Cancer Research and Treatment

Original Articles

Synergistic Antitumor Activity of Combination Therapy with a MET TKI Vabametkib and a Third-Generation EGFR TKI Lazertinib in MET-Amplified EGFR-Mutant NSCLC: Dong Kwon Kim, Jin Woo Park, Hyeon Bin Cho, Su Jin Choi, Sung Sook Lee, YeongMun Kim, Jii Bum Lee, Sun Min Lim, Mi Ra Yu, Byoung Chul Cho; Received December 23, 2025 Accepted March 18, 2026 Published online March 31, 2026; DOI: https://doi.org/10.4143/crt.2025.1399 [Accepted]

Abstract PDF: Purpose
Third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKIs) improved outcomes in EGFR-mutant non-small cell lung cancer (NSCLC); however, the subsequent development of resistance emphasizes the necessity of overcoming this therapeutic limitation. MET amplification is one of the major resistance mechanism in EGFR-mutant NSCLC, bypassing EGFR inhibition by activating cell survival, proliferation, and metastasis. Combining MET- and EGFR-TKIs is thus emerging as a promising therapeutic strategy to overcome resistance to EGFR TKIs.
Materials and Methods
This study aimed to investigate the combination of the selective MET TKI vabametkib and a third-generation EGFR TKI lazertinib in MET-amplified EGFR TKI resistance models. Inhibition of downstream signaling and cell proliferation by vabametkib plus lazertinib were evaluated in osimertinib-resistance NSCLC cell lines (HCC827-AR) and patient-derived organoid (YUO-010) by western blot and Cell Titer-Glo assay.
Results
In vitro studies demonstrated that vabametkib plus lazertinib synergistically inhibited EGFR/MET phosphorylation, leading to markedly enhanced anti-proliferative effects through downstream PI3K/AKT and MAPK pathway blockade. To investigate the antitumor effects in in vivo, we employed two patient-derived xenograft (PDX) models (YHIM-1035(1) and YHIM-1053) harboring MET amplification, as characterized by whole-exome sequencing or droplet digital PCR (ddPCR). Consistent with the in vitro findings, treatment with vabametkib plus lazertinib produced pronounced suppression of tumor growth in both models through a synergistic mechanism.
Conclusion
These findings establish vabametkib plus lazertinib as a promising strategy for MET-amplified NSCLC, currently under evaluation in an ongoing phase II clinical trial (NCT05541822).

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Non-Response to Durvalumab and Supraclavicular Nodal Involvement Predict Early Brain Metastasis After CCRT Followed by Durvalumab Consolidation in Stage III NSCLC: Yoo Kyung Choi, Yeon-Sil Kim, Yoo-Kang Kwak, Yun Hee Lee, Sung-Hwan Kim, Soo-Yoon Sung, Seok Hyun Son, Kyu Hye Choi; Received November 11, 2025 Accepted February 19, 2026 Published online February 20, 2026; DOI: https://doi.org/10.4143/crt.2025.1244 [Accepted]

Abstract PDF: Purpose
To identify predictors of brain metastasis in patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with definitive concurrent chemoradiotherapy (CCRT) followed by durvalumab consolidation.
Materials and Methods
We retrospectively analyzed 138 patients with unresectable stage III NSCLC treated with definitive CCRT followed by durvalumab from 2018 to 2024. The primary endpoint was brain metastasis incidence. Univariate and multivariate logistic regression analyses identified factors associated with brain metastasis development.
Results
With a median follow-up of 18.7 months (range, 1.2–73.3), brain metastasis occurred in 18 of 138 patients (13.0%). In multivariate analysis, non-responders to durvalumab (OR 4.86, 95% CI 1.69-13.96, p=0.003) and initial supraclavicular nodal (SCN) involvement (OR 2.89, 95% CI 0.99-8.48, p=0.05) were independent predictors of brain metastasis. Non-responders demonstrated accelerated central nervous system (CNS) progression, with 63.6% developing brain metastases within 6 months versus 28.6% in responders. PD-L1 ≥50% was associated with improved OS but not with brain metastasis incidence. All patients who developed brain metastases were EGFR/ALK wild-type.
Conclusion
Non-responders to durvalumab and supraclavicular nodal involvement were significant predictors of brain metastasis in NSCLC treated with CCRT followed by durvalumab. These findings support risk-adapted CNS surveillance strategies in high-risk patients.

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Postoperative Radiotherapy May Improve Survival in Certain Patients with pN2 Non-Small Cell Lung Cancer Who Do Not Have Extranodal Extension: Seung Hyuck Jeon, Changhoon Song, Jae Hyun Jeon, Jin-Haeng Chung, Sukki Cho, Kwhanmien Kim, Sanghoon Jheon, Se Hyun Kim, Yu Jung Kim, Jae-Sung Kim; Received June 20, 2025 Accepted February 1, 2026 Published online February 3, 2026; DOI: https://doi.org/10.4143/crt.2025.644 [Accepted]

Abstract PDF: Purpose
The aim of this study was to identify subgroups of patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) who may benefit from postoperative radiotherapy (PORT). Particular attention was given to evaluating whether extranodal extension (ENE) influences the therapeutic efficacy of PORT.
Materials and Methods
A total of 231 patients with pN2 NSCLC who underwent surgical resection followed by adjuvant chemotherapy at a single institution were analyzed retrospectively. Propensity score matching was performed to compare treatment outcomes according to the receipt of PORT.
Results
Propensity score matching yielded 99 matched pairs of patients with no significant differences in clinical parameters. There were no significant differences in the overall survival (OS; p=0.11) and disease-free survival (DFS; p=0.29) between the PORT and no PORT groups. However, PORT significantly improved the locoregional recurrence (LRR)-free rate (p=0.011), whereas the distant metastasis-free rate was comparable between groups (p=0.64). In subgroup analyses, PORT was associated with improved OS in patients with 1–3 positive N2 lymph nodes (p=0.013) and with significantly improved DFS among patients without ENE (p=0.046) or lymphatic invasion (p=0.032).
Conclusion
Although PORT did not improve OS or DFS in the matched overall cohort, it significantly reduced LRR. Subgroup analyses suggested potential benefits in patients with limited nodal burden and in those without ENE or lymphatic invasion. These findings, however, should be interpreted cautiously given small subgroup sizes and inherent limitations of retrospective design.

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Biomarker Testing Practices for Non-small Cell Lung Cancer: Survey Insights from South Korean Pathology Laboratories: Sehui Kim, Dajeong Kim, Lucia Kim, Wan-Seop Kim; Received August 27, 2025 Accepted January 28, 2026 Published online January 30, 2026; DOI: https://doi.org/10.4143/crt.2025.927 [Accepted]

Abstract PDF: Purpose
Molecular biomarker testing is essential for lung cancer management and precision medicine. This study evaluated biomarker testing practices for non-small cell lung cancer across pathology laboratories in South Korea.
Materials and Methods
A nationwide survey of 30 pathology laboratories assessed testing policies, biomarker adoption, testing platforms, next-generation sequencing (NGS) implementation, reporting practices, turnaround times (TATs), and perceived challenges.
Results
All institutions routinely performed biomarker testing; 20 (66.7%) employed reflex testing at least in part. Tissue was the primary specimen type, and cytology and liquid biopsy specimens were accepted by 90.0% and 46.7% of institutions, respectively. For non-squamous NSCLC, all institutions tested EGFR, ALK, ROS1, and PD-L1, with additional testing for BRAF (86.7%) and KRAS (80.0%); other actionable targets were rarely tested outside NGS. In squamous NSCLC, PD-L1 was routinely assessed, whereas other drivers were tested less frequently. All institutions performed tissue-based NGS using companion diagnostic (CDx) and/or non-CDx platforms, and liquid biopsy–based NGS was available in 46.7% of institutions. Median TATs were 2–3, 5, 9, 19, and 15 days for immunohistochemistry, polymerase chain reaction, fluorescence in situ hybridization, tissue-based NGS, and liquid biopsy–based NGS, respectively. Reported barriers included limited sample availability, workforce shortages, prolonged TATs, regulatory restrictions, and lack of standardization.
Conclusion
Biomarker testing is widely implemented in South Korea, with increasing integration of NGS. Despite alignment with international recommendations, systemic and policy reforms are needed to harmonize workflows, reduce variability, and optimize precision oncology.

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Circulating Tumor Cell-based Molecular Responses Stratify EGFR-TKI Efficacy in Patients with EGFR-Mutant Lung Cancer: Seoyoung Lee, Chaeyeon Kim, Chang Gon Kim, Min Hee Hong, Mina Han, Wonrak Son, Gamin Kim, Hyeong Jung Woo, Hyun Young Shin, Jungmin Lee, Minseok S Kim, Hye Ryun Kim; Received June 29, 2025 Accepted January 26, 2026 Published online January 27, 2026; DOI: https://doi.org/10.4143/crt.2025.672 [Accepted]

Abstract PDF: Purpose
Circulating tumor cell (CTC) is a promising minimally invasive biomarker for EGFR-mutant non-small cell lung cancer (NSCLC). However, the rarity of CTCs and limitations in their isolation and molecular characterization hinder their clinical utility, particularly in predicting treatment outcomes. This study evaluates the potential of CTC molecular response to predict treatment efficacy and guide therapy in patients with EGFR-mutant NSCLC undergoing EGFR-tyrosine kinase inhibitors (TKI) therapy.
Materials and Methods
Seventy-seven patients with EGFR-mutant NSCLC treated with EGFR-TKIs were enrolled. CTCs were isolated using continuous centrifugal microfluidic technology (CCM-CTCD) and compared with ctDNA and tissue biopsy for EGFR mutation analysis. Patients were categorized as CTC molecular responders or non-responders based on a ≥ 44.4% reduction in CTC count from baseline. Progression-free survival (PFS) and tumor burden changes were evaluated.
Results
CTC responders had significantly longer PFS (46.3 vs. 13.6 months, p=0.007) and greater tumor burden reduction (-37.7% vs. -35.2%, p=0.218) compared to non-responders. The CCM-CTCD demonstrated concordance with the cobas test while exhibiting higher sensitivity for EGFR mutation detection among 46 patients who underwent both tests simultaneously. Mutational discordance among tissue, ctDNA, and CTCs highlighted tumor heterogeneity. CTC profiling complemented traditional methods for identifying genomic alterations and predicting early progression.
Conclusion
CTC analysis using CCM-CTCD shows potential as a biomarker for predicting treatment response and prognosis in EGFR-mutant NSCLC. Stratification by CTC molecular response may inform risk-adapted treatment; however, its clinical utility remains to be established. Prospective studies are warranted to validate these findings and determine the role of CTC-guided decision-making.

