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37 "Dong-Wan Kim"
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Case Report
Molecular and Treatment Characteristics of SMARCB1 or SMARCA4-Deficient Undifferentiated Tumor: Retrospective Case Series
Hyeon Gyu Kang, Jiwon Koh, Tae Min Kim, Doo Hee Han, Tae-Bin Won, Dong-Wan Kim, Dong-Young Kim, Bhumsuk Keam
Cancer Res Treat. 2024;56(3):967-971.   Published online February 13, 2024
DOI: https://doi.org/10.4143/crt.2023.1308
AbstractAbstract PDFPubReaderePub
SMARCB1 or SMARCA4-deficient sinonasal carcinoma or thoracic undifferentiated tumor has aggressive nature with a poor prognosis. Patients with this disease were diagnosed by immunohistochemistry or next-generation sequencing. Those who were able to receive a surgery tended to be cured, while the others treated with chemotherapy, radiation therapy, or immune checkpoint inhibitor were often insensitive to these therapies. However, one having CD274 (PD-L1) amplification showed the response to immune checkpoint inhibitor and a good prognosis. We believed that this report could provide promising information for determining the optimal treatment option.
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Original Articles
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
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Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset
Ki Hyeong Lee, Byoung Chul Cho, Myung-Ju Ahn, Yun-Gyoo Lee, Youngjoo Lee, Jong-Seok Lee, Joo-Hang Kim, Young Joo Min, Gyeong-Won Lee, Sung Sook Lee, Kyung-Hee Lee, Yoon Ho Ko, Byoung Yong Shim, Sang-We Kim, Sang Won Shin, Jin-Hyuk Choi, Dong-Wan Kim, Eun Kyung Cho, Keon Uk Park, Jin-Soo Kim, Sang Hoon Chun, Jangyoung Wang, SeokYoung Choi, Jin Hyoung Kang
Cancer Res Treat. 2024;56(1):48-60.   Published online June 27, 2023
DOI: https://doi.org/10.4143/crt.2023.453
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC).
Materials and Methods
Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS).
Results
In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib.
Conclusion
Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

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  • First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis
    Jietao Ma, Xiaoxue Pang, Shuling Zhang, Letian Huang, Li Sun, Chengbo Han
    Scientific Reports.2024;[Epub]     CrossRef
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  • 1 Crossref
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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
  • 3,231 View
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Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non–Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis
Byoung Chul Cho, Dong-Wan Kim, Ullas Batra, Keunchil Park, Sang-We Kim, Cheng-Ta Yang, Pei-Jye Voon, Virote Sriuranpong, K. Govind Babu, Khalid Amin, Yingbo Wang, Paramita Sen, Khemaies Slimane, Sarayut Geater
Cancer Res Treat. 2023;55(1):83-93.   Published online March 25, 2022
DOI: https://doi.org/10.4143/crt.2021.1571
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial.
Materials and Methods
Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events.
Results
At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively.
Conclusion
Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Citations

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  • Economic Evaluation of Targeted Therapies for Anaplastic Lymphoma Kinase– and ROS1 Fusion–Positive Non–Small Cell Lung Cancer in India
    Dharna Gupta, Nidhi Gupta, Navneet Singh, Shankar Prinja
    JCO Global Oncology.2024;[Epub]     CrossRef
  • Uniqueness of lung cancer in Southeast Asia
    Vanita Noronha, Atul Budukh, Pankaj Chaturvedi, Srikanth Anne, Anshu Punjabi, Maheema Bhaskar, Tarini P. Sahoo, Nandini Menon, Minit Shah, Ullas Batra, Shrinidhi Nathany, Rajiv Kumar, Omshree Shetty, Trupti Pai Ghodke, Abhishek Mahajan, Nivedita Chakrabar
    The Lancet Regional Health - Southeast Asia.2024; 27: 100430.     CrossRef
  • Small intestinal metastasis in a lung adenocarcinoma patient with concurrent EML4-ALK V3 and TP53 mutations after distinct responses to tyrosine kinase inhibitors: A case report
    Lingling Zhu, Yingchun Zhao, Yongqian Zhang, Zhai Liu, Wenhua Ma, Ying Guo, Qian Wang, Yan Guo, Hengxu Lv, Min Zhao
    Heliyon.2024; 10(19): e38839.     CrossRef
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  • 288 Download
  • 2 Web of Science
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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

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  • 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
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    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
    Journal of Agricultural and Food Chemistry.2023; 71(48): 18802.     CrossRef
  • Erlotinib

    Reactions Weekly.2022; 1907(1): 208.     CrossRef
  • 8,794 View
  • 330 Download
  • 5 Web of Science
  • 6 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.

