Cancer Research and Treatment

Original Articles

Phase II Efficacy and Safety of Pembrolizumab with Platinum Based Chemotherapy in Non–Small Cell Lung Cancer Patients with Untreated, Asymptomatic Brain Metastasis (PHOEBS): Junkyu Kim, Miran Han, Jinyong Kim, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Myung-Ju Ahn; Received October 10, 2025 Accepted March 18, 2026 Published online March 19, 2026; DOI: https://doi.org/10.4143/crt.2025.1100 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Brain metastases are a serious complication in non–small cell lung cancer (NSCLC). However, data regarding efficacy of immune checkpoint inhibitors and chemotherapy combinations are limited. This phase II study aimed to evaluate the intracranial efficacy and safety of pembrolizumab and chemotherapy in treatment-naïve NSCLC patients with asymptomatic brain metastases.
Materials and Methods
This single-arm, phase II trial was conducted at Samsung Medical Center, Korea. Eligible patients had stage IV NSCLC with asymptomatic, untreated brain metastases and no epidermal growth factor receptor or anaplastic lymphoma kinase alterations. Patients received pembrolizumab with chemotherapy every 3 weeks for 4 cycles, followed by pembrolizumab with or without maintenance chemotherapy up to 35 cycles. The primary endpoint was intracranial objective response rate (icORR). Secondary endpoints included intracranial progression-free survival (icPFS), intracranial duration of response (icDoR), objective response rate, progression-free survival (PFS), overall survival (OS), and safety.
Results
Between February 2021 and June 2024, a total of 13 patients were enrolled. Due to challenges in recruiting patients, enrollment was discontinued after the 13 patients. The icORR was 46.2% (95% confidence interval [CI], 19.2 to 74.9), with six patients achieving partial response. The median icPFS was 9.8 months (95% CI, 5.2 to 21.5), and median icDoR was 9.3 months (95% CI, 4.0 to 20.3). Median PFS and OS were 7.2 months (95% CI, 2.4 to 12.3) and 10.7 months (95% CI, 7.2 to 21.5), respectively. Most treatment-related adverse events were grade 1-2.
Conclusion
Pembrolizumab combined with chemotherapy demonstrated encouraging intracranial activity and manageable safety profile in NSCLC patients with untreated, asymptomatic brain metastases.

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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.

Citations

Citations to this article as recorded by

Rates of Nodal Upstaging following Systematic Endobronchial Ultrasound Lymph Node Staging in Non-Metastatic Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
John Zhu, Matthew Bricknell, Jack M. Watson, Tracy L. Leong, Daniel P. Steinfort
Respiration.2026; : 1. CrossRef
SEPAR–SECT recommendations for perioperative invasive mediastinal staging of non-small cell lung cancer
Sergi Call, Maribel Botana-Rial, Rosa Cordovilla, Carlos Gálvez, David Gómez de Antonio, Virginia Leiro-Fernández, Carlos Martínez-Barenys, José Luís Recuero-Díaz, José Sanz-Santos, Pere Serra-Mitjà, Ramón Rami-Porta
Cirugía Española.2026; 104(8): 800335. CrossRef
SEPAR–SECT Recommendations for Perioperative Invasive Mediastinal Staging of Non-small Cell Lung Cancer
Sergi Call, Maribel Botana-Rial, Rosa Cordovilla, Carlos Gálvez, David Gómez de Antonio, Virginia Leiro-Fernández, Carlos Martínez-Barenys, José Luís Recuero-Díaz, José Sanz-Santos, Pere Serra-Mitjà, Ramón Rami-Porta
Archivos de Bronconeumología.2026; 62(8): 557. CrossRef
SEPAR–SECT recommendations for perioperative invasive mediastinal staging of non-small cell lung cancer
Sergi Call, Maribel Botana-Rial, Rosa Cordovilla, Carlos Gálvez, David Gómez de Antonio, Virginia Leiro-Fernández, Carlos Martínez-Barenys, José Luís Recuero-Díaz, José Sanz-Santos, Pere Serra-Mitjà, Ramón Rami-Porta
Cirugía Española (English Edition).2026; 104(8): 800335. CrossRef
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
Prevalence and Risk Factors for Pathologic N2 Disease in Resected Lung Cancers Assessed as N0 or N1 Disease on Preoperative Imaging
Yura Ahn, Sang Min Lee, Jooae Choe, Sehoon Choi, Kyung-Hyun Do, Joon Beom Seo
American Journal of Roentgenology.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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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.

