Prevention Research最新文献

{"title":"Abstract 2603: What's more in serrated lesions: interobserver agreement and molecular features","authors":"F. Ambrosi, C. Ricci, Federico Chiarucci, Stefano Chilotti, Doriana Donatella Di Nanni, A. G. Corradini, Maria Antonietta Cumiento, D. Biase, M. Fiorentino","doi":"10.1158/1538-7445.AM2021-2603","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2603","url":null,"abstract":"Introduction: Serrated lesions are a heterogeneous group of lesions routinely evaluated with different morphologic subtypes, and colorectal carcinogenesis has been related to the understanding of the serrated pathway in these lesions. In this setting, BRAF V600E mutation has been demonstrated as a marker for the serrated carcinogenic evolution, while the mismatch repair protein (MMR) was recognized in a small subset of hyperplastic polyps. Design: This study aimed to evaluate the interobserver agreement among 6 pathologists in the morphological diagnosis of the serrated lesion according to WHO Classification; furthermore, the additional MMR (MLH1, PMS2, MSH2, MSH6) and BRAF V600E (VE1) mutation status were studied by immunohistochemistry and NGS analysis. Results: We evaluated 52 serrated lesions of the colon retrieved from our pathology archives in 2019. The cohort included 48 patients: 21 males and 27 females, with a mean age of 67 years (range 50-89), of which 77.1% were identified according to regional screening protocol. All hematoxylin and eosin slides were independently reviewed by each pathologist, who classified all samples according to the WHO Classification of Digestive System Tumor (Fleiss Kappa: 0.75). The immunohistochemical expression of MMR and BRAF was evaluated in 42 samples. Loss of MLH1 and PMS2 was recorded in one serrated sessile lesion (LSS) with dysplasia, but NGS analysis resulted negative. In contrast, BRAF V600E IHC resulted positive in 22 samples (52.4%), specifically in 5 hyperplastic polyps (71.4%), 10 LSS (66.6%), 5 LSS with dysplasia (45.5%) and 2 adenomatous polyps (100%), 1 TSA negative. All BRAF V600E IHC positive cases were confirmed by NGS analysis. Conclusion: To conclude, the interobserver agreement for morphological classification of serrated lesions resulted substantial; however, behind the morphological appearance, BRAF V600E resulted in predominant mutation in LSS and hyperplastic polyps, these observations confirmed the possibility to improve the classification with IHC BRAF V600E; especially for hyperplastic polyps, it may be crucial to identify precancerous lesions and different clinical management. Citation Format: Francesca Ambrosi, Costantino Ricci, Federico Chiarucci, Stefano Chilotti, Doriana Donatella Di Nanni, Angelo Gianluca Corradini, Maria Antonietta Cumiento, Dario De Biase, Michelangelo Fiorentino. What9s more in serrated lesions: interobserver agreement and molecular features [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2603.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81015548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract LB013: Clinical validation of a targeted methylation-based multi-cancer early detection test","authors":"E. Klein, D. Richards, A. Cohn, M. Tummala, R. Lapham, D. Cosgrove, G. Chung, J. Clement, Jingjing Gao, N. Hunkapiller, A. Jamshidi, K. Kurtzman, M. Seiden, C. Swanton, Minetta C. Liu","doi":"10.1158/1538-7445.AM2021-LB013","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB013","url":null,"abstract":"Introduction: A multi-cancer early detection (MCED) test as a complement to existing screening tests could increase the number of cancer cases detected in a population, potentially improving patient outcomes and survival as well as decreasing harmful and aggressive treatments. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was designed to develop and validate a blood-based MCED test analyzing plasma cell-free DNA (cfDNA) to detect cancer signals across multiple cancer types and simultaneously predict their signal origin. Here, the results of the third and final pre-specified CCGA validation sub-study for a refined MCED test in a large cohort in preparation for clinical use are reported. Methods: CCGA is a prospective, multicenter, case-control, observational study with longitudinal follow-up (overall population N=15,254). In this sub-study (n=5309), key primary objectives were to evaluate test performance for cancer signal detection (specificity, overall sensitivity, sensitivity by clinical stage) and signal origin prediction (accuracy). cfDNA from evaluable samples was analyzed using a targeted methylation bisulfite sequencing assay and a machine learning algorithm. The classifier was trained to target a specificity of 99.4% and locked before analysis of the independent validation set. Overall, 4077 participants comprised the independent validation set with confirmed status (cancer: n=2823; non-cancer: n=1254 with non-cancer status confirmed at year-one follow-up). MCED test results are reported for this confirmed status set. Results: Mean (SD) age in the cancer and non-cancer groups was 62.6 (11.76) and 56.2 (12.63) years, respectively. Specificity for cancer signal detection was 99.5% (1248/1254; 95% confidence interval: 99.0-99.8%). Overall sensitivity for cancer signal detection was 51.5% (1453/2823; 49.6-53.3%); sensitivity increased with stage (Stage I: 16.8% [14.5-19.5%], Stage II: 40.4% [36.8-44.1%], Stage III: 77.0% [73.4-80.3%], Stage IV: 90.1% [87.5-92.2%]). Stage I-III sensitivity was 67.6% (593/877; 64.4-70.6%) in a pre-specified set of 12 high-signal cancers accounting for ~63% of annual US cancer deaths [1] and was 40.7% (863/2118; 38.7-42.9%) in all cancers. Cancer signals were detected across >50 cancer types [2]. Overall accuracy of signal origin prediction in true positives was 88.7% (87.0-90.2%). Conclusions: In this pre-specified, large-scale, clinical validation sub-study of CCGA, the MCED test detected cancer signals across >50 cancer types, which is critical to maximize the number of cancer cases detected in a population. This MCED test performed with high specificity and high accuracy of signal origin prediction. These data lay the foundation for population-scale clinical implementation of this test. 1.US Mortality Data 1969-2016 (www.seer.cancer.gov); based on 2015-2016. 