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21 "Miso Kim"
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Original Articles
Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience
Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im
Received March 23, 2024  Accepted August 18, 2024  Published online August 21, 2024  
DOI: https://doi.org/10.4143/crt.2024.296    [Accepted]
AbstractAbstract PDFSupplementary Material
Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform – FiRST Cancer Panel (FCP) – over seven years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. 97.6% of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53(56.2%), PIK3CA(31.2%), GATA3(13.8%), BRCA2(10.2%), and amplifications of CCND1(10.8%), FGF19(10.0%), and ERBB2(9.5%). NGS analysis of ERBB2 amplification correlated well with HER2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. 10.3% of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.  
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.
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Lung and Thoracic cancer
Analytical and Clinical Validation of a Highly Sensitive NGS-Based ctDNA Assay with Real-World Concordance in Non–Small Cell Lung Cancer
Hanbaek Yi, Jeonghwan Youk, Yoojoo Lim, Hanseong Roh, Dongsoo Kyung, Hwang-Phill Kim, Duhee Bang, Bhumsuk Keam, Tae-Min Kim, Miso Kim, Dong-Wan Kim, Tae-You Kim
Cancer Res Treat. 2024;56(3):765-773.   Published online January 8, 2024
DOI: https://doi.org/10.4143/crt.2023.1294
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay.
Materials and Methods
Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results.
Results
The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R2=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations.
Conclusion
The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

Citations

Citations to this article as recorded by  
  • Next-generation sequencing impact on cancer care: applications, challenges, and future directions
    Mariano Zalis, Gilson Gabriel Viana Veloso, Pedro Nazareth Aguiar Jr., Nathalia Gimenes, Marina Xavier Reis, Silvio Matsas, Carlos Gil Ferreira
    Frontiers in Genetics.2024;[Epub]     CrossRef
  • Profiling Cell-Free DNA from Malignant Pleural Effusion for Oncogenic Driver Mutations in Patients with Treatment-Naive Stage IV Adenocarcinoma: A Multicenter Prospective Study
    Shih-Chieh Chang, Yu-Feng Wei, Chung-Yu Chen, Yi-Chun Lai, Po-Wei Hu, Jui-Chi Hung, Cheng-Yu Chang
    Molecular Diagnosis & Therapy.2024; 28(6): 803.     CrossRef
  • Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer
    Sohyun Hwang, Seonjeong Woo, Beodeul Kang, Haeyoun Kang, Jung Sun Kim, Sung Hwan Lee, Chang Il Kwon, Dong Soo Kyung, Hwang-Phill Kim, Gwangil Kim, Chan Kim, Hong Jae Chon
    Journal of Hepatology.2024;[Epub]     CrossRef
  • 4,585 View
  • 334 Download
  • 2 Web of Science
  • 3 Crossref
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Special Article
Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP
Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim
Cancer Res Treat. 2024;56(3):721-742.   Published online November 29, 2023
DOI: https://doi.org/10.4143/crt.2023.1043
AbstractAbstract PDFPubReaderePub
In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.
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Original Articles
Sarcoma
Case Series of Soft Tissue Sarcoma Patients with Brain Metastasis with Implications from Genomic and Transcriptomic Analysis
Changhee Park, Rokhyun Kim, Jaeyong Choi, Miso Kim, Tae Min Kim, Ilkyu Han, Jong-Il Kim, Han-Soo Kim
Cancer Res Treat. 2024;56(2):665-674.   Published online September 27, 2023
DOI: https://doi.org/10.4143/crt.2023.864
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Brain metastasis rarely occurs in soft tissue sarcoma (STS). Here, we present five cases of STS with brain metastases with genetic profiles.
Materials and Methods
We included five patients from Seoul National University Hospital who were diagnosed with STS with metastasis to the brain. Tissue from the brain metastasis along with that from the primary site or other metastases were used for DNA and RNA sequencing to identify genetic profiles. Gene expression profiles were compared with sarcoma samples from The Cancer Genome Atlas.
Results
The overall survival after diagnosis of brain metastasis ranged from 2.2 to 34.3 months. Comparison of mutational profiles between brain metastases and matched primary or other metastatic samples showed similar profiles. In two patients, copy number variation profiles between brain metastasis and other tumors showed several differences including MYCL, JUN, MYC, and DDR2 amplification. Gene ontology analysis showed that the group of genes significantly highly expressed in the brain metastasis samples was enriched in the G-protein coupled receptor activity, structural constituent of chromatin, protein heterodimerization activity, and binding of DNA, RNA, and protein. Gene set enrichment analysis showed enrichment in the pathway of neuroactive ligand-receptor interaction and systemic lupus erythematosus.
Conclusion
The five patients had variable ranges of clinical courses and outcomes. Genomic and transcriptomic analysis of STS with brain metastasis implicates possible involvement of complex expression modification and epigenetic changes rather than the addition of single driver gene alteration.
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Lung and Thoracic cancer
Targeting CD73 to Overcomes Resistance to First-Generation EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer
Miso Kim, Soyeon Kim, Jeemin Yim, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Dong-Wan Kim, Dae Seog Heo
Cancer Res Treat. 2023;55(4):1134-1143.   Published online May 23, 2023
DOI: https://doi.org/10.4143/crt.2023.311
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
In patients with epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitors (TKIs) improve response rate and survival. However, most patients eventually develop resistance. This study aimed to identify the role of CD73 in EGFR-mutant NSCLC and explore whether CD73 inhibition may serve as a therapeutic strategy in NSCLC patients with acquired resistance to EGFR-TKIs.
Materials and Methods
We evaluated the prognostic role of CD73 expression in EGFR-mutant NSCLC using tumor samples from a single institution. We silenced CD73 in EGFR-TKI–resistant cell lines using short hairpin RNA (shRNA) targeting CD73 and also transfected a vector alone as a negative control. Using these cell lines, cell proliferation and viability assays, immunoblot assays, cell cycle analysis, colony-forming assays, flow cytometry, and apoptosis analysis were performed.
Results
High expression of CD73 was associated with shorter survival in patients with metastatic EGFR-mutant NSCLC treated with first-generation EGFR-TKI. CD73 inhibition synergistically inhibited cell viability with first-generation EGFR-TKI treatment compared with the negative control. When CD73 inhibition and EGFR-TKI treatment were combined, G0/G1 cell cycle arrest was induced through the regulation of p21 and cyclin D1. In addition, the apoptosis rate was increased in CD73 shRNA-transfected cells treated with EGFR-TKI.
Conclusion
High expression of CD73 adversely affects the survival of patients with EGFR-mutant NSCLC. The study demonstrated that inhibiting CD73 in EGFR-TKI–resistant cell lines resulted in increased apoptosis and cell cycle arrest, which overcame the acquired resistance to first-generation EGFR-TKIs. Further research is needed to determine whether blocking CD73 plays a therapeutic role in EGFR-TKI–resistant patients with EGFR-mutant NSCLC.

