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Normal Brain-Sparing Radiotherapy versus Whole Brain Radiotherapy for Multiple Brain Metastasis from Non-Small Cell Lung Cancer
Sangjoon Park, Jaeho Cho, Kyung Hwan Kim, Hong In Yoon, Chang Geol Lee
Received July 23, 2024  Accepted December 2, 2024  Published online December 3, 2024  
DOI: https://doi.org/10.4143/crt.2024.679    [Accepted]
AbstractAbstract PDF
Purpose
The efficacy and lower neurotoxicity of normal brain-sparing radiotherapy (NBS-RT) with systemic therapy in treating multiple brain metastases from non-small cell lung cancer (NSCLC) is underexplored. This study compares whole-brain radiotherapy (WBRT) and NBS-RT for multiple brain metastases in NSCLC, focusing on treatment outcomes and leukoencephalopathy.
Materials and Methods
This retrospective study included 503 patients with NSCLC with multiple brain metastases at a single center, treated with either WBRT or NBS-RT. Post-RT treatments included chemotherapy, targeted therapy, or immunotherapy. Main outcomes measured were intracranial control, overall survival (OS), and leukoencephalopathy incidence.
Results
In this study, 441 patients received WBRT and 62 received NBS-RT, with median ages of 62 and 61 years, respectively. A significant portion of both groups, 77.3% in WBRT and 80.6% in NBS-RT, received post-RT systemic therapy. The median number of brain metastases was 10 for WBRT and 12 for NBS-RT, with median maximal diameters of 11.7 mm in WBRT and 14.4 mm in NBS-RT. After a median follow-up of 10.9 months for WBRT and 11.8 months for NBS-RT, there were no significant differences in intracranial progression (p=0.516) or OS (p=0.492) between the groups. However, WBRT patients had a higher incidence of leukoencephalopathy than NBS-RT patients (p=0.013).
Conclusion
NBS-RT combined with systemic therapy was as effective in treating multiple brain metastases as WBRT and was less toxic. NBS-RT-based strategies deserve further investigation in a prospective setting.
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Unraveling the Impact of Sarcopenia-Induced Lymphopenia on Treatment Response and Prognosis in Patients with Stage III Non-Small Cell Lung Cancer: Insights for Optimizing Chemoradiation and Immune Checkpoint Inhibitor
Joongyo Lee, Kyung Hwan Kim, Jina Kim, Chang Geol Lee, Jaeho Cho, Hong In Yoon, Yeona Cho
Received May 23, 2024  Accepted October 29, 2024  Published online October 30, 2024  
DOI: https://doi.org/10.4143/crt.2024.493    [Accepted]
AbstractAbstract PDF
Purpose
Sarcopenia is a poor prognostic factor in non-small cell lung cancer (NSCLC). However, its prognostic significance in patients with NSCLC receiving immune checkpoint inhibitors (ICIs) and its relationship with lymphopenia remain unclear. We aimed to investigate the prognostic role of sarcopenia and its effect on lymphocyte recovery in patients with stage III NSCLC treated with concurrent chemoradiotherapy (CCRT) followed by ICI.
Materials and Methods
We retrospectively evaluated 151 patients with stage III NSCLC who received definitive CCRT followed by maintenance ICI between January 2016 and June 2022. Sarcopenia was evaluated by measuring the skeletal muscle area at the L3 vertebra level using computed tomography scans. Lymphocyte level changes were assessed based on measurements taken before and during CCRT and at 1, 2, 3, 6, and 12 months post-CCRT completion.
Results
Even after adjusting for baseline absolute lymphocyte count through propensity score-matching, patients with pre-radiotherapy (RT) sarcopenia (n=86) exhibited poor lymphocyte recovery and a significantly high incidence of grade ≥3 lymphopenia during CCRT. Pre-RT sarcopenia and grade ≥3 lymphopenia during CCRT emerged as prognostic factors for overall survival and progression-free survival, respectively. Concurrent chemotherapy dose adjustments, objective response after CCRT, and discontinuation of maintenance ICI were also analyzed as independent prognostic factors.
Conclusion
Our results demonstrated an association between pre-RT sarcopenia and poor survival, concurrent chemotherapy dose adjustments, and impaired lymphocyte recovery after definitive CCRT. Moreover, CCRT-induced lymphopenia not only contributed to poor prognosis but may have also impaired the therapeutic efficacy of subsequent maintenance ICI, ultimately worsening treatment outcomes.
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Lung and Thoracic cancer
Association of Immune-Related Adverse Events and the Efficacy of Anti–PD-(L)1 Monotherapy in Non–Small Cell Lung Cancer: Adjusting for Immortal-Time Bias
Ying Yu, Ning Chen, Sizhe Yu, Wanji Shen, Wanchen Zhai, Hui Li, Yun Fan
Cancer Res Treat. 2024;56(3):751-764.   Published online January 2, 2024
DOI: https://doi.org/10.4143/crt.2023.1118
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The association between immune-related adverse events (irAEs) and survival outcomes in non–small cell lung cancer (NSCLC) patients treated with programmed death-(ligand) 1 [PD-(L)1] inhibitors remains controversial, partly due to variations in dealing with immortal-time bias (ITB).
Materials and Methods
We retrospectively enrolled 425 advanced NSCLC patients who received anti–PD-(L)1 monotherapy between January 2016 and June 2021, stratifying them into irAE (n=127) and non-irAE (n=298) groups. The primary endpoint was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Landmark (2-, 3-, 6-, and 9-month) and time-dependent Cox analyses were performed to eliminate ITB.
Results
With a median follow-up of 38.8 months, the occurrence of overall irAEs was significantly associated with superior PFS (11.2 vs. 3.4 months, p < 0.001) and OS (31.4 vs. 14.0 months, p < 0.001), which persisted in landmark and time-dependent Cox analyses. For the main organ-specific irAEs, skin, thyroid, and hepatic irAEs, respectively, showed significantly improved survival compared to the non-irAE group, whereas pneumonitis did not. Single-organ irAEs had the best outcomes compared with multi-organ or no irAE, which also held across subgroups of skin, thyroid, and hepatic irAEs. Moreover, severe grade irAEs and immunotherapy discontinuation had a detrimental effect on survival, systemic steroid therapy showed little effect, while immunotherapy resumption had tolerable safety and a trend of improved survival.
Conclusion
After adequately adjusting ITB, the occurrence of overall irAEs predicts for favorable efficacy of anti–PD-(L)1 monotherapy in NSCLC, with better outcomes observed in patients with skin, thyroid, or hepatic irAEs, particularly those with single-organ involvement.

Citations

Citations to this article as recorded by  
  • Management, biomarkers and prognosis in people developing endocrinopathies associated with immune checkpoint inhibitors
    Shintaro Iwama, Tomoko Kobayashi, Hiroshi Arima
    Nature Reviews Endocrinology.2025;[Epub]     CrossRef
  • Development of pituitary dysfunction and destructive thyroiditis is associated with better survival in non-small cell lung cancer patients treated with programmed cell death-1 inhibitors: a prospective study with immortal time bias correction
    Koji Suzuki, Tomoko Kobayashi, Tetsushi Izuchi, Koki Otake, Masahiko Ando, Tomoko Handa, Takashi Miyata, Mariko Sugiyama, Takeshi Onoue, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Megumi Inoue, Makoto Ishii, Hiroshi Arima, Shintaro Iw
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Associations between Immune-related Adverse Events and Prognosis in Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy
    Yusuke Inoue, Naoki Inui
    Internal Medicine.2024;[Epub]     CrossRef
  • The impact of immune-related adverse events on the outcome of advanced gastric cancer patients with immune checkpoint inhibitor treatment
    Tianhang Zhang, Haitao Lv, Jiasong Li, Shasha Zhang, Jingjing Zhang, Siqi Wang, Yingnan Wang, Zhanjun Guo
    Frontiers in Immunology.2024;[Epub]     CrossRef
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Combination of the LARS1 Inhibitor, BC-LI-0186 with a MEK1/2 Inhibitor Enhances the Anti-Tumor Effect in Non–Small Cell Lung Cancer
Sang Hoon Lee, Eun Young Kim, Jung Min Han, Gyoonhee Han, Yoon Soo Chang
Cancer Res Treat. 2023;55(3):851-864.   Published online March 20, 2023
DOI: https://doi.org/10.4143/crt.2022.1527
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth and proliferation by growth factor coordination and amino acid availability. Leucyl-tRNA synthetase 1 (LARS1) senses the intracellular leucine concentration and mediates amino acid-induced activation of mTORC1. Thus, LARS1 inhibition could be useful in cancer treatment. However, the fact that mTORC1 can be stimulated by various growth factors and amino acids suggests that LARS1 inhibition alone has limitations in inhibiting cell growth and proliferation. We investigated the combined effects of BC-LI-0186, a LARS1 inhibitor, and trametinib, an MEK inhibitor, on non–small cell lung cancer (NSCLC).
Materials and Methods
Protein expression and phosphorylation were observed by immunoblotting, and genes differentially expressed between BC-LI-0186–sensitive and –resistant cells were identified by RNA sequencing. The combined effect of the two drugs was inferred from the combination index values and a xenograft model.
Results
LARS1 expression was positively correlated with mTORC1 in NSCLC cell lines. BC-LI-0186 treatment of A549 and H460 cells maintained in media supplemented with fetal bovine serum revealed paradoxical phosphorylation of S6 and activation of mitogen- activated protein kinase (MAPK) signaling. Compared with BC-LI-0186–sensitive cells, –resistant cells showed enrichment of the MAPK gene set. The combination of trametinib and BC-LI-0186 inhibited the phosphorylation of S6, MEK, and extracellular signal-regulated kinase and their synergistic effects were confirmed in a mouse xenograft model.
Conclusion
The combination of BC-LI-0186 and trametinib inhibited the non-canonical mTORC1-activating function of LARS1. Our study demonstrated a new therapeutic approach for NSCLC without targetable driver mutations.

