Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

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 Res Treat. 2024;56(2):502-512. Published online December 4, 2023; DOI: https://doi.org/10.4143/crt.2023.840

Abstract PDF Supplementary Material PubReader ePub: Purpose
It is unclear whether performing endosonography first in non–small cell lung cancer (NSCLC) patients with radiological N1 (rN1) has any advantages over surgery without nodal staging. We aimed to compare surgery without endosonography to performing endosonography first in rN1 on the overall survival (OS) of patients with NSCLC.
Materials and Methods
This is a retrospective analysis of patients with rN1 NSCLC between 2013 and 2019. Patients were divided into ‘no endosonography’ and ‘endosonography first’ groups. We investigated the effect of nodal staging through endosonography on OS using propensity score matching (PSM) and multivariable Cox proportional hazard regression analysis.
Results
In the no endosonography group, pathologic N2 occurred in 23.0% of patients. In the endosonography first group, endosonographic N2 and N3 occurred in 8.6% and 1.6% of patients, respectively. Additionally, 51 patients were pathologic N2 among 249 patients who underwent surgery and mediastinal lymph node dissection (MLND) in endosonography first group. After PSM, the 5-year OSs were 68.1% and 70.6% in the no endosonography and endosonography first groups, respectively. However, the 5-year OS was 80.2% in the subgroup who underwent surgery and MLND of the endosonography first group. Moreover, in patients receiving surgical resection with MLND, the endosonography first group tended to have a better OS than the no endosonography group in adjusted analysis using various models.
Conclusion
In rN1 NSCLC, preoperative endosonography shows better OS than surgery without endosonography. For patients with rN1 NSCLC who are candidates for surgery, preoperative endosonography may help improve survival through patient selection.

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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

Abstract PDF Supplementary Material PubReader ePub

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.

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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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The Incidence and Risk Factors of Chronic Pulmonary Infection after Radiotherapy in Patients with Lung Cancer: Yeonseok Choi, Jae Myoung Noh, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Hongryull Pyo, Yong Chan Ahn, Byeong-Ho Jeong; Cancer Res Treat. 2023;55(3):804-813. Published online January 3, 2023; DOI: https://doi.org/10.4143/crt.2022.1305

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to investigate cumulative incidence and risk factors associated with chronic pulmonary infection (CPI) development after radiotherapy for lung cancer.
Materials and Methods
We retrospectively analyzed 1,872 patients with lung cancer who received radiotherapy for lung cancer from 2010-2014, had a follow-up period of ≥ 3 months after radiotherapy, and did not have CPI at the time of radiotherapy. CPI was defined as pulmonary tuberculosis, non-tuberculous mycobacterial pulmonary disease, chronic pulmonary aspergillosis, or pulmonary actinomycosis. The cumulative incidence of CPI and overall survival (OS) were estimated using the Kaplan-Meier method, and a multivariable Cox proportional hazards analysis was performed to identify risk factors associated with CPI development.
Results
The median follow-up period was 2.3 years with OS rates of 55.6% and 37.6% at 2 and 5 years, respectively. CPI developed in 59 patients at a median of 1.8 years after radiotherapy, with cumulative incidence rates of 1.1%, 3.4%, 5.0%, and 6.8% at 1, 3, 5, and 7 years, respectively. A lower body mass index, interstitial lung disease, prior pulmonary tuberculosis, larger clinical target volume, history of lung cancer surgery or radiation pneumonitis, and use of inhaled corticosteroids were independent risk factors for CPI development.
Conclusion
The long-term survival rate of lung cancer patients receiving radiotherapy was not low, but the cumulative incidence of CPI gradually increased to 6.8% at 7 years after radiotherapy. Therefore, close monitoring of CPI development is required in surviving patients with risk factors.

