectal cancer (1310 cases). 105 cases (0.8%) with IDH mutations were identified. The average age for patients harboring IDH mutations was 59 years (range, 29-80 years). Among all the IDH mutations cases, 49 (47%) were biliary tract cancer, 25 (24%) were liver cancer, 16 (15%) were lung cancer and 7 (7%) were colorectal cancer. The most common IDH variant were IDH1 and IDH2 which were discovered in 84 cases and 21 cases, respectively. IDH1 R132C mutation represents 45.7% (n = 48) of all IDH mutations. Other mutations found affecting either IDH1 at Arg132 included R132L (n = 24), R132G (n = 5), R132H (n = 5) and R132S (n = 2) or IDH2 at Arg172 (R172K most frequently). In addition, IDH1/2 gene was most frequently co-mutated with TP53 and ARID1A. Conclusions: Somatic IDH1/2 mutations are found in multiple solid tumors and patients with IDH1/2 mutations may benefit from IDH1/2 inhibitors in the future.
Association of rs7372209 single nucleotide polymorphism in gene for miRNA-26a-1 with tumor localization and disease outcome in patients with colorectal cancer from Bulgaria.
Authors: Mihaylova Galya , Ivanova Desislava , Tasinov Oscan , Nazifova-Tasinova Neshe , Petrova Veneta , Pavlov Pavel , Manev Rostislav , Mirchev Milko , Conev Nikolay Vladimirov , Mihaylova Zhasmina , Donev Ivan , Radanova Maria
Published: May 2020

e13656

Background: A retrospective study was carried out to investigate the association of functional rs7372209 single nucleotide polymorphism (SNP) in the 5'- region of pri-miRNA- 26a1 gene with a risk of colorectal cancer (CRC) in a Bulgarian population, to evaluate its role as a potential prognostic or predictive biomarker for the disease and to studied its affection on the expression of miRNA-26a-1 in patients with CRC. Methods: 101 patients with colorectal metastatic disease and 90 healthy volunteers, all Caucasians from Bulgaria, were genotyped for rs7372209 SNP by qPCR method. The expression levels of miRNA-26a in sera also have been determined. U6 was used as endogenous constitutively expressed control. Relative gene expression was calculated using 2−∆∆Ct method. Results: TT genotype in rs7372209 SNP was significantly overrepresented in CRC patients with right-sided colon cancer when compared with CRC patients with left-sided colon cancer, and rectal cancer (33% vs. 8%, OR = 6.13, 95% CI: 1.56–23.97, p = 0.009). Patients with TT genotype in rs7372209 SNP had significantly (p = 0.041) longer mean overall survival (OS) of 26 months (95% CI: 21.76–34.18) as compared to those with CT and CC genotypes – 19 months (95% CI: 16.43–22.20). Expression levels of miR-26a in sera were significantly higher in CRC patients compared to healthy volunteers. The ROC analysis revealed that miR-26a can effectively discriminate between CRC patients and the healthy volunteers (AUC = 0.830, 95% CI: 0.77–0.89, p < 0.001). Patients with TT genotype in rs7372209 SNP had a numeric lower mean level of miR-26a-1 – 4.702 in comparison with patients that harboring CT or CC genotype – 6.507. Conclusions: Our data suggest that high serum levels of miR-26a-1 are potentially useful as a diagnostic biomarker for CRC. Although, that patients with ТТ genotype had often more aggressive right-sided colon cancer they had longer mean overall survival than patients harboring CT or CC genotype of rs7372209.
Landscape of germline mutations in 1144 patients (Pts) with gastrointestinal (GI) cancers.
Authors: Salem Mohamed E. , Amacker-North Lisa , Gleason Mariah , Athens Aly , Worrilow William Mills , McNeely Lindsay , Broyhill Katherine , Puccini Alberto , Kim Edward S. , Elrefai Sara
Published: May 2020