Citations

Citations to this article as recorded by  
  • Comprehensive pan-cancer analysis of CD73: Explore its association with prognosis and tumor immune microenvironment
    Chen Chen, Sasa Liu, Yanfen Ma
    Heliyon.2024; 10(22): e40329.     CrossRef
  • 3,230 View
  • 274 Download
  • 1 Crossref
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Erratum
ERRATUM: Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se Jin Jang, Dae Young Zang, Tae Won Kim, Jin Hyoung Kang, Jee Hyun Kim
Cancer Res Treat. 2023;55(3):1061-1061.   Published online April 21, 2023
DOI: https://doi.org/10.4143/crt.2021.1115.E
Corrects: Cancer Res Treat 2022;54(1):1
PDFPubReaderePub
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Special Article
Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se Jin Jang, Dae Young Zang, Tae Won Kim, Jin Hyoung Kang, Jee Hyun Kim
Cancer Res Treat. 2022;54(1):1-9.   Published online December 13, 2021
DOI: https://doi.org/10.4143/crt.2021.1115
Correction in: Cancer Res Treat 2023;55(3):1061
AbstractAbstract PDFPubReaderePub
Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

Citations

Citations to this article as recorded by  
  • Expert Consensus on Molecular Tumor Boards in Taiwan: Joint Position Paper by the Taiwan Oncology Society and the Taiwan Society of Pathology
    Ming-Huang Chen, Wan-Shan Li, Bin-Chi Liao, Chiao-En Wu, Chien-Feng Li, Chia-Hsun Hsieh, Feng-Che Kuan, Huey-En Tzeng, Jen-Fan Hang, Nai-Jung Chiang, Tse-Ching Chen, Tom Wei-Wu Chen, John Wen-Cheng Chang, Yao-Yu Hsieh, Yen-Lin Chen, Yi-Chen Yeh, Yi-Hsin L
    Journal of Cancer Research and Practice.2024;[Epub]     CrossRef
  • Pragmatic nationwide master observational trial based on genomic alterations in advanced solid tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II
    Sun Young Kim, Jee Hyun Kim, Tae-Yong Kim, Sook Ryun Park, Shinkyo Yoon, Soohyeon Lee, Se-Hoon Lee, Tae Min Kim, Sae-Won Han, Hye Ryun Kim, Hongseok Yun, Sejoon Lee, Jihun Kim, Yoon-La Choi, Kui Son Choi, Heejung Chae, Hyewon Ryu, Gyeong-Won Lee, Dae Youn
    BMC Cancer.2024;[Epub]     CrossRef
  • Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort
    I. Vanni, L. Pastorino, V. Andreotti, D. Comandini, G. Fornarini, M. Grassi, A. Puccini, E. T. Tanda, A. Pastorino, V. Martelli, L. Mastracci, F. Grillo, F. Cabiddu, A. Guadagno, S. Coco, E. Allavena, F. Barbero, W. Bruno, B. Dalmasso, S. E. Bellomo, C. M
    Journal of Translational Medicine.2024;[Epub]     CrossRef
  • Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP
    Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun
    Journal of Pathology and Translational Medicine.2024; 58(4): 147.     CrossRef
  • Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP
    Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun
    Cancer Research and Treatment.2024; 56(3): 721.     CrossRef
  • Nationwide precision oncology pilot study: KOrean Precision Medicine Networking Group Study of MOlecular profiling-guided therapy based on genomic alterations in advanced solid tumors (KOSMOS) KCSG AL-20-05
    T.-Y. Kim, S.Y. Kim, J.H. Kim, H.A. Jung, Y.J. Choi, I.G. Hwang, Y. Cha, G.-W. Lee, Y.-G. Lee, T.M. Kim, S.-H. Lee, S. Lee, H. Yun, Y.L. Choi, S. Yoon, S.W. Han, T.-Y. Kim, T.W. Kim, D.Y. Zang, J.H. Kang