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Real World Efficacy and Safety of First Line Chemo Immunotherapy in Extensive Stage Small Cell Lung Cancer and its association with molecular subtype: Miran Han, Sehhoon Park, Se-Hoon Lee, Junkyu Kim, Jin-yong Kim, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn; Received September 3, 2025 Accepted November 4, 2025 Published online November 5, 2025; DOI: https://doi.org/10.4143/crt.2025.971 [Accepted]

Abstract PDF: Purpose
Small cell lung cancer (SCLC) is an aggressive malignancy with poor outcomes. IMpower133 and CASPIAN established platinum–etoposide plus anti–PD-L1 antibody as standard first-line therapy for extensive-stage SCLC (ES-SCLC). Real-world data in Korean patients are scarce. We evaluated the effectiveness and safety of first-line chemo-immunotherapy in ES-SCLC and compared outcomes with pivotal trials.
Materials and Methods
We retrospectively reviewed patients diagnosed with ES-SCLC between 2018 and 2021. Overall survival (OS), progression-free survival (PFS), and time to next treatment (TTNT) were analyzed using Kaplan–Meier methods. Multivariate Cox regression identified prognostic factors. Objective response rate (ORR) was assessed by RECIST v1.1, and histological subtypes evaluated.
Results
Among 177 patients, median age was 66 years (range, 42–91), with 63.8% aged ≥65; most were male (92.7%) and ECOG 0–1 (91.5%). Smoking history was present in 80.8%. Baseline brain and liver metastases occurred in 27.7% and 26%. Median follow-up was 27.2 months (range, 3.9–43.2). ORR was 74.5% (95% CI, 67.1–81.1). Median OS, PFS, and TTNT were 12.4 (95% CI, 11.6–14.9), 5.3 (95% CI, 5.1–5.87), and 5.6 months (95% CI, 1.43–38.27). In 49 patients with brain metastases, ORR was 63.2%, with no difference in efficacy. Local therapy for brain metastases improved OS (HR 0.42; p=0.012), while PFS was not different. Treatment-related adverse events occurred in 90%, primarily grade ≥2 cytopenias; the most common immune-related event was grade 1 rash.
Conclusion
In this real-world Korean cohort, first-line chemo-immunotherapy achieved outcomes comparable to pivotal trials, supporting its role as standard care for ES-SCLC in clinical practice.

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Prognostic Impact of Organ-Specific Metastasis in Non-Small-Cell Lung Cancer: Woo Kyung Ryu, Munkhtsatsral Ganbaatar, Nuri Park, Hyun Young Lee, Hwan-Cheol Kim, Jeong-Seon Ryu, Jun Hyeok Lim; Received March 3, 2025 Accepted October 2, 2025 Published online October 10, 2025; DOI: https://doi.org/10.4143/crt.2025.238 [Accepted]

Abstract PDF: Purpose
Prognostic stratification is essential in non-small-cell lung cancer (NSCLC) to guide treatment decisions. While the TNM staging system has evolved to refine the M category based on metastatic burden, it does not account for differences in prognosis based on the specific organ affected. This study evaluates whether incorporating organ-specific metastasis improves prognostic discrimination in stage IV NSCLC.
Materials and Methods
We conducted a retrospective cohort study using data from the Korean Central Cancer Registry (2014–2018). Patients with stage IV NSCLC were classified according to the 9th edition TNM classification: M1b (single-organ, single metastasis), M1c1 (multiple metastases within a single organ), and M1c2 (multiple organ metastases). Survival outcomes were compared across groups using Kaplan-Meier analysis and Cox proportional hazards modeling.
Results
Among 3,165 patients, 56.5% had single-organ metastases, while 43.5% had multiple organ metastases. Median overall survival (OS) was longest in M1b (8.0 months), followed by M1c1 (6.0 months), and shortest in M1c2 (5.9 months) (p<0.001). However, survival varied by metastatic organ. Liver, adrenal, and uncommon-site metastases were associated with significantly worse OS, even among M1b patients. Some M1b and M1c1 patients with high-risk organ metastases had worse survival than M1c2 patients, challenging the TNM-defined prognostic hierarchy.
Conclusion
The current TNM M category does not fully capture the prognostic impact of metastatic organ involvement. Incorporating organ-specific metastases into staging and prognostic models could refine risk stratification and improve personalized treatment approaches for stage IV NSCLC.

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Lung and Thoracic cancer

Comparison of Surveillance with Low-Dose and Contrast-Enhanced Chest Computed Tomography in Patients Disease-Free for 2 Years after Curative Resection for Lung Cancer: Bubse Na, Ji Hyeon Park, Kwon Joong Na, Samina Park, Chang Hyun Kang, Young Tae Kim, In Kyu Park; Cancer Res Treat. 2026;58(2):454-464. Published online June 5, 2025; DOI: https://doi.org/10.4143/crt.2025.256

Abstract PDF Supplementary Material PubReader ePub: Purpose
Low-dose chest computed tomography (LDCT) is recommended for surveillance 2–3 years after curative resection of non-small cell lung cancer (NSCLC); however, supporting clinical evidence is limited. This study compared LDCT with contrast-enhanced chest computed tomography (CECT) in terms of recurrence detection and overall survival (OS) in patients 2 years after curative resection of NSCLC.
Materials and Methods
Among patients who underwent curative resection for NSCLC between January 2011 and December 2017 and survived for 2 years without recurrence, 2,083 patients were included. Comparisons between the LDCT and CECT groups were performed in both the entire cohort and propensity score-matched cohort. The primary outcome was the difference in overall survival. Secondary outcomes included time-to-recurrence, recurrence-free survival, and post-recurrence survival in each group.
Results
In the propensity score-matched population, the 5-year OS (96.0% for LDCT, 98.0% for CECT, p=0.097) and recurrence-free survival (RFS) (95.4% for LDCT, 96.0% for CECT, p=0.761) did not differ. The OS and RFS did not differ in subgroup analyses stratified by pathologic stage and histologic type. In the competing risk analysis, the overall 5-year cumulative incidence of recurrence did not differ between the two groups (4.56% for LDCT, 3.93% for CECT, p=0.765). When stratified by pathologic stage and histologic type, there was no significant difference in the cumulative incidence of recurrence. The distribution of recurrence sites did not differ between groups.
Conclusion
Similar OS and RFS were observed in LDCT and CECT surveillance in patients who achieved a 2-year disease-free status after curative resection for NSCLC.

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The Role of Circulating Tumor Cell as a Promising Biomarker in the Evaluation of Pulmonary Nodules: A Prospective Study: Shijie Wang, Changdan Xu, Xiaohong Xu, Weipeng Shao, Guohui Wang, Xiongtao Yang, Liwei Gao, Feng Teng, Hongliang Sun, Yue Zhao, Hongxiang Feng, Guangying Zhu; Cancer Res Treat. 2026;58(1):128-140. Published online March 27, 2025; DOI: https://doi.org/10.4143/crt.2024.841

Abstract PDF Supplementary Material PubReader ePub

Purpose
Our previous study showed that circulating tumor cell (CTC) count combined with gene mutation detection might help differentiate benign and malignant pulmonary nodules (PNs). Herein, we aimed to expand the study cohort and conduct further sequencing analysis.
Materials and Methods
Patients with PNs were included, and CTCs were identified before operation. Low-coverage whole-genome sequencing (LC-WGS) and lung cancer-related targeted gene sequencing were performed on CTCs. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. The differences in CTC counts among subgroups classified by demographic–clinical characteristics were analyzed. LC-WGS–based copy number variation (CNV) analysis and targeted gene mutation analysis were conducted.
Results
A total of 172 patients were included. CTC count of 2.5 was identified by the ROC curves as the optimal diagnostic cutoff. The sensitivity and specificity of CTC count for differentiating benign and malignant PNs were 54.2% and 78.6%, respectively. The diagnostic sensitivity and specificity of combined CTC count, radiological nodule type, and any malignant imaging features were 84.7% and 71.4%, respectively. The CTC counts were significantly greater in patients with aggressive tumors, later stage, and spread through air spaces. CTCs from malignant cases had more CNVs than those from benign cases.
Conclusion
CTC count can be used in identifying malignant PNs. The diagnostic efficacy can be improved if combined with computed tomography imaging characteristics. Further CNV analysis might help differential diagnosis. Greater CTC count might suggest more aggressive tumors. CTC detection can provide important information and guidance for subsequent management of PNs.

