Cancer Research and Treatment

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

Abstract PDF: Purpose
Brain metastases are a serious complication in non-small cell lung cancer (NSCLC). However, data regarding efficacy of immune checkpoint inhibitors and chemotherapy combinations are limited. This phase II study aimed to evaluate the intracranial efficacy and safety of pembrolizumab and chemotherapy in treatment-naïve NSCLC patients with asymptomatic brain metastases.
Materials and Methods
This single-arm, phase II trial was conducted at Samsung Medical Center, Korea. Eligible patients had stage IV NSCLC with asymptomatic, untreated brain metastases and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alterations. Patients received pembrolizumab with chemotherapy every 3 weeks for 4 cycles, followed by pembrolizumab with or without maintenance chemotherapy up to 35 cycles. The primary endpoint was intracranial objective response rate (icORR). Secondary endpoints included intracranial progression free survival (icPFS), intracranial duration of response (icDoR), objective response rate (ORR), progression free survival (PFS), overall survival, and safety.
Results
Between February 2021 and June 2024, a total of 13 patients were enrolled. Due to challenges in recruiting patients, enrollment was discontinued after the 13 patients. The icORR was 46.2% (95% CI, 19.2–74.8), with 6 patients achieving partial response. The median icPFS was 9.8 months (95% CI, 5.2–21.5), and median icDoR was 9.3 months (95% CI, 4.0–20.3). Median PFS and overall survival was 7.2 months (95% CI, 2.4–12.3) and 10.7 months (95% CI, 7.2–21.5), respectively. Most treatment-related adverse events were grade 1–2.”
Conclusion
Pembrolizumab combined with chemotherapy demonstrated encouraging intracranial activity and manageable safety profile in NSCLC patients with untreated, asymptomatic brain metastases.

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Comparative Clinical and Economic Analysis of Robotic versus Video-assisted thoracoscopic Anatomical Resection for Lung Cancer: Ji Hyeon Park, Young Eun Hong, Hana Shim, Taeyoung Yun, Bubse Na, Kwon Joong Na, Hyun Joo Lee, In Kyu Park, Young Tae Kim, Chang Hyun Kang; Received February 27, 2025 Accepted March 16, 2026 Published online March 18, 2026; DOI: https://doi.org/10.4143/crt.2025.230 [Accepted]

Abstract PDF: Purpose
This study aimed to compare the clinical outcomes and costs of robotic-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) in patients undergoing minimally invasive anatomical resection for primary lung cancer.
Materials and Methods
A retrospective analysis was conducted on 2,086 patients who underwent surgery at a single institution from January 2017 to July 2020, including 134 RATS and 1,952 VATS cases. Propensity score matching (PSM) was applied, resulting in 268 matched patients (134 RATS and 134 VATS). Cost data were obtained from hospital billing files, encompassing 20 categories, including total hospitalization fees, anesthesia fees, surgery fees, costs of surgical instruments and materials, and general examination fees.
Results
After PSM, RATS patients had a shorter median postoperative stay (5 days vs. 6 days, p = 0.009) and lower thoracotomy conversion rate (1.5% vs. 14.9%, p < 0.001) than VATS. However, RATS incurred higher total costs by an average of $1,230 (p < 0.001), mainly due to increased surgical expenses ($1,163, p < 0.001). In multivariate analysis, RATS (12.41%, p < 0.001), neoadjuvant therapy (13.3%, p = 0.005), complications (4.2%, p < 0.001), and length of stay (2.0%, p < 0.001) were found to be associated with higher costs.
Conclusion
Although RATS has been shown to reduce the thoracotomy conversion rate and length of hospital stay, it incurs higher costs than VATS, primarily due to increased surgical expenses. The justification for RATS should be further evaluated through sustainability and cost-effectiveness studies with long-term follow-up.

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Effect of Smoking Cessation Duration on Lung Cancer Incidence: A Nationwide Retrospective Cohort Study in Korea: Myeong Geun Choi, Min-Ho Kim, Hong Jin Kim, Eun Mi Chun; Received October 10, 2025 Accepted February 25, 2026 Published online February 26, 2026; DOI: https://doi.org/10.4143/crt.2025.1099 [Accepted]

Abstract PDF: Purpose
While smoking cessation is known to reduce lung cancer risk, the extent to which smoking cessation duration mitigates lung cancer risk remains unclear. This study aimed to analyze the association between smoking cessation duration and the reduction in lung cancer incidence using large-scale health insurance data from Korea.
Materials and Methods
In this retrospective cohort study, we utilized the cohort from the Korea National Health Insurance Corporation. Approximately 50% of the adults aged ≥50 years who underwent health examinations in 2009–2013 were randomly sampled and followed using medical and health examination records. The participants were classified into three groups: never-smokers, former smokers, and current smokers, and the incidence rates of lung cancer were compared among these groups.
Results
We analyzed 165,512 individuals selected through propensity score matching (82,756 never-smokers, 41,378 former smokers, and 41,378 current smokers). Lung cancer risk significantly decreased after two years of smoking cessation (2–3 years after cessation: hazard ratio 0.760, p<0.001) but remained higher than that of never-smokers for up to 10 years. Subgroup analyses revealed similar tendencies among males, whereas no consistent patterns were observed among females. Moreover, a longer duration of smoking cessation was generally required for heavy smokers (≥20 pack-years) than for light smokers (<20 pack-years).
Conclusion
This nationwide cohort study highlights the significant impact of smoking cessation duration on lung cancer risk, emphasizing the substantial benefits of even short-term cessation regardless of prior smoking history.