Citations

Citations to this article as recorded by  
  • LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma
    Longfei Fan, Zhongqiang Qin, Di Wu, Yunchuan Yang, Yigang Zhang, Bo Xie, Jingyu Qian, Jianzhu Wei, Zhaoying Wang, Peipei Yang, Zhen Qian, Mu Yuan, Ziyi Zhu, Yulin Tan, Yi Tan
    International Journal of General Medicine.2024; Volume 17: 2203.     CrossRef
  • Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer
    Hasan Alsharoh, Paul Chiroi, Ekaterina Isachesku, Radu Andrei Tanasa, Ovidiu-Laurean Pop, Radu Pirlog, Ioana Berindan-Neagoe
    Biomedicines.2024; 12(7): 1489.     CrossRef
  • UCHL1 Overexpression Is Related to the Aggressive Phenotype of Non-small Cell Lung Cancer
    Chi Young Kim, Eun Hye Lee, Se Hyun Kwak, Sang Hoon Lee, Eun Young Kim, Min Kyoung Park, Yoon Jin Cha, Yoon Soo Chang
    Tuberculosis and Respiratory Diseases.2024; 87(4): 494.     CrossRef
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Diagnostic Performance of Endosonography to Detect Mediastinal Lymph Node Metastasis in Patients with Radiological N1 Non–Small Cell Lung Cancer
Bo-Guen Kim, Jong Ho Cho, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Jhingook Kim, Young Mog Shim, Byeong-Ho Jeong
Cancer Res Treat. 2023;55(3):832-840.   Published online March 2, 2023
DOI: https://doi.org/10.4143/crt.2022.1428
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Guidelines recommend that non–small cell lung cancer (NSCLC) patients with suspected hilar lymph node (LN) metastases should undergo invasive mediastinal LN staging prior to surgical treatment via endosonography. We evaluated the diagnostic performance of endosonography for detecting occult mediastinal metastases (OMM) and determined the factors associated with OMM in NSCLC patients with radiological N1.
Materials and Methods
Patients with confirmed primary NSCLC with radiological N1 who underwent endosonography for nodal staging assessment from January 2013 to December 2019 were retrospectively analyzed.
Results
The prevalence of OMM was found to be 83/279 (29.7%) and only 38.6% (32/83) were diagnosed via endosonography. However, five of them were confirmed as N3 by endosonography. The overall diagnostic sensitivity, negative predictive value, accuracy, and area under the curve of endosonography were 38.6%, 79.4%, 81.7%, and 0.69, respectively. In multivariable analysis, central tumor (adjusted odds ratio [aOR], 2.05; 95% confidence interval [CI], 1.15 to 3.68; p=0.016), solid tumor (aOR, 10.24; 95% CI, 1.32 to 79.49; p=0.026), and adenocarcinoma (aOR, 3.01; 95% CI, 1.63 to 5.55; p < 0.001) were related to OMM in radiological N1 NSCLC patients.
Conclusion
Although the sensitivity of endosonography for detecting OMM was only 40%, the prevalence of OMM was not low (30%) and some cases even turned out to be N3 diseases. Clinicians should be aware that OMM may be more likely in patients with central, solid, and adenocarcinomatous tumor when performing nodal staging in radiological N1 NSCLC via endosonography.

Citations

Citations to this article as recorded by  
  • Incorporating Lymph Node Size at CT as an N1 Descriptor in Clinical N Staging for Lung Cancer
    Yura Ahn, Sang Min Lee, Jooae Choe, Se Hoon Choi, Kyung-Hyun Do, Joon Beom Seo
    Radiology.2025;[Epub]     CrossRef
  • EBUS‐TBNA for mediastinal staging of centrally located T1N0M0 non‐small cell lung cancer clinically staged with PET/CT
    Pere Serra Mitjà, Bruno García‐Cabo, Ignasi Garcia‐Olivé, Joaquim Radua, Ramón Rami‐Porta, Lluís Esteban, Bienvenido Barreiro, Sergi Call, Carmen Centeno, Felipe Andreo, Carme Obiols, Juan Manuel Ochoa, Mireia Martínez‐Palau, Nina Reig, Mireia Serra, José
    Respirology.2024; 29(2): 158.     CrossRef
  • Clinical Effect of Endosonography on Overall Survival in Patients with Radiological N1 Non–Small Cell Lung Cancer
    Bo-Guen Kim, Byeong-Ho Jeong, Goeun Park, Hong Kwan Kim, Young Mog Shim, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Jong Ho Cho
    Cancer Research and Treatment.2024; 56(2): 502.     CrossRef
  • Clinical utility of artificial intelligence–augmented endobronchial ultrasound elastography in lymph node staging for lung cancer
    Yogita S. Patel, Anthony A. Gatti, Forough Farrokhyar, Feng Xie, Waël C. Hanna
    JTCVS Techniques.2024; 27: 158.     CrossRef
  • Artificial Intelligence Algorithm Can Predict Lymph Node Malignancy from Endobronchial Ultrasound Transbronchial Needle Aspiration Images for Non-Small Cell Lung Cancer
    Yogita S. Patel, Anthony A. Gatti, Forough Farrokhyar, Feng Xie, Waël C. Hanna
    Respiration.2024; : 1.     CrossRef
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Genomic Characteristics and the Potential Clinical Implications in Oligometastatic Non–Small Cell Lung Cancer
Rongxin Liao, Kehong Chen, Jinjin Li, Hengqiu He, Guangming Yi, Mingfeng Huang, Rongrong Chen, Lu Shen, Xiaoyue Zhang, Zaicheng Xu, Zhenzhou Yang, Yuan Peng
Cancer Res Treat. 2023;55(3):814-831.   Published online January 12, 2023
DOI: https://doi.org/10.4143/crt.2022.1315
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis.
Materials and Methods
We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity.
Results
We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation.
Conclusion
Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

Citations

Citations to this article as recorded by  
  • Prognostic and Predictive Biomarkers of Oligometastatic NSCLC: New Insights and Clinical Applications
    Mandy Jongbloed, Martina Bortolot, Leonard Wee, Jarno W.J. Huijs, Murillo Bellezo, Rianne D.W. Vaes, Frank Aboubakar Nana, Koen J. Hartemink, Dirk K.M. De Ruysscher, Lizza E.L. Hendriks
    JTO Clinical and Research Reports.2024; 5(12): 100740.     CrossRef
  • Genomic characteristics of PD-L1-Induced resistance to EGFR-TKIs in lung adenocarcinoma
    Guangming Yi, Fanghao Cai, Liangzhong Liu, Rongxin Liao, Xuan Jiang, Zhenzhou Yang, Xiaoyue Zhang
    Future Oncology.2024; 20(40): 3477.     CrossRef
  • 4,416 View
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  • 2 Web of Science
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Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer
Jang Ho Lee, Eun Young Kim, Cheol-Kyu Park, Shin Yup Lee, Min ki Lee, Seong-Hoon Yoon, Jeong Eun Lee, Sang Hoon Lee, Seung Joon Kim, Sung Yong Lee, Jun Hyeok Lim, Tae-Won Jang, Seung Hun Jang, Kye Young Lee, Seung Hyeun Lee, Sei Hoon Yang, Dong Won Park, Chan Kwon Park, Hye Seon Kang, Chang Dong Yeo, Chang-Min Choi, Jae Cheol Lee
Cancer Res Treat. 2023;55(1):112-122.   Published online July 19, 2022
DOI: https://doi.org/10.4143/crt.2022.381
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea.
Materials and Methods
Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints.
Results
A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects.
Conclusion
Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Citations