Citations

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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
    Internal Medicine.2023; 62(8): 1157.     CrossRef
  • Conversion surgery for recurrent hepatic angiosarcoma after systemic chemotherapy with paclitaxel
    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
  • Management of Cutaneous Angiosarcoma: an Update Review
    Siwei Bi, Ai Zhong, Xiya Yin, Jingyi Li, Ying Cen, Junjie Chen
    Current Treatment Options in Oncology.2022; 23(2): 137.     CrossRef
  • 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
  • 8,387 View
  • 178 Download
  • 4 Web of Science
  • 4 Crossref
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Lung cancer
Real-World Experience of Nivolumab in Non-small Cell Lung Cancer in Korea
Sun Min Lim, Sang-We Kim, Byoung Chul Cho, Jin Hyung Kang, Myung-Ju Ahn, Dong-Wan Kim, Young-Chul Kim, Jin Soo Lee, Jong-Seok Lee, Sung Yong Lee, Keon Uk Park, Ho Jung An, Eun Kyung Cho, Tae Won Jang, Bong-Seog Kim, Joo-Hang Kim, Sung Sook Lee, Im-II Na, Seung Soo Yoo, Ki Hyeong Lee
Cancer Res Treat. 2020;52(4):1112-1119.   Published online May 15, 2020
DOI: https://doi.org/10.4143/crt.2020.245
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program.
Materials and Methods
Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected.
Results
Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data.
Conclusion
This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

Citations

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  • Advances in reprogramming of energy metabolism in tumor T cells
    Liu Xuekai, Song Yan, Chu Jian, Song Yifei, Wu Xinyue, Zhang Wenyuan, Han Shuwen, Yang Xi
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • Effectiveness and Safety of PD-1 Inhibitors’ Treatment for Patients with Non-Small-Cell Lung Cancer in China: A Real-World Study
    Ning Wan, Yongbang Chen, Liqing Lu, Bing Wang, Liuliu He, Hongyi Liang, Fei Xie, Xiaoshun Jian, Bo Ji, Jianping Zhang, Hammoda Abu-Odah
    European Journal of Cancer Care.2024; 2024: 1.     CrossRef
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    Qiang Chen, Shuo Ying, Jianwen Qin, Li Zhang
    Frontiers in Oncology.2024;[Epub]     CrossRef
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    Ana Ortega-Franco, Clare Hodgson, Haseem Raja, Mathew Carter, Colin Lindsay, Sarah Hughes, Laura Cove-Smith, Paul Taylor, Yvonne Summers, Fiona Blackhall, Raffaele Califano
    Targeted Oncology.2022; 17(4): 453.     CrossRef
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    Handai Xia, Wengang Zhang, Yuqing Zhang, Xiaoling Shang, Yanguo Liu, Xiuwen Wang
    Frontiers in Oncology.2022;[Epub]     CrossRef
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    Donghui Wang, Cen Chen, Yanli Gu, Wanjun Lu, Ping Zhan, Hongbing Liu, Tangfeng Lv, Yong Song, Fang Zhang
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Broad-Spectrum Antibiotic Regimen Affects Survival in Patients Receiving Nivolumab for Non-Small Cell Lung Cancer
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    Pharmaceuticals.2021; 14(5): 445.     CrossRef
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    Reactions Weekly.2021; 1855(1): 269.     CrossRef
  • Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis
    Zhe Zhao, Xinfeng Wang, Jinghan Qu, Wei Zuo, Yan Tang, Huijuan Zhu, Xiaoguang Chen
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • 10,461 View
  • 308 Download
  • 15 Web of Science
  • 9 Crossref
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Osimertinib in Patients with T790M-Positive Advanced Non-small Cell Lung Cancer: Korean Subgroup Analysis from Phase II Studies
Myung-Ju Ahn, Ji-Youn Han, Dong-Wan Kim, Byoung Chul Cho, Jin-Hyoung Kang, Sang-We Kim, James Chih-Hsin Yang, Tetsuya Mitsudomi, Jong Seok Lee
Cancer Res Treat. 2020;52(1):284-291.   Published online July 23, 2019
DOI: https://doi.org/10.4143/crt.2019.200
AbstractAbstract PDFPubReaderePub
Purpose
Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR sensitizing mutation and EGFR T790M and has demonstrated efficacy in non-small cell lung cancer (NSCLC) central nervous system (CNS) metastases. We present results of a subgroup analysis of Korean patients from the pooled data of two global phase II trials: AURA extension (NCT01802632) and AURA2 (NCT02094261).
Materials and Methods
Enrolled patients had EGFR T790M-positive NSCLC and disease progression during or after EGFR-TKI therapy. Patients received osimertinib 80 mg orally once daily until disease progression. The primary endpoint was objective response rate (ORR).
Results
In total, 66 Korean patients received osimertinib treatment with a median treatment duration of 19 months. In the evaluable-for-response population (n=62), ORR was 74% (95% confidence interval [CI], 61.5 to 84.5) and median duration of response was 9.8 months (95% CI, 7.1 to 16.8). In the full analysis set (n=66), median progression-free survival was 10.9 months (95% CI, 8.3 to 15.0; data cutoff November 1, 2016), and median overall survival was 29.2 months (95% CI, 24.8 to 35.7; data cutoff May 1, 2018). Eight patients with CNS metastases were evaluable for response, none of whom showed CNS progression. The most common adverse events were rash (53%), cough (33%), paronychia, diarrhea, and decreased appetite (each 32%).
Conclusion
Efficacy and safety profiles of osimertinib in this subgroup are consistent with the global phase II pooled population, which supports osimertinib as a recommended treatment for Korean patients with T790M positive NSCLC.