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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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Assessing Radiation Pneumonitis Through Functional Lung Imaging: A Single Photon Emission Computed Tomography (SPECT)-Based Approach in Lung Cancer: Joo-Hyun Chung, Soo Jin Lee, Ji Young Kim, Hae Jin Park; Received November 13, 2025 Accepted February 18, 2026 Published online February 19, 2026; DOI: https://doi.org/10.4143/crt.2025.1248 [Accepted]

Abstract PDF: Purpose
To develop models to assess the risk of symptomatic radiation pneumonitis (SRP) (Common Terminology Criteria for Adverse Events 4.03 grade ≥ 2) in lung cancer patients by utilizing single-photon emission computed tomography (SPECT) for functional lung volume identification and dosimetric analysis.
Materials and Methods
This retrospective study included 71 lung cancer patients who underwent SPECT before radiotherapy from 2018 to 2024. Perfusion and ventilation SPECT images were co-registered with planning CT to define functional and anatomical lung volumes. Functional lung was defined as voxels with ≥ 20% of the maximum intensity on SPECT. Models to assess the risk of SRP were constructed using Cox regression and evaluated using corrected Akaike Information Criterion (AICc) and time-dependent receiver operating characteristic analysis.
Results
At a median follow-up of 16.8 months, 19 of 71 patients (26.8%) developed SRP. Factors significantly associated with SRP risk included planning target volume ≥ 150 mL, percentage of total perfusion-defined functional lung receiving ≥ 10 Gy (pVf10) exceeding that of total anatomical lung receiving ≥ 10 Gy (V10), percentage of total ventilation-defined lung receiving ≥ 10 Gy (vVf10) ≥ 45%, and ipsilateral vVf10 ≥ 60% (p=0.004, 0.004, 0.024, and 0.007, respectively). Among the three models, the model incorporating additional ventilation-based parameters demonstrated the best performance (AICc = 85.81, area under the curve = 0.819).
Conclusion
SPECT-based dosimetric parameters derived from perfusion and ventilation are significantly associated with the risk of SRP. Incorporating SPECT may improve risk stratification and enable lung-sparing strategies.

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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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Immunosuppressive Tumor Microenvironment in Colorectal Cancer Lung Metastases: Implications for Recurrence After Metastasectomy: Minsuk Kwon, Min-Kyue Shin, Minae An, Yeong Jeong Jeon, Tae Hee Hong, Jung Kyong Shin, Sung Hee Lim, Yoonah Park, Yong Beom Cho, Seung Tae Kim, Yong Soo Choi, Jeeyun Lee; Received July 3, 2025 Accepted December 8, 2025 Published online December 17, 2025; DOI: https://doi.org/10.4143/crt.2025.691 [Accepted]

Abstract PDF Supplementary Material: Purpose
Colorectal cancer (CRC) lung metastases exhibit high recurrence rates after resection, underscoring the need for improved therapeutic strategies. This study aimed to characterize the tumor microenvironment (TME) of CRC lung metastases and identify the factors associated with recurrence.
Materials and Methods
Fifteen CRC patients who underwent lung metastasectomy were enrolled. Multiplex immunohistochemistry (IHC), whole exome sequencing, transcriptome profiling, and single-cell RNA sequencing (scRNA-seq) were conducted on matched tumor, adjacent and distant normal lung tissues. Immune cell populations and gene expression profiles were analyzed and correlated with clinical recurrence outcomes.
Results
Exome and transcriptome analyses revealed frequent TP53, KRAS, and APC mutations. Most tumors corresponded to consensus molecular subtypes 2 and 4, characterized by immune-depleted and fibrotic features. Tumors showed downregulation of effector T and NK cell signatures. IHC revealed reduced density and increased distance of CD8+ T cells and macrophages from the epithelial cells. scRNA-seq demonstrated increased regulatory T cells and decreased NK and effector T cells in tumor. Tumor-associated macrophages (TAMs), particularly SPP1 (osteopontin)-expressing subsets, were markedly enriched in tumor and correlated with suppressed effector T cella activity. High SPP1 expression was associated with early recurrence and poor overall survival. Patients with recurrence had higher proportion of PD-1+ CD8+ T cells in adjacent normal tissues.
Conclusion
Immunosuppressive features including enrichment of SPP1+ TAMs and depletion of effector T and NK cells contribute to recurrence after CRC lung metastasectomy. Therapeutic strategies targeting both TAMs and T cells may enhance clinical outcomes in this patient population.

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Changes in Uptake, Participant Disparities, and Screening Outcomes of the Korean National Lung Cancer Screening Program: A Five-Year Experience: Chang Kyun Choi, Na-Young Lee, Mina Suh, Kui Son Choi, Yeol Kim; Received January 15, 2025 Accepted November 6, 2025 Published online November 10, 2025; DOI: https://doi.org/10.4143/crt.2025.067 [Accepted]

Abstract PDF: Purpose
Low-dose computed tomography (LDCT) is effective in reducing lung cancer mortality among high-risk smokers. The Korean National Lung Cancer Screening Program (KNLCS), the world’s first nationwide lung cancer screening initiative using LDCT, was launched in 2019. This study aimed to evaluate the KNLCS uptake rates in relation to participants’ economic status and changes in positive screening rates across screening rounds.
Materials and Methods
Data from the National Health Insurance Service (NHIS) and National Cancer Screening Information System for 2019–2023 were analyzed. Eligible participants in the KNLCS were current smokers aged 54–74 years with a smoking history of at least 30 pack-years. The KNLCS provides counseling by physicians on screening results and smoking cessation. Screening uptake rates, counseling rates, and Lung CT Screening Reporting and Data System (Lung-RADS) distributions were assessed.
Results
Screening uptake rates increased from 24.7% in 2019 to 51.2% in 2023 (p < 0.001). Economic disparities were observed, with higher-income groups showing consistently higher uptake rates than lower-income group. Screening positive rates has been decreased from 9.1% in 2019 to 7.0% in 2023 according to increasing the proportion of subsequent screening participants. The inter-institutional variance in Lung-RADS category 4 decreased significantly over the years (p < 0.001).
Conclusion
The KNLCS rapidly increased screening uptake rates by systematically inviting eligible participants. Positive screening rates decreased primarily due to a reduction in Lung-RADS category 3 findings in subsequent rounds.