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  • The importance of re-biopsy in the era of molecular therapy for lung cancer
    Nensi Lalic, Daliborka Bursac, Marko Bojovic, Marko Nemet, Ivan Ergelasev
    Srpski arhiv za celokupno lekarstvo.2024; 152(3-4): 209.     CrossRef
  • Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine
    Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
    Pathology.2024; 56(5): 653.     CrossRef
  • Real‐world study of lazertinib as second‐line or greater treatment in advanced non‐small cell lung cancer
    Jeong Uk Lim, Kyuhwan Kim, Kyu Yean Kim, Hye Seon Kang, Ah. Young Shin, Chang Dong Yeo, Sung Kyoung Kim, Chan Kwon Park, Sang Haak Lee, Seung Joon Kim
    Thoracic Cancer.2024; 15(19): 1513.     CrossRef
  • Comparative effectiveness of lazertinib in patients with EGFR T790M-positive non-small-cell lung cancer using a real-world external control
    Ha-Lim Jeon, Meesong Kwak, Sohee Kim, Hye-Yeon Yu, Ju-Young Shin, Hyun Ae Jung
    Scientific Reports.2024;[Epub]     CrossRef
  • A Randomized, Multi-Center, Open Label Study to Compare the Safety and Efficacy between Afatinib Monotherapy and Combination Therapy with HAD-B1 for the Locally Advanced or Metastatic NSCLC Patients with EGFR Mutations
    Eunbin Kwag, Soo-Dam Kim, Seong-Hoon Shin, Chulho Oak, So-Jung Park, Jun-Yong Choi, Seong Hoon Yoon, In-Cheol Kang, Mi-Kyung Jeong, Hyun Woo Lee, Sun-Hwi Bang, Ji Woong Son, Sanghun Lee, Seung Joon Kim, Hwa-Seung Yoo
    Integrative Cancer Therapies.2024;[Epub]     CrossRef
  • Clinical utility of repeated rebiopsy for EGFR T790M mutation detection in non-small cell lung cancer
    Eun Hye Lee, Se Hyun Kwak, Kyeong Yeon Kim, Chi Young Kim, Sang Hoon Lee, Seok-Jae Heo, Yoon Soo Chang, Eun Young Kim
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study
    Qing Zhou, He-Long Zhang, Li-Yan Jiang, Yuan-Kai Shi, Yuan Chen, Jin-Ming Yu, Cai-Cun Zhou, Yong He, Yan-Ping Hu, Zong-An Liang, Yue-Yin Pan, Wen-Lei Zhuo, Yong Song, Gang Wu, Gong-Yan Chen, You Lu, Cui-Ying Zhang, Yi-Ping Zhang, Ying Cheng, Shun Lu, Chan
    Journal of Cancer Research and Clinical Oncology.2023; 149(12): 10771.     CrossRef
  • 6,822 View
  • 324 Download
  • 9 Web of Science
  • 7 Crossref
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Clinical Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer Patients with Liver Metastases: A Network Meta-Analysis of Nine Randomized Controlled Trials
Qing Yin, Longguo Dai, Ruizhu Sun, Ping Ke, Liya Liu, Bo Jiang
Cancer Res Treat. 2022;54(3):803-816.   Published online October 25, 2021
DOI: https://doi.org/10.4143/crt.2021.764
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This network meta-analysis (NMA) was conducted to compare the efficacy of immune checkpoint inhibitors in advanced non–small cell lung cancer (NSCLC) patients with liver metastases.
Materials and Methods
English literature was retrieved from the PubMed, American Society of Clinical Oncology, and European Society for Medical Oncology databases from January 2015 to January 2021. We pooled the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) using an NMA and ranked treatments by the surface under the cumulative ranking curve. Publication bias was evaluated by Begg’s and Egger’s tests. STATA 15.0 was used for the sensitivity analysis, and the remaining statistical analyses were performed using R 4.0.2.
Results
Nine eligible phase III randomized controlled trials were included, including 1,141 patients with liver metastases. Pembrolizumab+chemotherapy ranked highest, followed by atezolizumab+bevacizumab+chemotherapy and nivolumab. However, no significant difference in OS rates was observed across these three treatments (HR, 0.98; 95% confidence interval [CI], 0.43 to 2.22 for pembrolizumab+chemotherapy vs. atezolizumab+bevacizumab+chemotherapy; HR, 0.91; 95% CI, 0.52 to 1.57 for pembrolizumab+chemotherapy vs. nivolumab). Regarding the PFS rate, atezolizumab+bevacizumab+chemotherapy and pembro-lizumab+chemotherapy ranked highest and no significant difference was observed between them (HR, 0.79; 95% CI, 0.36 to 1.70 for atezolizumab+bevacizumab+chemotherapy vs. pembrolizumab+chemotherapy).
Conclusion
Pembrolizumab+chemotherapy, atezolizumab+bevacizumab+chemotherapy, and nivolumab were superior to other treatments in NSCLC patients with liver metastases. These new findings may help clinicians better select therapeutic strategies for NSCLC patients with liver metastases.

Citations

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  • Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with liver metastases
    Fan-jie Qu, Yi Zhou, Shuang Wu
    British Journal of Cancer.2024; 130(2): 165.     CrossRef
  • Effectiveness and Safety of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in Pulmonary Sarcomatoid Carcinoma
    Daisuke Hazama, Kenji Nakahama, Hiroaki Kodama, Akito Miyazaki, Koichi Azuma, Yosuke Kawashima, Yuki Sato, Kentaro Ito, Yoshimasa Shiraishi, Keita Miura, Takayuki Takahama, Satoshi Oizumi, Yoshinobu Namba, Satoshi Ikeda, Hiroshige Yoshioka, Asuka Tsuya, Y
    JTO Clinical and Research Reports.2024; 5(1): 100613.     CrossRef
  • Evolving landscape of treatments targeting the microenvironment of liver metastases in non-small cell lung cancer
    Lingling Zhu, Xianzhe Yu, Xiaojun Tang, Chenggong Hu, Lei Wu, Yanyang Liu, Qinghua Zhou
    Chinese Medical Journal.2024; 137(9): 1019.     CrossRef
  • Treatment Options for Patients with Non-Small Cell Lung Cancer and Liver Metastases
    Vesna Ćeriman Krstić, Natalija Samardžić, Milija Gajić, Milan Savić, Biljana Šeha, Marina Roksandić Milenković, Dragana Jovanović
    Current Issues in Molecular Biology.2024; 46(12): 13443.     CrossRef
  • Assessing the Relationship Between Liver Metastases and the Survival of Patients With Non-Small Cell Lung Cancer After Immune Checkpoint Inhibitors Treatment: A Systematic Review and Meta-Analysis
    Huilin Xu, Pingpo Ming, Zhenyu Zhao, Nan Zhao, Dingjie Zhou, Xixian Tang, Dedong Cao
    Integrative Cancer Therapies.2023;[Epub]     CrossRef
  • Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis
    Handai Xia, Wengang Zhang, Yuqing Zhang, Xiaoling Shang, Yanguo Liu, Xiuwen Wang
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • 7,822 View
  • 255 Download
  • 7 Web of Science
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Case Report
EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation
Sehhoon Park, Bo Mi Ku, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Se-Hoon Lee, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2020;52(4):1288-1290.   Published online June 22, 2020
DOI: https://doi.org/10.4143/crt.2020.278
AbstractAbstract PDFPubReaderePub
The non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutation eventually acquires resistant to either first or second-generation EGFR tyrosine kinase inhibitor (TKI). As the following option, targeting EGFR T790M with third-generation EGFR TKI is now established as a standard treatment option. In this study, we are reporting the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. The patients showed resistance to the treatment by acquiring the additional EGFR C797S mutation in cis which is also confirmed from the patient-derived cell lines.

Citations

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  • Research Advances of Small Molecule EGFR-TKIs in NSCLC
    亚南 胡
    Pharmacy Information.2024; 13(01): 1.     CrossRef
  • An assessment of EGFR and HER2 inhibitors with structure activity relationship of fused pyrimidine derivatives for breast cancer: a brief review
    Prasad Sanjay Dhiwar, Gurubasavaraja Swamy Purawarga Matada, Rohit Pal, Ekta Singh, Abhishek Ghara, Lalmohan Maji, Sindhuja Sengupta, Ganesh Andhale
    Journal of Biomolecular Structure and Dynamics.2024; 42(3): 1564.     CrossRef
  • The efficacy of almonertinib and anlotinib combination therapy for advanced non‐small‐cell lung cancer patients who continued to experience cancer progression during third‐generation EGFR‐TKI treatment: a retrospective study
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    BMB Reports.2021; 54(7): 386.     CrossRef
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Original Articles
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.

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    Frontiers in Oncology.2021;[Epub]     CrossRef
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Caspase Recruitment Domain Containing Protein 9 Suppresses Non-Small Cell Lung Cancer Proliferation and Invasion via Inhibiting MAPK/p38 Pathway
Linyue Pan, Yuting Tan, Bin Wang, Wenjia Qiu, Yulei Yin, Haiyan Ge, Huili Zhu
Cancer Res Treat. 2020;52(3):867-885.   Published online March 11, 2020
DOI: https://doi.org/10.4143/crt.2019.606
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Caspase recruitment domain containing protein 9 (CARD9) has been demonstrated to be a pro-tumor factor in various cancers. However, our previous study found a significant decrease of CARD9 in malignant pleural effusion compared with benign pleural effusion. So we investigated the role of CARD9 in non-small cell lung cancer (NSCLC) and its working mechanism.
Materials and Methods
Immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction were used to detect the expression of CARD9 in specimens of NSCLC patients. The Cancer Genome Atlas (TCGA) databasewas also used to analyze the expression of CARD9 in NSCLC and its predicting value for prognosis. Immunofluorescence was used for CARD9 cellular location. Cell growth assay, clonal formation assay, wound healing assay, matrigel invasion assay, and flow cytometry were used to test cell proliferation, migration, invasion, apoptosis, and cycle progression of NSCLC cells with CARD9 knockdown or CARD9 overexpression. Co-immunoprecipitation was used to identify the interaction between CARD9 and B-cell lymphoma 10 (BCL10). SB203580 was used to inhibit p38 activation.
Results
CARD9 was decreased in NSCLC tissues compared with normal tissues; low CARD9 expression was associated with poor survival. CARD9 was expressed both in tumor cells and macrophages. Downregulation of CARD9 in NSCLC cells enhanced the abilities of proliferation, invasion and migration via activated MAPK/p38 signaling, while overexpression of CARD9 presented antitumor effects. BCL10 was identified to interact with CARD9.
Conclusion
We demonstrate that CARD9 is an independent prognostic factor in NSCLC patients and inhibits proliferation, migration, and invasion by suppressing MAPK/p38 pathway in NSCLC cells.