Citations

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  • Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer
    S.-H. Lee, J. Menis, T.M. Kim, H.R. Kim, C. Zhou, S.A. Kurniawati, K. Prabhash, H. Hayashi, D.D.-W. Lee, M.S. Imasa, Y.L. Teh, J.C.-H. Yang, T. Reungwetwattana, V. Sriuranpong, C.-E. Wu, Y. Ang, M. Sabando, M. Thiagarajan, H. Mizugaki, V. Noronha, M. Yuli
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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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Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer
Dong-Wan Kim, Hoon-Gu Kim, Joo-Hang Kim, Keunchil Park, Hoon-Kyo Kim, Joung Soon Jang, Bong-Seog Kim, Jin-Hyoung Kang, Kyung Hee Lee, Sang-We Kim, Hun Mo Ryoo, Jin-Soo Kim, Ki Hyeong Lee, Jung Hye Kwon, Jin-Hyuk Choi, Sang Won Shin, Seokyung Hahn, Dae Seog Heo
Cancer Res Treat. 2019;51(1):119-127.   Published online March 12, 2018
DOI: https://doi.org/10.4143/crt.2018.019
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This randomized phase III study was designed to compare the efficacy and safety of irinote-can plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC).
Materials and Methods
Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival.
Results
A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP.
Conclusion
The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.

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Phase 1 Studies of Poziotinib, an Irreversible Pan-HER Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors
Tae Min Kim, Keun-Wook Lee, Do-Youn Oh, Jong-Seok Lee, Seock-Ah Im, Dong-Wan Kim, Sae-Won Han, Yu Jung Kim, Tae-You Kim, Jee Hyun Kim, Hyesun Han, Woo Ho Kim, Yung-Jue Bang
Cancer Res Treat. 2018;50(3):835-842.   Published online August 29, 2017
DOI: https://doi.org/10.4143/crt.2017.303
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity againstwild type of epidermal growth factorreceptor(EGFR) family kinases including EGFR, HER2, and HER4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety, and antitumor activity against advanced solid tumors.
Materials and Methods
Standard 3+3 dose escalation scheme using two different dosing schedules were studied: once daily, 14-day on, and 7-day off (intermittent schedule); and once daily continuous dosing with food effect. Additional patients were enrolled in an expansion cohort.
Results
A total of 75 patients were enrolled in the two studies. The most common drug-related treatment-emergent adverse eventswere diarrhea,rash, stomatitis, pruritus, and anorexia. Doselimiting toxicities were grade 3 diarrhea in the intermittent schedule and grade 3 anorexia and diarrhea in the continuous dosing schedule. The MTDs were determined as 24 mg/day in the intermittent dosing schedule and 18 mg/day in the continuous dosing schedule. Eight (16%) and 24 (47%) of 51 evaluable patients in the intermittent schedule achieved partial response (PR) and stable disease (SD), respectively. Four (21%) and six (32%) of 19 evaluable patients in continuous dosing schedule achieved PR and SD, respectively. Patients with PR (n=7) or SD ≥ 12 weeks (n=7) had HER2 amplification (n=7; breast cancer, 5; and stomach cancer, 2) and EGFR amplification (n=1, squamous cell lung cancer).
Conclusion
Poziotinib was safe and well tolerated in patients with advanced solid tumors. It showed an encouraging activity against EGFR-mutant and HER2-amplified cancers.

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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.