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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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PHF10 is a Novel Substrate of Keap1 to Protect Non-Small-Cell Lung Cancer (NSCLC) Cells Against Oxidative Stress and Confer Ferroptosis Resistance: Xuan Lu, Ningning Kang, Yajun Chen, Xinru Zhao, Donglin Zhu, Jun Yang, Yong Yang, Hongya Xie; Received June 18, 2025 Accepted October 31, 2025 Published online November 3, 2025; DOI: https://doi.org/10.4143/crt.2025.635 [Accepted]

Abstract PDF: Purpose
Keap1 mutations mainly caused NRF2-dependent anti-oxidative stress responses, yet whether there are other downstream substrates and pathways remains unknown. This study aimed to uncover the role of Keap1 mutations in regulating PHF10-NRF2 axis in NSCLC and ferroptosis evasion.
Materials and Methods
Tandem affinity purification with mass spectrometry was used to screen peptides. Co-IP and ubiquitination assays were used to confirm the Keap1-PHF10 axis. A series of analyses in cell lines, patient samples, and xenograft models were conducted to uncover the functional dependency between Keap1 and NRF2. Transmission electron microscope was used to detect mitochondrion swelling under ferroptosis.
Results
Here, we reported that Keap1 binds and promotes polyubiquitination and degradation of PHF10, a subunit of the PBAF complex. NSCLC-associated Keap1 mutations are incapable of degrading PHF10, and thus induces PHF10 proteins stability. PHF10 ablation shows synthetic lethality in Keap1-deficient NSCLC cells. Mechanistically, PHF10 interacts with NRF2 to activate its downstream targets and enhance the NRF2-dependent anti-oxidative stress capacity in NSCLC. PHF10 recruits SMARCA2, one core cBAF subunit, to increase chromatin accessibility in NRF2-binding transcriptional regions. Cancer-associated Keap1 mutants confer resistance to ROS-induced cell death via accumulating PHF10-SMARCA2 complex. Increased PHF10 further induced ferroptosis resistance in Keap1-deficient NSCLC. Lastly, we utilized one small molecule inhibitor, SMARCA2-IN-8, to inhibit progression of Keap1-deficient NSCLC murine models.
Conclusion
Together, our study highlight the synthetic lethal relationship between Keap1 and PHF10, and provide targeting PHF10-SMARCA2 complex as an effective option to hit Keap1-deficient NSCLC.

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Predictive Role of Baseline Peripheral Lung SUVmax on PET/CT for Immune-Related Pneumonitis and Adverse Events in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Kun Ho Kim, Seong Min Kim, Jeong Eun Lee, Song Soo Kim, Da Hyun Kang, Chaeuk Chung; Received May 22, 2025 Accepted October 22, 2025 Published online October 28, 2025; DOI: https://doi.org/10.4143/crt.2025.548 [Epub ahead of print]

Abstract PDF Supplementary Material: Purpose
Immune checkpoint inhibitors (ICIs) offer durable responses in lung cancer patients lacking actionable mutations or with resistance to prior therapies. However, predicting their efficacy and associated immune-related adverse events (irAEs), such as severe pneumonitis, remains a clinical challenge. This study investigated the predictive value of positron emission tomography/computed tomography (PET/CT)–derived metabolic parameters for pneumonitis and other irAEs in lung cancer patients treated with ICIs.
Materials and Methods
We retrospectively analyzed 151 patients with advanced non–small cell lung cancer (NSCLC) who received ICIs as first-line treatment, either as monotherapy or in combination. Pre-treatment PET/CT was used to measure maximum standardized uptake value (SUVmax) at the primary tumor, tumor-uninvolved peripheral lung, and metastatic sites. Pneumonitis and irAEs were assessed using clinical and radiological findings.
Results
Pneumonitis, severe pneumonitis (grade ≥ 3), and irAEs occurred in 26.5%, 19.9%, and 37.1% of patients, respectively. A peripheral SUVmax cutoff of > 1.1 significantly predicted pneumonitis (area under the curve, 0.720; p < 0.001). High peripheral SUVmax was associated with higher rates of pneumonitis (42.9% vs. 12.3%, p < 0.001), severe pneumonitis (31.4% vs. 9.9%, p=0.001), and irAEs (46.4% vs. 29.5%, p=0.038). In multivariate analysis, high peripheral SUVmax independently predicted pneumonitis (odds ratio [OR], 4.621; 95% confidence interval [CI], 1.868 to 11.431; p=0.001), severe pneumonitis (OR, 2.848; 95% CI, 1.043 to 7.779; p=0.041), and irAEs (OR, 2.509; 95% CI, 1.114 to 5.504; p=0.022).
Conclusion
Baseline peripheral SUVmax on PET/CT may serve as a noninvasive biomarker for predicting immune-related pneumonitis and other irAEs in NSCLC patients receiving ICIs, supporting early risk identification.