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Invasive aspergillosis complicated in a patient with non-small cell lung cancer harboring RET fusion during treatment with RET-TKIs: a case report and literature review
Kaidiriye Setiwalidi, Yimeng Li, Yuyan Ma, Zhanpeng Hao, Yujia Zhao, Yuxin Zhang, Xuan Liang, Tao Tian, Zhiping Ruan, Yu Yao, Xiao Fu
Frontiers in Oncology.2024;[Epub] CrossRef

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The Impact of EGFR Tyrosine Kinase Inhibitor on the Natural Course of Concurrent Subsolid Nodules in Patients with Non–Small Cell Lung Cancer: Noeul Kang, Ki Hwan Kim, Byeong-Ho Jeong, Kyungjong Lee, Hojoong Kim, O Jung Kwon, Myung-Ju Ahn, Jeonghee Cho, Ho Yun Lee, Sang-Won Um; Cancer Res Treat. 2022;54(3):817-826. Published online November 9, 2021; DOI: https://doi.org/10.4143/crt.2021.822

Abstract PDF Supplementary Material PubReader ePub

Purpose
The role of epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) in the management of persistent subsolid nodules (SSNs) is unclear. This study aimed to investigate the impact of EGFR-TKIs on concurrent SSNs in patients with stage IV non–small cell lung cancer (NSCLC).
Materials and Methods
Patients who received an EGFR-TKI for at least 1 month for stage IV NSCLC and had concurrent SSN(s) that had existed for at least 3 months on chest computed tomography were included in this retrospective study. Size change of each nodule before and after EGFR-TKI therapies were evaluated using a cutoff value of 2 mm; increase (≥ 2 mm), decrease (≤ –2 mm), and no change (–2 mm < size change < +2 mm).
Results
A total of 77 SSNs, 51 pure ground-glass (66.2%) and 26 part-solid nodules (33.8%), were identified in 59 patients who received gefitinib (n=45) and erlotinib (n=14). Among 58 EGFR mutation analysis performed for primary lung cancer, 45 (77.6%) were EGFR mutant. The proportions of decrease group were 19.5% (15/77) on per-nodule basis and 25.4% (15/59) on per-patient basis. Four SSNs (5.2%) disappeared completely. On per-patient based multivariable analysis, EGFR exon 19 deletion positivity for primary lung cancer was associated with a decrease after initial EGFR-TKI therapy (adjusted odds ratio, 4.29; 95% confidence interval, 1.21 to 15.29; p=0.025).
Conclusion
Approximately 20% of the concurrent SSNs decreased after the initial EGFR-TKI therapy. EGFR exon 19 deletion positivity for primary lung cancer was significantly associated with the size change of concurrent SSNs.

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Genetic Polymorphisms of ACE1 Rs4646994 Associated with Lung Cancer in Patients with Pulmonary Nodules: A Case–Control Study
Rong Qiao, Siyao Sang, Jiajun Teng, Hua Zhong, Hui Li, Baohui Han
Biomedicines.2023; 11(6): 1549. CrossRef
Deep learning analysis to predict EGFR mutation status in lung adenocarcinoma manifesting as pure ground-glass opacity nodules on CT
Hyun Jung Yoon, Jieun Choi, Eunjin Kim, Sang-Won Um, Noeul Kang, Wook Kim, Geena Kim, Hyunjin Park, Ho Yun Lee
Frontiers in Oncology.2022;[Epub] CrossRef

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Prevalence of Mutations in Discoidin Domain-Containing Receptor Tyrosine Kinase 2 (DDR2) in Squamous Cell Lung Cancers in Korean Patients: Mi-Sook Lee, Eun Ah Jung, Sung Bin An, Yu Jin Kim, Doo-Yi Oh, Ji-Young Song, Sang-Won Um, Joungho Han, Yoon-La Choi; Cancer Res Treat. 2017;49(4):1065-1076. Published online January 25, 2017; DOI: https://doi.org/10.4143/crt.2016.347