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Crizotinib versus Chemotherapy in Asian Patients with ALK-Positive Advanced Non-small Cell Lung Cancer
Makoto Nishio, Dong-Wan Kim, Yi-Long Wu, Kazuhiko Nakagawa, Benjamin J. Solomon, Alice T. Shaw, Satoshi Hashigaki, Emiko Ohki, Tiziana Usari, Jolanda Paolini, Anna Polli, Keith D. Wilner, Tony Mok
Cancer Res Treat. 2018;50(3):691-700.   Published online July 6, 2017
DOI: https://doi.org/10.4143/crt.2017.280
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib in Asian subpopulations of two global phase III trials.
Materials and Methods
This analysis evaluated previously treated and untreated patients in two randomized, openlabel phase III trials of crizotinib versus chemotherapy in ALK-positive advanced NSCLC in second-line (PROFILE 1007) and first-line settings (PROFILE 1014). Efficacy and safety were analyzed by race in the intention-to-treat and “as-treated” populations for efficacy and safety endpoints, respectively.
Results
In previously treated (n=157) and untreated (n=157) Asian patients, PFS was statistically significantly longer with crizotinib versus chemotherapy (hazard ratio for PFS, 0.526; 95% confidence interval, 0.363 to 0.762; p < 0.001 and hazard ratio, 0.442; 95% confidence interval, 0.302 to 0.648; p < 0.001, respectively). Similar antitumor activity was seen in the non-Asian and overall populations. ORRs were statistically significantly higher with crizotinib versus chemotherapy in both Asian and non-Asian previously treated and untreated patients (p < 0.05). The most common treatment-emergent adverse events (any grade)with crizotinib were vision disorder, diarrhea, and nausea, which were observed at a comparable incidence across Asian and non-Asian populations, irrespective of previous treatment status. Most adverse events were mild to moderate in severity.
Conclusion
These data, currently the only analysis showing Asian and non-Asian populations in the same study, support the efficacy and safety of crizotinib in Asian patients with previously treated or untreated ALK-positive advanced NSCLC.

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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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    Wen Zheng, Yuhuan Gao, Xiaoyan Ke, Weijing Zhang, Liping Su, Hanyun Ren, Ningjing Lin, Yan Xie, Meifeng Tu, Weiping Liu, Lingyan Ping, Zhitao Ying, Chen Zhang, Lijuan Deng, Xiaopei Wang, Yuqin Song, Jun Zhu
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Korean Cancer Patients’ Awareness of Clinical Trials, Perceptions on the Benefit and Willingness to Participate
Yoojoo Lim, Jee Min Lim, Won Jae Jeong, Kyung-Hun Lee, Bhumsuk Keam, Tae-Yong Kim, Tae Min Kim, Sae-Won Han, Do Youn Oh, Dong-Wan Kim, Tae-You Kim, Dae Seog Heo, Yung-Jue Bang, Seock-Ah Im
Cancer Res Treat. 2017;49(4):1033-1043.   Published online April 7, 2017
DOI: https://doi.org/10.4143/crt.2016.413
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to assess current levels of awareness of clinical trials (CTs), perceptions regarding their benefits and willingness to participate to CTs among Korean cancer patients.
Materials and Methods
From December 2012 to August 2015, we distributed questionnaires to cancer patients receiving systemic anti-cancer therapy at Seoul National University Hospital, Seoul, Korea.
Results
A total of 397 out of 520 requested patients (76.3%) responded to the survey. Among the 397 patients, 62.5% were female and the median age was 52 years. Overall, 97.4% (387/397) answered that they have at least heard of CTs. When asked about their level of awareness, 23.8% (92/387) answered that they could more than roughly explain about CTs. The average visual analogue scale score of CT benefit in all patients was 6.43 (standard deviation, 2.20). Patients who were only familiar with the term without detailed knowledge of the contents had the least expectation of benefit from CTs (p=0.015). When asked about their willingness to participate in CTs, 56.7% (225/397) answered positively. Patients with higher levels of awareness of CTs showed higher willingness to participate (p < 0.001). Heavily treated patients and patients with previous experience regarding CTs also showed a higher willingness to participate (p < 0.001). The perceived benefit of CTs was higher in the group willing to participate (p=0.026).
Conclusion
The patient’s level of awareness regarding CTs was positively related to the positive perception and willingness to participate. Although the general awareness of CTs was high, a relatively large proportion of patients did not have accurate knowledge; therefore, proper and accurate patient education is necessary.

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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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Post-bevacizumab Clinical Outcomes and the Impact of Early Discontinuation of Bevacizumab in Patients with Recurrent Malignant Glioma
Yongjun Cha, Yu Jung Kim, Se-Hoon Lee, Tae-Min Kim, Seung Hong Choi, Dong-Wan Kim, Chul-Kee Park, Il Han Kim, Jee Hyun Kim, Eunhee Kim, Byungse Choi, Chae-Yong Kim, In Ah Kim, Dae Seog Heo
Cancer Res Treat. 2017;49(1):129-140.   Published online May 18, 2016
DOI: https://doi.org/10.4143/crt.2015.466
AbstractAbstract PDFPubReaderePub
Purpose
Bevacizumab±irinotecan is effective for treatment of recurrent malignant gliomas. However, the optimal duration of treatment has not been established.
Materials and Methods
Ninety-four consecutive patients with recurrent malignant glioma who were treated with bevacizumab at our institutions were identified. Patients who continued bevacizumab until tumor progression were enrolled in a late discontinuation (LD) group, while those who stopped bevacizumab before tumor progression were enrolled in an early discontinuation (ED) group. Landmark analyses were performed at weeks 9, 18, and 26 for comparison of patient survival between the two groups.
Results
Among 89 assessable patients, 62 (69.7%) and 27 (30.3%) patients were categorized as the LD and ED groups, respectively. According to landmark analysis, survival times from weeks 9, 18, and 26 were not significantly different between the two groups in the overall population. However, the LD group showed a trend toward increased survival compared to the ED group among responders. In the ED group, the median time from discontinuation to disease progression was 11.4 weeks, and none of the patients showed a definite rebound phenomenon. Similar median survival times after disease progression were observed between groups (14.4 weeks vs. 15.7 weeks, p=0.251). Of 83 patients, 38 (45.8%) received further therapy at progression, and those who received further therapy showed longer survival in both the LD and ED groups.
Conclusion
In recurrent malignant glioma, duration of bevacizumab was not associated with survival time in the overall population. However, ED of bevacizumab in responding patients might be associated with decreased survival.