e13660

Background: The efficacy of PARP inhibitors in germline BRCA-mutated pancreatic adenocarcinoma (PC) and immune checkpoint inhibitors in dMMR colorectal cancer (CRC) shows the importance of genetic testing. We aimed to characterize the frequency of pathogenic/likely pathogenic germline variants (PLPVs) in GI cancer pts. Methods: A retrospective review of pts referred to the Levine Cancer Institute Genetics Program was conducted. Genetic testing used a focused hereditary cancer 4-43 gene panel or pan-cancer 82-84 gene panel. Results: Out of 1144 GI cancer pts seen between 2010 and 2019, 869 underwent germline testing, and 199 (23%) pts had at least one PLPV in a hereditary cancer susceptibility gene, while 253 (29.3%) had a variant of uncertain significance. Of 630 CRC pts, 24% had a PLPV and 13% harbored a germline mutation in DNA MMR genes and were diagnosed with Lynch Syndrome, representing ~50% of all pts with a PLPV. Other germline PLPVs were found in APC, ATM, BRCA1, BRCA2, CHEK2, MUTYH, and PALB2. Of 163 PC pts, 16.6% had a PLPV in ATM, BRCA2, CDKN2A, and MEN1. Gastric cancer pts (17%) had germline PLPVs in APC, BRCA2, CDH1, MLH1, and MSH2; biliary cancer pts (17%) had germline PLPVs in PALB2, RAD50, and PTCH1; and GIST pts (60%) had PLPVs in SDHA or SDHB. Conclusions: Germline mutations were found in 23% of GI cancer pts, underlining the importance of multigene germline testing. Knowledge of inherited GI cancer risk helps determine the likelihood of benefit from possible specific targeted therapies. Genetic testing and counseling pose a challenge, but implications for pts with hereditary syndromes are highly significant. [Table: see text]
Clinical characters of somatic DNA damage repair (DDR) gene mutations in Chinese NSCLC patients.
Authors: Ma Ke , Rong Hao , Zhu Changbin , Zhang Huachuan , He Jintao , Xiao Bo , Zhu Jiang , Peng Jun
Published: May 2020

e13665

Background: Chinese NSCLC patients displayed unique genetic profile. NSCLC patients with DNA damage repair gene mutations showed distinct clinical appearance as well as superior response to immunotherapy. This study aims to disclose distribution of DNA damage mutations as well as their clinical characters in Chinese NSCLC patients. Methods: One hundred and ten patients with pathologically confirmed NSCLC were consecutively recruited from 2016-2018 in our center. Genomic DNA was captured and sequenced for 508 cancer related genes by BGI-seq 500. Raw data was processed followed by variant calling via in-house developed pipeline. Results: 89 (of 110) patients with median age of 55 years old (33-74 years) were included into final analysis due to complete follow-up as well as sufficient FFPE tissue for successful genomic profiling. Among them, 12 patients were squamous NSCLC, 72 patients were non-squamous NSCLC. Among 89 patients, 22 patients (24.7%) carried 36 mutations in 21 DDR genes (BRCA2 n = 6, BAP1 n = 3, ARID1A n = 2, ATM n = 2, ATR n = 2, BLM n = 2, FANCF n = 2, PARP1 n = 2,BARD1 n = 1,BRCA1 n = 1,CHEK2 n = 1, FANCD2 n = 1,FANCE n = 1,FANCG n = 1,FANCM N = 1,NBN n = 1,PARP3 n = 1,POLQ n = 1,RAD50 n = 1,RAD51C n = 1), most of them belongs to homologous recombination repair pathway (n = 19, 21.34%).8 patients carried compound mutations in DDR genes. No difference was found in age of initial diagnosis between DDR mutated and DDR wild type patients. While, ever smokers (RR (95%CI): 2.12 (1.37-3.20),P = 0.003), squamous NSCLC (RR(95%CI):4.47 (1.62-12.03), P = 0.006), male (RR (95%CI): 1.77(1.23-2.44),P = 0.006) displayed significantly higher prevalence of DDR gene mutations. Only one stage I patient carried DDR mutation(P = 0.008). Conclusions: In this study, mutation spectrum of DDR genes was proposed in Chinese NSCLC patients. DDR gene mutations more possibly occurred in male, higher disease stage as well as in squamous NSCLC and smokers. These findings show potential relevance to disease prognosis which needs further investigation.
A retrospective three-year analysis using real-world data on uptake of broad-based NextGen sequencing panels in community oncology practices.
Authors: Gierman Hinco J. , Pai Nikhil , Catasus Casey , Tam Alvin , Labrador Monica , Donaldson Joseph , Singaraju Mallika , Singleton Nick , Verniero John , Smith Robert E. , Scott Jeffrey A.
Published: May 2020