Citations

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Integrated CT Radiomics and Circulating Tumor Cell Analysis in Predicting Lung Adenocarcinoma Invasion: A Dual-Center Study with Implications for Personalized Treatment
Qingtao Zhao, Runzhe Wang, Qingxin Zhao, Dahu Ren, Lingxin Kong, Xiaopeng Zhang, Guochen Duan
OncoTargets and Therapy.2026; Volume 19: 1. CrossRef
Establishment of a multi-targeted magnetic combined enrichment system for circulating tumor cells in gastric cancer and analysis of their genomic profiles
Linfei Huang, Yuelu Ruan, Lei Zhu, Jing Xu
Journal of Biomaterials Applications.2026;[Epub] CrossRef

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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

Abstract PDF Supplementary Material PubReader ePub

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

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Associations between Immune-related Adverse Events and Prognosis in Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy
Yusuke Inoue, Naoki Inui
Internal Medicine.2026; 65(1): 71. CrossRef
Impact of immune-related adverse events on treatment outcomes in advanced esophageal squamous cell carcinoma treated with immune checkpoint inhibitors
Tianhang Zhang, Xiao Chen, Jianhua Wu, Jiasong Li, Zhukun Qin, Ruijie Cao, Wei Guo, Zhanjun Guo, Haiyan Fan
Frontiers in Immunology.2026;[Epub] CrossRef
Immune-Related Thyroid Dysfunction in PD-L1 High Non-Oncogene-Addicted NSCLC Treated with First-Line Pembrolizumab: Incidence, Timing, and Predictive Impact
Filip Marković, Mihailo Stjepanović, Milica Kontić
Current Oncology.2026; 33(2): 109. CrossRef
Association of Immune‐Related Adverse Events and the Efficacy of Immune Checkpoint Inhibitors in Non‐Small Cell Lung Cancer: Adjusting for Immortal Time Bias
Yoshiki Kuwabara, Hiroyuki Ohya, Maiko Osawa, Kota Shiraishi, Itsuka Matsumoto, Shigeru Ishii, Shin Yokosuka, Masatoshi Abe, Tomoyuki Takahashi, Yuichiro Kawano, Hiroaki Nishimura, Maiko Toda‐Sasaki, Yumiko Kobayashi‐Ogawa, Satoshi Kikuchi, Yusuke Hirata,
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Yuan-Tsung Tseng, Chang-Sung Tsai, Mita Restinia, Chih-Wei Tseng, Ting-Yu Chen, Chung-Yi Li
Diabetes Research and Clinical Practice.2026; 236: 113236. CrossRef
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Hideyuki Katsura, Yukio Suga, Shinji Kimoto, Reiko Ando Makihara, Hiroshi Ota, Hitomi Toi, Naoko Takata, Hiroaki Ikesue
International Journal of Clinical Oncology.2026;[Epub] CrossRef
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Shintaro Iwama, Tomoko Kobayashi, Hiroshi Arima
Nature Reviews Endocrinology.2025; 21(5): 289. CrossRef
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Yanyan Zhu, Daxia Cai, Jiangle Jiang, Jianfei Tu, Zhifeng Tian, Xiayan Zhang, Songmei Luo, Yonghui Wang
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Kaori Matsumoto, Tatsuo Kanda, Junichiro Wakatsuki, Young-Jin Kim, Ritsuko Yokouchi, Naho Sato, Yuko Hasegawa, Kenji Amemiya, Yosuke Hirotsu, Sumio Hirose, Yushi Imai, Shinya Takaoka, Hiroyuki Amano, Yukiko Asakawa, Kouwa Nagasaka, Yoshiki Asahina, Yuichi
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Bicheng Zhang, Yuxiao Song, Qian Min, Weiting Cheng, Jun Wang, Yang Fu, Jiaxin Yin
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Min Xiao, Lan Qian, Qiu Zhao, Jian Ma, Qianxiao Li, Qian Liu, Zhiyan Bi
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Yun Xu, Baoliang Zhong, Chunlin Yu, Qingjian Hou, Wenying Chen, Wen Zheng, Wenxiong Zhang, Tonggang Zhou
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Mengying Qian, Ping Ma, Yu Zhao, Hao Jiang, LiYang Gao, Gaoyang Lin, Difan Duan, Jinmin Guo
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Frontiers in Immunology.2024;[Epub] CrossRef

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Intrathoracic Progression Is Still the Most Dominant Failure Pattern after First-Line Chemo-immunotherapy in Extensive-Stage Small-Cell Lung Cancer: Implications for Thoracic Radiotherapy: Dowook Kim, Hak Jae Kim, Hong-Gyun Wu, Joo Ho Lee, Suzy Kim, Tae Min Kim, Jin-Soo Kim, Byoung Hyuck Kim; Cancer Res Treat. 2024;56(2):430-441. Published online November 6, 2023; DOI: https://doi.org/10.4143/crt.2023.931

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment.
Materials and Methods
We retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group.
Results
The median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively).
Conclusion
In ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control.

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Consolidative thoracic radiotherapy in the immunotherapy era for extensive-stage small cell lung cancer: a systematic review and meta-analysis with emphasis on brain and liver metastases
Dominik Wróbel, Bartosz Wojewoda, Wiktoria Ziółek, Paweł Michał Potocki, Jędrzej Borowczak
Radiotherapy and Oncology.2026; 216: 111328. CrossRef
Efficacy and safety of early radiotherapy combined with first-line chemo-immunotherapy in extensive-stage small-cell lung cancer: a multi-center analysis
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Hao Zhou, Huan Zhao, Shuming Shi, Tao Hu, Li Li, Shuai Wang, Zhe Zhang, Shuanghu Yuan
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Combining Immunotherapy with Anlotinib in Extensive-Stage Small Cell Lung Cancer: A Multicenter Analysis of Efficacy and Safety
Guogang Gao, Meiling Sun, Zhongfei Yang, Jingyi Li, Huaijun Ji, Ge Yu
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Efficacy and safety of first-line chemotherapy combined with immune checkpoint inhibitors for extensive-stage small cell lung cancer patients: a real-world propensity score matching study
Bin Jia, Chenyi Zhou, Fei Zhao, Xiaoru Song, Yuan Ding, Xiyin Wang, Boying Wu, Huina Wang, Quanman Hu, Shuaiyin Chen
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Meta‑analysis of the efficacy and safety of thoracic radiotherapy for extensive‑stage small cell lung cancer in the era of immunotherapy
Meiqiao Jiang, Lihua Shao, Yuanzhaoyun Long, Jinning Sun, Shihong Wei
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Meiling Sun, Huaijun Ji, Fang Deng, Jingyi Li, Ning Xu, Yu Li
BMC Cancer.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

Abstract PDF Supplementary Material PubReader ePub

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.

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Leucyl-tRNA synthetase promotes malignant progression in diffuse large B-cell lymphoma by regulating glycolysis via the LRPPRC/HIF-1α/HK2 axis
Weiming Zhang, Nasha Yu, Xiangxiang Song, Xing Zhong
Human Cell.2025;[Epub] CrossRef
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

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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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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MLL4 Regulates the Progression of Non–Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis: Yang Yang, Rongfang Qiu, Qiaoyou Weng, Ziwei Xu, Jingjing Song, Siyu Zhao, Miaomiao Meng, Dengke Zhang, Chunli Kong, Hailin Wang, Min Xu, Zhongwei Zhao, Jiansong Ji; Cancer Res Treat. 2023;55(3):778-803. Published online January 26, 2023; DOI: https://doi.org/10.4143/crt.2022.1042

Abstract PDF Supplementary Material PubReader ePub

Purpose
Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis.
Materials and Methods
RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis.
Results
We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties.
Conclusion
Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

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KMT2D Induces M1 Macrophage Polarization to Repress Non-small Cell Lung Cancer Progression via Transcription Activation of ITGAL
Wen-Tao Wang, Jie Yang, Peng-Fei Jiang
Iranian Journal of Pharmaceutical Research.2025;[Epub] CrossRef
A positive feedback loop of OTUD1 and c-Jun driven by leptin expedites stemness maintenance in ovarian cancer
Jingtao Wang, Fan Yang, Yurou Chen, Yuzhu Xing, Juyuan Huang, Jing Cao, Jiaqiang Xiong, Yanyan Liu, Qiuyan Zhao, Manwen Luo, Jie Xiong, Guanlan Fan, Qiongying Lyu, Feng Li, Wei Zhang
Oncogene.2025; 44(22): 1731. CrossRef
TENT5/FAM46: An Enigmatic Family of Secretory Tuners
Daniel Lacidogna, Sara Pennacchio, Enrico Milan
Traffic.2025;[Epub] CrossRef
In Silico Analysis of Post-COVID-19 Condition (PCC) Associated SNP rs9367106 Predicts the Molecular Basis of Abnormalities in the Lungs and Brain Functions
Amit K. Maiti
International Journal of Molecular Sciences.2025; 26(14): 6680. CrossRef
The MLL4: Roles in cell differentiation, adipogenesis and cancer
Yu Zhang, Kaili Lv, Xubin Ma, Liang Wang, Yichao Xu
Biochemical Pharmacology.2025; 242: 117371. CrossRef
Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer
Linxiang Zhang, Xueying Zhang, Yan Shi, Yuhan Ni, Jiaojiao Fei, Zhixin Jin, Wenjuan Li, Xiaojing Wang, Nan Wu
Frontiers in Oncology.2024;[Epub] CrossRef
The multifaceted role of SOX2 in breast and lung cancer dynamics
Kiavash Hushmandi, Seyed Hassan Saadat, Seyedalireza Mirilavasani, Salman Daneshi, Amir Reza Aref, Noushin Nabavi, Rasoul Raesi, Afshin Taheriazam, Mehrdad Hashemi
Pathology - Research and Practice.2024; 260: 155386. CrossRef
PIK3IP1: structure, aberration, function, and regulation in diseases
Yingjie Jia, Pengxing He, Xubin Ma, Kaili Lv, Ying Liu, Yichao Xu
European Journal of Pharmacology.2024; 977: 176753. CrossRef
UBQLN4 promotes the proliferation and invasion of non-small cell lung cancer cell by regulating PI3K/AKT pathway
Li He, Heng Chen, Bin Ruan, Li He, Ming Luo, Yulun Fu, Rui Zou
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Role of histone methyltransferase KMT2D in BMSC osteogenesis via AKT signaling
Zhichun Zhang, Yanyan Guo, Xuejun Gao, Xiaoyan Wang, Chanyuan Jin
Regenerative Therapy.2024; 26: 775. CrossRef
Landscape of targeted therapies for lung squamous cell carcinoma
Qiuxuan Chen, Xiaoshuo Zheng, Weiting Cheng, Jian Li
Frontiers in Oncology.2024;[Epub] 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

Abstract PDF Supplementary Material PubReader ePub

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.