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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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Special Article
Tolerability and Outcomes of First-Line Pemetrexed-Cisplatin Followed by Gefitinib Maintenance Therapy Versus Gefitinib Monotherapy in Korean Patients with Advanced Nonsquamous Non-small Cell Lung Cancer: A Post Hoc Descriptive Subgroup Analysis of a Randomized, Phase 3 Trial
Jin Hyoung Kang, Myung-Ju Ahn, Dong-Wan Kim, Eun Kyung Cho, Joo-Hang Kim, Sang Won Shin, Xin Wang, Jong Seok Kim, Mauro Orlando, Keunchil Park
Cancer Res Treat. 2016;48(2):458-464.   Published online October 14, 2015
DOI: https://doi.org/10.4143/crt.2015.135
AbstractAbstract PDFPubReaderePub
Purpose
We recently reported on a randomized, open-label, phase 3 trial comparing pemetrexed-cisplatin chemotherapy followed by gefitinib maintenance therapy (PC/G) with gefitinib monotherapy in patients with non-small cell lung cancer (NSCLC). Here, we report on a post hoc subgroup analysis of that study assessing the demographics and disposition of the Korean patient subgroup, and comparing the tolerability of PC/G and gefitinib monotherapy and the tumor response with respect to epidermal growth factor receptor (EGFR) status.
Materials and Methods
Patients, who were ≥ 18 years, chemonaïve, Korean, light ex-smokers/never-smokers with advanced NSCLC, were randomly assigned (1:1) to PC/G or gefitinib monotherapy. Treatment-emergent adverse events (TEAEs) were graded, and tumor response was measured as change in lesion sum from baseline at best response. The study was registered with ClinicalTrials. gov, NCT01017874.
Results
Overall, 111 Korean patients were treated (PC/G, 51; gefitinib, 60). Between-arm characteristics were balanced and similar to those of the overall population. Treatment discontinuations due to adverse events were low (PC/G: 1, 2.0%; gefitinib: 7, 11.7%). Overall, 92 patients (82.9%) reported ≥ 1 TEAE (PC/G, 44; gefitinib, 48); few patients (PC/G, 16; gefitinib, 7) reported severe TEAEs; the most frequent was neutropenia (PC/G arm) and elevated alanine aminotransferase (gefitinib arm). The lesion sum was decreased by PC/G treatment in most patients, regardless of EGFRmutation status, while gefitinib monotherapy reduced the lesion sum in EGFR-positive patients but had no effect in EGFR-negative patients.
Conclusion
Our results confirm that both PC/G and gefitinib were well tolerated in Korean patients, regardless of EGFR status; however, patients with EGFR wild-type NSCLC may not benefit from gefitinib monotherapy.

Citations

Citations to this article as recorded by  
  • Gefitinib for advanced non-small cell lung cancer
    Esther HA Sim, Ian A Yang, Richard Wood-Baker, Rayleen V Bowman, Kwun M Fong
    Cochrane Database of Systematic Reviews.2018;[Epub]     CrossRef
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Original Articles
VEGF and Ki-67 Overexpression in Predicting Poor Overall Survival in Adenoid Cystic Carcinoma
Seongyeol Park, Soo Jeong Nam, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Se-Hoon Lee, J. Hun Hah, Tack-Kyun Kwon, Dong-Wan Kim, Myung-Whun Sung, Dae Seog Heo, Yung-Jue Bang
Cancer Res Treat. 2016;48(2):518-526.   Published online July 14, 2015
DOI: https://doi.org/10.4143/crt.2015.093
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate potential prognostic factors in patients with adenoid cystic carcinoma (ACC). Materials and Methods A total of 68 patients who underwent curative surgery and had available tissue were enrolled in this study. Their medical records and pathologic slides were reviewed and immunohistochemistry for basic fibroblast growth factor, fibroblast growth factor receptor (FGFR) 2, FGFR3, c-kit, Myb proto-oncogene protein, platelet-derived growth factor receptor beta, vascular endothelial growth factor (VEGF), and Ki-67 was performed. Univariate and multivariate analysis was performed for determination of disease-free survival (DFS) and overall survival (OS).
Results
In univariate analyses, primary site of nasal cavity and paranasal sinus (p=0.022) and Ki-67 expression of more than 7% (p=0.001) were statistically significant factors for poor DFS. Regarding OS, perineural invasion (p=0.032), high expression of VEGF (p=0.033), and high expression of Ki-67 (p=0.007) were poor prognostic factors. In multivariate analyses, primary site of nasal cavity and paranasal sinus (p=0.028) and high expression of Ki-67 (p=0.004) were independent risk factors for poor DFS, and high expression of VEGF (p=0.011) and Ki-67 (p=0.011) showed independent association with poor OS. Conclusion High expression of VEGF and Ki-67 were independent poor prognostic factors for OS in ACC.