    ESMO Open.2024; 9(10): 103709.     CrossRef
  • Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers
    Yongjun Cha, Sheehyun Kim, Sae-Won Han
    Cancer Research and Treatment.2023; 55(2): 367.     CrossRef
  • Mutational evolution after chemotherapy‐progression in metastatic colorectal cancer revealed by circulating tumor DNA analysis
    Sheehyun Kim, Yongjun Cha, Yoojoo Lim, Hanseong Roh, Jun‐Kyu Kang, Kyung‐Hun Lee, Min Jung Kim, Ji Won Park, Seung‐Bum Ryoo, Hwang‐Phill Kim, Seung‐Yong Jeong, Kyu Joo Park, Sae‐Won Han, Tae‐You Kim
    International Journal of Cancer.2023; 153(3): 571.     CrossRef
  • Establishing molecular pathology curriculum for pathology trainees and continued medical education: a collaborative work from the Molecular Pathology Study Group of the Korean Society of Pathologists
    Jiwon Koh, Ha Young Park, Jeong Mo Bae, Jun Kang, Uiju Cho, Seung Eun Lee, Haeyoun Kang, Min Eui Hong, Jae Kyung Won, Youn-La Choi, Wan-Seop Kim, Ahwon Lee
    Journal of Pathology and Translational Medicine.2023; 57(5): 265.     CrossRef
  • Implementation of Precision Oncology in the National Healthcare System: A Statement Proposal Endorsed by Italian Scientific Societies
    Gianpiero Fasola, Maria C. Barducci, Valeria D. Tozzi, Luigi Cavanna, Saverio Cinieri, Francesco Perrone, Carmine Pinto, Antonio Russo, Anna Sapino, Francesco Grossi, Giuseppe Aprile
    JCO Precision Oncology.2023;[Epub]     CrossRef
  • Development of two 410-cancer-gene panel tests for solid tumors and liquid biopsy based on genome data of 5,143 Japanese cancer patients
    Yuji SHIMODA, Takeshi NAGASHIMA, Kenichi URAKAMI, Fukumi KAMADA, Sou NAKATANI, Maki MIZUGUCHI, Masakuni SERIZAWA, Keiichi HATAKEYAMA, Keiichi OHSHIMA, Tohru MOCHIZUKI, Sumiko OHNAMI, Shumpei OHNAMI, Takeshi KAWAKAMI, Kentaro YAMAZAKI, Haruyasu MURAKAMI, H
    Biomedical Research.2022; 43(4): 115.     CrossRef
  • Clinical Implication of Molecular Tumor Board
    Soohyeon Lee
    The Korean Journal of Medicine.2022; 97(5): 319.     CrossRef
  • Somatic Mutations of TP53 Identified by Targeted Next-Generation Sequencing Are Poor Prognostic Factors for Primary Operable Breast Cancer: A Single-Center Study
    Jung Ho Park, Mi Jung Kwon, Jinwon Seo, Ho Young Kim, Soo Kee Min, Lee Su Kim
    Journal of Breast Cancer.2022; 25(5): 379.     CrossRef
  • 9,902 View
  • 524 Download
  • 11 Web of Science
  • 13 Crossref
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Original Articles
Breast cancer
A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer
Jung Sun Kim, Koung Jin Suh, Dae-Won Lee, Go-un Woo, Miso Kim, Se Hyun Kim, Han Suk Ryu, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, So Yeon Park, In Ae Park, Jee Hyun Kim, Seock-Ah Im
Cancer Res Treat. 2022;54(2):488-496.   Published online August 13, 2021
DOI: https://doi.org/10.4143/crt.2021.394
AbstractAbstract PDFPubReaderePub
Purpose
We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients.
Materials and Methods
This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled.
Results
A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction.
Conclusion
This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.

