{"title":"Abstract 458: Characterization of ATRX polyclonal, application of immunohistochemical analysis on astrocytoma and glioblastoma","authors":"J. Diaz, Tatiana Scoggin, Jason A. Ramos","doi":"10.1158/1538-7445.AM2021-458","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-458","url":null,"abstract":"Introduction: Alpha thalassemia/mental retardation syndrome X-linked (ATRX) plays a role in chromatin regulation and maintenance of telomeres. It regulates incorporation of histone H3.3 into telomeric chromatin. ATRX is also a major component of various essential cellular pathways such as DNA replication and repair, chromatin higher-order structure regulation, and gene transcriptional regulation. ATRX loss was observed in grades II/III astrocytomas, oligoastrocytomas, oligodendrogliomas, and glioblastomas. In grades II/III gliomas, most ATRX‐loss cases had IDH1/2 mutations. Assessment of ATRX loss by IHC staining captures the majority of mutations, giving a reasonable sensitivity in neuropathology diagnostics. In this study, the specificity and sensitivity of ATRX were analyzed on multiple tissues focusing on Astrocytoma and Glioblastoma tissues. Materials and Methods: IHC staining has been performed by using formalin-fixed paraffin-embedded tissue with standard deparaffinization steps and a heat-induced retrieval method using a citrate buffer solution in a pressure cooker (Decloaking chamber). Antibody was incubated for 30 minutes, followed by HRP detection and DAB solution for visualization. Slides were stained using semi-automated staining system (intelliPATH). ATRX polyclonal antibody [Biocare Medical, California, USA] diluted in a carrier at an optimal concentration with standard protocol. Results: ATRX stained 44% of diffuse and anaplastic astrocytoma and 57% of glioblastoma. Also, cross-reactivity testing determined ATRX polyclonal may stain normal brain in some cases. A more comprehensive data evaluation shown below: Conclusions: ATRX polyclonal shows a potential advantage when diagnosing brain tumors (especially astrocytoma and glioblastomas) even if some cross reactivity can be observed. ATRX in conjunction with other brain marker antibodies can offer a better tool in diagnosing brain tumors. Citation Format: Jose Jonathan Diaz, Tatiana Scoggin, Jason Ramos. Characterization of ATRX polyclonal, application of immunohistochemical analysis on astrocytoma and glioblastoma [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 458.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84875116","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}
S. Flach, K. Howarth, S. Hackinger, C. Pipinikas, K. McLay, G. Marsico, C. Walz, O. Gires, M. Canis, P. Baumeister
{"title":"Abstract 553: Personalized circulating tumor DNA analysis in head and neck squamous cell carcinoma: Preliminary results of the Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and NeckSquamous Cell Carcinoma (LIONESS) study","authors":"S. Flach, K. Howarth, S. Hackinger, C. Pipinikas, K. McLay, G. Marsico, C. Walz, O. Gires, M. Canis, P. Baumeister","doi":"10.1158/1538-7445.AM2021-553","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-553","url":null,"abstract":"Introduction Head and neck squamous cell carcinoma (HNSCC) remains a substantial burden to global health. Despite evolving therapies, 5-year survival is less than 50% and unlike other cancers, reliable biomarkers to monitor treatment response do not exist. Cell-free circulating tumor DNA (ctDNA) is an emerging biomarker but has not yet been studied sufficiently for HNSCC. The detection of ctDNA as a marker of minimal residual disease following curative-intent treatment holds promise for identifying patients at an increased risk of relapse, who may benefit from adjuvant radio(chemo)therapy or facilitate close monitoring with repeat resection if needed. Methods We conducted a single-center prospective experimental evidence-generating cohort study to assess ctDNA in 30 patients with p16-negative HNSCC (stages I-IVB) who received primary surgical treatment with curative intent at our institution. Whole exome sequencing (WES) was performed on formalin-fixed paraffin-embedded tumor tissue to a median depth of 