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To ablate or not to ablate? Outcomes of local ablative treatments (LAT) for oncogene addicted (OA) oligo-metastatic (OM) non-small cell lung cancer (NSCLC): A systematic review
Fabrizio Citarella, Cristina Fragale, Matteo Fiorenti, Maria Luisa Di Guglielmo, Noemi Mindicini, Alessio Cortellini, Alessandro Russo, Giuseppe Bronte
Critical Reviews in Oncology/Hematology.2026; 218: 105096. CrossRef
Frequency and Prognostic Impact of Local Ablation Therapy for Oligoprogression in Non‐Small Cell Lung Cancer
Daisuke Morinaga, Jun Sakakibara‐Konishi, Ryohei Kamada, Masahiro Kashima, Kosuke Tsuji, Shotaro Ito, Megumi Furuta, Tetsuaki Shoji, Yuta Takashima, Hidenori Kitai, Yasuyuki Ikezawa, Hiroshi Taguchi, Tatsuya Kato, Yoshiki Shinomiya, Kanako C Hatanaka, Yut
Thoracic Cancer.2025;[Epub] CrossRef
Insights on Oligometastatic Non-Small-Cell Lung Cancer
Augusto Valdivia, Pau Mascaro-Baselga, Clara Salva-de Torres, Abraham Geng-Cahuayme, Sara Torresan, Jesus Yaringaño, Ilaria Priano, Patricia Iranzo, Nuria Pardo, Laura Masfarre, Oriol Mirallas, Karen Farfan, Susana Cedres, Pedro Rocha, Alex Martinez-Marti
Cancers.2025; 17(15): 2451. CrossRef
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

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The Role of Brain Radiotherapy before First-Line Afatinib Therapy, Compared to Gefitinib or Erlotinib, in Patients with EGFR-Mutant Non–Small Cell Lung Cancer: Hyun Ae Jung, Sehhoon Park, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun; Cancer Res Treat. 2023;55(2):479-487. Published online December 27, 2022; DOI: https://doi.org/10.4143/crt.2022.1344

Abstract PDF Supplementary Material PubReader ePub

Purpose
Brain metastasis is common in patients with epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer (NSCLC) at initial presentation. A previous study showed that brain radiotherapy (RT) before first-generation (first-G) EGFR–tyrosine kinase inhibitor (TKI) therapy is associated with longer overall survival than TKI therapy alone. However, there is no data regarding the role of additional brain RT before afatinib therapy.
Materials and Methods
Between October 2014 and June 2019, EGFR-mutant NSCLC patients with brain metastases who started first-G EGFR-TKIs (gefitinib or erlotinib) or afatinib as first-line therapy were retrospectively analyzed. This study compared overall survival and intracranial progression-free survival (PFS) between patients who received EGFR-TKIs alone and EGFR-TKIs with brain RT and either a first-G EGFR-TKI or afatinib, respectively.
Results
The median follow-up duration was 29.6 months (range, 1.5 to 116.9 months). In the first-G EGFR-TKI group (n=155), 94 patients (60.6%) received the first-G EGFR-TKI alone and 61 patients (39.4%) received brain RT prior to their first-G EGFR-TKI. In the afatinib group (n=204), 126 patients (61.8%) received afatinib alone and 78 patients (38.2%) received brain RT prior to afatinib. There was no difference in overall survival rates between the groups with RT (35.6 months: 95% confidence interval [CI], 27.9 to 43.3) and without RT (31.4 months: 95% CI, 23.9 to 38.9) in the afatinib group (p=0.58), but there was a significant difference in overall survival in the first-G EGFR-TKI group in a manner favoring additional brain RT (41.1 months: 95% CI, 30.5 to 51.7 vs. 25.8 months: 95% CI, 20.1 to 31.5; p=0.02). Meanwhile, median intracranial PFS was not different between patients who received EGFR-TKI therapy alone vs. EGFR-TKI therapy with brain RT in both the first-G EGFR-TKI (p=0.39) and afatinib (p=0.24) groups.
Conclusion
Afatinib therapy alone showed comparable survival outcomes to those of afatinib with brain RT. The current study suggests that brain RT could be an optional, not mandatory, treatment modality when afatinib therapy is considered in patients with EGFR-mutant NSCLC.

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Lile Xiong, Xiufen Yang, Hua Yuan, Lan Qin, Binghu Lin, Fengjiao Chen, Yi Wen
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Dacomitinib in EGFR-mutant non-small-cell lung cancer with brain metastasis: a single-arm, phase II study
H.A. Jung, S. Park, S.-H. Lee, J.S. Ahn, M.-J. Ahn, J.-M. Sun
ESMO Open.2023; 8(6): 102068. CrossRef
Recent advances progress of targeted drugs combined with radiotherapy for advanced non-small cell lung cancer: a review
Jiamin Xu, Zhongming Wang
Frontiers in Oncology.2023;[Epub] CrossRef

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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

Abstract PDF Supplementary Material PubReader ePub

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.

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Young Saing Kim, Eun Young Lee, Hyun Woo Lee, Jin-Hyuk Choi, Tae-Hwan Kim, Yong Won Choi, Mi Sun Ahn
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Nensi Lalic, Daliborka Bursac, Marko Bojovic, Marko Nemet, Ivan Ergelasev
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Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
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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
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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
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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

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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

Abstract PDF Supplementary Material PubReader ePub

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.

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Immune checkpoint inhibitor-related efficacy in non-small cell lung cancer: real-world incidence and management practices of 208 patients
Yufang Lu, Pengcheng Liu, Changxiu Ma, Hui Liu, Ying Zhang, Dahai Zhao
BMC Cancer.2026;[Epub] CrossRef
Immunotherapy in liver metastases: Challenges, emerging evidence, and future directions
Hoang Tran Pham, Zhong-Yi Dong, Margarita De Alba, Chasen Cottle, Ming-Yi Zhang, Joseph B Parker, Renee Morecroft-Phillipps, Keyur Chaludiya, Demarcus Ingram, Ayesha N Ahmad, Zhen Zeng, Michael M Mohseni, Zi-Zhen Zhang, Libardo Rueda Prada, Muhammad Ali,
World Journal of Clinical Oncology.2026;[Epub] CrossRef
The Mechanism of Lactic Acid Regulating Platelet-Derived Microparticles to Affect the Biological Characteristics of Human Lung Adenocarcinoma
红艳刘
Advances in Clinical Medicine.2025; 15(01): 274. CrossRef
The efficacy and safety of immune combination therapy in patients with driver gene-negative non-small cell lung cancer with liver metastasis: a systematic review and network meta-analysis
Weixing Zhao, Bo Li, Yujia Gu, Xiaoni Jin, Zirui Li, Wanjing Guo, Xinxin Lu, Jun Jiang
BMC Cancer.2025;[Epub] CrossRef
VEGF-A splicing variant in plasma is a predictive potential biomarker of bevacizumab in advanced non-squamous non-small cell lung cancer
Akira Matsui, Masahiro Morise, Ryosuke Kikuchi, Fumie Kinoshita, Atsuo Suzuki, Ichidai Tanaka, Makoto Ishii, Shingo Matsumoto, Koichi Goto
Journal of Chemotherapy.2025; : 1. CrossRef
Retinal Sensitivity Loss and Beyond in KCNV2-Related Retinopathy: The First Genetically Confirmed Case in Türkiye
Özlem Ural Fatihoğlu, Ayşe Bozkurt Oflaz, Özlem Özkan, Hande Taylan Şekeroğlu, Ali Osman Saatçi
Turkish Journal of Ophthalmology.2025; 55(6): 352. CrossRef
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

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The Feasibility of Using Biomarkers Derived from Circulating Tumor DNA Sequencing as Predictive Classifiers in Patients with Small-Cell Lung Cancer: Yu Feng, Yutao Liu, Mingming Yuan, Guilan Dong, Hongxia Zhang, Tongmei Zhang, Lianpeng Chang, Xuefeng Xia, Lifeng Li, Haohua Zhu, Puyuan Xing, Hongyu Wang, Yuankai Shi, Zhijie Wang, Xingsheng Hu; Cancer Res Treat. 2022;54(3):753-766. Published online October 5, 2021; DOI: https://doi.org/10.4143/crt.2021.905

Abstract PDF Supplementary Material PubReader ePub

Purpose
To investigate the feasibility of biomarkers based on dynamic circulating tumor DNA (ctDNA) to classify small cell lung cancer (SCLC) into different subtypes.
Materials and Methods
Tumor and longitudinal plasma ctDNA samples were analyzed by next-generation sequencing of 1,021 genes. PyClone was used to infer the molecular tumor burden index (mTBI). Pre-treatment tumor tissues [T1] and serial plasma samples were collected (pre-treatment [B1], after two [B2], six [B3] cycles of chemotherapy and at progression [B4]).
Results
Overall concordance between T1 and B1 sequencing (n=30) was 66.5%, and 89.5% in the gene of RB1. A classification method was designed according to the changes of RB1 mutation, named as subtype Ⅰ (both positive at B1 and B2), subtype Ⅱ (positive at B1 but negative at B2), and subtype Ⅲ (both negative at B1 and B2). The median progressive-free survival for subtype Ⅰ patients (4.5 months [95%CI: 2.6-5.8]) was inferior to subtype Ⅱ (not reached, p<0.0001) and subtype Ⅲ (10.8 months [95%CI: 6.0-14.4], p=0.002). The median overall survival for subtype Ⅰ patients (16.3 months [95%CI: 5.3-22.9]) was inferior to subtype Ⅱ (not reached, p=0.01) and subtype Ⅲ (not reached, p=0.02). Patients with a mTBI dropped to zero at B2 had longer median overall survival (not reached vs. 19.5 months, p=0.01). The changes of mTBI from B4 to B1 were sensitive to predict new metastases, with a sensitivity of 100% and a specificity of 85.7%.
Conclusion
Monitoring ctDNA based RB1 mutation and mTBI provided a feasible tool to predict the prognosis of SCLC.

