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Trends and Clinical Characteristics of Next-Generation Sequencing–Based Genetic Panel Tests: An Analysis of Korean Nationwide Claims Data
Mi Jang, Hae Yong Pak, Ja Yoon Heo, Hyunsun Lim, Yoon-La Choi, Hyo Sup Shim, Eun Kyung Kim
Cancer Res Treat. 2024;56(1):27-36.   Published online September 7, 2023
DOI: https://doi.org/10.4143/crt.2023.844
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
In the modern era of precision medicine, next-generation sequencing (NGS) is employed for a variety of clinical purposes. The aim of this study was to investigate the trends and clinical characteristics of NGS testing in South Korea.
Materials and Methods
This nationwide, population-based, retrospective cohort study examined National Health Insurance Service claims data from 2017 to 2021 for NGS and from 2008 to 2021 for gene-targeted anticancer drugs.
Results
Among the total 98,748 claims, there were 51,407 (52.1%) solid cancer panels, 30,173 (30.5%) hereditary disease panels, and 17,168 (17.4%) hematolymphoid cancer panels. The number of annual claims showed a persistent upward trend, exhibiting a 5.4-fold increase, from 5,436 in 2017 to 29,557 in 2021. In the solid cancer panel, colorectal cancer was the most common (19.2%), followed by lung cancer (18.8%). The annual claims for targeted cancer drugs have increased 25.7-fold, from 3,932 in 2008 to 101,211 in 2020. Drugs for the treatment of lung cancer accounted for 488,819 (71.9%) claims. The number of patients who received non-hereditary NGS testing has substantially increased, and among them, the count of patients prescribed targeted anticancer drugs consistently rose from 508 (13.9%) in 2017 to 2,245 (12.3%) in 2020.
Conclusion
This study highlights the rising nationwide demand for comprehensive genetic testing for disease diagnosis and treatment following NGS reimbursement by the National Health Insurance in South Korea, in addition to the need for greater utilization of targeted anticancer drugs.
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Lung and Thoracic cancer
Clinical Impact of Genomic and Pathway Alterations in Stage I EGFR-Mutant Lung Adenocarcinoma
Jae Seok Lee, Eun Kyung Kim, Kyung A Kim, Hyo Sup Shim
Cancer Res Treat. 2024;56(1):104-114.   Published online July 24, 2023
DOI: https://doi.org/10.4143/crt.2023.728
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We investigated the clinical impact of genomic and pathway alterations in stage I epidermal growth factor receptor (EGFR)–mutant lung adenocarcinomas, which have a high recurrence rate despite complete surgical resection.
Materials and Methods
Out of the initial cohort of 257 patients with completely resected stage I EGFR-mutant lung adenocarcinoma, tumor samples from 105 patients were subjected to analysis using large-panel next-generation sequencing. We analyzed 11 canonical oncogenic pathways and determined the number of pathway alterations (NPA). Survival analyses were performed based on co-occurring alterations and NPA in three patient groups: all patients, patients with International Association for the Study of Lung Cancer (IASLC) pathology grade 2, and patients with recurrent tumors treated with EGFR–tyrosine kinase inhibitor (TKI).
Results
In the univariate analysis, pathological stage, IASLC grade, TP53 mutation, NPA, phosphoinositide 3-kinase pathway, p53 pathway, and cell cycle pathway exhibited significant associations with worse recurrence-free survival (RFS). Moreover, RPS6KB1 or EGFR amplifications were linked to a poorer RFS. Multivariate analysis revealed that pathologic stage, IASLC grade, and cell cycle pathway alteration were independent poor prognostic factors for RFS (p=0.002, p < 0.001, and p=0.006, respectively). In the grade 2 subgroup, higher NPA was independently associated with worse RFS (p=0.003). Additionally, in patients with recurrence treated with EGFR-TKIs, co-occurring TP53 mutations were linked to shorter progression-free survival (p=0.025).
Conclusion
Genomic and pathway alterations, particularly cell cycle alterations, high NPA, and TP53 mutations, were associated with worse clinical outcomes in stage I EGFR-mutant lung adenocarcinoma. These findings may have implications for risk stratification and the development of new therapeutic strategies in early-stage EGFR-mutant lung cancer patients.
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Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection
Yoon Ah Cho, Ji Myung Chung, Hyunmi Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
Cancer Res Treat. 2019;51(3):1052-1063.   Published online October 24, 2018
DOI: https://doi.org/10.4143/crt.2018.411
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The relationship between head and neck squamous cell carcinoma (HNSCC) and subtypes of tropomyosin-related kinase (Trk) has not been studied in-depth. In this study, we evaluated the expression patterns of TrkA, TrkB, and panTrk and their clinicopathological significance as well as association with p16 expression and human papilloma virus (HPV) status.
Materials and Methods
Total of 396 radically resected oropharyngeal (n=121) and non-oropharyngeal (n=275) HNSCCs were included. Immunohistochemistry for TrkA, TrkB, and panTrk was performed. In addition, p16 immunohistochemistry was performed to assess the HPV status. Using HPV-negative HNSCC cell lines, FaDu and CAL27, HPV type 16 E6/E7 gene was transfected, and then changes of TrkA and TrkB expression were analyzed.
Results
In the clinical samples of HNSCC, high expression of TrkA and panTrk were more associated with oropharyngeal and p16 positive squamous cell carcinoma (SCC). In patients with completely resected (R0-resected) oropharyngeal SCC, high TrkA expression was related to superior overall survival and recurrence-free survival (RFS). In patients with R0-resected oral cavity SCC, high panTrk was related to poor RFS. In HPV type E6/E7 gene-transfected FaDu and CAL27 cell lines, increase of TrkA expression was observed.
Conclusion
It seems that expression pattern of panTrk and TrkA differed according to anatomical sites of HNSCC and was closely related to p16 expression and patient prognosis. Trk expression should be considered in the context of anatomical site, p16 expression or HPV status and Trk subtypes.