e13668

Background: There are over 100 FDA approved targeted therapies across 15 cancer types, offering improved outcomes over existing therapies. However, many of these require genetic testing, for example, advanced non-small cell lung cancer (aNSCLC) patients have over 15 targeted therapies requiring a DNA-based test. Doing multiple tests can exhaust sample, while increasing cost and turn-around time. NGS panels, often with hundreds of genes, can address some of these issues. Here we asked across aNSCLC patients if the use of NGS panels has increased over the last 3 years in community oncology practices. Methods: The Integra Connect database, which includes electronic medical record (EMR) and claims data on over 1,000,000 US cancer patients, was queried across five community oncology practices to identify aNSCLC patients (stage IIIB or IV) treated between January 2017 and January 2020. Manual chart review abstracted tumor type, stage, treatment, and testing. Patients tested for all 7 NCCN recommended genes (EGFR, ALK, ROS1, BRAF, MET, RET, ERBB2) were grouped as “NGS Panel”, patients with less genes as “Single Gene/Small Panel”, and patients with no evidence of testing as “No Test”. A Chi-Square test was used to compare actionable results between patients with NGS panels versus small panels. Results: 1,007 aNSCLC patients were analyzed and showed a doubling of the use of broad-based NGS testing from 13% in 2017 to 26% in 2019 across over 100 oncologists (table). 23% of patients had actionable results when tested on broad-based panels versus 17% using single gene or small panels (p = .048). Targeted therapies were used in 17% of broad-based tested patients, versus 15% in patients tested for single genes or small panels. Conclusions: We see an uptake of broad-based NGS testing in community oncology, which can lead to more actionable results and better utilization of targeted therapies for those patients. However, this seems to be caused by providers shifting from small panels to large panels, rather than an overall increase in testing, as we do not see the percentage of untested patients decrease. [Table: see text]
The prognostic role of somatic BRCA mutations in ovarian cancer: Preliminary results from an observational multicenter cohort study.
Authors: Piombino Claudia , Toss Angela , Bologna Alessandra , Gasparini Elisa , Tarantino Vittoria , Filieri Maria Elisabetta , Cottafavi Luca , Giovanardi Filippo , Marcheselli Luigi , Marchi Isabella , Domati Federica , Venturelli Marta , Barbieri Elena , Grandi Giovanni , Tenedini Elena , Tagliafico Enrico , Cortesi Laura
Published: May 2020