Citations

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  • Long-term outcomes of a randomized, open-label, phase II study comparing cabazitaxel versus paclitaxel as neoadjuvant treatment in patients with triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE)
    P. Meyer-Wilmes, J. Huober, M. Untch, J.-U. Blohmer, W. Janni, C. Denkert, P. Klare, T. Link, K. Rhiem, C. Bayer, M. Reinisch, V. Bjelic-Radisic, D.M. Zahm, C. Hanusch, C. Solbach, G. Heinrich, A.D. Hartkopf, A. Schneeweiss, P. Fasching, N. Filmann, V. Ne
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    Vikas Talreja, Sangeeta Khetwani, Ethirajan Nanadagopal, Nilesh Eknath Borkar, Kunal Khobragade
    International Journal of Molecular and Immuno Oncology.2024; 9: 46.     CrossRef
  • Safety and efficacy of generic nab-paclitaxel-based therapy in Chinese patients with malignant tumors in a real-world setting: a multicenter prospective observational study
    Fei He, Yancai Sun, Wenzhou Zhang, Qiongshi Wu, Donghang Xu, Zaixian Bai, Zhiying Hao, Weiyi Feng, Kanghuai Zhang, Jiang Liu, Mei Dong, Guangxuan Liu, Guohui Li
    Discover Oncology.2024;[Epub]     CrossRef
  • Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study
    Zhichao Tian, Shuping Dong, Yang Yang, Shilei Gao, Yonghao Yang, Jinpo Yang, Peng Zhang, Xin Wang, Weitao Yao
    BMC Cancer.2022;[Epub]     CrossRef
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    Reactions Weekly.2022; 1926(1): 383.     CrossRef
  • Natural Taxanes: From Plant Composition to Human Pharmacology and Toxicity
    Ľuboš Nižnanský, Denisa Osinová, Roman Kuruc, Alexandra Hengerics Szabó, Andrea Szórádová, Marián Masár, Žofia Nižnanská
    International Journal of Molecular Sciences.2022; 23(24): 15619.     CrossRef
  • A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma
    Hua Yang, Mu-Zi-he Zhang, Hui-wei Sun, Yan-tao Chai, Xiaojuan Li, Qiyu Jiang, Jun Hou
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • 7,176 View
  • 220 Download
  • 5 Web of Science
  • 7 Crossref
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Lung and Thoracic cancer
Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non–Small Cell Lung Cancer
Chaelin Lee, Miso Kim, Dong-Wan Kim, Tae Min Kim, Soyeon Kim, Sun-Wha Im, Yoon Kyung Jeon, Bhumsuk Keam, Ja-Lok Ku, Dae Seog Heo
Cancer Res Treat. 2022;54(1):140-149.   Published online May 3, 2021
DOI: https://doi.org/10.4143/crt.2021.385
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs.
Materials and Methods
We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening.
Results
In cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs.
Conclusion
Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

Citations

Citations to this article as recorded by  
  • A Constitutive EGFR Kinase Dimer to Study Inhibitor Pharmacology
    Justin J. Kim, Ilse K. Schaeffner, David E. Heppner, Ciric To, Pasi A. Jänne, Tyler S. Beyett, Michael J. Eck
    Molecular Pharmacology.2024; 105(2): 97.     CrossRef
  • Tumor-associated Macrophages Mediate Gefitinib Resistance in Lung Cancer through HGF/c-met Signaling Pathway
    Xiali Tang, Yu Chen, Demin Jiao, Xiang Liu, Jun Chen, Yongyang Liu, Chunyan Jiang, Qingyong Chen
    Anti-Cancer Agents in Medicinal Chemistry.2024; 24(1): 30.     CrossRef
  • Colorectal cancer harboring EGFR kinase domain duplication response to EGFR tyrosine kinase inhibitors
    Tomohiro Kondo, Osamu Kikuchi, Yoshihiro Yamamoto, Tomohiko Sunami, Yafeng Wang, Keita Fukuyama, Tomoki Saito, Hideto Nakahara, Sachiko Minamiguchi, Masashi Kanai, Atsushi Sueyoshi, Manabu Muto
    The Oncologist.2024;[Epub]     CrossRef
  • Research progress on the role of bypass activation mechanisms in resistance to tyrosine kinase inhibitors in non-small cell lung cancer
    Ziyang Jiang, Zhihan Gu, Xiaomin Yu, Tao Cheng, Bofu Liu
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Molecular Targets and Mechanisms of Casein-Derived Tripeptides Ile-Pro-Pro and Val-Pro-Pro on Hepatic Glucose Metabolism
    Chenyang Wang, Lin Zheng, Mouming Zhao
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  • Erlotinib

    Reactions Weekly.2022; 1907(1): 208.     CrossRef
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Sarcoma
Real-World Clinical Outcomes and Prognostic Factors for Patients with Advanced Angiosarcoma who Received Systemic Treatment
Changhee Park, Miso Kim, Yoonjin Kwak, Kyung Chul Moon, Se Hyun Kim, Bhumsuk Keam, Yu Jung Kim, Tae Min Kim, Dong-Wan Kim
Cancer Res Treat. 2021;53(4):1195-1203.   Published online February 1, 2021
DOI: https://doi.org/10.4143/crt.2020.1337
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Angiosarcoma is a highly aggressive mesenchymal tumor. Although systemic chemotherapy is often considered for the inoperable or metastatic angiosarcoma, the outcome of such treatment is unsatisfactory and poorly delineated.
Materials and Methods
We reviewed electronic medical records of 75 patients with angiosarcoma who were treated with systemic chemotherapy for inoperable or metastatic disease. Patients were classified as having liver involvement if they had either primary or metastatic hepatic lesions.
Results
Among the patients evaluated, 51 patients were male (68%) and 24 patients (32%) had primary cutaneous angiosarcoma. Liver involvement was present in 28 patients (37.3%). A total of 59 patients received first-line weekly paclitaxel (wPac) and showed an objective response rate (ORR) of 23.7% (n=14), a median progression free survival (mPFS) of 4.0 months (95% confidence interval [CI] 3.0–6.1), and a median overall survival (mOS) of 10.2 months (95% CI 7.0–14.6). Among patients without liver involvement, patients receiving wPac (n=35) had significantly prolonged mPFS (5.8 vs. 3.2 months, respectively, p=0.014) with a tendency for prolonged mOS (13.8 vs. 11.6 months, respectively, p=0.13) than those receiving other regimens (n=12). A total of 24 patients received second- or later-line pazopanib monotherapy and showed an ORR of 16.7% (n=4), a mPFS of 2.4 months (95% CI 1.8–4.3) and a mOS of 5.4 months (95% CI 3.5–NA).
Conclusion
Treatment with first-line wPac and later-line pazopanib seems to provide survival benefit, especially for patients with advanced angiosarcoma without liver involvement.