Citations

Citations to this article as recorded by  
  • NTRK Gene Expression Analysis in Oral Squamous Cell Carcinoma Mexican Population
    Lilibeth Stephania Escoto-Vasquez, Javier Portilla-Robertson, Josué Orlando Ramírez-Jarquín, Luis Fernando Jacinto-Alemán, Alejandro Alonso-Moctezuma, Carla Monserrat Ramírez-Martínez, Osmar Alejandro Chanes-Cuevas, Fabiola Salgado-Chavarria
    Dentistry Journal.2024; 12(10): 327.     CrossRef
  • Accuracy of magnetic resonance imaging in the assessment of depth of invasion in tongue carcinoma: A systematic review and meta-analysis
    Kondajji Ramachandra Vijayalakshmi, Vanshika Jain
    National Journal of Maxillofacial Surgery.2023; 14(3): 341.     CrossRef
  • CYLD Alterations in the Tumorigenesis and Progression of Human Papillomavirus–Associated Head and Neck Cancers
    Zhibin Cui, Hyunseok Kang, Jennifer R. Grandis, Daniel E. Johnson
    Molecular Cancer Research.2021; 19(1): 14.     CrossRef
  • Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer
    Zijian Chen, Zenghong Huang, Yanxin Luo, Qi Zou, Liangliang Bai, Guannan Tang, Xiaolin Wang, Guangwen Cao, Meijin Huang, Jun Xiang, Huichuan Yu
    Journal of Translational Medicine.2021;[Epub]     CrossRef
  • Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma
    Cheol Keun Park, Jayoon Heo, Won Sik Ham, Young-Deuk Choi, Sang Joon Shin, Nam Hoon Cho
    Cancer Research and Treatment.2021; 53(4): 1174.     CrossRef
  • Clinical Significance of Trk Receptor Expression as a New Therapeutic Target in Hepatocellular Carcinoma
    Sangjoon Choi, Sujin Park, Yoon Ah Cho, Cheol-Keun Park, Sang Yun Ha
    Pathology & Oncology Research.2020; 26(4): 2587.     CrossRef
  • Overexpression of wild type or a Q311E mutant MB21D2 promotes a pro‐oncogenic phenotype in HNSCC
    Daniel E. Gracilla, Praveen Kumar Korla, Ming‐Tsung Lai, An‐Jen Chiang, Wen‐Shiung Liou, Jim Jinn‐Chyuan Sheu
    Molecular Oncology.2020; 14(12): 3065.     CrossRef
  • NOVA1 induction by inflammation and NOVA1 suppression by epigenetic regulation in head and neck squamous cell carcinoma
    Eun Kyung Kim, Yoon Ah Cho, Mi-kyoung Seo, Hyunmi Ryu, Byoung Chul Cho, Yoon Woo Koh, Sun Och Yoon
    Scientific Reports.2019;[Epub]     CrossRef
  • Characterization of head and neck squamous cell carcinoma arising in young patients: Particular focus on molecular alteration and tumor immunity
    Hyang Joo Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
    Head & Neck.2019; 41(1): 198.     CrossRef
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Initial Response to Treatment was Highly Associated with the Prognosis of Childhood Rhabdomyosarcoma: A Retrospective Analysis of a Single Center Experience in Korea
Jeong A Park, Eun Kyung Kim, Hyoung Jin Kang, Hee Young Shin, Il Han Kim, Hyo Seop Ahn
Cancer Res Treat. 2008;40(3):111-115.   Published online September 30, 2008
DOI: https://doi.org/10.4143/crt.2008.40.3.111
AbstractAbstract PDFPubReaderePub
Purpose

Following the introduction of a multimodal approach to diagnosis and treatment, the prognosis of rhabdomyosarcoma (RMS) has markedly improved over the last three decades. However, there are few data on treatment outcomes in Korean patients.

