bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline DNA repair gene mutations in Taiwan prostate cancer patients.
Authors: Huang Wilson , Yeh Shauh-Der 
Published: May 2020

e13640 Background: Genetic testing for inherited mutations in DNA-repair genes such as BRCA1, BRCA2, ATM, PALP2, FANCA has been proposed for high-risk and metastatic prostate cancer patients for personalized therapy and management. Although the prevalence of germline DNA-repair gene mutations among Caucasian populations are known, the frequency of such mutations in Taiwan prostate cancer patients has not been established. In this study, we performed next-generation sequencing (NGS) analysis of BRCA1, BRCA2, ATM, PALP2, and FANCA in 49 prostate cancer patients stratified according to the NCCN risk criteria using blood sample collected from a single hospital center. Methods: 4ml whole blood samples are collected in EDTA tube from prostate cancer patients of low-intermediate, high to very high, regional, and metastatic risks. The samples are subjected to buffy coat fractionation, genomic DNA extraction, library preparation, full-exon NGS, and comparative analysis with all known germline variants. We identified and correlated the frequency of germline DNA-repair gene mutations with patient’s age at diagnosis, Gleason grades, initial PSA, family history of prostate cancer, and NCCN risk. Results: A total of 49 blood samples were tested and analyzed for BRCA1, BRCA2, ATM, PALP2, and FANCA mutations. Among all cases, 6.1% (3/49, 95% confidence interval [CI]: - 0.6%-12.8%) carried pathogenic mutations: 2.0% (1/49) in BRCA1, 2.0% (1/49) in BRCA2, and 2.0% (1/49) in ATM. They were compatible with previously reported mutations and no new germline variants were detected. These mutations were associated with initial PSA and NCCN risk; all identified mutations belonged to Gleason grade 5 and high to very high risk subgroups. No clinical association was observed with patient’s age of diagnosis and family history. Conclusions: In this single hospital center study, we observed a modest incidence of DNA-repair gene mutations in the Taiwan prostate cancer cohort. Germline DNA-repair gene mutations were observed in high risk prostate cancer patients with the highest Gleason grade. Frequencies of the mutations did not differ significantly according to age at diagnosis or family history of prostate cancer. These results were similar to the reported findings in the Caucasian populations. Our findings confirmed the necessity of genetic testing in Taiwan prostate cancer patients. [Table: see text]
Prevalence & pathogenic features of hereditary breast/ovarian cancer syndromes: Implementation of a genetic/familiar cancer risk assessment unit.
Authors: Ramón Jorge , Rodriguez Rey Laura , García Luis Eduardo , Sánchez Cabrero Darío , Higuera Oliver , Gallego Alejandro , Ruiz Gimenez Leticia , Rodriguez Salas Nuria 
Published: May 2020