e13674

Background: BRCA germline (gBRCA) mutations occur in 11-15% of women with unselected ovarian cancers (OC), whereas somatic BRCA (sBRCA) mutations occur in approximately 5-7% of cases. The impact of sBRCA mutations on OC outcome is still debated. Methods: With the aim to explore the prognostic role of sBRCA mutations, the BRCA mutational status of 149 non-mucinous and non-borderline OC and their clinical-pathological features were evaluated. BRCA1 and BRCA2 mutational profiles, either for sequence variants or copy number alterations, were evaluated by amplicon next-generation sequencing (NGS) technology. Results: 29 (19.5%) patients carried a gBRCA mutation (12.7% BRCA1 and 6.7% BRCA2). 26 (17.5%) patients presented a sBRCA mutation (6.7% BRCA1, 10% BRCA2, 0.6% BRCA1+BRCA2). Patients carrying a gBRCA mutation were slightly younger (57 years) than the others (60 years). The FIGO stage at the diagnosis was III-IV in 77.2% of cases, with no significant difference among subgroups. The most frequent histotype was serous for all the subgroups (93.1% in gBRCA, 84.6% in sBRCA, 77.7% in BRCA-negative, p = 0.08). 80.7% of sBRCA mutation carriers, 62.1% of gBRCA mutation carriers and 62.7% of BRCA-negative patients underwent upfront surgery (p = 0.46). 29.1% of sBRCA mutation carriers, 17.8% of gBRCA mutation carriers and 25.6% of BRCA-negative patients presented macroscopic residual disease after surgery (p = 0.68). Although non-statistically significant, gBRCA-associated OC were more likely to be platinum-sensitive (96.6%) than the other patients (92% in sBRCA and 87.1% in BRCA-negative patients). Overall, the median platinum-free interval (PFI) resulted shorter in sBRCA mutation patients compared to gBRCA and BRCA-negative patients (p = 0.051). No patient took PARP inhibitors as maintenance after the first line therapy. Also progression free survival 2 (PFS2) resulted shorter for sBRCA mutation patients (p = 0.008). Three sBRCA and 5 gBRCA mutation carriers took a PARP inhibitor as maintenance after the second line therapy. Finally, sBRCA mutated patients showed worse overall survival (OS) compared to the other subgroups (p = 0.014). Conclusions: Overall, 19.5% of OC patients presented a gBRCA mutation, while 17.5% of patients showed sBRCA mutations. sBRCA-related OC did not show significantly differences in clinical-pathological features (stage at diagnosis, histotype, time to surgery and residual after surgery). To our knowledge this is the first study showing shorter PFI, PFS2 and OS in patients carrying sBRCA mutations.
The positive correlation between tumor mutation burden and the purity of tumor samples in non–small cell lung cancer and colorectal cancer.
Authors: Tong Jian , Zhang Xiaoni , Qu Hongyue , Yang Qing , Duan Jingxian , Xu Mingyan
Published: May 2020

e13683

Background: Tumor mutation burden (TMB) is reported to be a biomarker for predicting immunotherapy responses in patients with non–small cell lung cancer (NSCLC). To provide a more accurate calculation of TMB, the correlation between tumor purity and TMB was investigated. Methods: 959 patients were enrolled in this study from July 2019 to January 2020, including 663 patients with primary NSCLC and 296 patients with primary colorectal cancer (CRC). Formalin-Fixed Paraffin-Embedded (FFPE) and paired white blood cells were collected from each patient. These FFPE samples were stained with HE for the evaluation of tumor purity. DNA was extracted from samples and sequenced using a 605-gene panel on the Illumina platform (approximately 3,000× coverage). TMB was calculated for each sample based on the sequencing data. Results: The median TMB of 663 NSCLC patients was 2.29mut/Mb, and the TMB is positively correlated with the purity of tumor samples. Among samples in which tumor cells accounted for ≥40% of the sample cells (n = 456), the median TMB reached 2.29 mut/Mb, and 90.35% (412/456) patients had a TMB higher than 0 mut/Mb. In samples that tumor cells accounted for 20% to 40% of sample cells (n = 120), the median TMB was 1.53mut/Mb and 72.5% (87/120) of patients had a TMB larger than 0 mut/Mb. The median TMB was 0.76 mut/Mb for samples contained less than 20% of tumor cells, and only 50.57% (44/87) patients had a TMB larger than 0 mut/Mb. Similar results were obtained in 296 CRC samples, which exhibited a median TMB of 3.55mut/Mb. Tumor cells accounted for 40% of the sample cells in 191 cases. The median TMB of those samples was 4 mut/Mb, and 96.34% (184/191) samples had a TMB larger than 0 mut/Mb. When tumor cells accounted for 20% to 40% of total sample cells, the median TMB was 2.94mut/Mb, and 94.44% (51/54) of patients had a TMB larger than 0 mut/Mb. In 50 samples that contained less than 20% of tumor cells, the median TMB was 2.29mut/Mb, and 80 % (40/50) samples had a TMB larger than 0 mut/Mb. Conclusions: TMB is positively correlated with the purity of tumor samples. Moreover, data suggest that the TMB is more reliable when tumor cells account for more than 40% of the sample population.