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Clinical Characteristics and Outcomes of Non-small Cell Lung Cancer Patients with HER2 Alterations in Korea
Kangkook Lee, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2020;52(1):292-300.   Published online July 26, 2019
DOI: https://doi.org/10.4143/crt.2019.186
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Human epidermal growth factor receptor 2 (HER2) alterations are found in approximately 1%-3% of non-small cell lung cancers (NSCLCs). We evaluated the clinical features and outcomes of NSCLC harboring HER2 alteration detected by next-generation sequencing (NGS) in Korea.
Materials and Methods
A total of 1,108 patients who were diagnosed with NSCLC between December 2015 and December 2017 were screened and analyzed by NGS. Medical records were reviewed retrospectively to analyze the clinical characteristics and outcomes from various treatments.
Results
HER2 alterations were identified in 36 NSCLC patients. Of the patients, 22 (61.1%) had an exon 20 in-frame insertion mutation, 15 (41.7%) had HER2 amplification, and one had both. The median patient age was 58 years, 55.6% were male, and 50.0% were never-smokers. Adenocarcinoma was predominant (88.9%). The most common metastatic site was bone (58.3%), and 66.7% of patients were stage IV at initial diagnosis. Six patients (16.7%) had a coexistent sensitizing epidermal growth factor receptor (EGFR) mutation, and two patients (5.6%) had anaplastic lymphoma kinase (ALK) rearrangement. With a median 14 months of follow-up, the median progression-free survival of first-line treatment was 6 months (95% confidence interval, 4.172 to 7.828), and median overall survival was not reached. The proportions of adenocarcinoma, never-smokers, and metastasis to the liver were higher in the exon 20 in-frame insertion mutation group, whereas coexistence of EGFR mutation was more frequently found in the HER2 amplification group.
Conclusion
HER2-altered NSCLC showed distinct clinical features. Moreover, different characteristics were identified between the HER2 in-frame insertion mutation group and the HER2 amplification group.

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  • Clinicopathologic and Molecular Characteristics of HER2 (ERBB2)-Altered Non–Small Cell Lung Cancer: Implications for Precision Medicine
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Dummy Run of Quality Assurance Program before Prospective Study of Hippocampus-Sparing Whole-Brain Radiotherapy and Simultaneous Integrated Boost for Multiple Brain Metastases from Non-small Cell Lung Cancer: Korean Radiation Oncology Group (KROG) 17-06 Study
Eunah Chung, Jae Myoung Noh, Kyu Chan Lee, Jin Hee Kim, Weon Kuu Chung, Yang-Gun Suh, Jung Ae Lee, Ki Ho Seol, Hong Gyun Wu, Yeon Sil Kim, O Kyu Noh, Jae Won Park, Dong Soo Lee, Jihae Lee, Young Suk Kim, Woo-Yoon Park, Min Kyu Kang, Sunmi Jo, Yong Chan Ahn
Cancer Res Treat. 2019;51(3):1001-1010.   Published online October 15, 2018
DOI: https://doi.org/10.4143/crt.2018.415
AbstractAbstract PDFPubReaderePub
Purpose
Lung Cancer Subcommittee of Korean Radiation Oncology Group (KROG) has recently launched a prospective clinical trial (KROG 17-06) of hippocampus-sparing whole brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in treating multiple brain metastases from non-small cell lung cancer. In order to improve trial quality, dummy run studies among the participating institutions were designed. This work reported the results of two-step dummy run procedures of the KROG 17-06 study.
Materials and Methods
Two steps tested hippocampus contouring variability and radiation therapy planning compliance. In the first step, the variation of the hippocampus delineation was investigated for two representative cases using the Dice similarity coefficients. In the second step, the participating institutions were requested to generate a HS-WBRT with SIB treatment plan for another representative case. The compliance of the treatment plans to the planning protocol was evaluated.
Results
In the first step, the median Dice similarity coefficients of the hippocampus contours for two other dummy run cases changed from 0.669 (range, 0.073 to 0.712) to 0.690 (range, 0.522 to 0.750) and from 0.291 (range, 0.219 to 0.522) to 0.412 (range, 0.264 to 0.598) after providing the hippocampus contouring feedback. In the second step, with providing additional plan priority and extended dose constraints to the target volumes and normal structures, we observed the improved compliance of the treatment plans to the planning protocol.
Conclusion
The dummy run studies demonstrated the notable inter-institutional variability in delineating the hippocampus and treatment plan generation, which could be decreased through feedback from the trial center.

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Clinical Outcomes of EGFR Exon 20 Insertion Mutations in Advanced Non-small Cell Lung Cancer in Korea
Seonggyu Byeon, Youjin Kim, Sung Won Lim, Jang Ho Cho, Sehoon Park, Jiyun Lee, Jong-Mu Sun, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2019;51(2):623-631.   Published online July 23, 2018
DOI: https://doi.org/10.4143/crt.2018.151
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for approximately 4% of all EGFR mutations. Given the rarity of this mutation, its clinical outcomes are not fully established.
Materials and Methods
Between 2009 and 2017, non-small cell lung cancer (NSCLC) patients who showed an exon 20 insertion were retrospectively reviewed for clinical characteristics and outcomes, including responses to chemotherapy (CTx) or targeted therapy.
Results
Of 3,539 NSCLC patients who harbored an activating EGFR mutation, 56 (1.6%) had an exon 20 insertion. Of the advanced NSCLC patients, 27 of 1,479 (1.8%) had an exon 20 insertion. The median overall survival was 29.4 months (95% confidence interval 9.3 to 49.6) for 27 advancedNSCLC patients. The 22 patientswho received systemic CTx achieved a 50.0% response rate and a 77.2% disease control rate, with 4.2 months of progressionfree survival. Six patients received EGFR tyrosine kinase inhibitors (TKIs). Three of the four patients that had only an exon 20 insertion showed progressive disease, while one showed stable disease. The othertwo patients had an exon 20 insertion and another EGFR mutation and achieved a partial response.
Conclusion
The incidence of an exon 20 insertion mutation is rare in Korea and occasionally accompanied by other common EGFR mutations. Although the response to systemic CTx. in these patients is comparable to that of patients with other mutations, the response rate to firstor second-generation EGFR TKIs is quite low. Therefore, the development of a more efficient agent is urgently needed.

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EGFR Mutation Is Associated with Short Progression-Free Survival in Patients with Stage III Non-squamous Cell Lung Cancer Treated with Concurrent Chemoradiotherapy
Song Ee Park, Jae Myoung Noh, You Jin Kim, Han Sang Lee, Jang Ho Cho, Sung Won Lim, Yong Chan Ahn, Hongryull Pyo, Yoon-La Choi, Joungho Han, Jong-Mu Sun, Se Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2019;51(2):493-501.   Published online June 18, 2018
DOI: https://doi.org/10.4143/crt.2018.125
AbstractAbstract PDFPubReaderePub
Purpose
This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT).
Materials and Methods
From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status.
Results
Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression.
Conclusion
EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.

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Randomized Phase II Study of Pemetrexed Versus Gefitinib in Previously Treated Patients with Advanced Non-small Cell Lung Cancer
Young Saing Kim, Eun Kyung Cho, Hyun Sun Woo, Junshik Hong, Hee Kyung Ahn, Inkeun Park, Sun Jin Sym, Sun Young Kyung, Shin Myung Kang, Jeong-Woong Park, Sung Hwan Jeong, Jinny Park, Jae Hoon Lee, Dong Bok Shin
Cancer Res Treat. 2016;48(1):80-87.   Published online March 2, 2015
DOI: https://doi.org/10.4143/crt.2014.307
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to evaluate the efficacy and safety of pemetrexed versus gefitinib in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. Materials and Methods Patients with advanced (stage IIIB or IV) or recurrent NSCLC were randomly assigned to receive either 500 mg/m² of pemetrexed intravenously every 3 weeks or gefitinib 250 mg/day orally. The primary end point was progression-free survival (PFS) at 6 months.
Results
A total of 95 patients were enrolled (47 for pemetrexed and 48 for gefitinib). Most patients were male (72%) and current/ex-smokers (69%), and 80% had non-squamous cell carcinoma. The epidermal growth factor receptor (EGFR) mutation status was determined in 38 patients (40%); one patient per each arm was positive for EGFRmutation. The 6-month PFS rates were 22% and 15% for pemetrexed and gefitinib, respectively (p=0.35). Both arms showed an identical median PFS of 2.0 months and a median overall survival (OS) of 8.5 months. In EGFR wild-type patients, higher response rate (RR) and longer PFS as well as OS were achieved via pemetrexed compared with gefitinib, although there were no significant differences (RR: 39% vs. 9%, p=0.07; median PFS: 6.6 months vs. 3.1 months, p=0.45; median OS: 29.6 months vs. 12.9 months, p=0.62). Toxicities were mild in both treatment arms. Frequently reported toxicities were anemia and fatigue for pemetrexed, and skin rash and anorexia for gefitinib. Conclusion Both pemetrexed and gefitinib had similar efficacy with good tolerability as second-line treatment in unselected patients with advanced NSCLC. However, pemetrexed is considered more effective than gefitinib for EGFR wild-type patients.