e13645 Background: Currently studies found more than 25 genes associated with inherited Breast/Ovarian cancer. This syndrome shows morphologic, immunophenotic and molecular differences in comparison with sporadic ones. For example, BRCA1/2 are commonly ductal invasive carcinomas, with high grade of differentiation and high mitotic index, showing expression of basal o myoepithelial markers and overexpression of cell cycle proteins. Our study describe the outcomes since the implementation of Genetic/Familiar cancer risk assessment a tertiary hospital. Methods: A retrospective chart review was performed among all patients evaluated in Genetic counseling clinic in our hospital, since September 2008 to March 2019. Patients who fulfill criteria for Breast/Ovarian Cancer syndromes were included. We were specially interested in those with pathogenic, likely pathogenic or uncertain significance variants. All variants were named according to the practice of the BIC database, and the GenBank entries. Description on clinical features of tumor and frequency of implicated genes are considered for statistical analysis. All data were calculated in Stata IC 15. Results: 320 patients were eligible, 62,2% (n = 199) had cancer diagnosis. The most frequent tumor diagnosis was breast, 68,8% (n = 137), featured by: ductal carcinoma (82,5%), high grade differentiation (55,2%), triple negative (22,6%), local/locally advanced stage (86,13%) and bilateral component (16,1%). 11,6% had Breast cancer and 3,4% Ovarian cancer as second malignancies, respectively. Variant alterations were found in 24 different genes. BRCA 2 had the highest frequency (40,9%; n = 139 variants detected), BRCA 1 (24,7%; n = 84), ATM(7,4%; n = 25), PALB2(5,3%;n = 18) and BRIP1(2,9%, n = 10). 230 variants (68,3%) were pathogenic or likely pathogenic variants. Pathogenic mutation variant distribution in BRCA2 were c.3264dupT (n = 12); c.6275_6276delTT (n = 8); c.9026_9030delATCAT (n = 8). The most frequent mutations in BRCA1 were: c.1674delA (n = 7); c.302-1G > A (n = 4); c.3331_3334delCAAG(n = 4). Among all patient with BRCA 1/2 mutations, 30,7% were undergone to prophylactic surgery, without statistical association with survival (p = 0,310). Conclusions: Our findings support literature about highly relation between BRCA1/2 and Breast/Ovarian Cancer. In our population, BRCA2 showed high frequency of pathogenic mutations. Patients with BRCA mutations and prophylactic mastectomy did not show statistical benefit in survival.
Cancer risks associated with the HOXB13 c.251G> A variant in men and women referred for hereditary cancer genetic testing.
Authors: Jones Melanie , Rosenthal Eric Thomas , Copeland Karen , Kidd John , Bernhisel Ryan , Comeaux Matthew , Rawson Randi , Mancini-Dinardo Debora 
Published: May 2020

e13653 Background: The HOXB13 c.251G > A (p.G84E) variant is associated with increased prostate cancer risk, possibly at younger ages. Studies on this variant have focused primarily on men, although genetic testing for hereditary cancer risk is most often performed in women. There remains a need to assess whether male and female carriers of this variant have increased risk for other cancers. Methods: We identified male and female carriers of the HOXB13 c.251G > A (p.G84E) variant among individuals referred for hereditary cancer panel genetic testing from October 2018 – December 2019. Non-carriers had no pathogenic variants in any gene or variants of uncertain significance in HOXB13. Personal and family (1st- and 2nd-degree relative) cancer histories were obtained from provider-completed test request forms. Multivariable logistic regression (MLR) models were conducted separately for males and females to estimate cancer risks for the variant as odds ratios (ORs), and 95% Wald confidence intervals (CIs) adjusted for age, ancestry and personal/family cancer history. Results: The analysis included 197,978 patients: 4.5% (8,998/197,978) male and 95.5% (188,980/197,978) female. The HOXB13 variant was present in 0.44% (40/8,998) of tested males, 45% (18/40) of whom had a diagnosis of prostate cancer. The variant was present in 0.32% (621/188,980) of tested females. Male carriers with prostate cancer were diagnosed at younger ages (median, 56; Interquartile ratio [IQR], 52, 62) than non-carriers (median, 63; IQR, 57,70), but this difference was not statistically significant. The MLR model calculated a 3.30 OR for prostate cancer in male carriers of c.251C > A ( P = 0.01; 95% CI 1.30-8.39). In an analysis combining males and females, carriers were significantly more likely to report prostate cancer in a family member than non-carriers ( P = 3.5 x 10−7; OR 1.61, 95% CI 1.34-1.93). There was no apparent association with increased risk for other cancers among carriers versus non-carriers, or among relatives of carriers compared with relatives of non-carriers. Conclusions: The HOXB13 c.251G > A (p.G84E) variant was associated with significantly increased risk of prostate cancer, confirming previously published studies. We found no evidence of association with other cancers. For unaffected male carriers, who may frequently be identified through testing of a female relative, identification of this HOXB13 variant provides an opportunity for more precise prostate cancer risk stratification and screening.
Technical validation of a high-sensitivity target capture NGS assay using unique molecular identifier approach.
Authors: Mao Ruifang , Xiao Shanshan , Lin Rui , Wang Yuchen , Wang Tao 
Published: May 2020