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  • Hepatic Angiosarcoma with Peliosis Hepatis
    Kensuke Kitsugi, Kazuhito Kawata, Moe Matsumoto, Masahiro Umemura, Tomohiko Hanaoka, Maho Yamashita, Shingo Takatori, Jun Ito, Kazuyoshi Ohta, Takeshi Chida, Hidenao Noritake, Takafumi Suda
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    Yuta Ushida, Takafumi Sato, Tomotaka Kato, Yasuyuki Shigematsu, Hiromichi Ito, Takeshi Suzuki, Yosuke Inoue, Yoshihiro Ono, Atsushi Oba, Yu Takahashi
    Clinical Journal of Gastroenterology.2022; 15(2): 427.     CrossRef
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    Siwei Bi, Ai Zhong, Xiya Yin, Jingyi Li, Ying Cen, Junjie Chen
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  • Results of NC-6300 (Nanoparticle Epirubicin) in an Expansion Cohort of Patients with Angiosarcoma
    Richard F Riedel, Victoria Chua, Ania Moradkhani, Natalie Krkyan, Amir Ahari, Atsushi Osada, Sant P Chawla
    The Oncologist.2022; 27(10): 809.     CrossRef
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Breast cancer
Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients
Mihong Choi, Jiyeon Han, Bo Ram Yang, Myoung-jin Jang, Miso Kim, Dae-Won Lee, Tae-Yong Kim, Seock-Ah Im, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh, Kyung-Hun Lee
Cancer Res Treat. 2021;53(1):65-76.   Published online September 23, 2020
DOI: https://doi.org/10.4143/crt.2020.430
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer.
Materials and Methods
We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer.
Results
Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05).
Conclusion
Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

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Bevacizumab Plus Erlotinib Combination Therapy for Advanced Hereditary Leiomyomatosis and Renal Cell Carcinoma-Associated Renal Cell Carcinoma: A Multicenter Retrospective Analysis in Korean Patients
Yeonjoo Choi, Bhumsuk Keam, Miso Kim, Shinkyo Yoon, Dalyong Kim, Jong Gwon Choi, Ja Young Seo, Inkeun Park, Jae Lyun Lee
Cancer Res Treat. 2019;51(4):1549-1556.   Published online March 25, 2019
DOI: https://doi.org/10.4143/crt.2019.086
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genetic syndrome resulting from germline mutations in fumarate hydratase. The combination of bevacizumab plus erlotinib showed promising interim results for HLRCC-associated RCC. Based on these results, we analyzed the outcome of bevacizumab plus erlotinib in Korean patients with HLRCC-associated RCC.
Materials and Methods
We retrospectively reviewed the efficacy and safety of bevacizumab plus erlotinib in patients with HLRCC-associated RCC who were confirmed to have germline mutations in fumarate hydratase. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were progression-free survival (PFS) and overall survival (OS).
Result
We identified 10 patients with advanced HLRCC-associated RCC who received bevacizumab plus erlotinib. Median age at diagnosis was 41 years, and five of the patients had received the combination as first- or second-line treatments. The ORR was 50% and the median PFS and OS were 13.3 and 14.1 months, respectively. Most adverse events were predictable and manageable by conventional measures, except for one instance where a patient died of gastrointestinal bleeding.
Conclusion
This is the first real-world outcome of the treatment of advanced HLRCC-associated RCC. Bevacizumab plus erlotinib therapy showed promising activity with moderate toxicity. We should be increasingly aware of HLRCC-associated RCC and bevacizumab plus erlotinib should be a first-line treatment for this condition, unless other promising data are published.

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Alterations in PD-L1 Expression Associated with Acquisition of Resistance to ALK Inhibitors in ALK-Rearranged Lung Cancer
Su-Jung Kim, Soyeon Kim, Dong-Wan Kim, Miso Kim, Bhumsuk Keam, Tae Min Kim, Yusoo Lee, Jaemoon Koh, Yoon Kyung Jeon, Dae Seog Heo
Cancer Res Treat. 2019;51(3):1231-1240.   Published online December 31, 2018
DOI: https://doi.org/10.4143/crt.2018.486
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to evaluate the relationships between the resistance of anaplastic lymphoma kinase (ALK)‒positive non-small cell lung cancer (NSCLC) to ALK inhibitors and the programmed cell death-1/programmed cell death–ligand 1 (PD-L1) pathway, we evaluated alterations in PD-L1 following acquisition of resistance to ALK inhibitors in ALK-positive lung cancer.
Materials and Methods
We established ALK inhibitor-resistant cell lines (H3122CR1, LR1, and CH1) by exposing the parental H3122 ALK-translocated NSCLC cell line to ALK inhibitors. Then, the double-resistant cell lines H3122CR1LR1 and CR1CH1 were developed by exposing the H3122CR1 to other ALK inhibitors. We compared the alterations in PD-L1 expression levels using western blotting, flow cytometry, and quantitative polymerase chain reaction. We also investigated gene expression using RNA sequencing. The expression of PD-L1 in the tumors from 26 ALK-positive metastatic NSCLC patients (11 ALK inhibitor-naïve and 15 ALK inhibitor-resistant patients) was assessed by immunohistochemistry and analyzed.
Results
PD-L1 was expressed at higher levels in ALK inhibitor-resistant cell lines than in the ALK inhibitor-naïve parental cell line at the total protein, surface protein, and mRNA levels. Furthermore, PD-L1 expression in the double-resistant cell lines was much higher than that in the single resistant cell lines. RNA sequencing demonstrated that expression of immune-related genes were largely involved in ALK inhibitor resistance. The mean value of the PD-L1 H-score was 6.5 pre-treatment and 35.0 post-treatment, and the fold difference was 5.42 (p=0.163).
Conclusion
PD-L1 expression increased following acquisition of ALK inhibitor resistance in ALK-positive NSCLC cell lines and tumors.