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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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Impact of Occupational Lead Exposure on Lung Cancer Risk in Korean Male Workers: A Retrospective Cohort Study: Kyung-Eun Lee, Sanggil Lee, Jin-Ha Yoon, Shinhee Ye; Received March 12, 2025 Accepted September 30, 2025 Published online October 2, 2025; DOI: https://doi.org/10.4143/crt.2025.282 [Accepted]

Abstract PDF: Purpose
In 2006, the IARC reported that inorganic lead is carcinogenic in animals but with limited evidence in humans. In addition, some studies have reported that exposure to lead increases the risk of lung cancer, but this remains controversial. Therefore, we aimed to assess the risk of developing lung cancer according to blood lead levels in workers with occupational lead exposure.
Materials and Methods
A retrospective cohort study of male workers with 2009 blood lead (PbB) concentrations was conducted using nationwide special health examination data (SHED) from 2009 to 2021 and cancer registry data from 1999 to 2020 from the Republic of Korea. Standardized incidence ratios (SIRs) for lung cancer risk at each PbB level were calculated with a five-year wash-out period, adjusting for age, smoking status, duration of exposure, and the number of co-exposures to lung carcinogens.
Results
The study included 26,092 workers with an average follow-up period of 9.98 years. Compared with workers with PbB levels <3.130 µg/dL, the adjusted SIRs for lung cancer risk were 2.95 (95% confidence interval [CI]: 1.47–5.27) and 3.13 (95% CI: 1.82–5.00) for workers with PbB levels of 3.130–4.899 and ≥4.900 µg/dL, respectively, indicating a significant dose-response trend.
Conclusion
This study demonstrates a significant association between lead exposure and an increased risk of lung cancer, highlighting the need for stronger occupational health policies and ongoing monitoring of workers exposed to lead. The observed dose-response relationship underscores the importance of reassessing current occupational safety standards and strengthening measures to reduce lead exposure in the workplace.

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Genomic Insights into Innate Resistance in Early-Stage EGFR-Mutant Non-Small Cell Lung Cancer: A Comprehensive Analysis of Next-Generation Sequencing Data: Hayoung Seong, Soo Han Kim, Mi-Hyun Kim, Ahrong Kim, Ju Sun Song, Jung Seop Eom; Received January 28, 2025 Accepted August 19, 2025 Published online August 25, 2025; DOI: https://doi.org/10.4143/crt.2025.114 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Comprehensive genomic profiling of early-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations remains limited. This study aimed to investigate genomic profiles of early- and advanced-stage EGFR-mutant NSCLC and identify potential innate resistance mechanisms to EGFR-tyrosine kinase inhibitors (TKIs) using targeted next-generation sequencing (NGS).
Materials and Methods
This retrospective observational study analyzed genomic profiles of patients with early-stage (IA-IIIA) and advanced-stage (IIIB-IV) EGFR-mutant NSCLC from the Lung Cancer NGS registry. Targeted NGS was performed to assess concurrent genetic alterations (GAs), tumor mutational burden (TMB), and variant allele frequency (VAF) of EGFR mutations.
Results
Overall, 160 patients (100 early-stage and 60 advanced-stage) were analyzed. The proportion of patients with concurrent GAs was not significantly different between stages (82.0% vs. 91.7%, p=0.092). Median TMB was 3.8 mutations/Mb in both stages, with no significant difference (p=0.206). However, the median VAF of EGFR mutations was significantly lower in early-stage compared to that in advanced-stage (19.3% vs. 29.6%, p=0.002). While TMB remained unchanged with disease progression (p=0.192), VAF of EGFR mutations increased significantly (p < 0.001). Moreover, the frequencies of concurrent single nucleotide variants and copy number variants were significantly lower in early-stage NSCLC.
Conclusion
Genomic heterogeneity in EGFR-mutant NSCLC arises early in tumorigenesis. The comparable TMB and lower VAF of EGFR mutations in early-stage disease suggest that innate resistance to EGFR-TKIs may be driven by concurrent GAs, supporting the consideration of combination therapies even in early-stage EGFR-mutant NSCLC.

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Preferential Sensitivity of the EGFR L858M/L861R Mutation to Second-Generation EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer: Chaelin Lee, Sheehyun Kim, Soyeon Kim, Taekeun Park, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Jeonghwan Youk; Received March 11, 2025 Accepted August 19, 2025 Published online August 20, 2025; DOI: https://doi.org/10.4143/crt.2025.279 [Epub ahead of print]

Abstract PDF Supplementary Material

Purpose
Non–small cell lung cancer (NSCLC) frequently harbors targetable epidermal growth factor receptor (EGFR) mutations. However, rare variants such as EGFR L858M or L861R remain poorly characterized. This study aimed to elucidate the oncogenic potential and EGFR tyrosine kinase inhibitors (TKIs) sensitivity of the EGFR L858M/L861R mutation to inform personalized treatment strategies.
Materials and Methods
Tumor samples from an NSCLC patient were analyzed using targeted panel sequencing and confirmed with the FoundationOne Liquid CDx assay. EGFR-mutant constructs, including L858M, L858R, L861R, L861Q, L858M/L861R, and L858R/L861Q, were generated and transduced into various cell lines. Cell viability, immunoblot, and soft agar colony formation assays were conducted to assess the oncogenicity and drug sensitivity, while computational protein modeling and docking simulations evaluated the drug-binding affinities of EGFR-TKIs.
Results
Ba/F3 cells expressing the EGFR L858M/L861R mutation exhibited robust interleukin-3–independent proliferation accompanied by markedly increased EGFR phosphorylation, while NIH-3T3 cells showed anchorage-independent colony formation. Compared to other mutations, cells expressing EGFR L858M/L861R mutation were less sensitive to first-generation EGFR-TKIs (gefitinib, erlotinib) and third-generation EGFR-TKIs (osimertinib, lazertinib), whereas second-generation EGFR-TKIs (afatinib, poziotinib) demonstrated potent inhibitory effects. Computational modeling revealed a narrower drug-binding efficiency of first-generation inhibitors.
Conclusion
The EGFR L858M/L861R mutation drives strong oncogenic signaling and exhibits preferential sensitivity to second-generation EGFR-TKIs. These findings underscore the importance of accurate molecular diagnosis for guiding effective, personalized therapeutic strategies in NSCLC.