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Reduced Dose Intensities of Doxorubicin in Elderly Patients with DLBCL in Rituximab Era
Hyerim Ha, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Se-Hoon Lee, Dong-Wan Kim, Chul Woo Kim, Dae Seog Heo
Cancer Res Treat. 2016;48(1):304-311.   Published online April 9, 2015
DOI: https://doi.org/10.4143/crt.2014.339
AbstractAbstract PDFPubReaderePub
Purpose
The dose intensity of doxorubicin (DID) is important to the survival of diffuse large B cell lymphoma (DLBCL) patients. However, due to expected toxicities, most elderly patients cannot receive full doses of anthracyclines. The purpose of this study was to evaluate the effect of DID on the survival of elderly DLBCL patients (age ≥ 70 years) in the rituximab era.
Materials and Methods
We analyzed 433 DLBCL patients who were treated with R-CHOP between December 2003 and October 2011 at the Seoul National University Hospital. Of these patients, 19.2% were aged ≥ 70 years. We analyzed the survival outcomes according to DID.
Results
Significantly poorer overall survival (OS) was observed for patients aged ≥ 70 years (2-year OS rate: 59.9% vs. 84.2%; p < 0.001). DID ≤ 10 mg/m2/wk had a significant effect on the OS and progression-free survival (PFS) in elderly patients (2-year OS rate: 40.0% in DID ≤ 10 mg/m2/wk vs. 62.6% in DID > 10 mg/m2/wk; p=0.031; 2-year PFS: 35.0% vs. 65.7%; p=0.036). The OS on each 1.7 mg/m2/wk doxorubicin increment above 10 mg/m2/wk in elderly patients was not significant among the groups (2-year OS rate: 75.0% in DID 10.0- 11.7 mg/m2/wk vs. 66.7% in DID 15.0-16.7 mg/m2/wk; p=0.859). Treatment related mortality was not related to DID.
Conclusion
DID can be reduced up to 10 mg/m2/wk in elderly DLBCL patients in the rituximab era. Maintenance of DID > 10 mg/m2/wk and judicious selection of elderly patients who are tolerant to DID is necessary.

Citations

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Gefitinib-Induced Interstitial Lung Disease in Korean Lung Cancer Patients
Seung-Hoon Beom, Dong-Wan Kim, Sung Hoon Sim, Bhumsuk Keam, Jin Hyun Park, Jeong-Ok Lee, Tae Min Kim, Se-Hoon Lee, Dae Seog Heo
Cancer Res Treat. 2016;48(1):88-97.   Published online March 3, 2015
DOI: https://doi.org/10.4143/crt.2014.201
AbstractAbstract PDFPubReaderePub
Purpose
Interstitial lung disease (ILD) is a serious adverse effect of gefitinib. We examined the incidence and clinical characteristics of drug-induced ILD in Korean non-small cell lung carcinoma patients treated with gefitinib. Materials and Methods A retrospective cohort study was performed in non-small cell lung cancer (NSCLC) patients who started gefitinib treatment at Seoul National University Hospital from January 2002 through December 2011. Patients who developed new abnormal radiologic findings with respiratory symptoms after gefitinib treatment were defined as having possible adverse pulmonary reactions. The patients’ medical records were reviewed independently by investigators to identify the causes of pulmonary toxicities. Results Among the 1,114 patients evaluated, 128 patients (11.5%) developed pulmonary adverse reactions after taking gefitinib. An infectious complication occurred in 98 patients (8.8%) and 15 patients (1.3%) developed ILD. Nine of the 15 patients (60.0%) with gefitinib-induced ILD experienced a fatal clinical course that met either the Common Terminology Criteria for Adverse Events grade 4 (n=3) or grade 5 (n=6). In the multivariate analysis, a lower serum albumin level (≤ 3.0 g/dL) at baseline was significantly associated with the development of gefitinib-induced ILD (odds ratio, 3.91; 95% confidence interval, 1.20 to 12.71). Conclusion The incidence of gefitinib-induced ILD in Korean NSCLC patients was similar to that reported worldwide, but lower than values reported for Japanese population. ILD was usually a lifethreatening adverse effect of gefitinib, and the development of ILD was significantly associated with a lower baseline serum albumin level.