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Acquired Resistance of MET-Amplified Non-small Cell Lung Cancer Cells to the MET Inhibitor Capmatinib
Seulki Kim, Tae Min Kim, Dong-Wan Kim, Soyeon Kim, Miso Kim, Yong-Oon Ahn, Bhumsuk Keam, Dae Seog Heo
Cancer Res Treat. 2019;51(3):951-962.   Published online October 10, 2018
DOI: https://doi.org/10.4143/crt.2018.052
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Amplified mesenchymal-epithelial transition factor, MET, is a receptor tyrosine kinase (RTK) that has been considered a druggable target in non-small cell lung cancer (NSCLC). Although multiple MET tyrosine kinase inhibitors (TKIs) are being actively developed for MET-driven NSCLC, the mechanisms of acquired resistance to MET-TKIs have not been well elucidated. To understand the mechanisms of resistance and establish therapeutic strategies, we developed an in vitro model using the MET-amplified NSCLC cell line EBC-1.
Materials and Methods
We established capmatinib-resistant NSCLC cell lines and identified alternative signaling pathways using 3′ mRNA sequencing and human phospho-RTK arrays. Copy number alterations were evaluated by quantitative polymerase chain reaction and cell proliferation assay; activation of RTKs and downstream effectors were compared between the parental cell line EBC-1 and the resistant cell lines.
Results
We found that EBC-CR1 showed an epidermal growth factor receptor (EGFR)‒dependent growth and sensitivity to afatinib, an irreversible EGFR TKI. EBC-CR2 cells that had overexpression of EGFR-MET heterodimer dramatically responded to combined capmatinib with afatinib. In addition, EBC-CR3 cells derived from EBC-CR1 cells that activated EGFR with amplified phosphoinositide-3 kinase catalytic subunit α (PIK3CA) were sensitive to combined afatinib with BYL719, a phosphoinositide 3-kinase α (PI3Kα) inhibitor.
Conclusion
Our in vitro studies suggested that activation of EGFR signaling and/or genetic alteration of downstream effectors like PIK3CA were alternative resistance mechanisms used by capmatinib-resistant NSCLC cell lines. In addition, combined treatments with MET, EGFR, and PI3Kα inhibitors may be effective therapeutic strategies in capmatinib-resistant NSCLC patients.

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The Risk of Herpes Zoster in Patients with Non-small Cell Lung Cancer according to Chemotherapy Regimens: Tyrosine Kinase Inhibitors versus Cytotoxic Chemotherapy
Ji Young Choi, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo, Seong Jin Jo
Cancer Res Treat. 2019;51(1):169-177.   Published online April 5, 2018
DOI: https://doi.org/10.4143/crt.2017.491
AbstractAbstract PDFPubReaderePub
Purpose
Despite the successful use of tyrosine kinase inhibitors (TKIs) in cancer patients, their effect on herpes zoster development has not been studied. The aim of this study was to evaluate and compare the effects of epidermal growth factor receptor (EGFR) TKI and cytotoxic chemotherapy on the risk of herpes zoster development in non-small cell lung cancer (NSCLC) patients.
Materials and Methods
We conducted a medical review of all eligible NSCLC patients in Seoul National University hospital between 2002 and 2015. We classified patients based on whether they previously underwent EGFR TKI therapy into either the TKI group or the cytotoxic group. We compared the incidence rates of herpes zoster during TKI therapy and cytotoxic chemotherapy. Additionally, the longitudinal risk of herpes zoster from TKIs was analyzed using the incidence rate ratio (IRR) of the TKI group to the cytotoxic group and the log-rank test of the Kaplan-Meier method.
Results
Of the 2,981 NSCLC patients, 54 patients (1.54%) developed herpes zoster. In the TKI group (2,002 patients), the IRR of herpes zoster during TKI therapy compared to that during cytotoxic chemotherapy was 1.05 (95% confidence interval [CI], 0.53 to 2.09). The IRR of the TKI group compared to the cytotoxic group was 1.33 (95% CI, 0.64 to 2.76). The Kaplan-Meier cumulative risk of both groups was not significantly different.
Conclusion
Our results show that the incidence rate of herpes zoster in the TKI group was not statistically different from the incidence in the cytotoxic group during and after chemotherapy in NSCLC patients.