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Real-World Outcomes and Subsequent Treatment Patterns in Patients with Advanced Non-Small Cell Lung Cancer and Atypical EGFR Mutations Receiving First-Line Osimertinib Monotherapy
Jorge J. Nieva, Xuejun Wang, Deborah Doroshow, Leslie Servidio, Miranda Cooper, Yan Kwan Lau, Pritesh S. Karia, Jacqulyne Robichaux
Oncology and Therapy.2026; 14(1): 225. CrossRef

1,964 View
139 Download
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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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Trends and Outcomes of Lung Cancer Surgery in South Korea: Joon Beom Park, Su-Jin Cho, Myung-Il Hahm, Danbee Kang, Seong Yong Park; Cancer Res Treat. 2026;58(2):443-453. Published online May 27, 2025; DOI: https://doi.org/10.4143/crt.2025.295

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study analyzed nationwide trends in lung cancer surgery in South Korea over 14 years, focusing on surgical volume, patient demographics, surgical approaches, and outcomes.
Materials and Methods
We performed a retrospective cohort study using nationwide health insurance claims data (124,334 cases) and robotic surgery data (1,740 cases) provided by the manufacturer. Patients who underwent lung cancer surgery between 2010 and 2023 were included. Annual trends were assessed using the annual percentage change (APC), and logistic as well as linear regression models were used to identify predictors of mortality and prolonged hospital stay.
Results
The annual surgical volume increased from 4,557 in 2010 to 14,184 in 2023 (APC, 8.86%; p < 0.001). Video-assisted thoracoscopic surgery (VATS) became the predominant approach, rising from 52.9% to 94.8% (APC, 4.11%; p < 0.001). Sub-lobar resections increased, with wedge resections growing from 9.0% to 18.5% (APC, 5.72%; p < 0.001) and segmentectomies from 3.0% to 17.9% (APC, 14.63%; p < 0.001). The proportion of female patients increased from 32.0% to 44.7% (APC, 2.39%; p < 0.001), while patients aged 70-79 years increased from 26.3% to 32.3% (APC, 1.60%; p < 0.001) and those aged ≥ 80 years from 2.0% to 6.2% (APC, 9.63%; p < 0.001). The median hospital stay decreased from 13 to 7 days (APC, –4.34%; p < 0.001), and 30-day mortality declined from 2.45% to 0.76% (APC, –8.32%; p < 0.001).
Conclusion
Lung cancer surgery in Korea has increased substantially, with a notable shift toward minimally invasive and lung-sparing techniques that have improved outcomes. However, persistent disparities underscore the need for a national surgical registry.

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Clinical Relevance of Starting Alectinib at a Reduced Dose in Patients with ALK-Positive Non–Small Cell Lung Cancer: Junkyu Kim, Min-Ji Kim, Jinyong Kim, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun; Cancer Res Treat. 2026;58(2):434-442. Published online April 24, 2025; DOI: https://doi.org/10.4143/crt.2024.1209

Abstract PDF Supplementary Material PubReader ePub: Purpose
Alectinib has been approved for anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC) at 300 mg twice daily in Japan, lower than global standard of 600 mg twice daily. This study evaluated the clinical relevance of the reduced dose by comparing outcomes between the two doses.
Materials and Methods
This study included patients with advanced ALK-positive NSCLC who received alectinib at Samsung Medical Center, Korea. The progression-free survival (PFS), overall survival, cumulative incidence of central nervous system (CNS) progression, and safety profiles were retrospectively reviewed and compared.
Results
Among 306 patients, 32 and 274 received alectinib at either 300 or 600 mg twice daily, respectively. The 300 mg group showed a slight but not significant advantage in PFS (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.44 to 1.51; p=0.51) and overall survival (HR, 0.51; 95% CI, 0.20 to 1.21; p=0.13). Superior outcome with 300 mg was remarkable in patients with lower body weight (≤ 60 kg), but diminished in patients with higher body weights. Patients with baseline brain metastasis in the 300 mg group exhibited a slight increase in incidence of CNS failure (HR, 1.76; 95% CI, 0.53 to 5.8; p=0.36). Although the safety profiles were mostly mild, adverse events were more frequent in the 600 mg group, 50% of which requiring dose reduction.
Conclusion
Alectinib at 300 mg twice daily seems an acceptable dose in East Asians with ALK-positive NSCLC. Notably, our data favor 300 mg twice daily in patients with lower body weight and no baseline brain metastasis, considering the more tolerable safety profiles and the potential to reduce medical costs.

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Gastrointestinal cancer

Deciphering the Risk of Developing Lung Cancer after the Diagnosis of Gastric Cancer with Genetic Evidence: A European and East Asian Populations–Based Mendelian Randomization Analysis: Jiansheng Chen, Aiming Zeng, Yunzhe Yu, Sida Sun, Liqun Liao, Siwei Huang, Zhongshan Yang, Junfeng Zhou, Weijie Wu; Cancer Res Treat. 2026;58(1):242-251. Published online April 18, 2025; DOI: https://doi.org/10.4143/crt.2024.875