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Cell-free and extrachromosomal DNA profiling of small cell lung cancer
Roya Behrouzi, Alexandra Clipson, Kathryn L. Simpson, Fiona Blackhall, Dominic G. Rothwell, Caroline Dive, Florent Mouliere
Trends in Molecular Medicine.2025; 31(1): 64. CrossRef
New insight in early detection and precision medicine in small cell lung cancer: liquid biopsy as innovative clinical tool
Sara Santamaria, Barbara Cardinali, Matteo Rovere, Silvia Marconi, Simone Nardin, Gianluca Sacco, Lucrezia Barcellini, Lucia Del Mastro, Carlo Genova, Simona Coco
Critical Reviews in Clinical Laboratory Sciences.2025; 62(6): 404. CrossRef
Liquid biopsy in diagnosis and monitoring of treatment efficacy in patients with small cell lung cancer
Natalia Galant, Anna Grenda, Paweł Krawczyk, Mateusz Pięt, Janusz Milanowski
Molecular Biology Reports.2025;[Epub] CrossRef
Intercalated Avelumab plus platinum-based chemotherapy in patients with Extensive-Stage Small-Cell Lung cancer (PAVE): Final outcome, immunophenotypic and biomarker analysis of a multi-center phase II Hellenic Cooperative Oncology Group study
Helena Linardou, Kyriaki Papadopoulou, Nikolaos Korfiatis, Anna Goussia, Epaminondas Samantas, Gerasimos Aravantinos, Athina Christopoulou, Nikolaos Spathas, Elena Fountzilas, Amanda Psyrri, Georgia-Angeliki Koliou, Soultana Meditskou, Epaminondas Kosmas,
European Journal of Cancer.2025; 228: 115660. CrossRef
State of the art in treatment of small cell lung cancer
Roya Behrouzi, Fiona Blackhall
Therapeutic Advances in Medical Oncology.2025;[Epub] CrossRef
Circulating tumor DNA as liquid biopsy in lung cancer: Biological characteristics and clinical integration
Changshu Li, Jun Shao, Peiyi Li, Jiaming Feng, Jingwei Li, Chengdi Wang
Cancer Letters.2023; 577: 216365. CrossRef
Prognostic and predictive impact of molecular tumor burden index in non‐small cell lung cancer patients
Fan Yang, Min Tang, Liang Cui, Jing Bai, Jiangyong Yu, Jiayi Gao, Xin Nie, Xu Li, Xuefeng Xia, Xin Yi, Ping Zhang, Lin Li
Thoracic Cancer.2023; 14(31): 3097. CrossRef
Genomic and Gene Expression Studies Helped to Define the Heterogeneity of Small-Cell Lung Cancer and Other Lung Neuroendocrine Tumors and to Identify New Therapeutic Targets
Ugo Testa, Elvira Pelosi, Germana Castelli
Onco.2022; 2(3): 186. CrossRef

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Comparison of the Predictive Power of a Combination versus Individual Biomarker Testing in Non–Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Hyojin Kim, Hyun Jung Kwon, Eun Sun Kim, Soohyeon Kwon, Kyoung Jin Suh, Se Hyun Kim, Yu Jung Kim, Jong Seok Lee, Jin-Haeng Chung; Cancer Res Treat. 2022;54(2):424-433. Published online July 7, 2021; DOI: https://doi.org/10.4143/crt.2021.583

Abstract PDF Supplementary Material PubReader ePub

Purpose
Since tumor mutational burden (TMB) and gene expression profiling (GEP) have complementary effects, they may have improved predictive power when used in combination. Here, we investigated the ability of TMB and GEP to predict the immunotherapy response in patients with non–small cell lung cancer (NSCLC) and assessed if this combination can improve predictive power compared to that when used individually.
Materials and Methods
This retrospective cohort study included 30 patients with NSCLC who received immune checkpoint inhibitors (ICI) therapy at the Seoul National University Bundang Hospital. programmed cell death-ligand-1 (PD-L1) protein expression was assessed using immunohistochemistry, and TMB was measured by targeted deep sequencing. Gene expression was determined using NanoString nCounter analysis for the PanCancer IO360 panel, and enrichment analysis were performed.
Results
Eleven patients (36.7%) showed a durable clinical benefit (DCB), whereas 19 (63.3%) showed no durable benefit (NDB). TMB and enrichment scores (ES) showed significant differences between the DCB and NDB groups (p=0.044 and p=0.017, respectively); however, no significant correlations were observed among TMB, ES, and PD-L1. ES was the best single biomarker for predicting DCB (area under the curve [AUC], 0.794), followed by TMB (AUC, 0.679) and PD-L1 (AUC, 0.622). TMB and ES showed the highest AUC (0.837) among other combinations (AUC [TMB and PD-L1], 0.777; AUC [PD-L1 and ES], 0.763) and was similar to that of all biomarkers used together (0.832).
Conclusion
The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies.

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Molecular characteristics, clonal relatedness and surgical outcomes of pulmonary mixed invasive mucinous and non-mucinous adenocarcinoma: a retrospective cohort study
Xinyi Shi, Yang Wang, Nan Yao, Bowen Xue, Lei Guo, Liming Xu, Changbin Zhu, Guiping Qin, Jianming Ying, Yutao Liu, Weihua Li
Molecular Biomedicine.2026;[Epub] CrossRef
Microdroplet-enhanced chip platform for high-throughput immunotherapy marker screening from extracellular vesicle RNAs and membrane proteins
Chuanhao Tang, Zaizai Dong, Shi Yan, Bing Liu, Zhiying Wang, Long Cheng, Feng Liu, Hong Sun, Yimeng Du, Lu Pan, Yuhao Zhou, Zhiyuan Jin, Libo Zhao, Nan Wu, Lingqian Chang, Xiaojie Xu
Biosensors and Bioelectronics.2025; 267: 116748. CrossRef
Visualising the Truth: A Composite Evaluation Framework for Score-Based Predictive Model Selection
Uraquitan Lima Filho, Tiago Alexandre Pais, Ricardo Jorge Pais
BioMedInformatics.2025; 5(3): 55. CrossRef
The DDR-immune fitness score: a biomarker for guiding parp and immunotherapy synergy in extensive-stage small cell lung cancer
Yinxu Zhang, Xiaoyang Chen, Dai Wang, Xuan Zhou, Yuxi Wang, Guangyu Zhang, Xiaomei Liu
Frontiers in Oncology.2025;[Epub] CrossRef
Characterization of Ferroptosis-Associated Subtypes in Psoriasis and the Potential of CHAC1 as a Diagnostic Biomarker Based on Machine Learning
Junming Chen, Jiayi Zhan, Ying Zhou
Clinical, Cosmetic and Investigational Dermatology.2025; Volume 18: 3277. CrossRef
Exploring the ferroptosis-related gene lipocalin 2 as a potential biomarker for sepsis-induced acute respiratory distress syndrome based on machine learning
Jiayi Zhan, Junming Chen, Liyan Deng, Yining Lu, Lianxiang Luo
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2024; 1870(4): 167101. CrossRef
Evaluation of Blood Tumor Mutation Burden for the Efficacy of Second-Line Atezolizumab Treatment in Non-Small Cell Lung Cancer: BUDDY Trial
Cheol-Kyu Park, Ha Ra Jun, Hyung-Joo Oh, Ji-Young Lee, Hyun-Ju Cho, Young-Chul Kim, Jeong Eun Lee, Seong Hoon Yoon, Chang Min Choi, Jae Cheol Lee, Sung Yong Lee, Shin Yup Lee, Sung-Min Chun, In-Jae Oh
Cells.2023; 12(9): 1246. CrossRef
Unveiling the role of regulatory T cells in the tumor microenvironment of pancreatic cancer through single-cell transcriptomics and in vitro experiments
Wei Xu, Wenjia Zhang, Dongxu Zhao, Qi Wang, Man Zhang, Qiang Li, Wenxin Zhu, Chunfang Xu
Frontiers in Immunology.2023;[Epub] CrossRef
Facilitating “Omics” for Phenotype Classification Using a User-Friendly AI-Driven Platform: Application in Cancer Prognostics
Uraquitan Lima Filho, Tiago Alexandre Pais, Ricardo Jorge Pais
BioMedInformatics.2023; 3(4): 1071. CrossRef
Current state and challenges of emerging biomarkers for immunotherapy in hepatocellular carcinoma (Review)
Mo Cheng, Xiufeng Zheng, Jing Wei, Ming Liu
Experimental and Therapeutic Medicine.2023;[Epub] CrossRef

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Lung Cancer

Inhibition of lncRNA KCNQ1OT1 Improves Apoptosis and Chemotherapy Drug Response in Small Cell Lung Cancer by TGF-β1 Mediated Epithelial-to-Mesenchymal Transition: Deyu Li, Qin Tong, Yuane Lian, Zhizhong Chen, Yaru Zhu, Weimei Huang, Yang Wen, Qiongyao Wang, Shumei Liang, Man Li, Jianjing Zheng, Zhenhua Liu, Huanxin Liu, Linlang Guo; Cancer Res Treat. 2021;53(4):1042-1056. Published online March 9, 2021; DOI: https://doi.org/10.4143/crt.2020.1208

Abstract PDF Supplementary Material PubReader ePub

Purpose
Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required.
Materials and Methods
In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance.
Results
The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells.
Conclusion
Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

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The regulatory role of the KCNQ1OT1/miR-107 axis in benign airway stenosis: Dual modulation of TGF-β signaling via TGFBR2 and Wnt signaling via Wnt3a in airway granulation tissue
Cheng Xue, Wanyu Wang, Qihong Zhuang, Yihua Lin
International Journal of Biological Macromolecules.2026; 335: 149323. CrossRef
Molecular mechanism of ZC3H13 -mediated ferroptosis in doxorubicin resistance of triple negative breast cancer
Li Huang, Lei Han, Shuai Liang, Guohui Han
Cell Biology and Toxicology.2025;[Epub] CrossRef
Mechanistic insights on the role of competing endogenous RNA regulatory networks (ceRNETs) in small cell lung cancer
Sachin Kumar
Advances in Cancer Biology - Metastasis.2024; 10: 100117. CrossRef
A review on the role of KCNQ1OT1 lncRNA in human disorders
Mohammad Taheri, Zeinab Shirvani-Farsani, Atefeh Harsij, Mohadeseh Fathi, Sheyda Khalilian, Soudeh Ghafouri-Fard, Aria Baniahmad
Pathology - Research and Practice.2024; 255: 155188. CrossRef
Hydroquinidine Demonstrates Remarkable Antineoplastic Effects on Non-small Cell Lung Cancer Cells
Mervenur Yavuz, Turan Demircan
Current Molecular Medicine.2024; 24(9): 1159. CrossRef
Overcoming multi-drug resistance in SCLC: a synergistic approach with venetoclax and hydroxychloroquine targeting the lncRNA LYPLAL1-DT/BCL2/BECN1 pathway
Shuxin Li, Jianyi Lv, Zhihui Li, Qiuyu Zhang, Jing Lu, Xueyun Huo, Meng Guo, Xin Liu, Changlong Li, Jinghui Wang, Hanping Shi, Li Deng, Zhenwen Chen, Xiaoyan Du
Molecular Cancer.2024;[Epub] CrossRef
A review of the complex interplay between chemoresistance and lncRNAs in lung cancer
Ghaliah Obaid Alnefaie
Journal of Translational Medicine.2024;[Epub] CrossRef
Research Progress of Liver Metastasis Mechanisms and Predictive Indicators in Small Cell Lung Cancer
雪任
Journal of Clinical Personalized Medicine.2024; 03(02): 180. CrossRef
Non-coding RNAs in lung cancer: molecular mechanisms and clinical applications
Ying Liu, Wei Ding, Jianxun Wang, Xiang Ao, Junqiang Xue
Frontiers in Oncology.2023;[Epub] CrossRef
Biological role of long non-coding RNA KCNQ1OT1 in cancer progression
Kai Zhan, Huafeng Pan, Zhang Zhou, Wenqian Tang, Zhining Ye, Shaogang Huang, Lei Luo
Biomedicine & Pharmacotherapy.2023; 169: 115876. CrossRef
Non-coding genome in small cell lung cancer between theoretical view and clinical applications
Xiaomeng Yin, Jiqiao Yang, Hang Wang, Yuling Luo, Zeyi Qin, Lei Deng, Xuelei Ma
Seminars in Cancer Biology.2022; 86: 237. CrossRef
KCNQ1OT1: An Oncogenic Long Noncoding RNA
Patrice Cagle, Qi Qi, Suryakant Niture, Deepak Kumar
Biomolecules.2021; 11(11): 1602. CrossRef