Materials and Methods

We performed a retrospective analysis of 77 patients with RMS diagnosed and treated at Seoul National University Children's Hospital between 1986 and 2005.

Results

The overall 5-year survival and event-free survival rates for all patients were 77% and 59%, respectively. The Intergroup Rhabdomyosarcoma Study clinical grouping and initial response to treatment (20-week response) were important prognostic factors.

Conclusions

The outcome of childhood RMS was closely associated with the initial staging and the initial response to treatment. Modulating therapies according to initial responses and risk factors is critical, and new treatment strategies for high-risk patients are needed.

Citations

Citations to this article as recorded by  
  • Adherence to Treatment, Response and Patterns of Failure in Pediatric Parameningeal Rhabdomyosarcoma: Experience From a Tertiary Cancer Care Center From India
    Soumyajit Roy, Sushmita Pathy, Bidhu K. Mohanti, Subhash Chander, Ahitagni Biswas
    Journal of Pediatric Hematology/Oncology.2017; 39(2): e62.     CrossRef
  • Pediatric rhabdomyosarcoma in India: A single-center experience
    Deepak Bansal, Anirban Das, Amita Trehan, Rakesh Kapoor, Naresh K. Panda, Radhika Srinivasan, Nandita Kakkar, Kushaljit S. Sodhi, Akshay K. Saxena, Katragadda Lakshmi Narasimha Rao
    Indian Pediatrics.2017; 54(9): 735.     CrossRef
  • The impact of radiotherapy on clinical outcomes in parameningeal rhabdomyosarcoma
    Yunseon Choi, Do Hoon Lim
    Radiation Oncology Journal.2016; 34(4): 290.     CrossRef
  • Rhabdomyosarcoma Treatment and Outcome at a Multidisciplinary Pediatric Cancer Center in Lebanon
    Maysaa Salman, Hani Tamim, Fouad Medlej, Tarek El-Ariss, Fatima Saad, Fouad Boulos, Toufic Eid, Samar Muwakkit, Nabil Khoury, Miguel Abboud, Raya Saab
    Pediatric Hematology and Oncology.2012; 29(4): 322.     CrossRef
  • Solid tumours of childhood
    Bruce O. Okoye
    Surgery (Oxford).2010; 28(8): 382.     CrossRef
  • Primary meningeal rhabdomyosarcoma associated with chronic subdural effusion
    Ji Yeoun Lee, Bo Sung Kim, Ji Hoon Phi, Hyoung Jin Kang, Sung-Hye Park, Kyu-Chang Wang, Il Han Kim, Byung-Kyu Cho, Seung-Ki Kim
    Journal of Neurosurgery: Pediatrics.2010; 5(2): 167.     CrossRef
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Prognostic Factors in Non-Hodgkin's Lymphoma Patients Treated by Autologous Stem Cell Transplantation: A Single Center Experience
Cheolwon Suh, Sang Hee Kim, Hyo Jung Kim, Geundoo Jang, Eun Kyung Kim, Ok Bae Ko, Shin Kim, Hee Jung Sohn, Jung Shin Lee, M. Wookun Kim, Jooryung Huh
Cancer Res Treat. 2005;37(5):294-301.   Published online October 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.5.294
AbstractAbstract PDFPubReaderePub
Purpose

Autologous stem cell transplantation (ASCT) is increasingly used in patients with non-Hodgkin's lymphoma (NHL). Various clinical parameters-were evaluated to obtain significant predictors of the outcome following ASCT in patients with NHL.

Materials and Methods

Between April 1994 and December 2003, ASCT was performed on 80 patients with NHL at the Asan Medical Center.