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The Impact of Skin Problems on the Quality of Life in Patients Treated with Anticancer Agents: A Cross-Sectional Study
Jaewon Lee, Jin Lim, Jong Seo Park, Miso Kim, Tae-Yong Kim, Tae Min Kim, Kyung-Hun Lee, Bhumsuk Keam, Sae-Won Han, Je-Ho Mun, Kwang Hyun Cho, Seong Jin Jo
Cancer Res Treat. 2018;50(4):1186-1193.   Published online December 14, 2017
DOI: https://doi.org/10.4143/crt.2017.435
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Patients treated with anticancer agents often experience a variety of treatment-related skin problems, which can impair their quality of life.
Materials and Methods
In this cross-sectional study, Dermatology Life Quality Index (DLQI) and clinical information were evaluated in patients under active anticancer treatment using a questionnaire survey and their medical records review.
Results
Of 375 evaluated subjects with anticancer therapy, 136 (36.27%) and 114 (30.40%) were treated for breast cancer and colorectal cancer, respectively. We found that women, breast cancer, targeted agent use, and longer duration of anticancer therapy were associated with higher dermatology-specific quality of life distraction. In addition, itching, dry skin, easy bruising, pigmentation, papulopustules on face, periungual inflammation, nail changes, and palmoplantar lesions were associated with significantly higher DLQI scores. Periungual inflammation and palmoplantar lesions scored the highest DLQI.
Conclusion
We believe our findings can be helpful to clinicians in counseling and managing the patients undergoing anticancer therapy.

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The Effect of Hospice Consultation on Aggressive Treatment of Lung Cancer
Shin Hye Yoo, Bhumsuk Keam, Miso Kim, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo
Cancer Res Treat. 2018;50(3):720-728.   Published online July 14, 2017
DOI: https://doi.org/10.4143/crt.2017.169
AbstractAbstract PDFPubReaderePub
Purpose
The aims of this study were to investigate trends of aggressive treatment of non-small cell lung cancer (NSCLC) patients at the end-of-life (EOL) during the recent 5 years and examine the relationship between hospice consultation (HC) and aggressive care.
Materials and Methods
The medical records of 789 patients with stage IIIB-IV NSCLC at Seoul National University Hospital (SNUH) who received palliative chemotherapy and died from 2010 to 2014 were retrospectively reviewed. Indicators of aggressive treatment were evaluated, and the association of HC with these indicators was analyzed.
Results
During the last 5 years, the frequency of HC increased from 26.7% to 43.6%. The time interval from last chemotherapy to death increased, and the proportion of patients who received palliative chemotherapy, visited an emergency room, were admitted to intensive care unit, during the last month of life, and died in SNUH significantly decreased over time. Referral to HC was significantly associated with lower intensive care unit admission rates, lower out-of-hospital death rates, and less use of the chemotherapy within 1 month prior to death. Overall survival did not differ by HC.
Conclusion
The pattern of cancer care nearthe EOL has become less aggressivewhen HCwas provided. The positive association of HCwith better EOL care suggests that providing HC at the optimal time might help to avoid futile aggressive treatment.

Citations

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    Jeong-Han Kim, Shin Hye Yoo, Bhumsuk Keam, Dae Seog Heo
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Comparison of Native Escherichia coli L-Asparaginase versus Pegylated Asparaginase, in Combination with Ifosfamide, Methotrexate, Etoposide, and Prednisolone, in Extranodal NK/T-Cell Lymphoma, Nasal Type
Hyun Jee Kim, Chan-Young Ock, Tae Min Kim, Sung Hee Lee, Ju-Yeun Lee, Sun hoi Jung, Yoon Sook Cho, Miso Kim, Bhumsuk Keam, Dong-Wan Kim, Il Han Kim, Dae Seog Heo
Cancer Res Treat. 2018;50(3):670-680.   Published online July 3, 2017
DOI: https://doi.org/10.4143/crt.2017.051
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The aim of this study was to compare asparaginase-related toxicities in two asparaginase preparations, namely native Escherichia coli L-asparaginase (L-ASP) and pegylated asparaginase (PEG-ASP) in combination with ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) in natural killer (NK)/T-cell lymphoma (NTCL).
Materials and Methods
A total of 41 NTCL patients who received IMEP plus native E. coli L-ASP or PEG-ASP at Seoul National University Hospital were included in this study between January 2013 and March 2016. IMEP/ASP treatment consisted of ifosfamide, methotrexate, etoposide, plus native E. coli L-ASP (6,000 IU/m2 on days 1, 3, 5, 7, 9, and 11) or PEG-ASP (2,500 IU/m2 on day 1) every 3 weeks. ASP-related toxicities, toxicity patterns, length of hospital stay, and clinical outcomes were compared between the different treatment groups.
Results
The frequency of ASP-related toxicities was similar between the IMEP plus native E. coli L-ASP group and the PEG-ASP group apart from hypofibrinogenemia (native E. coli L-ASP vs. PEG-ASP group, 86.4% vs. 36.8%; p=0.001). Although post-treatment transaminase and albumin levels were significantly high and low, respectively, hepatotoxicity gradients before and after treatment did not differ significantly between the groups. Since PEG-ASP was given at an outpatient clinic in some patients, length of hospital stay was significantly shorter in the IMEP plus PEG-ASP group (median, 4.0 vs. 6.0 days; p=0.002). A favorable tendency of clinical outcomes was observed in NTCL patients treated with IMEP plus PEG-ASP (complete remission rate, 73.7% vs. 45.5%; p=0.067).
Conclusion
IMEP plus PEG-ASP showed similar ASP-related toxicities, shorter length of hospital stay, and a trend towards improved clinical outcomes compared with IMEP plus native E. coli L-ASP in NTCL.