Abstract PDF Supplementary Material PubReader ePub

Purpose
The discoidin domain-containing receptor tyrosine kinase 2 (DDR2) is known to contain mutations in a small subset of patients with squamous cell carcinomas (SCC) of the lung. Studying the DDR2 mutations in patients with SCC of the lung would advance our understanding and guide the development of therapeutic strategies against lung cancer.
Materials and Methods
We selected 100 samples through a preliminary genetic screen, including specimens from biopsies and surgical resection, and confirmed SCC by histologic examination. DDR2 mutations on exons 6, 15, 16, and 18 were analyzed by Sanger sequencing of formalin-fixed, paraffin-embedded tissue samples. The functional effects of novel DDR2 mutants were confirmed by in vitro assays.
Results
We identified novel somatic mutations of DDR2 in two of the 100 SCC samples studied. One mutation was c.1745T>A (p.V582E) and the other was c.1784T>C (p.L595P), and both were on exon 15. Both patients were smokers and EGFR/KRAS/ALK-triple negative. The expression of the mutant DDR2 induced activation of DDR2 by the collagen ligand and caused enhanced cell growth and tumor progression. Moreover, dasatinib, a DDR2 inhibitor, showed potential efficacy against DDR2 L595P mutant–bearing cells.
Conclusion
Our results suggest that a mutation in DDR2 occurs naturally with a frequency of about 2% in Korean lung SCC patients. In addition, we showed that each of the novel DDR2 mutations were located in a kinase domain and induced an increase in cell proliferation rate.

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Potentially functional variants of PARK7 and DDR2 in ferroptosis‐related genes predict survival of non‐small cell lung cancer patients
Huilin Wang, Hongliang Liu, Xiaozhun Tang, Guojun Lu, Sheng Luo, Mulong Du, David C. Christiani, Qingyi Wei
International Journal of Cancer.2025; 156(4): 744. CrossRef
Advances in the Treatment of Rare Mutations in Non-Small Cell Lung Cancer
Yanning Sun, Li Ma, Xiaofei Zhang, Zhaoxia Wang
OncoTargets and Therapy.2024; Volume 17: 1095. CrossRef
Discoidin Domain Receptor 2: A New Target in Cancer
Xiaoxiao Xu, Tong Yu, Zhenxing Wang
Oncology Research and Treatment.2022; 45(4): 205. CrossRef
Unearthing novel fusions as therapeutic targets in solid tumors using targeted RNA sequencing
Sungbin An, Hyun Hee Koh, Eun Sol Chang, Juyoung Choi, Ji-Young Song, Mi-Sook Lee, Yoon-La Choi
Frontiers in Oncology.2022;[Epub] CrossRef
Squamous cell lung cancer: Current landscape and future therapeutic options
Sally C.M. Lau, Yuanwang Pan, Vamsidhar Velcheti, Kwok Kin Wong
Cancer Cell.2022; 40(11): 1279. CrossRef
Complex roles of discoidin domain receptor tyrosine kinases in cancer
V. Mehta, H. Chander, A. Munshi
Clinical and Translational Oncology.2021; 23(8): 1497. CrossRef
The Yin and Yang of Discoidin Domain Receptors (DDRs): Implications in Tumor Growth and Metastasis Development
Sandra Majo, Patrick Auguste
Cancers.2021; 13(7): 1725. CrossRef
Mutational Landscape of DDR2 Gene in Lung Squamous Cell Carcinoma Using Next-generation Sequencing
Charles Ricordel, Alexandra Lespagnol, Francisco Llamas-Gutierrez, Marie de Tayrac, Mallorie Kerjouan, Alice Fievet, Houda Hamdi-Rozé, Amyrat Aliouat, Benoit Desrues, Jean Mosser, Hervé Léna
Clinical Lung Cancer.2018; 19(2): 163. CrossRef
Extracellular matrix functions in lung cancer
Martin Götte, Ilona Kovalszky
Matrix Biology.2018; 73: 105. CrossRef
Subjecting appropriate lung adenocarcinoma samples to next‐generation sequencing‐based molecular testing: challenges and possible solutions
Weihua Li, Tian Qiu, Yun Ling, Shugeng Gao, Jianming Ying
Molecular Oncology.2018; 12(5): 677. CrossRef
Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells
Ugo Testa, Germana Castelli, Elvira Pelosi
Cancers.2018; 10(8): 248. CrossRef
Distribution of KRAS, DDR2, and TP53 gene mutations in lung cancer: An analysis of Iranian patients
Zahra Fathi, Seyed Ali Javad Mousavi, Raheleh Roudi, Farideh Ghazi, Sumitra Deb
PLOS ONE.2018; 13(7): e0200633. CrossRef

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