Abstract PDF Supplementary Material PubReader ePub: Purpose
Lung cancer is frequently observed as a second primary malignancy following gastric cancer, yet the genetic causality between them remains uncertain. This study aims to evaluate the causal relationship between gastric and lung cancers using Mendelian randomization (MR) analysis.
Materials and Methods
Single nucleotide polymorphisms associated with gastric and lung cancers were selected from genome-wide association study in East Asian and European populations as instrumental variables. The causal effects between gastric and lung cancers were evaluated using univariable and multivariable MR analysis, with the inverse variance weighted (IVW) method serving as the primary criterion. Heterogeneity and sensitivity analyses were performed to ensure the robustness of the findings.
Results
Univariable MR analysis demonstrated that genetic susceptibility to gastric cancer in the European population was significantly associated with an increased risk of lung cancer (IVW: odds ratio [OR], 1.285; 95% confidence interval [CI], 1.072 to 1.541; p=6.83E-03), which was consistently validated in the East Asian population (IVW: OR, 1.356; 95% CI, 1.114 to 1.651; p=2.40E-03). Multivariable MR analysis further indicated that the significant positive causal relationship between gastric cancer and lung cancer persisted in both populations after adjusting for confounding factors (all p < 0.05). Conversely, no significant causal relationship was observed for the risk of developing gastric cancer following the diagnosis of lung cancer in either population (p > 0.05).
Conclusion
This study confirms that genetic susceptibility to gastric cancer increases the risk of lung cancer. This finding provides a theoretical basis for exploring the underlying biological mechanisms and suggests that enhancing lung cancer screening in patients with gastric cancer may be necessary to improve patient prognosis.

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Lung and Thoracic cancer

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.

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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

2,757 View
109 Download
1 Web of Science
1 Crossref

The Profile of Gut Microbiota in Carcinogenesis Driven by Mutant EGFR in Non–Small Cell Lung Cancer: Da-Som Kim, Eun Hye Kim, Ji Yong Kim, Dong Ha Kim, Yun Jung Choi, Jaeyi Jeong, Young Hoon Sung, Dong-Cheol Woo, Chong Jai Kim, Jae Cheol Lee, Miyong Yun, Jin-Yong Jeong, Jin Kyung Rho; Cancer Res Treat. 2026;58(1):115-127. Published online March 4, 2025; DOI: https://doi.org/10.4143/crt.2024.1177

Abstract PDF PubReader ePub

Purpose
Accumulating evidence has clarified that gut dysbiosis is involved in lung cancer development and progression. Although the relationship between tumors and gut microbiota has been extensively studied using clinical samples, no studies have examined the association between mutant epidermal growth factor receptor (EGFR)–induced lung carcinogenesis and dysbiosis in gut microbiota. Therefore, we investigated the gut microbiota profiles in stool samples from human lung-specific conditional EGFR-mutant transgenic mice during lung tumor carcinogenesis.
Materials and Methods
Stool samples were collected before tamoxifen treatment (V1) and at each time point following mutant EGFR expression in lung tissue (V2) and lung tumor appearance (V3). Fecal 16S rRNA taxonomy was analyzed to assess microbial diversity, composition, and dynamic changes at each time point.
Results
We found that microbiota richness and diversity were significantly elevated when tumors developed and grew in the lung. Phylogenetic analysis of the microbial community revealed that Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Rhodospirillaceae, Odoribacteraceae, and Desulfovibrionaceae showed a significant increase at the V3 stage compared to the V1 stage at the family level. In contrast, Lactobacillaceae, Bacteroidaceae, Muribaculaceae, Coriobacteriaceae, and Rikenellaceae significantly decreased at the V3 stage compared to the V1 stage. Furthermore, Lactobacillus species, also known as short chain fatty acid-producing bacteria, were relatively abundant at the V1 stage but were depleted with the occurrence of lung tumors at the V3 stage.
Conclusion
Changes in gut microbiota, such as Lactobacillus species, may be a predictive factor for the emergence and progression of tumors in an animal model of lung adenocarcinoma induced by mutant EGFR.

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Microbiome and EGFR -mutant non-small cell lung cancer: a complex interplay
Serena Eccher, Marco Sposito, Ilaria Mariangela Scaglione, Luca Pasqualin, Michele Rota, Adele Bonato, Lucia Longo, Alice Avancini, Ilaria Trestini, Daniela Tregnago, Jessica Insolda, Michele Milella, Sara Pilotto, Lorenzo Belluomini
Expert Review of Clinical Immunology.2026; : 1. CrossRef
Gut microbiota and metabolites: emerging prospects in the treatment of non-small cell lung cancer
Jing-Mian Jiao, Chen-Guang Liu, Dan Zang, Jun Chen
Frontiers in Immunology.2025;[Epub] CrossRef
Study on the Impact of Changes in Intestinal Microbiota Structure of Lung Cancer Patients on the Efficacy of Immune Checkpoint Inhibitors
静鲁
Advances in Clinical Medicine.2025; 15(11): 744. CrossRef

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3 Web of Science
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Novel Bronchoscopy Method for Molecular Profiling of Lung Cancer: Targeted Washing Technique: Mi-Hyun Kim, Hayoung Seong, Hyojin Jang, Saerom Kim, Wanho Yoo, Soo Han Kim, Jeongha Mok, Kwangha Lee, Ki Uk Kim, Min Ki Lee, Jung Seop Eom; Cancer Res Treat. 2026;58(1):107-114. Published online February 26, 2025; DOI: https://doi.org/10.4143/crt.2024.1128

Abstract PDF Supplementary Material PubReader ePub

Purpose
There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the epidermal growth factor receptor (EGFR) mutation.
Materials and Methods
A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue.
Results
In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22.0%, 9.8%, and 29.3%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 36.6%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 82.9% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation.
Conclusion
We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

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Comparison of the safety and efficacy of remimazolam for sedation during bronchoscopy: a meta-analysis of randomized controlled trials
Yupei Yuan, Chunlei Chang, Jing Zhang, Liang Liang
PeerJ.2026; 14: e20552. CrossRef