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Phase II Study of Irinotecan and Cisplatin Combination Chemotherapy in Metastatic, Unresectable Esophageal Cancer
Miso Kim, Bhumsuk Keam, Tae-Min Kim, Hoon-Gu Kim, Jin-Soo Kim, Sung Sook Lee, Seong Hoon Shin, Min Kyoung Kim, Keon Uk Park, Dong-Wan Kim, Hwan Jung Yun, Jong Seok Lee, Dae Seog Heo
Cancer Res Treat. 2017;49(2):416-422.   Published online July 28, 2016
DOI: https://doi.org/10.4143/crt.2016.121
AbstractAbstract PDFPubReaderePub
Purpose
The objective of this multicenter phase II study was to evaluate the efficacy and safety of irinotecan and cisplatin combination chemotherapy in metastatic, unresectable esophageal cancer.
Materials and Methods
Patients were treated with irinotecan 65 mg/m2 and cisplatin 30 mg/m2 on days 1 and 8 of each 21-day treatment cycle. The primary endpoint was response rate, and secondary endpoints were survival, duration of response, initial metabolic response rate, and toxicity.
Results
A total of 27 patients with squamous cell histology were enrolled in the study. The median age of the patients was 61 years. The objective response rate of the 20 patients in the perprotocol group was 30.0% (90% confidence interval [CI], 13.2 to 46.9). The median follow-up duration was 10.0 months, and the median progression-free survival and overall survival were 4.5 months (95% CI, 1.6 to 6.2) and 8.8 months (95% CI, 4.7 to 10.5), respectively. Four of 13 patients (30.8%) evaluated showed initial metabolic response. The median duration of response for partial responders was 5.0 months (range, 3.4 to 8.0 months). The following grade 3/4 treatment-related hematologic toxicities were reported: neutropenia (40.7%), anaemia (22.2%), and thrombocytopenia (7.4%). Two patients experienced febrile neutropenia. The most common grade 3/4 non-hematologic toxicities were asthenia (14.8%) and diarrhoea (11.1%).
Conclusion
Irinotecan and cisplatin combination chemotherapy showed modest anti-tumour activity and manageable toxicity for patients with metastatic, unresectable esophageal cancer.

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The Effect of Induction Chemotherapy Using Docetaxel, Cisplatin, and Fluorouracil on Survival in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Meta-Analysis
Ryul Kim, Seokyung Hahn, Junghoon Shin, Chan-Young Ock, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo
Cancer Res Treat. 2016;48(3):907-916.   Published online November 17, 2015
DOI: https://doi.org/10.4143/crt.2015.359
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to compare the survival of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (CRT) alone with that of patients undergoing induction chemotherapy (IC) using docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by CRT.
Materials and Methods
A search of the PubMed, EMBASE, and Cochrane Library databases was performed in April 2015 and abstracts from the American Society of Clinical Oncology meetings (2008-2014) were reviewed. Summaries of the results were pooled using a fixed-effect model, and the risk of bias was evaluated using the Cochrane tool.
Results
A total of six relevant trials comprising 1,280 patients were identified. There was no statistically significant overall survival (OS) advantage for TPF prior to CRT (TPF/CRT) over CRT alone (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.79 to 1.09; p=0.339). Progression- free survival (PFS) was significantly longer in the TPF/CRT arms (HR, 0.82; 95% CI, 0.70 to 0.95; p=0.009). Patients with non-oropharyngeal LA-HNSCC obtained the greatest OS and PFS benefits from TPF (HR, 0.68; 95% CI, 0.47 to 0.99; p=0.043 and HR, 0.67; 95% CI, 0.48 to 0.94; p=0.022, respectively). The complete response rate was significantly increased (risk ratio [RR], 1.34; 95% CI, 1.14 to 1.56; p < 0.001), and the distant metastasis rate tended to decrease (RR, 0.65; 95% CI, 0.40 to 1.04; p=0.071) in the TPF/CRT arms.
Conclusion
IC with TPF followed by CRT is not superior to CRT alone for OS. However, PFS and the complete response rate were significantly improved in the TPF/CRT arms. TPF/CRT for patients with nonoropharyngeal LA-HNSCC provided clear survival advantages.

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Case Report
Adenoid Cystic Carcinoma of the Breast: A Case Series of Six Patients and Literature Review
Miso Kim, Dae-Won Lee, Jin Im, Koung Jin Suh, Bhumsuk Keam, Hyeong-Gon Moon, Seock-Ah Im, Wonshik Han, In Ae Park, Dong-Young Noh
Cancer Res Treat. 2014;46(1):93-97.   Published online January 15, 2014
DOI: https://doi.org/10.4143/crt.2014.46.1.93
AbstractAbstract PDFPubReaderePub
Adenoid cystic carcinoma (ACC) of the breast is a very rare and indolent tumor with a favorable prognosis, despite its triple-negative status. Due to its rarity, there has been no consensus regarding treatments, and treatment guidelines have not been established. Here, we report on six patients with ACC of the breast. All of the patients initially presented with localized disease and no axillary lymph node metastases. Although some of our patients developed local recurrence or distant metastases, all patients had a favorable clinical course, and to date, none of the patients has died from complications of her disease. Here, we described the clinicopathologic features of ACC of the breast and review the current literature.

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