250x. For each patient, we selected up to 48 somatic variants for personalized ctDNA assay design. We used the RaDaRTM assay to analyze serial pre- and post-operative plasma samples (range 2-6) for evidence of minimal residual disease or recurrence. Results In a subset of patients analyzed to evaluate the performance of RaDaR, personalized panels were designed with between 34 and 48 somatic variants (median 48). Preliminary data shows 100% ctDNA detection in baseline samples taken prior to surgery at tumor fractions ranging from 312 ppm (equivalent to 0.03% AF) to 7579 ppm (equivalent to 0.76% AF). In post-surgery samples, ctDNA could be detected at levels as low as 26 ppm (equivalent to 0.0026% AF). Analysis of follow-up plasma samples will be presented along with data from the full patient cohort. Conclusions This study illustrates the potential of ctDNA as a biomarker in HNSCC and demonstrates the feasibility of personalized ctDNA assays for the detection of minimal residual disease post-treatment and for monitoring for early detection of relapse. Citation Format: Susanne Flach, Karen Howarth, Sophie Hackinger, Christodoulos Pipinikas, Kirsten McLay, Giovanni Marsico, Christoph Walz, Olivier Gires, Martin Canis, Philipp Baumeister. Personalized circulating tumor DNA analysis in head and neck squamous cell carcinoma: Preliminary results of the Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and NeckSquamous Cell Carcinoma (LIONESS) study [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 553.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","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":"90852409","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}
Linlin Zhang, Xin Wang, Hui-sheng Song, F. Meng, G. Yu, D. Zhong
{"title":"Abstract 374: NGS based profiling of homologous recombination genes to predict response to platinum-based chemotherapy in NSCLC","authors":"Linlin Zhang, Xin Wang, Hui-sheng Song, F. Meng, G. Yu, D. Zhong","doi":"10.1158/1538-7445.AM2021-374","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-374","url":null,"abstract":"Background: In the era of precision medicine, better response of anti-tumor therapies attribute to detection of specific molecular markers. However, up to the present no validated biomarker for platinum-based chemotherapy could be used in clinic. Next-generation sequencing (NGS) technology has been applied for non-small cell lung cancer (NSCLC) molecular typing for years. Whether analysis of homologous recombination (HR) gene mutations based on NGS results could predict the efficiency of platinum-based therapy in NSCLC is still obscure. Methods: NGS has been performed for screening homologous recombination (HR) gene mutations, as well as common driver genes in NSCLC, with tumor samples. Advanced or metastatic NSCLC patients receiving platinum-based chemotherapy were included for efficacy analysis. Results: 129 patients with HR genes information were included for analysis. Among the 129 patients, 55 patients were received platinum-based chemotherapy. The efficiency results showed the objective response rates (ORR) of patients with BRCA1/2 and without BRCA1/2 mutations were 71.4% and 31.3%; and the median progression free survival (PFS) were 7.5 and 5.6 months(p=0.161), respectively. The ORR of patients with and without HR genes mutations were 57.9% and 25.0%; and the median PFS were 8.0 and 5.3 months (p=0.039), respectively. Conclusions: NGS based profiling of BRCA1/2 and other gene mutations in HR pathways have a promising predictive value for efficacy of platinum-based chemotherapy in advance and metastatic NSCLC. Citation Format: Linlin Zhang, Xin Wang, Hui Song, Fanlu Meng, Guowei Yu, Diansheng Zhong. NGS based profiling of homologous recombination genes to predict response to platinum-based chemotherapy in NSCLC [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 374.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87484286","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}
Stefano Rossetti, Aaron Broege, Joanna Sabat, Shu Z. Wiley, S. Khan, Catherine E. Kuzmicki, I. Macneil, Brian Sullivan, Lance G. Laing