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Pemetrexed-Erlotinib, Pemetrexed Alone, or Erlotinib Alone as Second-Line Treatment for East Asian and Non-East Asian Never-Smokers with Locally Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer: Exploratory Subgroup Analysis of a Phase II Trial
Dae Ho Lee, Jung Shin Lee, Jie Wang, Te-Chun Hsia, Xin Wang, Jongseok Kim, Mauro Orlando
Cancer Res Treat. 2015;47(4):616-629.   Published online November 24, 2014
DOI: https://doi.org/10.4143/crt.2014.051
AbstractAbstract PDFPubReaderePub
Purpose
This subgroup analysis of a phase II trial was conducted to assess possible ethnicity-based trends in efficacy and safety in East Asian (EA) and non-EA populations with nonsquamous non-small cell lung cancer (NSCLC).
Materials and Methods
Never-smoker patients (n=240) with locally advanced or metastatic nonsquamous NSCLC included 133 EA patients randomized to pemetrexed supplemented with dexamethasone, folic acid, and vitamin B12 plus erlotinib (pemetrexed-erlotinib) (n=41), erlotinib (n=49), or pemetrexed (n=43), and 107 non-EA patients randomized to pemetrexed-erlotinib (n=37), erlotinib (n=33), or pemetrexed (n=37). The primary endpoint, progression-free survival (PFS), was analyzed using a multivariate Cox model.
Results
Consistent with the results of the overall study, a statistically significant difference in PFS among the three arms was noted in the EA population favoring pemetrexed-erlotinib (overall p=0.003) as compared with either single-agent arm (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29 to 0.79; p=0.004 vs. erlotinib; HR, 0.40; 95% CI, 0.23 to 0.70; p=0.001 vs. pemetrexed). The EA patients treated with pemetrexed-erlotinib achieved a longer median PFS (7.4 months) compared with erlotinib (4.5 months) and pemetrexed (4.0 months). The PFS results also numerically favored pemetrexed-erlotinib in the non-EA population (overall p=0.210) (HR, 0.62; 95% CI, 0.37 to 1.05; p=0.078 vs. erlotinib; HR, 0.75; 95% CI, 0.42 to 1.32; p=0.320 vs. pemetrexed) (median PFS: pemetrexed-erlotinib, 6.7 months; erlotinib, 3.0 months; pemetrexed, 4.4 months).
Conclusion
The PFS results from this subset analysis in both EA and non-EA populations are consistent with the results in the overall population. The PFS advantage for pemetrexed-erlotinib is significant compared with the single agents in EA patients.

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Clinical Responses and Prognostic Indicators of Concurrent Chemoradiation for Non-small Cell Lung Cancer
Dong-Soo Lee, Yeon-Sil Kim, Jin-Hyoung Kang, Sang-Nam Lee, Young-Kyoun Kim, Myung-Im Ahn, Dae-Hee Han, Ie-Ryung Yoo, Young-Pil Wang, Jae-Gil Park, Sei-Chul Yoon, Hong-Seok Jang, Byung-Oak Choi
Cancer Res Treat. 2011;43(1):32-41.   Published online March 31, 2011
DOI: https://doi.org/10.4143/crt.2011.43.1.32
AbstractAbstract PDFPubReaderePub
PURPOSE
To evaluate treatment outcomes and prognostic factors in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiation.
MATERIALS AND METHODS
From January 2005 to June 2009, 51 patients were treated with concurrent chemoradiation for 3 different aims: locally advanced stage III, locally recurrent disease, and postoperative gross residual NSCLC. Median age was 63 years. Distribution of stages by the 6th edition of American Joint Committee on Cancer (AJCC) was as follows: IIIA (37.3%), IIIB (56.9%). Chemotherapy was administered every week concurrently with radiation using one of the following regimens: paclitaxel (60 mg/m2), docetaxel+cisplatin (20 mg/m2+20 mg/m2), cisplatin (30 mg/m2). Total radiation dose was 16-66.4 Gy (median, 59.4 Gy).
RESULTS
Median follow-up duration was 40.8 months. The overall response rate was 84.3% with 23 complete responses. The median survival duration for the overall patient group was 17.6 months. The 3-year survival rate was 17.8%. A total of 21 patients had recurrent disease at the following sites: loco-regional sites (23.6%), distant organs (27.5%). In the multivariate analysis of the overall patient group, a clinical tumor response (p=0.002) was the only significant prognostic factor for overall survival (OS). In the multivariate analysis of the definitive chemoradiation arm, the use of consolidation chemotherapy (p=0.022), biologically equivalent dose (BED)10 (p=0.007), and a clinical tumor response (p=0.030) were the significant prognostic factors for OS.The median survival duration of the locally recurrent group and the postoperative gross residual group were 26.4 and 23.9 months, respectively.
CONCLUSION
Our study demonstrated that clinical tumor response was significantly associated with OS in the overall patient group. Further investigations regarding the optimal radiation dose in the definitive chemoradiation and the optimal treatment scheme in locally recurrent NSCLC would be required.

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    Cancer Chemotherapy and Pharmacology.2013; 71(4): 893.     CrossRef
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Gemcitabine and Carboplatin Combination Chemotherapy for Elderly Patients with Advanced Non-small Cell Lung Cancer: A Feasibility Study
Young Jin Yuh, Hyo Rak Lee, Sung Rok Kim
Cancer Res Treat. 2008;40(3):116-120.   Published online September 30, 2008
DOI: https://doi.org/10.4143/crt.2008.40.3.116
AbstractAbstract PDFPubReaderePub
Purpose

Although platinum based chemotherapy is known to improve the survival duration for the patients with non-small cell lung cancer, the role of platinum for elderly patient is not yet clear. We administered gemcitabine and carboplatin combination therapy to elderly patients with NSCLC. The aim of this study was to evaluate the efficacy and toxicities of this regimen for elderly patients.

Materials and Methods

The eligibility criteria were as follows: pathologically confirmed NSCLC, an age ≥65 years, advanced disease with stage IIIB or IV and the patients were chemotherapy-naive. The treatment regimen was as follows; gemcitabine 1,000 mg/m2 was administered on days 1 and 8 and carboplatin AUC=5 was administered on day 1. This regimen was repeated every 3 weeks. The efficacy was evaluated in terms of the response rate, the time to progression and the overall survival duration.

Results

From Dec 2001 to Feb 2005, a total of 20 patients were entered into this study. The median patient age was 68 years (range: 65~75). 19 patients were evaluable for their treatment response. A partial response was obtained in 8 patients (response rate: 42.1%, 95% CI: 19.4~64.8%). The median time to progression and the survival duration were 136 days and 453 days, respectively. Among a total of 65 cycles of treatment, grade 3 or 4 leukopenia and thrombocytopenia were observed in 7.7% and 13.9% of the cycles, respectively. Grade 3 or 4 vomiting was observed in 7.7% of the cycles. Grade 3 skin rash developed in 1.5% of the cycles. 1 patient died of septic shock after chemotherapy.

Conclusions

Gemcitabine and carboplatin combination chemotherapy was relatively safe and effective for treating elderly patients with NSCLC.

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  • Gefitinib-Integrated Regimen versus Chemotherapy Alone in Heavily Pretreated Patients with Epidermal Growth Factor Receptor–Mutated Lung Adenocarcinoma: A Case-Control Study
    Nan-Jie Zhao, Zhao Sun, Yuzhou Wang, Xiaohong Ning, Ning Jia, Changting Meng, Yingyi Wang
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    Medical Oncology.2013;[Epub]     CrossRef
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    Kyu-Hyoung Lim, Hui-Young Lee, Seo-Young Song
    Chinese Medical Journal.2013; 126(24): 4644.     CrossRef
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    Fumio Imamura, Makoto Nishio, Rintaro Noro, Masahiro Tsuboi, Norihiko Ikeda, Akira Inoue, Yoshinobu Ohsaki, Yukio Kimura, Kazumi Nishino, Junji Uchida, Takeshi Horai
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    G. Genestreti, N. Giovannini, M. Frizziero, M. Maglie, S. Sanna, S. Cingarlini, A.M. Molino, S. Piciucchi, G.L. Cetto, A. Santo
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The Efficacy and Safety of Padexol® (Paclitaxel) and Cisplatin for Treating Advanced Non-small Cell Lung Cancer
Hoon-Kyo Kim, Jun Suk Kim, Hun Mo Ryoo, Dong Gun Shin, Byoung Young Shim, Kyong Hwa Park, Sung Hwa Bae, Chi Hong Kim
Cancer Res Treat. 2006;38(2):66-71.   Published online April 30, 2006
DOI: https://doi.org/10.4143/crt.2006.38.2.66
AbstractAbstract PDFPubReaderePub
Purpose

The authors conducted a multicenter study to evaluate the efficacy and safety of combination chemotherapy with Padexol® and cisplatin for treating patients with advanced non-small cell lung cancer (NSCLC).