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Pemetrexed Singlet Versus Nonpemetrexed-Based Platinum Doublet as Second-Line Chemotherapy after First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor Failure in Non-small Cell Lung Cancer Patients with EGFR Mutations
Sehhoon Park, Bhumsuk Keam, Se Hyun Kim, Ki Hwan Kim, Yu Jung Kim, Jin-Soo Kim, Tae Min Kim, Se-Hoon Lee, Dong-Wan Kim, Jong Seok Lee, Dae Seog Heo
Cancer Res Treat. 2015;47(4):630-637.   Published online February 16, 2015
DOI: https://doi.org/10.4143/crt.2014.244
AbstractAbstract PDFPubReaderePub
Purpose
Platinum-based doublet chemotherapy is the treatment of choice for patients with non-small cell lung cancer (NSCLC); however, the role of a platinum-based doublet as second-line therapy after failure of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for NSCLC patients has not yet been elucidated. The purpose of this study was to compare the clinical efficacy of pemetrexed versus a platinum-based doublet as second-line therapy after failure of EGFR TKI used as first-line therapy for NSCLC patients with EGFR mutations. Materials and Methods We designed a multicenter retrospective cohort study of 314 NSCLC patients with EGFR mutations who received an EGFR TKI as first-line palliative chemotherapy. Our analysis included 83 patients who failed EGFR TKI therapy and received second-line cytotoxic chemotherapy.
Results
Forty-six patients were treated using a platinum-based doublet and 37 patients were treated using singlet pemetrexed. The overall response rates of patients receiving a platinum-based doublet and patients receiving pemetrexed were17.4% and 32.4%, respectively (p=0.111). The median progression-free survival (PFS) of patients receiving pemetrexed was significantly longer than that of patients receiving a platinum-based doublet (4.2 months vs. 2.7 months, respectively; p=0.008). The hazard ratio was 0.54 (95% confidence interval, 0.34 to 0.86; p=0.009). Conclusion Our retrospective analysis found that second-line pemetrexed singlet therapy provided significantly prolonged PFS compared to second-line platinum-based doublet chemotherapy for NSCLC patients with EGFRmutations who failed first-line EGFR TKI. Conduct of prospective studies for confirmation of our results is warranted.

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Cancer Treatment near the End-of-Life Becomes More Aggressive: Changes in Trend during 10 Years at a Single Institute
Younak Choi, Bhumsuk Keam, Tae Min Kim, Se-Hoon Lee, Dong-Wan Kim, Dae Seog Heo
Cancer Res Treat. 2015;47(4):555-563.   Published online February 16, 2015
DOI: https://doi.org/10.4143/crt.2014.200
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to investigate and compare cancer treatment near the end-of-life (EOL) over a 10-year period. Materials and Methods Patients with advanced solid cancer at Seoul National University Hospital who received palliative chemotherapy and had died were enrolled. We categorized the consecutive patients according to two time periods: 2002 (n=57) and 2012 (n=206). Aggressiveness of cancer treatment near the EOL was evaluated.
Results
The median patient age was 62, and 65.4% of patients (n=172) were male. Time from the last chemotherapy to death (TCD) was found to have been significantly shortened, from 66.0 days to 34.0 days during 10 years (p < 0.001); 17% of patients received molecular targeted agents as the last chemotherapy regimen in 2012. The proportion of patients who received intensive care unit care within the last month increased from 1.8% in 2002 to 19.9% in 2012 (p < 0.001), and emergency room visits within the last month also increased from 22.8% to 74.8% (p < 0.001). Although hospice referral increased from 9.1% to 37.4% (p < 0.001), timing of referral was delayed from median 53 days to 8 days before death (p=0.004). Use of targeted agents as the last chemotherapy for over-two-regimen users was associated with shortened TCD (hazard ratio, 2.564; p=0.002). Conclusion Cancer treatment near the EOL became more aggressive over 10 years.