9,524 View
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Lung cancer

Phase II Study of Pemetrexed as a Salvage Chemotherapy for Thymidylate Synthase–Low Squamous Cell Lung Cancer: Mihong Choi, Heung Tae Kim, Ji-Youn Han, Geon Kook Lee, Soo-Hyun Lee, Kun Young Lim, Jungnam Joo, Hye Jin Won, Jin Soo Lee, Youngjoo Lee; Cancer Res Treat. 2021;53(1):87-92. Published online August 13, 2020; DOI: https://doi.org/10.4143/crt.2020.741

Abstract PDF Supplementary Material PubReader ePub

Purpose
Squamous cell carcinomas (SqCC) of the lung often express high levels of thymidylate synthase (TS), which is associated with primary resistance to pemetrexed. We explored the efficacy of pemetrexed in a selected population of patients with lung SqCC with low TS expression.
Materials and Methods
In this single-arm phase II trial, we enrolled 32 previously-treated patients with advanced lung SqCC exhibiting low immunohistochemical staining for TS (i.e., in 10% or less of tumor cells). The primary endpoint was 12-week progression-free survival (PFS) rate.
Results
Of 32 patients, eight patients (25%) had an Eastern Cooperative Oncology Group performance status of 2, and seven patients (22%) had previously received three or more lines of chemotherapy. The disease control rate from pemetrexed treatment was 30%, and no objective response was observed. The 12-week PFS rate was 24.5% (95% confidence interval [CI], 13.0 to 46.1). Median PFS was 1.3 months (95% CI, 1.3 to 2.7), and median overall survival was 11.8 months (95% CI, 8.1 to not applicable). Most of adverse events were grade 1 or 2.
Conclusion
Pemetrexed demonstrated modest activity as a salvage chemotherapy in patients with advanced lung SqCC with low TS expression, although its toxicity was generally manageable.

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Bioengineered miR-7-5p modulates non–small cell lung cancer cell metabolism to improve therapy
Gavin M. Traber, Mei-Juan Tu, Su Guan, Neelu Batra, Ai-Ming Yu
Molecular Pharmacology.2025; 107(1): 100006. CrossRef

9,241 View
132 Download
1 Crossref

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

Abstract PDF PubReader ePub

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.

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Structural Studies of Fourth-Generation EGFR Inhibitors Reveal Insights into Selective T790M and C797S Targeting
Tahereh Damghani, Shenghan Song, Kaly S. Lin, Jianing Li, David E. Heppner
ACS Medicinal Chemistry Letters.2026; 17(2): 531. CrossRef
Emerging Anti-Cancer and Repurposed Therapies for Overcoming Multidrug Resistance in Lung Cancer
Nilay Solanki, Pratham Shah, Sargam Kewalramani, Umang Shah, Mehul Patel, Swayamprakash Patel, Rajesh Maheshwari
Medical Oncology.2025;[Epub] CrossRef
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
Yu Zhang, Chengmeng Wang, Jing Zhao, Meng Wang
Thoracic Cancer.2024; 15(23): 1757. CrossRef
Successful treatment of a patient with advanced lung adenocarcinoma (EGFR-T790M and C797S cis) with lazertinib: A case report and literature review
Yue Fang, Qiankun Zhang, Weimin Wang, Juanjuan Tong, Xialin Li
Frontiers in Oncology.2023;[Epub] CrossRef
A Review on Fused Pyrimidine Systems as EGFR Inhibitors and Their Structure–Activity Relationship
Tanuja T. Yadav, Gulam Moin Shaikh, Maushmi S. Kumar, Meena Chintamaneni, Mayur YC
Frontiers in Chemistry.2022;[Epub] CrossRef
Structural Basis for Inhibition of Mutant EGFR with Lazertinib (YH25448)
David E. Heppner, Florian Wittlinger, Tyler S. Beyett, Tatiana Shaurova, Daniel A. Urul, Brian Buckley, Calvin D. Pham, Ilse K. Schaeffner, Bo Yang, Blessing C. Ogboo, Earl W. May, Erik M. Schaefer, Michael J. Eck, Stefan A. Laufer, Pamela A. Hershberger
ACS Medicinal Chemistry Letters.2022; 13(12): 1856. CrossRef
Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer
Kyu Sic You, Yong Weon Yi, Jeonghee Cho, Jeong-Soo Park, Yeon-Sun Seong
Pharmaceuticals.2021; 14(6): 589. CrossRef
Paired analysis of tumor mutation burden calculated by targeted deep sequencing panel and whole exome sequencing in non-small cell lung cancer
Sehhoon Park, Chung Lee, Bo Mi Ku, Minjae Kim, Woong-Yang Park, Nayoung K. D. Kim, Myung-Ju Ahn
BMB Reports.2021; 54(7): 386. CrossRef

10,978 View
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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

Abstract PDF Supplementary Material PubReader ePub

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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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

Abstract PDF Supplementary Material PubReader ePub

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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XiangBin Xin, Jing Zhang, YanQin Du, XiaoTing Jang, XinYi Tian, Fu Ma, Fang Chen
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Molecules.2023; 28(15): 5746. CrossRef
Sericin enhances ammonia detoxification by promotes urea cycle enzyme genes and activates hepatic autophagy in relation to CARD-9/MAPK pathway
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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

Abstract PDF Supplementary Material PubReader ePub

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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Targeting the Tumor Microenvironment in EGFR-Mutant Lung Cancer: Opportunities and Challenges
Jeong Uk Lim, Junyang Jung, Yeon Wook Kim, Chi Young Kim, Sang Hoon Lee, Dong Won Park, Sue In Choi, Wonjun Ji, Chang Dong Yeo, Seung Hyeun Lee
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Targeted Therapies in Non–Small Cell Lung Cancer
Ahmed Abdelmonem, Bidhan Bikram Shah, Mouza Al Shebli, Imad A. Tabbara
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Clinicopathologic and Molecular Characteristics of HER2 (ERBB2)-Altered Non–Small Cell Lung Cancer: Implications for Precision Medicine
Yurimi Lee, Boram Lee, Yoon-La Choi, Dong-Wook Kang, Joungho Han
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The frequency of EGFR gene mutations in a cohort of Romanian patients with non-small cell lung cancer and their association with PD-L1 expression level and ALK rearrangements
Ester-Andreea Cohn, Ortansa Csutak, Ecaterina Tataru
Revista Romana de Medicina de Laborator.2024; 32(3): 237. CrossRef
Antibody–Drug Conjugates for the Treatment of Non-Small Cell Lung Cancer with Central Nervous System Metastases
David J. H. Bian, Sara F. Cohen, Anna-Maria Lazaratos, Nathaniel Bouganim, Matthew Dankner
Current Oncology.2024; 31(10): 6314. CrossRef
ERBB2 mutation landscape in non-small cell lung cancer patients in Northeast China
Hui Li, Xiang Li, Shaowei Lan, Xuerong Zuo, Tianying Du, Ying Liu, Caixia Zhang, Jing Zhu, Ying Cheng
Tumori Journal.2023; 109(3): 276. CrossRef
Clinical characteristics and prognostic factors of patients with non-small cell lung cancer having HER2 alterations
Xiaoli Zhuo, Honglin Guo, Jun Ma, Jingjiang Lai, Lei Liu, Ke Yin, Jing Zhao, Jingliang Wang, Fengxian Jiang, Wei Xu, Xiaotian Yuan, Xiaoyan Lin, Guobin Fu
Journal of Cancer Research and Clinical Oncology.2023; 149(5): 2029. CrossRef
Real World Characteristics and Clinical Outcomes of HER2-Mutant Non–Small Cell Lung Cancer Patients Detected by Next-Generation Sequencing
Beung-Chul Ahn, Ye-Jeong Han, Hye Ryun Kim, Min Hee Hong, Byoung Chul Cho, Sun Min Lim
Cancer Research and Treatment.2023; 55(2): 488. CrossRef
Prevalence and clinicopathological associations of HER2 expression in non-small cell lung cancer: a retrospective study in Jordanian patients
Ola Abu Al Karsaneh, Arwa Al Anber, Mohammad ALQudah, Sahar Al-Mustafa, Hussien AlMa’aitah, Maher Sughayer
Diagnostic Pathology.2023;[Epub] CrossRef
Exploring the correlation between HER2 alterations and 18F-FDG PET/CT metabolic parameters and their prognostic value in EGFR-negative non-small-cell lung cancer patients
Maomei Ruan, Cheng Chang, Jianwen Sun, Liu Liu, Lihua Wang, Bei Lei, Hui Yan, He Zhang, Wenhui Xie, Yuetao Wang
Journal of Cancer Research and Clinical Oncology.2023; 149(16): 14493. CrossRef
Pyrotinib in Patients with HER2-Amplified Advanced Non–Small Cell Lung Cancer: A Prospective, Multicenter, Single-Arm Trial
Zhengbo Song, Dongqing Lv, Shi-Qing Chen, Jianjin Huang, Yuping Li, Shenpeng Ying, Xiaoyu Wu, Feng Hua, Wenxian Wang, Chunwei Xu, Ting Bei, Chan Gao, Zhijian Sun, Yiping Zhang, Shun Lu
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Consensus for HER2 alterations testing in non-small-cell lung cancer
S. Ren, J. Wang, J. Ying, T. Mitsudomi, D.H. Lee, Z. Wang, Q. Chu, P.C. Mack, Y. Cheng, J. Duan, Y. Fan, B. Han, Z. Hui, A. Liu, J. Liu, Y. Lu, Z. Ma, M. Shi, Y. Shu, Q. Song, X. Song, Y. Song, C. Wang, X. Wang, Z. Wang, Y. Xu, Y. Yao, L. Zhang, M. Zhao,
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Deciphering the Impact of HER2 Alterations on Non-Small-Cell Lung Cancer: From Biological Mechanisms to Therapeutic Approaches
Christophe Bontoux, Jonathan Benzaquen, Véronique Hofman, Simon Heeke, Paul Hannetel, Pierre Capela-Brosseau-Laborde, Charles-Hugo Marquette, Marius Ilié, Paul Hofman
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Meagan Miller, Nasser Hanna
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Katarzyna Wadowska, Iwona Bil-Lula, Łukasz Trembecki, Mariola Śliwińska-Mossoń
International Journal of Molecular Sciences.2020; 21(13): 4569. CrossRef
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Hao Wang, Zhihong Zhang, Ke Xu, Song Wei, Lailing Li, Lijun Wang
Oncology Letters.2019;[Epub] CrossRef