e13657 Background: Identification of a broad spectrum of somatic mutations is crucial to guide targeted therapy such as for non-small cell lung cancer (NSCLC) patients. In the clinical environment, it requires well validated NGS workflow both for the wet-lab and dry-lab procedures. Here we describe a high sensitivity target NGS assay to accurately capture single nucleotide variants (SNVs), short insertions and deletions (indels), copy number alterations and gene rearrangements for formalin-fixed paraffin-embedded (FFPE) NSCLC patient samples. Extensive analytical validation was performed following the checklists of College of American Pathologists. Methods: Next generation sequencing (NGS) libraries were prepared using extracted DNA from FFPE tissue NSCLC patient samples. The protocol for library generation was optimized in several steps and incorporated 10bp unique molecular identifiers (UMIs). The libraries were sequenced on Illumina HiSeq X-Ten platform. The sequence data was analyzed by an in-house bioinformatics pipeline to call somatic mutations at an average depth of 4000X. Results: We tested the accuracy of 68 clinical tumor samples that were also validated by conventional or alternative methods in the third party CAP accredited labs. We observed 100% sensitivity and 100% specificity compared with the other lab¡¯s validation results. To define the limit of detection (LOD) for different mutation types, clinical DNA samples containing different variants were diluted with normal DNA. The LODs for SNV (as in EGFR L858R) and indel (as in EGFR 19del) were 0.5% and 1%, respectively. Addressing the LOD of fusion and copy number alteration is usually challenging. Our NGS assay was able to achieve 2% LOD for gene rearrangement (fusion) and 3.5 copies for copy number amplification. The high reproducibility was also achieved by inter- and intra- replicate experiments. Our NGS assay showed better performance than other widely used commercial NGS assay panels. Conclusions: We have validated an NGS based approach with UMI technology that is able to achieve high accuracy and sensitivity as low as 0.5% for detection of somatic mutations, which will improve the clinical testing performance for NSCLC FFPE samples with low allele frequencies of driver mutations.
Application of MammaPrint test on Chinese patient with breast cancer.
Authors: Tian Chen , Fu Lili , Wei Jiyu , Yin Pengfei , Zhang Henghui 
Published: May 2020

e13671 Background: A 70-gene prognosis-signature, known as MammaPrint (MP), is validated as a good predictor of recurrence in patients with ER+/HER2- early stage breast cancer in Europe and America. Previous studies on Japanese and Korean breast cancer patients showed that the proportion of MP Low-Risk tumours is significantly lower than the percentage which reported in previous studies. Here we use MammaPrint to determine the gene profiles of breast cancer tumours from Chinese patients and investigate the test’s potential clinical applications. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumour samples or fresh tumour samples from 594 eligible breast cancer patients were collected from 97 hospitals in China. Tumor RNAs were isolated from samples and analyzed using RNA sequencing technology. Clinical risk was categorized based on the Adjuvant! algorithm as used in the MINDACT trial. Concordance between risk predicted by the MammaPrint and clinical characteristics were evaluated. We also analyzed the clinical-pathology features of patients and compared them to previous studies. Results: Overall, 315 patients were categorized as clinical high risk (182 were MP Low-Risk and 133 MP High-Risk), while 279 patients were categorized as clinical low risk (203 were MP Low-Risk and 76 MP High-Risk). The concordance rate between risk predicted by the MammaPrint and clinical characteristics was 56.57%. Among the clinical-pathology features, age, ER/PR/HER2 status, tumour grade and tumour size were significantly related to the genomic risk (p = 0.009, 0.003, < 0.001, 0.001, < 0.001, and 0.007 respectively). Conclusions: The proportion of MP Low-Risk tumours was 64.81%, which is similar to previous validated studies in Europe and America. Of the patients that were clinical high risk, 58% was categorized as MP Low-Risk, and this group of patients may have limited benefit from chemotherapy. Our results indicate that MammaPrint is applicable to Chinese patients and has potential value in clinical practice to avoid over-treatment.
Characteristics of probands with mutations predisposing to gynecologic cancers enrolled in a facilitated cascade testing protocol.
Authors: Hwang Kristina , Baumann Katherine , Brodsky Allison , Lutz Kathleen , Gerber Deanna , Martineau Jessica , Ginsburg Ophira M. , Smith Julia Anne , Levine Douglas A. , Pothuri Bhavana 
Published: May 2020