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Cisplatin-Based Chemotherapy Is a Strong Risk Factor for Thromboembolic Events in Small-Cell Lung Cancer
Yun-Gyoo Lee, Eunyoung Lee, Inho Kim, Keun-Wook Lee, Tae Min Kim, Se-Hoon Lee, Dong-Wan Kim, Dae Seog Heo
Cancer Res Treat. 2015;47(4):670-675.   Published online January 2, 2015
DOI: https://doi.org/10.4143/crt.2014.045
AbstractAbstract PDFPubReaderePub
Purpose
Cisplatin-associated arterial and venous thromboembolic events (TEEs) are becoming an increasing concern. In patients with small-cell lung cancer (SCLC) who are treated using cisplatin-based chemotherapy, we assume that the overall risk of TEEs is high. However, cisplatin-associated vascular toxicity in patients with SCLC has been overlooked to date. The aim of this study was to determine the incidence of TEEs in patients with SCLC and to analyze the predictors for TEE occurrence. Materials and Methods We retrospectively analyzed 277 patients who received chemotherapy for SCLC between 2006 and 2012. As the influence of chemotherapy on TEE occurrence developed after its initiation, a time-dependent Cox regression analysis was used to estimate the significant predictors for TEE. Results Among the 277 patients, 30 patients (11%) developed a TEE. The 3-month, 6-month, and 1-year cumulative incidences of TEEs were 5.0%, 9.1%, and 10.2%, respectively. Of 30 total TEEs, 22 (73%) occurred between the time of initiation and 4 weeks after the last dose of platinum-based chemotherapy. Approximately 218 patients (79%) received cisplatin-based chemotherapy. In multivariate analysis, cisplatin-based chemotherapy was an independent risk factor for TEE occurrence (hazard ratio [HR], 4.36; p=0.05). Variables including smoking status (common HR, 2.14; p=0.01) and comorbidity index (common HR, 1.60; p=0.05) also showed significant association with TEE occurrence. Conclusion The 1-year cumulative incidence of TEE is 10.2% in Asian patients with SCLC. Cisplatinbased chemotherapy in SCLC might be a strong predictor for the risk of TEE.

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The Impact of Molecularly Targeted Treatment on Direct Medical Costs in Patients with Advanced Non-small Cell Lung Cancer
June-Koo Lee, Dong-Wan Kim, Bhumsuk Keam, Tae Min Kim, Se-Hoon Lee, Young-Joo Kim, Dae Seog Heo
Cancer Res Treat. 2015;47(2):182-188.   Published online September 12, 2014
DOI: https://doi.org/10.4143/crt.2013.227
AbstractAbstract PDFPubReaderePub
Purpose
To investigate the impact of targeted treatment on direct medical costs of patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods Medical records of 108 stage IIIB/IV NSCLC patients treated in Seoul National University Hospital between 2003 and 2009, were reviewed to collect medical resources utilization data from the diagnosis of stage IIIB/IV NSCLC to the end of active anti-cancer treatment. The direct medical costs were calculated by multiplying the number of medical resources used by the unit price. All costs were expressed in US dollars for each patient. Results The mean total direct medical costs were $34,732 (standard deviation, 21,168) in the study cohort. The mean total direct medical costs were higher in epidermal growth factor receptor (EGFR) mutation (EGFR MT)–positive patients than EGFR wild-type (EGFR WT) patients ($41,403 vs. $30,146, p=0.005). However, the mean monthly direct medical costs did not differ significantly between EGFR MT–positive patients and EGFR WT patients ($2,120 vs. $2,702, p=0.119) because of the longer duration of active anti-cancer treatment in EGFR MT–positive patients. This discrepancy was mainly attributable to EGFR MT–positive patients’ lower non-chemotherapy costs ($948 vs. $1,522, p=0.007). The total and monthly direct medical costs of ALK fusion–positive patients who did not receive ALK inhibitors did not differ from WT/WT patients. Conclusion This study suggests that the availability of targeted agents for EGFR MT–positive patients lowers the mean monthly medical costs by prolonging survival and diminishing the use of other medical resources, despite the considerable drug costs.

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    Wolfgang Schuette, Peter Schirmacher, Wilfried E. E. Eberhardt, Manfred Dietel, Ute Zirrgiebel, Lars Muehlenhoff, Michael Thomas
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Nomogram Predicting Clinical Outcomes in Non-small Cell Lung Cancer Patients Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Bhumsuk Keam, Dong-Wan Kim, Jin Hyun Park, Jeong-Ok Lee, Tae Min Kim, Se-Hoon Lee, Doo Hyun Chung, Dae Seog Heo
Cancer Res Treat. 2014;46(4):323-330.   Published online July 14, 2014
DOI: https://doi.org/10.4143/crt.2013.120
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study was to develop a pragmatic nomogram for prediction of progressionfree survival (PFS) for the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in EGFR mutant non-small cell lung cancer (NSCLC).
Materials and Methods
A total of 306 recurred or metastatic NSCLC patients with EGFR mutation, who received EGFR TKIs, were enrolled in this study. We developed the nomogram, using a Cox proportional hazard regression model for PFS.
Results
The median PFS was 11.2 months. Response rate to EGFR TKI was 71.9%. Multivariate Cox model identified disease status, performance status, chemotherapy line, response to EGFR TKI, and bone metastasis as independent prognostic factors, and the nomogram for PFS was developed, based on these covariates. The concordance index for a nomogram was 0.708, and the calibration was also good.
Conclusion
We developed a nomogram, based on clinical characteristics, for prediction of the PFS to EGFR TKI in NSCLC patients with EGFR mutation.

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