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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

Abstract PDF PubReader ePub

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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G.Le Quellenec, T. Perennec, L. Ollivier, A.Dal Pra, A. Berlin, J. Martin, J. Thariat, S. Supiot
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Chloe Brooks, Elizabeth Miles, Peter J Hoskin
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Durvalumab with chemoradiotherapy for limited-stage small-cell lung cancer
Sehhoon Park, Jae Myoung Noh, Yoon-La Choi, Sang Ah Chi, Kyunga Kim, Hyun Ae Jung, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun
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Zoé Schmal, Claudia E. Rübe
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Non–coplanar whole brain radiotherapy is an effective modality for parotid sparing
Jaehyeon Park, Jae Won Park, Ji Woon Yea
Yeungnam University Journal of Medicine.2019; 36(1): 36. CrossRef

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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

Abstract PDF Supplementary Material PubReader ePub

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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Jose Luis Leal, Marliese Alexander, Malinda Itchins, Gavin M. Wright, Steven Kao, Brett G.M. Hughes, Nick Pavlakis, Stephen Clarke, Anthony J Gill, Hannah Ainsworth, Benjamin Solomon, Thomas John
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Caicun Zhou, Suresh S. Ramalingam, Tae Min Kim, Sang-We Kim, James Chih-Hsin Yang, Gregory J. Riely, Tarek Mekhail, Danny Nguyen, Maria R. Garcia Campelo, Enriqueta Felip, Sylvie Vincent, Shu Jin, Celina Griffin, Veronica Bunn, Jianchang Lin, Huamao M. Li
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Pathology & Oncology Research.2020; 26(3): 1595. CrossRef
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Lung Cancer.2020; 145: 186. CrossRef
Variability of EGFR exon 20 insertions in 24 468 Chinese lung cancer patients and their divergent responses to EGFR inhibitors
YanRu Qin, Hong Jian, Xiaoling Tong, Xue Wu, Fufeng Wang, Yang W. Shao, Xinmin Zhao
Molecular Oncology.2020; 14(8): 1695. CrossRef
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Lung Cancer.2020; 149: 53. CrossRef
Effectiveness of Treatments for Advanced Non–Small-Cell Lung Cancer With Exon 20 Insertion Epidermal Growth Factor Receptor Mutations
Jenn-Yu Wu, Chong-Jen Yu, Jin-Yuan Shih
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J. Chantharasamee, N. Poungvarin, P. Danchaivijitr, S. Techawatanawanna
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Ya Gao, Wies R. Vallentgoed, Pim J. French
Cancers.2018; 10(12): 489. CrossRef

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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

Abstract PDF PubReader ePub

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.