2,768 View
127 Download
2 Web of Science
1 Crossref

Association between Antipsychotic Drug and Survival in Patients with Lung Cancer Treated with Chemoradiotherapy: A Nationwide Korean Cohort Study: Dong-Yun Kim, In Gyu Hwang, Sun Mi Kim, Dae Ryong Kang, Tae-Hwa Go, Se Hwa Hong, Shin Young Park, Hyunho Lee, Jin Hwa Choi; Cancer Res Treat. 2025;57(4):1030-1039. Published online February 6, 2025; DOI: https://doi.org/10.4143/crt.2024.554

Abstract PDF Supplementary Material PubReader ePub: Purpose
Antipsychotic drugs (APDs) can be used to relieve psychological symptoms in patients with cancer. We investigated the nationwide use of APDs during concurrent chemoradiotherapy (CCRT) for patients with lung cancer and its association with overall survival (OS).
Materials and Methods
The National Health Service database was used in this retrospective cohort study. Patients diagnosed with lung cancer between 2010 and 2020 who received cisplatin-based CCRT were included. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine, and the APD prescription details included prescription time, dosage, and duration.
Results
Among the 23,099 patients with lung cancer treated with CCRT, 2,662 (11.5%) took APDs concurrently. Quetiapine (47.3%) and chlorpromazine (36.6%) were the frequently prescribed APDs. In the univariate analysis, patients prescribed APDs during CCRT had a significantly worse OS than those who did not take APDs. The 2-year OS rates for APD (+) and APD (–) patients were 20.4% and 36.4%, respectively (p < 0.001). Multivariable analyses revealed that APD prescription, male, age > 80 years, and comorbidities, such as hypertension, myocardial infarction, and depressive disorder, significantly influenced OS. In patients who used APDs during CCRT, APD prescription timing (pre-CCRT vs. during CCRT), dosage (low vs. high) and duration (within 6 months vs. over 6 months) had no significant difference.
Conclusion
Overall, 11.5% of patients with lung cancer used APDs during CCRT. Patients who used APDs during CCRT had poorer survival than those who did not. Further studies are required to elucidate the effects of APDs on patients with cancer.

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Tracing Metastatic Evolutionary Patterns in Lung Adenocarcinoma: Prognostic Dissection Based on a Multi-state Model: Geewon Lee, Yang-Jin Kim, Insuk Sohn, Jong Hoon Kim, Ho Yun Lee; Cancer Res Treat. 2025;57(4):1019-1029. Published online January 24, 2025; DOI: https://doi.org/10.4143/crt.2024.700

Abstract PDF Supplementary Material PubReader ePub

Purpose
After surgery for lung adenocarcinoma, a patient may experience various states of recurrence, with multiple factors potentially influencing the transitions between these states. Our purpose was to investigate the effects of clinical and pathological factors on tumor recurrence, death, and prognosis across various metastasizing pathways.
Materials and Methods
Our study group included 335 patients with all demographic and pathologic data available who underwent surgical resection for lung adenocarcinoma for more than 10 years. The following states of disease were defined: initial state, operation (OP); three intermediate states of local recurrence (LR), metastasis (Meta), and concurrent LR with metastasis (LR+Meta); and a terminal state, death. We identified eight transitions representing various pathways of tumor progression. We employed a multi-state model (MSM) to separate the impacts of multiple prognostic factors on the transitions following surgery.
Results
After surgery, approximately half of patients experienced recurrence. Specifically, 142 (42.4%), 54 (16.1%), and seven (2.1%) patients developed Meta, LR+Meta, and LR, respectively. Clinical and pathological factors associated with the transitions were different. Impact of pathological lymph node remained a risk factor for both OP to Meta (λ02, p=0.001) and OP to LR+Meta (λ03, p=0.001).
Conclusion
Lung adenocarcinoma displays a broad spectrum of clinical scenarios even after curative surgery. Incidence, risk factors, and prognosis varied across different pathways of recurrence in lung adenocarcinoma patients. The greatest implication of this MSM is its ability to predict the timing and type of clinical intervention that will have the greatest impact on survival.

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A‐to‐I RNA Edited miR‐3167 Restrains Malignant Behaviors of Lung Adenocarcinoma by Influencing SSR2‐Meditated Hippo Signaling
Dawei Qian, Dongsheng Zha, Yuanyao Sang, Jiangquan Tao, Bufeng Zhuang, Youshuang Cheng
Molecular Carcinogenesis.2025; 64(9): 1552. CrossRef

3,468 View
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1 Crossref

Lipid Metabolism Related Gene ACSL3 as a Biomarker for Predicting Immunotherapy Outcomes in Lung Adenocarcinoma: Taiping He, Jinhan Hu, Haoyue Guo, Meng Diao, Yuanyuan Wang, Yuhan Wu, Lei Cheng, Chao Zhao, Xuefei Li, Caicun Zhou; Cancer Res Treat. 2025;57(4):1000-1018. Published online January 20, 2025; DOI: https://doi.org/10.4143/crt.2024.1119