e13682 Background: We sought to evaluate the feasibility of obtaining genetic testing (GT) for first- or second-degree (1°, 2°) family members of a proband known to have actionable germline mutation associated with endometrial and/or ovarian cancer through a coordinated referral system. Here we characterize the initial probands and discuss the time frame of their enrollment in facilitated cascade testing (CT). Methods: Patients with pathogenic mutations associated with gynecologic cancers were determined from cancer genetics and gynecologic oncology clinics. Consenting patients completed a RedCap survey on personal cancer history and history of GT. They were then asked to contact 1° and/or 2° relatives regarding their GT results. Relatives were advised to contact our team. Relatives who consented to the study were referred for GT and contacted for follow up to ascertain whether they received GT and/or took action to reduce cancer risk. Results: From 3/2019- 1/2020, this study has accrued 39 probands. The median age was 39 years (range: 25-68). The most commonly expressed gene mutations were BRCA1 or BRCA2 (87.18%, n=34). Other mutations included BRIP1, MLH1, MSH2, MSH6, and PMS2. The majority (62%) of probands had no personal history of cancer. Among those who had a history of cancer (n=15), 80% had breast and/or ovarian cancer, and 80% reported their genetic mutation was discovered at or after the time of their cancer diagnosis. Median age at time of enrollment in CT was 49 years (range: 29-66) for patients with a history of cancer and 32 years (range: 25- 68) for those without, (p=0.009). Among all probands, the median time between mutation identification and enrollment in CT was 2 years (range=0 to 11). There was no significant difference in time between mutation identification and enrollment in CT when comparing those with and without cancer histories (p=0.5). Conclusions: These results suggest that patients with pathogenic mutations predisposing to gynecologic cancer are willing to undergo CT even if they have no personal history of cancer. Patients with a history of cancer tend to be older at time of enrollment in CT, likely because most discover their genetic mutation at or after the time of cancer diagnosis. With an average of 2 years elapsed between time of mutation identification and enrollment in CT, there is need for expansion of CT accessibility. Increased education and awareness among patients and providers in identifying those who may benefit from CT, screening, and risk reducing surgery to prevent cancer is needed.
Role of technology in a prospective surveillance and early intervention model for preventing lymphedema: The RE-AIM framework.
Authors: Stolldorf Deonni , Koelmeyer Louise , Boyages John , Nelms Jerrod , Gaitatzis Katrina , Ridner Sheila H. 
Published: May 2020

e14005 Background: Translation of research derived technology into busy clinical practice can be difficult. The effectiveness of technology translation can be assessed by applying the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) evaluation framework. Methods: The RE-AIM evaluation framework was applied to the use of bioimpedance spectroscopy (BIS) in the prospective surveillance and early intervention model of care for breast cancer survivors at risk of arm lymphedema. Data was obtained during an interim analysis from four hospital sites (public and private settings) in Australia who were participating in the PREVENT international study. Women with breast cancer were monitored for lymphedema from a pre-treatment baseline and at regular intervals for a minimum of 12-months. Results: Each of the RE-AIM framework components were evaluated at patient, practitioner and institutional levels. Patients in both public (n = 50) and private settings (n = 61) were Reached with BIS technology which demonstrated Effectiveness of early surveillance with 16 participants being identified for an early prevention intervention. Each of the four sites Adopted the use of BIS technology using various Implemented strategies like education of all stakeholders and development of referral and care pathways. Adherence rates for mandatory study visits was 88. 48% for the prospective surveillance and the early intervention model of care group and were Maintained for a minimum 12 months following completion of the recruitment phase of the study. Conclusions: The effectiveness of using a technology such as BIS in a prospective surveillance and early intervention model of care in breast cancer in both public and private settings has been demonstrated using the RE-AIM framework. The translation of research into clinical practice has been successfully achieved with the PREVENT study. Clinical trial information: NCT02167659.
Improving provider practice patterns in ordering FDG PET/CT for breast cancer patients at a safety-net hospital.
Authors: Abolghasemi Daria , Ho Tran , Short Jennifer , Subhedar Preeti , Okoli Joel , Gogineni Keerthi , Lin Jolinta Y , Yu David S. , Carter Teralyn , Yang Steven , Gabram Sheryl G. A. 
Published: May 2020