Materials and Methods

From November 2003 to April 2005, 42 chemo-naive patients with advanced NSCLC were enrolled into this study from 4 hospitals. The treatment consisted of Padexol® 175 mg/m2 as a 3-hr infusion, and this was followed by cisplatin 75 mg/m2 administered as an intravenous infusion with standard premedication. The treatment was repeated every 3 weeks.

Results

Among the 42 patients (pts), 33 pts were evaluable for response. On the per protocol analysis, 1 patient (pt) (3.0%) achieved complete response (CR), 17 pts (51.5%) achieved partial response (PR), 6 pts (18.2%) achieved stable disease (SD), and 9 pts (27.3%) progressed; therefore, the overall response rate was 54.6% (95% CI: 37.6~71.5%). On the intention-to-treat analysis, 1 pt (2.4%) achieved CR, 18 pts (42.9%) achieved PR, 11 pts (26.2%) achieved SD, and 9 pts (21.4%) progressed; therefore, the overall response rate was 45.2% (95% CI: 30.2~60.3%). The response, as evaluated by the investigators, was independently reviewed by 2 external radiologists and it was as follows; 13 PR (43.3%), 14 SD (46.7%) and 3 progressive disease (10%). The median duration of response was 5.9 months. The median follow-up duration was 10.3 months (range: 1.3 to 22.1 months). The median time to progression was 5.8 months (95% CI: 4.7 to 7.4 months). The median survival time on the intention-to-treat analysis was 10.5 months (95% CI: 8.1 to 18.8 months). The most common grade 3 or 4 hematologic toxicities were neutropenia (26/180 cycles, 14.4%), anemia (7/180 cycles, 3.9%) and febrile neutropenia (2/180 cycles, 1.1%). The most frequent grade 3 or 4 non-hematologic toxicities were nausea (14/42 patients, 14.3%), anorexia (3/42 patients, 7.1%) and myalgia (3/42 patients, 7.1%).

Conclusion

The authors observed that Padexol® was as good as the other paclitaxel (Taxol® or Genexol®) formulations when combined with cisplatin for treating patients with advanced NSCLC.

Citations

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  • The role of weekly nanoparticle albumin bound paclitaxel monotherapy as second line or later treatment for advanced NSCLC in China
    Puyuan Xing, Yixiang Zhu, Ling Shan, Sipeng Chen, Xuezhi Hao, Junling Li
    Oncotarget.2017; 8(50): 87442.     CrossRef
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    Jung Ho Lee, Mi Hye Kwon, Ji Hyun Jeoung, Go Eun Lee, Eu Gene Choi, Moon Jun Na, Hyun Min Cho, Young Jin Kim, Weon Kuu Chung, Young Jun Cho, Ji Woong Son
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Results of Curative Radiation Therapy with or without Chemotherapy for Stage III Unresectable Non-Small Cell Lung Cancer
Sung-Ja Ahn, Young-Chul Kim, Kyu-Sik Kim, Kyung-Ok Park, Woong-Ki Chung, Taek-Keun Nam, Byung-Sik Nah, Ju-Young Song, Mi-Sun Yoon
Cancer Res Treat. 2005;37(5):268-272.   Published online October 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.5.268
AbstractAbstract PDFPubReaderePub
Purpose

We retrospectively analyzed the patients who received curative radiotherapy for unresectable stage III NSCLC to investigate the impact of chemotherapy.

Materials and Methods

From 1998 to 2001, the records of 224 patients who completed curative radiotherapy for NSCLC were reviewed. There were 210 males and 14 females, and their median age was 64 years (range 38~83). 54 patients had stage IIIA disease and 170 patients had stage IIIB disease. Conventional radiotherapy was given and the radiation dose ranged from 50~70 Gy with a median of 60 Gy, and chemotherapy was combined for 116 patients (52%).

Results

The median survival, the 2-year, and 5-year actuarial survival rates of all 224 patients were 15 months, 30%, and 7%, respectively. The median survival of the patients with stage IIIA and IIIB disease were 21 months and 13 months, respectively (p=0.14). The median survival of patients who received chemoradiation was 18 months compared to 14 months for the patients who received RT alone (p=0.02). Among the chemoradiation group of patients, the median survival time of the patients who received 1 to 3 cycles of chemotherapy was 16 months and that for the patients who received more than 3 cycles was 22 months (p=0.07). We evaluated the effects of the timing of chemoradiation in 57 patients who received more than 3 cycles of chemotherapy. The median survival of the patients with the concurrent sequence was 25 months and that for the patients with the sequential chemotherapy was 19 months (p=0.81).

Conclusions

For advanced stage III non-small cell lung cancer patients who completed the curative radiotherapy, the addition of chemotherapy improved the survival compared to the patients who received radiotherapy alone.

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  • Treatment for Non-Small-Cell Lung Cancer and Circulating Tumor Cells
    Joel Mason, Benjamin Blyth, Michael P MacManus, Olga A Martin
    Lung Cancer Management.2017; 6(4): 129.     CrossRef
  • Clinical Responses and Prognostic Indicators of Concurrent Chemoradiation for Non-small Cell Lung Cancer
    Dong-Soo Lee, Yeon-Sil Kim, Jin-Hyoung Kang, Sang-Nam Lee, Young-Kyoun Kim, Myung-Im Ahn, Dae-Hee Han, Ie-Ryung Yoo, Young-Pil Wang, Jae-Gil Park, Sei-Chul Yoon, Hong-Seok Jang, Byung-Oak Choi
    Cancer Research and Treatment.2011; 43(1): 32.     CrossRef
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Usefulness of Additional Delayed Regional F-18 Fluorodeoxy-glucose Positron Emission Tomography in the Lymph Node Staging of Non-Small Cell Lung Cancer Patients
Young So, June-Key Chung, Jae Min Jeong, Dong Soo Lee, Myung Chul Lee
Cancer Res Treat. 2005;37(2):114-121.   Published online April 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.2.114
AbstractAbstract PDFPubReaderePub
Purpose

In this study, we examined whether additional, delayed regional FDG PET scans could increase the accuracy of the lymph node staging of NSCLC patients.

Materials and Methods

Among 87 patients who underwent open thoracotomy or mediastinoscopic biopsy under the suspicion of NSCLC, 35 (32 NSCLC and 3 infectious diseases) who had visible lymph nodes on both preoperative whole body scan and regional FDG PET scan were included. The following 3 calculations were made for each biopsy-proven, visible lymph node: maximum SUV of whole body scan (WB SUV), maximum SUV of delayed chest regional scan (Reg SUV), and the percent change of SUV between WB and regional scans (% SUV Change). ROC curve analyses were performed for WB SUVs, Reg SUVs and % SUV Changes.

Results

Seventy lymph nodes (29 benign, 41 malignant) were visible on both preoperative whole bodyscan and regional scan. The means of WB SUVs, Reg SUVs and % SUV Changes of the 41 malignant nodes, 3.71±1.08, 5.18±1.60, and 42.59±33.41%, respectively, were all significantly higher than those of the 29 benign nodes, 2.45±0.73, 3.00±0.89, and 22.71±20.17%, respectively. ROC curve analysis gave sensitivity and specificity values of 80.5% and 82.8% at a cutoff of 2.89 (AUC 0.839) for WB SUVs, 87.8% and 82.8% at a cutoff of 3.61 (AUC 0.891) for Reg SUVs, and 87.8% and 41.4% at a cutoff of 12.3% (AUC 0.671) for % SUV Changes.

Conclusion

Additional, delayed regional FDG PET scans may improve the accuracy of lymph node staging of whole body FDG PET scan by providing additional criteria of Reg SUV and % SUV Change.

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  • KSNM60 in Clinical Nuclear Oncology
    Seung Hwan Moon, Young Seok Cho, Joon Young Choi
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    Hyun-Cheol Kang, Hong-Gyun Wu, Tosol Yu, Hak Jae Kim, Jin Chul Paeng
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  • Imaging Atherosclerosis in the Carotid Arteries with F-18-Fluoro-2-deoxy-D-glucose Positron Emission Tomography: Effect of Imaging Time after Injection on Quantitative Measurement
    Minyoung Oh, Ji Young Kim, Kwang-Ho Shin, Seol Hoon Park, Jin-Sook Ryu, Jae Seung Kim, Hye-Jin Kim, Dong-Wha Kang, Dae Hyuk Moon
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A Phase II Trial of Docetaxel and Ifosfamide for Patients with Platinum-Resistant or Refractory Non-Small Cell Lung Cancer in a Salvage Setting
Gyeong-Won Lee, Jung-Hun Kang, Seok-Hyun Kim, Hea Yong Lee, Ho-Cheol Kim, Won-Sup Lee, Jong-Duk Lee, Young-Sil Hwang, Joung-Soon Jang, Jong-Seok Lee
Cancer Res Treat. 2004;36(5):287-292.   Published online October 31, 2004
DOI: https://doi.org/10.4143/crt.2004.36.5.287
AbstractAbstract PDFPubReaderePub
Purpose

We conducted a phase II study of docetaxel and ifosfamide chemotherapy for patients with platinum-resistant or refractory non-small-cell lung cancer (NSCLC) to evaluate the response and toxicity profiles as a salvage treatment.