Citations

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A Meta‐Analysis on the Incidence and Associated Factors of Pulmonary Fungal Infections in Lung Cancer Patients: Evidence Predominantly From Chinese Studies in the Chinese and English Literature
Liping Deng, Rong Yu, Bei Chen
Thoracic Cancer.2026;[Epub] CrossRef
External validation and updating of NTCP models for radiation pneumonitis: QUANTEC, Appelt, and a local simplified model
Zhi Chen, Heng Li, Lan Liang, Ming Fan, Shunping Huang, Peng Xue, Rui Kong, Zhenzhou Yang, Zhengjun Guo
Frontiers in Oncology.2026;[Epub] CrossRef
Chronic progressive pulmonary aspergillosis within the irradiated field after stereotactic body radiotherapy: two case reports
Nao Mamuro, Noriko Kishi, Yukinori Matsuo, Masahiro Yoneyama, Hiroyuki Inoo, Minoru Inoue, Takashi Mizowaki
International Cancer Conference Journal.2025; 14(2): 113. CrossRef
Predictive nomogram for risk of pulmonary infection in lung cancer patients undergoing radiochemotherapy: development and performance evaluation
Yujie Huang
American Journal of Cancer Research.2025; 15(2): 781. CrossRef
The Inter-Relationships Among the Risk Factors for Pulmonary Infection and the Diagnostic Utility of Inflammatory Markers in Patients with Non-Small Cell Lung Cancer
Wenwen Qin, Tiebin You, Tai Guo, Ruixin Tian, Xiaoman Cui, Ping Wang
Infection and Drug Resistance.2025; Volume 18: 1111. CrossRef
Incidence and predictors of pulmonary aspergillosis in patients with lung cancer: a systematic review and meta-analysis
Geling Teng, Feng Jin, Hua Zhang, Min Zhang
Frontiers in Medicine.2025;[Epub] CrossRef
Host Risk Factors for Tuberculosis
Vahid Asgharzadeh, Seyyed Amin Seyyed Rezaei, Mohammad Asgharzadeh, Jalil Rashedi, Hossein Samadi Kafil, Hossein Jalaei Nobari, Ahmad Ali Khalili, Mortaza Raeisi, Mahdi Asghari Ozma, Behroz Mahdavi Poor
Infectious Disorders - Drug Targets.2025;[Epub] CrossRef
Interaction between Dectin-1 gene polymorphisms and low weight on the risk of invasive pulmonary aspergillosis in patients with lung cancer undergoing surgery
Wenfang Jin, Yu Yao, Yanling Lv
Discover Oncology.2025;[Epub] CrossRef
Coexisting Lung Cancer and Pulmonary Tuberculosis: A Comprehensive Review From Incidence to Management
Wendi Zhou, Hongxu Lu, Jiamin Lin, Jialou Zhu, Jizhen Liang, Yalin Xie, Jinxing Hu, Ning Su
Cancer Reports.2025;[Epub] CrossRef
Risk factors for pulmonary infection after thoracoscopic radical resection of lung cancer in elderly patients with diabetes mellitus
Zi-Yuan Chen, Zhi-Qi Hong, Tie-Qiao Wang, Guo-Mei-Zhi Fu, Wen-Min Su, Cheng-Wei Zhou
World Journal of Diabetes.2025;[Epub] CrossRef
Clinical Analysis of Preoperative Nebulized Inhalation of Budesonide in Reducing Postoperative Complications in Patients Undergoing Lobectomy
紫燕姚
Nursing Science.2025; 14(10): 1920. CrossRef
Global trends, risk factors, and therapeutic associations of fungal pulmonary infections in lung cancer: A systematic review and meta-analysis
Milad Sheervalilou1, Mostafa Ghanei1, Masoud Arabfard1
Jornal Brasileiro de Pneumologia.2025; : e20250076. CrossRef
Tuberculosis and Lung Cancer: Insights from a Narrative Review
Antonio-Andrei Cotea, Ancuta-Alina Constantin, Florin-Dumitru Mihaltan
Cancers.2025; 18(1): 83. CrossRef
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.

Citations

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Exploration of the favorable duration for neoadjuvant targeted therapy in mutant non-small cell lung cancer
Mei Xie, Yinguang Zhang, Jie Gao, Hui Deng, Tao Xu, Weiwei Shi, Xidong Ma, Xuefeng Hao, Chenghao Zhang, Yu Chen, Bo Wei, Zhiqiang Xue, Xinying Xue
European Journal of Medical Research.2026;[Epub] CrossRef
Biology, detection, and management of incidental pulmonary nodules: the emerging role of targeted treatments. A review of the current literature and future perspectives
Ross A. Soo, Ji-Youn Han, James Chung-Man Ho, Calvin S.H. Ng, Lynette L.S. Teo, Elaine Shum, Sanjay Popat
Lung Cancer.2026; 220: 109558. CrossRef
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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