Results

Patients had various histological subtypes and disease status. The two year progression free survival (PFS) and overall survival for all patients were 34 and 31%, respectively. A univariate analysis showed the performance status, stage, modified extranodal involvement category, International Prognostic Index (IPI) at mobilization, disease status at mobilization, and history of radiation prior to mobilization as significant predictors of the outcome following ASCT. Four risk groups, with different 2 year PFS, were identified by the age adjusted IPI at mobilization (mAAIPI): low risk 44%; low intermediate risk 40%; high intermediate risk 19%; and high risk 0% (p=.0003). A multivariate analysis revealed 3 significant factors for the PFS: disease status, prior RT and mAAIPI.

Conclusion

The mAAIPI was found to be an independent predictor of the outcome of NHL patients undergoing ASCT. This powerful prognostic tool should be used to evaluate potential candidates for ASCT.

Citations

Citations to this article as recorded by  
  • Real-world Experience of Improvement in the Survival of Lymphoma and Myeloma Patients with Autologous Stem Cell Transplantation over a 25-year Period
    Hyungwoo Cho, Shin Kim, Kyoungmin Lee, Jung Sun Park, Cheolwon Suh
    The Korean Journal of Medicine.2021; 96(6): 501.     CrossRef
  • Disease characteristics of diffuse large B‐cell lymphoma predicting relapse and survival after autologous stem cell transplantation: A single institution experience
    Daria Gaut, Tahmineh Romero, David Oveisi, Grant Howell, Gary Schiller
    Hematological Oncology.2020; 38(1): 38.     CrossRef
  • Autologous stem cell transplantation for diffuse large B-cell lymphoma with residual extranodal involvement
    Ock Bae Ko, Geundoo Jang, Shin Kim, Jooryung Huh, Cheolwon Suh
    The Korean journal of internal medicine.2008; 23(4): 182.     CrossRef
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The Expressions of Cytokeratin 7 and 20 in Epithelial Tumors: A Survey of 91 Cases
Dong Hoon Kim, Jong Eun Joo, Eun Kyung Kim, Ho Jung Lee, Won Mi Lee
Cancer Res Treat. 2003;35(4):355-363.   Published online August 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.4.355
AbstractAbstract PDF
PURPOSE
This study was performed to determine the expressions of cytokeratin 7 and cytokeratin 20 in epithelial neoplasms, and to investigate their potential role in the differential diagnosis of carcinomas of various organs.
MATERIALS AND METHODS
We investigated 91 various cases of primary and metastatic cancers, using a panel of commercially available monoclonal antibodies against cytokeratins 7 and 20 (CK7 and CK20), by immunohistochemistryand an avidin-biotin immunoperoxidase technique. The specimens were formalin-fixed and paraffin- embedded, and examined using 4micrometer thick serial sections.
RESULTS
The expression of CK7 was seen in the majority of carcinoma cases, including transitional cell carcinomas (100%), pulmonary adenocarcinomas (100%), ovarian serous adenocarcinomas (100%), cholangiocarcinomas (70%), colonic adenocarcinomas (64.29%) and invasive ductal carcinomas (60%). The expression of CK20 was seen in the majority of colorectal carcinomas cases (85.72%), but was virtually absent in pulmonary adenocarcinomas (0%), uterine cervical carcinomas (0%), ovarian carcinomas (0%), prostatic adenocarcinomas (0%), adenocarcinomas of the gall bladder (0%) and cholangiocarcinomas (12.5%).
CONCLUSION
In the all cases investigated, either CK7 or CK20 immunophenotypes were conserved in the tumor cells of primary tumors and in those of the corresponding metastatic lesions. It is suggested that CK7/CK20 immunophenotyping, in metastatic carcinomas of an unknown origin, maybe useful in the determination of the primary site of the metastasis.

Citations

Citations to this article as recorded by  
  • Occult urothelial carcinoma with mediastinal metastasis: A case report
    Jingfan Zheng, Xintong Peng, Xiaoqing Li, Yuyu Chen, Xinyi Li, Ling Fu, Ao Li, Zhong Lu
    Oncology Letters.2024;[Epub]     CrossRef
  • Cytomorphology, immunoprofile, and clinicopathologic correlation of metastatic prostatic carcinoma
    Xiaoqi Lin, Qiuying Shi, Ximing J. Yang
    Human Pathology.2022; 130: 36.     CrossRef
  • Double cocktail immunostains with high molecular weight cytokeratin and GATA-3: useful stain to discriminate in situ involvement of prostatic ducts or acini from stromal invasion by urothelial carcinoma in the prostate
    Junghye Lee, Youngeun Yoo, Sanghui Park, Min-Sun Cho, Sun Hee Sung, Jae Y. Ro
    Journal of Pathology and Translational Medicine.2020; 54(2): 146.     CrossRef
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