2.Amin et al. CA Cancer J Clin. 2017;67:93e99. Citation Format: Eric A. Klein, Donald Richards, Allen Cohn, Mohan Tummala, Rosanna La","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89789915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2579: Links between obesity and secreted frizzled-related protein 4 (Sfrp4) in a murine model of colon cancer","authors":"Elaine M Glenny, Laura W. Bowers, Diana Li, J. Roper, S. Hursting","doi":"10.1158/1538-7445.AM2021-2579","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2579","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"127 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89885789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 110: Planned versus observed effect sizes in early phase chemoprevention trials","authors":"J. Eickhoff, Jen Birstler, Guanhua Chen, Zhumin Zhang, V. Sahasrabuddhe, E. Szabo, KyungMann Kim","doi":"10.1158/1538-7445.AM2021-110","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-110","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79448392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2568: Use of kinase inhibitors in Fanconi anemia oral cancercell lines","authors":"W. N. Jungbauer, Mustafa M. Ali, B. Wuertz, F. Ondrey","doi":"10.1158/1538-7445.AM2021-2568","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2568","url":null,"abstract":"Successful Fanconi anemia (FA) treatment allows greater longevity for these patients. However, there is a greatly increased risk of squamous malignancies of the head and neck which are quite deadly in these young patients. There is an unmet need for non DNA damaging therapies for this malignancy which could augment surgery. Our approach has been to examine potential treatments based on known pathophysiology of the disease which would be acceptable for this population so we examined the effects of metformin and pioglitazone, as well as two cell cycle kinase inhibitors, in FA and leukoplakia cell lines. We examined dose-dependent and combination effects on cell proliferation, as judged by MTT assay. We examined metformin, pioglitazone, the polo-like kinase 1 inhibitor, GSK461364, and Wee1 kinase inhibitor, AZD1775.In single agent studies, we observed dose-dependent decreases in cell proliferation with all 4 single agents. We observed decreased cell proliferation in all cell lines at 72 hours at clinically achievable serum levels of 85% to 55% of control levels (P Citation Format: Walter N. Jungbauer, Mustafa M. Ali, Beverly R. Wuertz, Frank G. Ondrey. Use of kinase inhibitors in Fanconi anemia oral cancercell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2568.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"232 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77007414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2548: Preclinical development of EARLI-001, a genetic platform producing cancer-activated synthetic biomarkers for the early detection of malignancies","authors":"Badriprasad Ananthanarayanan, Regina Nieu, Evan Bishop, Shireen S. Rudina, A. Harwig, Bijee George, D. Suhy","doi":"10.1158/1538-7445.AM2021-2548","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2548","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77390556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2531: Function-related indicator and outcomes of screening mammography in older women from the BCSC-Medicare Cohort","authors":"Dongyu Zhang, L. Abraham, J. Demb, D. Miglioretti, S. Advani, B. Sprague, L. Henderson, Tracy Onega, K. Wernli, L. Walter, K. Kerlikowske, J. Schousboe, E. O'Meara, D. Braithwaite","doi":"10.1158/1538-7445.AM2021-2531","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2531","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76871049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2611: Transcription factor-nucleosome dynamics inferred from plasma cfDNA delineates tumor and tumor-microenvironment phenotype","authors":"Satyanarayan Rao, A. Han, Alexis Zukowski, E. Kopin, P. Kabos, S. Ramachandran","doi":"10.1158/1538-7445.AM2021-2611","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2611","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83030996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2596: Stage-specific inhibition of NNK-induced lung carcinogenesis by 1,4-phenylenebis(methylene)seleno-aspirin (p-XS-Asp)","authors":"A. Raza, Amandeep Singh, C. Aliaga, D. Plano, Shantu Amin, Arun K. Sharma","doi":"10.1158/1538-7445.AM2021-2596","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2596","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73458256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 112: Analytical performance of a cfDNA-based targeted methylation multi-cancer early detection test for population-scale screening","authors":"G. Alexander, B. Jung, Lijuan Ji, E. Revenkova, Payal Shah, J. Brooks, Jeremy Carter, Zhao Dong, L. Eubank, Maryam Hosseini, Xin Hou, Hannah M Kiarie, Neda Ronaghi, Fabian E. Ortega, Madhuvanthi Ramaiah, Kate Rhodes, R. Shaknovich, Seyedmehdi Shojaee, S. Parpart-Li, N. Hunkapiller","doi":"10.1158/1538-7445.AM2021-112","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-112","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77007511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}