e14027 Background: Accurate staging is critical in determining treatment strategies in the management of breast cancer (BC) patients. FDG PET/CT is used to identify the presence of metastatic disease. The criteria for FDG PET/CT utilization is variable, including in any patient with nodal positivity, any patients with systemic symptoms, to those with Stage III disease or higher.. This practice variation has results in different patterns of ordering FDG PET/CT. The preliminary results of a Quality Oncology Practice Initiative (QOPI) audit performed in our Cancer Center in 2017 prompted concern for the over utilization of FDG PET/CT in our BC patients. We performed an initial audit of these practices in 2017 and confirmed these findings. The goal of this study was to re-measure our adherence to NCCN guidelines in 2019 after an educational session complimented by use of a checklist. Methods: A retrospective review was conducted for all BC patients who had FDG PET/CT ordered as initial treatment planning from 1/2017-12/2017. This revealed a 33% rate of failure to meet NCCN guidelines. We then educated our team about the NCCN guidelines for initial PET/CT ordering during our weekly multi-disciplinary conferences, created a test ordering checklist and compared the effect of this education on the use of PET/CT in patients treated at our institution from 1/2019-12/2019. Results: 65 female BC patients had an FDG PET/CT ordered to assist in initial treatment recommendation in 2017. Overall, 66.2% (n = 43) of patients met NCCN indications while 33.8% (n = 22) did not. In comparison to 2017 data, 71 female breast cancer patients had an FDG PET/CT ordered in 2019. Overall, 67 patients (94.4%) met NCCN criteria indications for undergoing FDG PET/CT while only 5 patients (5.6%) did not. Conclusions: Review of FDG PET/CT scans ordered for initial treatment in 2017 revealed that about one third of scans were ordered outside of NCCN guideline recommendations. After an educational session and implementation of a test ordering checklist, we found a marked reduction in the use of FDG PET/CT outside of NCCN guideline recommendations. Although our study is limited by small sample sizes, we identified a practice area that deviated from national recommendations and were able to improve our internal compliance in national guidelines through education and system modification.
Development and validation of a new clinical prediction model of catheter-related thrombosis in cancer patients.
Authors: Liu Binliang , Xie Junying , Sun Xiaoying , Wang Yanfeng , Yuan Zhong , Liu Xiyu , Huang Zhou , Wang Jiani , Mo Hongnan , Yi Zongbi , Guan Xiuwen , Li Lixi , Wang Wenna , Li Hong , Ma Fei , Zeng Yi-Xin 
Published: May 2020

e14031 Background: The central venous catheter brings convenience for drug delivery and improves comfort for cancer patients, it also causes serious complications. The most common one is catheter-related thrombosis (CRT). This study aimed to evaluate the incidence and risk factors of CRT in cancer patients, and to develop an effective prediction model for CRT in cancer patients. Methods: The development of our prediction model was based on the data of a retrospective cohort (n = 3131) from National Cancer Center. The validation of our prediction model was done in a prospective cohort from National Cancer Center (n = 685) and a retrospective cohort from Hunan Cancer Hospital (n = 61). The predictive accuracy and the discriminative ability were determined by the receiver operating characteristic curves and calibration plots. Results: Multivariate analysis demonstrated that sex, cancer type, catheter type, position of the catheter tip, chemotherapy status, and antiplatelet/anticoagulation status at baseline were independent risk factors for CRT. The area under receiver operating characteristic (ROC) curve of our prediction model was 0.741 (CI: 0.715-0.766) in the primary cohort; 0.754 (CI: 0.704-0.803) and 0.658 (CI: 0.470-0.845) in validation cohorts respectively. Good calibration and clinical impact were also shown in primary and validation cohorts. The high-risk group had a higher incidence of CRTs than the low-risk group in the primary cohort and two validation cohort (p < 0.001). Conclusions: Our model is a novel prediction tool for CRT risk which helps to assigning cancer patients into high-risk or low-risk group accurately. Our model will be valuable for clinicians in decision making of thromboprophylaxis.