Citations

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Unresectable stage III non-small-cell lung cancer: state of the art and challenges
Jordi Remon, Antonin Levy, Romane Gille, Isabelle Martel-Lafay, Martina Bortolot, Lizza E. L. Hendriks, Corinne Faivre-Finn, Natasha Leighl, Martin Reck, Maurice Pérol
Nature Reviews Clinical Oncology.2026; 23(1): 22. CrossRef
Patient-reported outcomes from the LAURA study: osimertinib in patients with unresectable stage III EGFR-mutated non-small cell lung cancer after definitive chemoradiotherapy
Edurne Arriola, Ignacio Casarini, Mustafa Özgüroğlu, Meijuan Huang, Toshiaki Takahashi, Xiaojing Lai, Koichi Goto, Kunlatida Maneenil, Ki Hyeong Lee, Manuel Cobo, Natalia Valdiviezo, Azura Evans, Ana Bolanos, Xiangning Huang, Rachel Lai, Suresh S. Ramalin
European Journal of Cancer.2026; 240: 116744. CrossRef
Comparison of treatment regimens for unresectable stage III epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer
Xin Dai, Qian Xu, Lei Sheng, Xue Zhang, Miao Huang, Song Li, Kai Huang, Jiahui Chu, Jian Wang, Jisheng Li, Yanguo Liu, Jianyuan Zhou, Shulun Nie, Lian Liu
Chinese Medical Journal.2025; 138(14): 1687. CrossRef
Economic Burden and Provider Referral Patterns Among Patients with Unresectable Stage III EGFR-Mutated NSCLC Receiving Chemoradiotherapy in the United States
YongJin Kim, Yong Zhu, Kristin J. Moore, Mary DuCharme, Dan James, Arber Shehu, Yanique Rattigan-Brown, Kim Ohaegbulam
Advances in Therapy.2025; 42(7): 3505. CrossRef
Emerging Role of Targeted Therapies Combined With Radiotherapy in Inoperable Stages I to III NSCLC: A Review From the IASLC ART Subcommittee
Sarah Bowen Jones, Clara Chan, Andrea R. Filippi, Ken Harada, Alexander V. Louie, Colin R. Lindsay, Ernest Nadal, Pablo Munoz Schuffenegger, David Woolf, Corinne Faivre-Finn
Journal of Thoracic Oncology.2025; 20(8): 1018. CrossRef
Mutation testing, treatment patterns, and outcomes in patients with unresectable stage III EGFR-mutated non-small cell lung cancer treated with chemoradiotherapy: Final analysis of a global real–world study
Myung-Ju Ahn, Steven H. Lin, Cheng-Ta Yang, Jii Bum Lee, Joel W. Neal, Kyoichi Okishio, Kazumi Nishino, Daniel Smith, Markus Rauter, Maria Jimenez, Feruza Nasirova, YongJin Kim
Lung Cancer.2025; 209: 108748. CrossRef
International cost-effectiveness analysis in osimertinib after chemoradiotherapy in stage III EGFR-mutated non-small cell lung cancer
Diya Tang, Xi Zou, Chaochao Wei, Xiaoyu Zhang
Frontiers in Public Health.2025;[Epub] CrossRef
Progression Free Survival in Lung Cancer Adenocarcinoma Wild Type Patients with Pemetrexed Regimen Combination of Cisplatin compared to Carboplatin
Ungky Agus Setyawan, Catur Purnamawati, Suryanti Pratiwi
Jurnal Klinik dan Riset Kesehatan.2025; 4(2): 87. CrossRef
Osimertinib before and after chemoradiotherapy for unresectable stage III EGFR-mutated NSCLC: NEOLA Trial Protocol
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Future Oncology.2025; 21(29): 3731. CrossRef
Targeted treatment for unresectable EGFR mutation-positive stage III non-small cell lung cancer: Emerging evidence and future perspectives
Terufumi Kato, Ignacio Casarini, Manuel Cobo, Corinne Faivre-Finn, Fiona Hegi-Johnson, Shun Lu, Mustafa Özgüroğlu, Suresh S. Ramalingam
Lung Cancer.2024; 187: 107414. CrossRef
Treatment patterns and survival analysis in patients with unresectable stage III EGFR-mutated non-small cell lung cancer
Huan-Wei Liang, Yang Liu, Xin-Bin Pan
Aging.2024;[Epub] CrossRef
Durvalumab after chemoradiotherapy in non‐small cell lung cancer with EGFR mutation: A real‐world study (HOT2101)
Kosuke Tsuji, Hidenori Mizugaki, Keiki Yokoo, Maki Kobayashi, Yosuke Kawashima, Nozomu Kimura, Hiroshi Yokouchi, Hajime Kikuchi, Toshiyuki Sumi, Yasutaka Kawai, Kenta Kobashi, Ryo Morita, Kenichiro Ito, Yasuo Kitamura, Hiroyuki Minemura, Keiichi Nakamura,
Cancer Science.2024; 115(4): 1273. CrossRef
Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study
Amin H. Nassar, So Yeon Kim, Jacqueline V. Aredo, Jamie Feng, Frances Shepherd, Chao Xu, David Kaldas, Jhanelle E. Gray, Thomas J. Dilling, Joel W. Neal, Heather A. Wakelee, Yufei Liu, Steven H. Lin, Tariq Abuali, Arya Amini, Yunan Nie, Tejas Patil, Anast
Journal of Thoracic Oncology.2024; 19(6): 928. CrossRef
Population Survival Kinetics Derived from Clinical Trials of Potentially Curable Lung Cancers
David J. Stewart, Katherine Cole, Dominick Bosse, Stephanie Brule, Dean Fergusson, Tim Ramsay
Current Oncology.2024; 31(3): 1600. CrossRef
Osimertinib after Chemoradiotherapy in Stage III EGFR -Mutated NSCLC
Shun Lu, Terufumi Kato, Xiaorong Dong, Myung-Ju Ahn, Le-Van Quang, Nopadol Soparattanapaisarn, Takako Inoue, Chih-Liang Wang, Meijuan Huang, James Chih-Hsin Yang, Manuel Cobo, Mustafa Özgüroğlu, Ignacio Casarini, Dang-Van Khiem, Virote Sriuranpong, Eduard
New England Journal of Medicine.2024; 391(7): 585. CrossRef
Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study
S. Lu, M.-J. Ahn, T. Reungwetwattana, M. Özgüroğlu, T. Kato, J.C.-H. Yang, M. Huang, F. Fujiki, T. Inoue, L.-V. Quang, V. Sriuranpong, D. Vicente, C. Fuentes, A.A. Chaudhry, L. Poole, E. Armenteros Monterroso, Y. Rukazenkov, T. van der Gronde, S.S. Ramali
Annals of Oncology.2024; 35(12): 1116. CrossRef
Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in patients with recurrent non-small cell lung cancer after definitive concurrent chemoradiation or radiotherapy
Jaewon Hyung, Hyunseok Yoon, Chang-Min Choi, Shinkyo Yoon, Dae Ho Lee, Sang-we Kim, Hyeong-ryul Kim, Su Ssan Kim, Si Yeol Song, Jae Cheol Lee
Journal of Cancer Research and Clinical Oncology.2023; 149(8): 4243. CrossRef
Real-world treatment patterns and clinical outcomes in EGFR-mutant locally advanced lung adenocarcinoma: A multi-center cohort study
Nan Bi, Kunpeng Xu, Hong Ge, Ming Chen, Mingyan E, Li Zhang, Jianzhong Cao, Xu Zhang, Xiao Ding, Bing Xia, Lujun Zhao, Lijie Han, Jiancheng Li, Chen Hu, Luhua Wang
Journal of the National Cancer Center.2023; 3(1): 65. CrossRef
Locally Advanced Lung Cancer
Sarah Oh, George N. Botros, Milan Patel, Missak Haigentz, Eshan Patel, Iaonnis Kontopidis, John Langenfeld, Matthew P. Deek, Salma K. Jabbour
Hematology/Oncology Clinics of North America.2023; 37(3): 533. CrossRef
Osimertinib combined with bevacizumab as the first‐line treatment in non‐small cell lung cancer patients with brain metastasis harboring epidermal growth factor receptor mutations
Ling Zhang, Yunhong You, Xueli Liu, Fengjuan Liu, Keke Nie, Youxin Ji
Thoracic Cancer.2023; 14(15): 1355. CrossRef
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Hongsik Kim, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn
Cancer Research and Treatment.2023; 55(2): 498. CrossRef
Efficacy of first-line tyrosine kinase inhibitor between unresectable stage III and stage IV EGFR-mutated non-small cell lung cancer patients
Yang Liu, Huan-Wei Liang, Xin-Bin Pan
Aging.2023;[Epub] CrossRef
Improved survival in patients with unresectable stage III EGFR‐mutant adenocarcinoma with upfront EGFR‐tyrosine kinase inhibitors
Sheng‐Yuan Wang, Ching‐Han Lai, Chian‐Wei Chen, Szu‐Chun Yang, Chao‐Chun Chang, Chia‐Ying Lin, Yi‐Ting Yen, Yau‐Lin Tseng, Po‐Lan Su, Chien‐Chung Lin, Wu‐Chou Su
Thoracic Cancer.2022; 13(2): 182. CrossRef
Nuclear accumulation of KPNA2 impacts radioresistance through positive regulation of the PLSCR1‐STAT1 loop in lung adenocarcinoma
Wei‐Chao Liao, Tsung‐Jen Lin, Yu‐Chin Liu, Yu‐Shan Wei, Guan‐Ying Chen, Hsiang‐Pu Feng, Yi‐Feng Chang, Hsin‐Tzu Chang, Chih‐Liang Wang, Hsinag‐Cheng Chi, Chun‐I Wang, Kwang‐Huei Lin, Wei‐Ting Ou Yang, Chia‐Jung Yu
Cancer Science.2022; 113(1): 205. CrossRef
An Observational Study on Treatment Outcomes in Patients With Stage III NSCLC in Taiwan: The KINDLE Study
Po-Lan Su, Gee-Chen Chang, Shih-Hsin Hsiao, Te-Chun Hsia, Meng-Chih Lin, Min-Hsi Lin, Jin-Yuan Shih, Cheng-Ta Yang, Sheng-Hsiung Yang, Yuh-Min Chen
JTO Clinical and Research Reports.2022; 3(3): 100292. CrossRef
Evaluating the Efficacy of EGFR-TKIs Combined With Radiotherapy in Advanced Lung Adenocarcinoma Patients With EGFR Mutation: A Retrospective Study
Yuxiang Wang, Wenjuan Yu, Jian Shi, Rong Qiu, Nan Jiang, Zhuofan Wang, Jie Yang, Zhongfei Jia, Meng Song
Technology in Cancer Research & Treatment.2022;[Epub] CrossRef
Durvalumab After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: Inferior Outcomes and Lack of Health Equity in Hispanic Patients Treated With PACIFIC Protocol (LA1-CLICaP)
Luis E. Raez, Oscar Arrieta, Diego F. Chamorro, Pamela Denisse Soberanis-Piña, Luis Corrales, Claudio Martín, Mauricio Cuello, Suraj Samtani, Gonzalo Recondo, Luis Mas, Zyanya Lucia Zatarain-Barrón, Alejandro Ruíz-Patiño, Juan Esteban García-Robledo, Cami
Frontiers in Oncology.2022;[Epub] CrossRef
The prognosis of non-small cell lung cancer patients according to endobronchial metastatic lesion
Yoonki Hong, Sunmin Park, Myoung Kyu Lee
Scientific Reports.2022;[Epub] CrossRef
First results of durvalumab after chemoradiotherapy in locally advanced non-small-cell lung cancer in Russia
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Meditsinskiy sovet = Medical Council.2022; (22): 12. CrossRef
Clinical outcomes and radiation pneumonitis after concurrent EGFR‐tyrosine kinase inhibitors and radiotherapy for unresectable stage III non‐small cell lung cancer
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Thoracic Cancer.2021; 12(6): 814. CrossRef
Durvalumab for Stage III EGFR-Mutated NSCLC After Definitive Chemoradiotherapy
Jacqueline V. Aredo, Isa Mambetsariev, Jessica A. Hellyer, Arya Amini, Joel W. Neal, Sukhmani K. Padda, Caroline E. McCoach, Jonathan W. Riess, Elwyn C. Cabebe, Jarushka Naidoo, Tariq Abuali, Ravi Salgia, Billy W. Loo, Maximilian Diehn, Summer S. Han, Hea
Journal of Thoracic Oncology.2021; 16(6): 1030. CrossRef
Einfluss der Molekularpathologie auf die onkologische Chirurgie von Leber- und Gallengangstumoren
Mazen A. Juratli, Benjamin Struecker, Shadi Katou, M. Haluk Morguel, Andreas Pascher
Der Chirurg.2021; 92(11): 1003. CrossRef
Locally Advanced, Unresectable Non-Small Cell Lung Cancer
Sonam Puri, Andreas Saltos, Bradford Perez, Xiuning Le, Jhanelle E. Gray
Current Oncology Reports.2020;[Epub] CrossRef
Real world data of durvalumab consolidation after chemoradiotherapy in stage III non-small-cell lung cancer
Hyun Ae Jung, Jae Myoung Noh, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Hongryull Pyo, Yong Chan Ahn, Keunchil Park
Lung Cancer.2020; 146: 23. CrossRef
Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small-Cell Lung Cancer (NSCLC)
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Pharmaceuticals.2020; 13(10): 273. CrossRef
MiRNAs: A New Approach to Predict and Overcome Resistance to Anticancer Drugs
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Clinical Cancer Drugs.2020; 7(2): 65. CrossRef
Incidence of brain metastasis in lung adenocarcinoma at initial diagnosis on the basis of stage and genetic alterations
Bumhee Yang, Hyun Lee, Sang-Won Um, Kyunga Kim, Jae Il Zo, Young Mog Shim, O Jung Kwon, Kyung Soo Lee, Myung-Ju Ahn, Hojoong Kim
Lung Cancer.2019; 129: 28. CrossRef
A Prediction Rule for Overall Survival in Non-Small-Cell Lung Cancer Patients with a Pathological Tumor Size Less Than 30 mm
Wang-Yu Zhu, Ke-xin Fang, Jian-ying He, Ri Cui, Yong-Kui Zhang, Han-bo Le
Disease Markers.2019; 2019: 1. CrossRef

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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

Abstract PDF PubReader ePub

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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Clinical Lung Cancer.2026; 27(2): 227. CrossRef
Adverse event profiles of EGFR-TKI: network meta-analysis and disproportionality analysis of the FAERS database
Jing Shi, Xinya Liu, Mengjiao Gao, Jian Yu, Ting Chai, Yun Jiang, Jiawei Li, Yuanming Zhang, Li Wu
Frontiers in Pharmacology.2025;[Epub] CrossRef
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Himani Aggarwal, Kerigo Ndirangu, Katherine B Winfree, Catherine Elizabeth Muehlenbein, Emily Zhu, Vanita Tongbram, Howard Thom
Journal of Comparative Effectiveness Research.2023;[Epub] CrossRef
Toxicity profile of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung cancer: A systematic review and network meta-analysis
Yi Zhao, Bo Cheng, Zisheng Chen, Jianfu Li, Hengrui Liang, Ying Chen, Feng Zhu, Caichen Li, Ke Xu, Shan Xiong, Weixiang Lu, Zhuxing Chen, Ran Zhong, Shen Zhao, Zhanhong Xie, Jun Liu, Wenhua Liang, Jianxing He
Critical Reviews in Oncology/Hematology.2021; 160: 103305. CrossRef
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Zhihao Zhang, Xiyong Wang, Huaiqing Xiao, Dongqiang Wu, Dongliang Zhang, Qun Yu, Linna Yuan, Tao Huang
Computational and Mathematical Methods in Medicine.2021; 2021: 1. CrossRef
A meta-analysis of the safety and effectiveness of pemetrexed compared with gefitinib for pre-treated advanced or metastatic NSCLC
Xiaoxin Lu, Shengshu Li, Weizong Chen, Dongyang Zheng, Yuzhu Li, Fang Li
Medicine.2020; 99(29): e21170. CrossRef
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Pteridines.2019; 30(1): 171. CrossRef
Gefitinib for advanced non-small cell lung cancer
Esther HA Sim, Ian A Yang, Richard Wood-Baker, Rayleen V Bowman, Kwun M Fong
Cochrane Database of Systematic Reviews.2018;[Epub] CrossRef
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Lung Cancer.2018; 123: 60. CrossRef
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Frontiers in Medicine.2017;[Epub] CrossRef

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