Materials and Methods

Between July 2000 and July 2004, 40 patients who had previously received platinum-based regimen as the first-line or second-line therapy were enrolled in this study. The treatment consisted of a docetaxel 75 mg/m2 intravenous infusion on day 1 and intravenous ifosfamide 3 g/m2 with Mesna® uroprotectione on day 1 through 3. This regimen was repeated every 3 weeks.

Results

One hundred thirty cycles of treatment were given, with a median of 3 cycles (range: 2~6 cycles). All the patients were evaluable for the response rate and toxicity profile. The major toxicity was myelosuppression. Grade 3~4 neutropenia occurred in 30 patients (75%) during treatment. Febrile neutropenia occurred in 16 patients (40%). Five of 40 patients (12.5%) had a partial response (95% confidence interval, 3.3~21.7%). The median time to disease progression was 2.65 months (range: 2.02~3.20 months), and the median survival was 5.24 months (range: 2.99~7.49 months).

Conclusion

Salvage chemotherapy with docetaxel and ifosfamide showed a low efficacy and a high proportion of severe neutropenia in patients with platinum-resistant or refractory advanced NSCLC.

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  • The Safety and Efficacy of Second-line Single Docetaxel (75 mg/m2) Therapy in Advanced Non-Small Cell Lung Cancer Patients who were Previously Treated with Platinum-based Chemotherapy
    Byoung Yong Shim, Chi Hong Kim, So Hyang Song, Meyung Im Ahn, Eun Jung Hong, Sung Whan Kim, Suzy Kim, Min Seop Jo, Deog Gon Cho, Kyu Do Cho, Jinyoung Yoo, Hoon-Kyo Kim
    Cancer Research and Treatment.2005; 37(6): 339.     CrossRef
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Expression of c-kit and p53 in Non-small Cell Lung Cancers
Jinyoung Yoo, Chi Hong Kim, So Hyang Song, Byoung Yong Shim, Youn Ju Jeong, Meyung Im Ahn, Sung Whan Kim, Deog Gon Cho, Min Seop Jo, Kyu Do Cho, Hong Joo Cho, Hoon-Kyo Kim
Cancer Res Treat. 2004;36(3):167-172.   Published online June 30, 2004
DOI: https://doi.org/10.4143/crt.2004.36.3.167
AbstractAbstract PDFPubReaderePub
Purpose

Increasing experimental evidence indicates that abnormal expression of c-kit may be implicated in the pathogenesis of a variety of solid tumors. It has been reported that over 70% of small cell lung cancer (SCLC) contain the c-kit receptor. In the present study, a c-kit analysis has been extended to non-small cell lung cancer (NSCLC). The expressions of p53, vascular endothelial growth factor (VEGF) and cd34, in addition to c-kit, were evaluated to investigate the correlations between these proteins and to determine their potential relationships with the clinicopathological data.

Materials and Methods

Paraffin-embedded tumor sections, obtained from 147 patients with NSCLC, were immunohistochemically investigated using anti-c-kit, anti-p53, anti-VEGF and anti-cd34 antibodies.

Results

c-kit was expressed in 40 (27%) of the tumors examined: 27% of the adenocarcinomas, 27% of the squamous cell carcinomas and 29% of the undifferentiated carcinomas. p53 and VEG F immunoreactivities were present in 107 (73%) and 110 (75%) carcinomas, respectively. Anti-cd34 was negative in all samples. No associations were established among these proteins. The c-kit, however, showed a strong correlation with the T factor: T1 (n=11), 0%; T2 (n=49), 16% and T3 (n=87), 37% (p=.006).

Conclusion

It is suggested that in NSCLC c-kit is expressed relatively frequently and may become a therapeutic target for the patients with inoperable or recurrent c-kit positive tumors. The alterations in p53 probably constitute an early event, whereas the activated c-kit may contribute to tumor progression.

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  • Protein Kinase C-δ–Mediated Recycling of Active KIT in Colon Cancer
    Misun Park, Won Kyu Kim, Meiying Song, Minhee Park, Hyunki Kim, Hye Jin Nam, Sung Hee Baek, Hoguen Kim
    Clinical Cancer Research.2013; 19(18): 4961.     CrossRef
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The Effect of ZD 1839 (Iressa(R)) in the Treatment of Refractory Non Small Cell Lung Cancer
Yong Tai Kim, Chul Kim, Joo Hyuk Sohn, So Young Park, Soo Young Park, Nae Choon Yu, Young Sam Kim, Se Kyu Kim, Joon Chang, Kil Dong Kim, Kyung Young Chung, Joo Hang Kim
Cancer Res Treat. 2003;35(6):502-506.   Published online December 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.6.502
AbstractAbstract PDF
PURPOSE
The aim of this study was to evaluate the efficacy and the safety of ZD 1839 (Iressa(R)) as a 3rd or 4th line chemotherapy regimen in NSCLC patients who are refractory to a previous chemotherapy regimen. MATERIALS AND METHODS: Twenty-five patients who were refractory to previous chemotherapy were selected for this study. The eligible patients had an ECOG performance status of 0 to 2, and an appropriate end organ function. ZD 1839 (Iressa(R))250 mg/d was orally administered until the patients experienced disease progression or unacceptable toxicity. RESULTS: Twenty-five patients were analyzed. The median age of the patients was 57 years. The response rate was 12.0% with partial responses in 3 patients. Fourteen patients (56%) remained in the stable disease state and 8 patients progressed. The median overall survival was 9.0 months (95% CI 6.7~11.2). The median progression free survival was 3 months (95% CI 2.2~3.8). Hematological toxicities of grade 3 or 4 neutropenia, anemia and thrombocytopenia were absent. Non-hematological toxicities were grade 2 or 3 skin rashes in 10 (40.0%) patients and 1 (4.0%) patient and grade 3 nausea in 3 (12.0%) patients. No patient failed to continue chemotherapy due to any drug-related adverse events.
CONCLUSION
The results suggest that ZD 1839 (Iressa(R)) monotherapy is effective and tolerable as a 3rd or 4th line salvage treatment for NSCLC patients refractory to previous chemotherapy regimens.