{"title":"Abstract 367: Sub-group of ovarian cancer patients with hyperactive RAS network signaling identified: Dynamic pathway activity test identifies patients that may benefit from PI3K/mTOR or PI3K/mTOR/BCL inhibitors","authors":"Stefano Rossetti, Aaron Broege, Joanna Sabat, Shu Z. Wiley, S. Khan, Catherine E. Kuzmicki, I. Macneil, Brian Sullivan, Lance G. Laing","doi":"10.1158/1538-7445.am2021-367","DOIUrl":"https://doi.org/10.1158/1538-7445.am2021-367","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84296104","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}
L. Kim, William Cheng, Yeun Ho Lee, M. Nam, W. K. Hur, J. Hwang, Y. Choi, W. Bae, C. Kang, Heayoon S. Cho, E. Yu, C. Jung, Eugene Kim, C. Low, Y. Chae
{"title":"Abstract 678: Exceptional response to PD-L1 inhibitor after radiation therapy in a patient with small cell neuroendocrine tumor of the prostate gland refractory to combination treatment with PD-1 and CTLA-4 inhibitors","authors":"L. Kim, William Cheng, Yeun Ho Lee, M. Nam, W. K. Hur, J. Hwang, Y. Choi, W. Bae, C. Kang, Heayoon S. Cho, E. Yu, C. Jung, Eugene Kim, C. Low, Y. Chae","doi":"10.1158/1538-7445.AM2021-678","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-678","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84425779","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}
Laura Kist de Ruijter, Pim P. van de Donk, J. S. Hooiveld-Noeken, D. Giesen, A. Ungewickell, B. Fine, Simon-Peter Williams, S. S. Bohorquez, M. Yadav, H. Koeppen, Jing Jing, S. Guelman, Mark T. Lin, M. Mamounas, J. Eastham, P. Kimes, A. Glaudemans, A. Brouwers, M. N. Hooge, J. Gietema, C. Schröder, W. Timens, M. Jalving, S. Elias, S. Oosting, D. J. Groot, E. D. Vries
{"title":"Abstract LB037:89ZED88082A PET imaging to visualize CD8+T cells in patients with cancer treated with immune checkpoint inhibitor","authors":"Laura Kist de Ruijter, Pim P. van de Donk, J. S. Hooiveld-Noeken, D. Giesen, A. Ungewickell, B. Fine, Simon-Peter Williams, S. S. Bohorquez, M. Yadav, H. Koeppen, Jing Jing, S. Guelman, Mark T. Lin, M. Mamounas, J. Eastham, P. Kimes, A. Glaudemans, A. Brouwers, M. N. Hooge, J. Gietema, C. Schröder, W. Timens, M. Jalving, S. Elias, S. Oosting, D. J. Groot, E. D. Vries","doi":"10.1158/1538-7445.AM2021-LB037","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB037","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88150745","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}
Yung-Chieh Fu, J. Yen, Alexander Aartyomenko, S. Gnerre, Caroline Weiport, E. Helman, A. Yablonovitch, S. Pettitt, Christopher Llord, A. Tutt, R. Nagy, J. Odegaard, Darya I. Chudova, Amirali Talasaz
{"title":"Abstract 25: Reversion patterns in homologous recombination repair genes in metastatic cancer patients profiled by cell-free DNA","authors":"Yung-Chieh Fu, J. Yen, Alexander Aartyomenko, S. Gnerre, Caroline Weiport, E. Helman, A. Yablonovitch, S. Pettitt, Christopher Llord, A. Tutt, R. Nagy, J. Odegaard, Darya I. Chudova, Amirali Talasaz","doi":"10.1158/1538-7445.AM2021-25","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-25","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"2012 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88156023","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 LB064: Long-term application of TTFields in anaplastic astrocytoma - a case study","authors":"D. Markovic","doi":"10.1158/1538-7445.AM2021-LB064","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB064","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"16 5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85401176","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}
Caroline Salmon, J. Levermann, P. Buderath, J. Kuhlmann, P. Wimberger, R. Kimmig, S. Kasimir-Bauer
{"title":"Abstract 594: Image-based identification of single circulating tumor cells in ovarian cancer patients for genomic analysis","authors":"Caroline Salmon, J. Levermann, P. Buderath, J. Kuhlmann, P. Wimberger, R. Kimmig, S. Kasimir-Bauer","doi":"10.1158/1538-7445.AM2021-594","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-594","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","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":"80288033","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}