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  • Serum Carcinoembryonic Antigen as an Index of the Therapeutic Effect of EGFR-TKIs in Patients with Advanced Non-Small Cell Lung Cancer
    Jin Hee Park, Sung Bin Kim, Sung Jin Nam, Su Hyeon Jeong, Chul Ho Oak, Tae Won Jang, Maan Hong Jung
    Journal of Lung Cancer.2010; 9(2): 97.     CrossRef
  • A review of the benefit–risk profile of gefitinib in Asian patients with advanced non‐small‐cell lung cancer
    Keunchil Park, Koichi Goto
    Current Medical Research and Opinion.2006; 22(3): 561.     CrossRef
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The Relation between Histopathologic Findings on Surgical Specimen and Outcomes in Patients with N2 Positive Stage IIIA Non-Small Cell Lung Cancer Receiving Preoperative Concurrent Radiochemotherapy and Surgery
Bo Kyong Kim, Kyoung Ju Kim, Yong Chan Ahn, Do Hoon Lim, Won Park, Joungho Han, Keunchil Park, Kwan Min Kim, Jhingook Kim, Young Mog Shim
Cancer Res Treat. 2003;35(6):497-501.   Published online December 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.6.497
AbstractAbstract PDF
PURPOSE
To evaluate the prognostic implication of histopathologic findings on the surgical specimens of N2 positive stage IIIA non-small cell lung cancer (NSCLC) patients who were treated with preoperative concurrent radiochemotherapy (CRCT) and surgery. MATERIALS AND METHODS: From May 1997 to April 2000, 48 patients with N2 positive stage IIIA NSCLC were treated with preoperative CRCT and surgery. Retrospective analyses were performed on 33 patients who underwent surgical resection. The thoracic radiation therapy (TRT) dose was 45 Gy over 5 weeks with a 1.8 Gy daily fraction using 10 MV X-rays. Chemotherapy consisted of two cycles of intravenous cisplatin (100 mg/m2, on days 1 and 29) and oral etoposide (50 mg/m2/day, on days 1~14 and 29~42), concurrently delivered with TRT. Surgery was performed around 4 weeks of the completion of CRCT. The median follow up was 18 months. The histopathologic findings, including the proportions of viable tumor cells, fibrosis, and necrosis, as well as the tumor and nodal statuses on the surgical specimens following the preoperative CRCT, were analyzed. RESULTS: The 3-year overall survival, disease-free survival, and local control rates were 46.1%, 49.5%, and 85.5%, respectively. Post-surgical stages decreased in 18 patients (54.5%), including 3 pathologic complete responses, were unchanged in 13 (39.4%), and increased in two (6.1%). On univariate analyses, the low proportion of the viable tumor cells was the only factor favorably affecting the overall survival rate (p=0.0386), and the histologic type of squamous cell carcinoma was a favorable factor affecting disease free survival rate (p=0.0452). On multivariate analyses, however, no factor affected the overall survival, disease free survival, or local control rates. CONCLUSION: The histopathologic findings of the proportion of viable tumor cells, fibrosis, and necrosis on the surgical specimens following preoperative CRCT had few prognostic implications on uni-and multi-variate analyses. Furthermore, the primary tumor and nodal responses to preoperative CRCT did not influence the outcomes. Longer-term follow-up with a larger number of patients, however, is awaited.
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Relationship between PTEN and Vascular Endothelial Growth Factor Expression in Non-Small Cell Lung Cancer
Mee Sook Roh, Jae Ik Lee, Doo Kyung Yang, Soo Keol Lee, Hyuk Chan Kwon, Mi Kyoung Park, Ki Baek Hwang, Jin A Jung
Cancer Res Treat. 2003;35(5):445-450.   Published online October 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.5.445
AbstractAbstract PDF
PURPOSE
This study was performed to determine the relationship between PTEN and vascular endothelial growth factor (VEGF) expression and to assess their roles in the tumor-induced angiogenesis and tumor progression in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissues, from 96 patients diagnosed with NSCLC, were evaluated for VEGF and PTEN expression using immunohistochemical methods. The results of the expression pattern of VEGF alone, or in combination with PTEN expression, were compared with clinicopathological parameters. RESULTS: VEGF expression was seen in 54 (56.3%) of the 96 NSCLCs evaluated, and was significantly correlated with histological type, and seen more frequently in adenocarcinomas compared to the other histological types (p<0.05). There were no significant associations between VEGF expression and tumor size, lymph node metastasis and stage. The microvessel density (MVD) determined by CD34 staining were significantly higher in tumors with VEGF expression (62.9+/-21.8) than those without (55.1+/-15.1). Loss of PTEN expression was seen in 33 (34.4%) of the 96 NSCLCs evaluated. VEGF expression was more frequently detected in the tumors with loss of PTEN expression (69.7%) than in those with PTEN expression (49.2%). When the combined VEGF/ PTEN phenotypes were divide into two groups; group I (VEGF-/PTEN+) and group II (VEGF-/ PTEN-, VEGF+/PTEN+, VEGF+/PTEN-), a significant correlation was also seen between the groups and the histologic types. There was a trend for the tumors in group II to show more frequent lymph node metastasis (50.0%) than those in group I (31.5%), although there was no statistical significance. The MVDs were significantly higher in group II (63.1+/-20.7) than in group I (53.4+/-17.2). CONCLUSION: These findings demonstrate an inverse correlation between the expressions of PTEN and VEGF. It is possible that PTEN may repress VEGF expression, and modulate VEGF-mediated angiogenesis, which suggests further analysis of the complex phenomenon of neo-angiogenesis in NSCLC is essential.

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  • Molecular and biological characterization of hepatitis B virus subgenotype F1b clusters: Unraveling its role in hepatocarcinogenesis
    María Mercedes Elizalde, Laura Mojsiejczuk, Micaela Speroni, Belén Bouzas, Luciana Tadey, Lilia Mammana, Rodolfo Héctor Campos, Diego Martín Flichman
    Frontiers in Microbiology.2022;[Epub]     CrossRef
  • KRAS mutant lung cancer cells are differentially responsive to MEK inhibitor due to AKT or STAT3 activation: Implication for combinatorial approach
    Young‐Kwang Yoon, Hwang‐Phill Kim, Sae‐Won Han, Do Youn Oh, Seock‐Ah Im, Yung‐Jue Bang, Tae‐You Kim
    Molecular Carcinogenesis.2010; 49(4): 353.     CrossRef
  • Phosphatase and Tensin Homolog Reconstruction and Vascular Endothelial Growth Factor Knockdown Synergistically Inhibit the Growth of Glioblastoma
    Hongbo Chen, Xiaomeng Shen, Caiping Guo, Huijun Zhu, Lanzhen Zhou, Yongqiang Zhu, Huixia Wang, Yi Zheng, Laiqiang Huang
    Cancer Biotherapy and Radiopharmaceuticals.2010; 25(6): 713.     CrossRef
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Review Article
Combined Modality Therapy for Locally Advanced Non-Small Cell Lung Cancer
L Chinsoo Cho, J Michael Dimaio, Randall Hughes, Phuc Nguyen, Paula Anderson, Hak Choy
Cancer Res Treat. 2003;35(5):373-382.   Published online October 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.5.373
AbstractAbstract PDF
The majority of non-small cell lung cancer patients present with locally advanced disease that may not be resectable. A single modality treatment such as thoracic radiotherapy often results in an inferior outcome when compared to combined modality treatment. Various combinations of radiotherapy, chemotherapy, and surgery have been tested in patients with locally advanced non-small-celllung cancer with promising results. The favorable results of the combined modality treatment are accompanied by a corresponding increase in treatment related morbidity. In this article, the results of the application of combined modality treatments in the management of locally advanced non-small cell lung cancer are reviewed.
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Original Articles
Effect of Combination Chemotherapy with Docetaxel Plus Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer
Hee Jung Kang, Min Kyoung Kim, Young Gil Kim, Jae Lyun Lee, Kyung Hee Lee, Myung Soo Hyun, Sung Hwa Bae, Hun Mo Ryoo
Cancer Res Treat. 2003;35(4):299-303.   Published online August 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.4.299
AbstractAbstract PDF
PURPOSE
This study was conducted to evaluate the efficacy and safety of combination chemotherapy, with docetaxel and cisplatin, as a first line treatment for advanced non-small cell lung cancer.
MATERIALS AND METHODS
Between March 1998 and December 2001, 35 patients with advanced non-small cell lung cancer were enrolled in this study. The patients were treated at 3-week intervals, with one course of a regimen consisting of docetaxel (75 mg/m2 IV for 1 hours) on day 1 and cisplatin (60 mg/m2 IV) on day 2.
RESULTS
The median age of the patients was 60.3 years. Of the 35 patients, 20 and 15 had stage IIIb and stage IV diseases, respectively. A complete response was observed in 1 patient and partial response in 15, with an overall response rate of 46%. The overall median survival duration was 40.3+/-25.2 weeks. The median time to progression and response duration were 21.6+/-5.5 and 15.1+/-5.9 weeks, respectively. The survival duration was statistically significantly longer in the response group (50.6 weeks) than in the non-response group (31.6 weeks) (p<0.05). Of the hematological side effects, grades III and IV leukopenia were observed in 4.8% of patients. Grades III and IV nausea and vomiting were observed in 48.5%, and grades I and II neuropathy in 11.4% of the treated patients. These toxicities were well tolerable and reversible. There were no hypersensitivity reactions.
CONCLUSION
Docetaxel and cisplatin combination chemotherapy is relatively effective and safe in advanced non-small cell lung cancer patients.
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Phase II Study of Gemcitabine and Vinorelbine as Second-Line Chemotherapy in Non-Small Cell Lung Cancer
Yoon Jae Kim, Joo Hyuk Sohn, Chul Kim, Yong Tai Kim, Hai Jin Kim, Joong Bae Ahn, Se Kyu Kim, Joon Chang, Nae Choon Yoo, Joo Hang Kim, Jae Yong Cho
Cancer Res Treat. 2003;35(4):294-298.   Published online August 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.4.294
AbstractAbstract PDF
PURPOSE
With the increased use of chemotherapy for non small cell lung cancer (NSCLC), a growing group of patients can now be considered for second-line chemotherapy. However, guidelines for the second line treatment remain to be developed. The objective of this study was to evaluate the efficacy and safety of the gemcitabine and vinorelbine combination therapy in patients with advanced NSCLC, pretreated with taxane and platinum based regimens. Gemcitabine has already demonstrated activity in this patient group, with the combination therapy having been reported to be well tolerated in previous phase I/II studies.
MATERIALS AND METHODS
Forty two patients with advanced NSCLC (stages III/IV), having received prior taxane and platinum based chemotherapy, with an ECOG performance status (PS) 0~2, and unimpaired hematopoietic and organ function, were treated with vinorelbine, 20 mg/m2, followed by gemcitabine, 1, 000 mg/m2, both administered on days 1, 8 and 15, every 4 weeks.
RESULTS
Out of the 42 patients enrolled, 41 were evaluable for their response, and all 42 for their toxicity. The patient's characteristics were as follows; median age=60 years (42~73), median PS=1 (range 0~2), a gender ratio 31: 11 males/females, with stages IIIA, IIIB and IV in 3, 14 and 25 cases. The objective responses included a partial response (PR) 8/41 (19.5%), a stable disease 15/41 (36.6%) and a progressive disease 18/41 (43.9%). The median time-to progression (TTP) and survival were 4 months, ranging from 2 to 14 months, and 8 months, ranging from 2 to 17+ months, respectively. Grade 3 neutropenia was seen in 19% of the patient, and there was no grade 4 neutropenia or episodes of febrile neutropenia. No grade 4 thrombocytopenia or other grade 3/4 non-hematological toxicities were observed.
CONCLUSION
The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC having failed prior taxane/platinum therapy.
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