Abstract PDF Supplementary Material PubReader ePub

Purpose
Investigate the role of lipid metabolism in the tumor immune microenvironment (TIME) of lung adenocarcinoma (LUAD) and identify vital lipid metabolism-related genes (LMRGs) that contribute to immunotherapy outcomes.
Materials and Methods
One thousand one hundred thirty LUAD patients were acquired utilizing public databases. Multiple algorithms were used to analyze the contribution of lipid metabolism in TIME. Importantly, cell lines, clinical samples (52 patients in surgery cohort and 36 in immunotherapy cohort), animal models, RNA sequencing (RNA-seq), experiments in protein and mRNA levels were conducted for identifying and validating key biomarker in LUAD immunotherapy.
Results
A prognostic signature comprising 33 LMRGs was developed and validated as an effective predictor of prognosis and TIME, with a C-index of 0.766 (95% confidence interval, 0.729 to 0.804). Additionally, we identified acyl-CoA synthetase long-chain family member 3 (ACSL3) as a potential biomarker for immunotherapy prognosis. The expression of ACSL3 was verified in 88 clinical tissues from LUAD patients, which indicated that elevated ACSL3 expression was correlated with worse progression-free survival (p < 0.001) and overall survival (p=0.008). Subsequent experiments revealed that knockdown of ACSL3 in vivo enhanced the efficacy of immunotherapy, potentially through increasing interferon-α secretion, as indicated by bulk RNA-seq and enzyme-linked immunosorbent assay analysis, thereby promoting the infiltration of antitumor immune cells.
Conclusion
The study established a model that accurately predicts immunotherapy response, prognosis, and TIME dynamics in LUAD patients. Notably, the pivotal role of ACSL3 in driving tumor progression and immune evasion was uncovered, offering novel insights into the optimization of immunotherapy strategies for LUAD.

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The multifaceted roles of the ACSL family in cancer: Metabolic reprogramming, ferroptosis regulation and tumour immune microenvironment remodelling
Haocai Li, Weijian Wang, Juncheng Zhan, Yuxiang Xiao, Xiaoping Chen, Chen Su, Peng Zhu
Clinical and Translational Medicine.2026;[Epub] CrossRef
Lipid Metabolism Reprogramming in Cancer: Insights into Tumor Cells and Immune Cells Within the Tumor Microenvironment
Rundong Liu, Chendong Wang, Zhen Tao, Guangyuan Hu
Biomedicines.2025; 13(8): 1895. CrossRef
Independent validation of lung adenocarcinoma prognostic risk scores incorporating cholesterol and estrogen metabolism related transcriptional biomarkers
Qian Zhu, Yuemei Zhang, Jian Ma, Yongjia Li, Hongya Liu, Zhongwen Gong, Ming Du, Xuemei Lian
Scientific Reports.2025;[Epub] CrossRef
Long-chain acyl-CoA synthetases: biological functions, diseases and therapeutic targets
Xiaoliang Deng, Yanqun Luo, Ying Gao, Tao Wu
Molecular Biomedicine.2025;[Epub] CrossRef

4,384 View
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4 Crossref

Factors Associated with Smoking Cessation of Participants in the National Lung Cancer Screening Program in Korea: Na-Young Yoon, Minji Seo, Nayoung Lee, Yeol Kim; Cancer Res Treat. 2025;57(4):989-999. Published online January 10, 2025; DOI: https://doi.org/10.4143/crt.2024.653

Abstract PDF Supplementary Material PubReader ePub

Purpose
Smoking cessation interventions for participants in lung cancer screening are essential for increasing the effectiveness of screening to reduce lung cancer mortality. This study aimed to investigate the factors that lead to smoking cessation after lung cancer screening.
Materials and Methods
The Korean National Lung Cancer Screening (KNLCS) Satisfaction Survey was conducted from 2021 to 2022 with approximately 1,000 samples per year among participants in KNLCS targeting 30 or more pack-year smokers. Factors associated with smoking cessation were analyzed based on the survey.
Results
Among 1,525 current smokers in the survey participants, 728 (47.7%) received screening result counseling from physician after screening and showed significantly higher smoking cessation rate than non-counseling participants (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.27 to 3.70). The participants who considered the counseling helpful were more likely to quit smoking (OR, 3.53; 95% CI, 2.00 to 6.22) and to reduce smoking amount (OR, 2.05; 95% CI, 1.54 to 2.71). Similarly, those who received physicians’ active recommendations to quit smoking were likely to quit smoking (OR, 2.20; 95% CI, 1.25 to 3.87) and to decrease smoking amount (OR, 1.30; 95% CI, 1.00 to 1.68). In contrast, participants who had no abnormal findings from screening tended to have no significant change in smoking status despite the physicians’ active recommendations to quit smoking.
Conclusion
Physicians’ active recommendations and effective counseling to quit smoking could be a key factor in increasing smoking cessation among lung cancer screening participants. Further research should be conducted to develop more effective strategies for smoking cessation to participants without abnormal findings in lung cancer screening.

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Quality, Standards, and Optimal Training of Radiologists for Lung Cancer Screening
Dorith Shaham, Ella A. Kazerooni
Journal of Thoracic Imaging.2026;[Epub] CrossRef
Leveraging the “Teachable Moment”: Impact of LDCT findings and counseling on smoking behavior
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The Synergistic Effect of PARP Inhibitors and Irinotecan in Small Cell Lung Cancer Cells: Songji Oh, Soyeon Kim, Bhumsuk Keam, Jeonghwan Youk, Tae Min Kim, Dong-Wan Kim, Miso Kim; Cancer Res Treat. 2025;57(4):1040-1050. Published online January 7, 2025; DOI: https://doi.org/10.4143/crt.2024.728

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study focused on combining irinotecan with poly(ADP-ribose) polymerase (PARP) inhibitors to explore the potential for novel combination therapeutics in small cell lung cancer (SCLC).
Materials and Methods
We selected 10 different SCLC cell lines with diverse mutational backgrounds in DNA damage response (DDR) pathway genes to evaluate the efficacy of the combination of three PARP inhibitors and irinotecan. After the cells were exposed to the drugs for 7 days, cell viability was measured, and a combination index was calculated. Apoptotic signaling was assessed via western blot, and DNA damage was evaluated using an alkaline comet assay.
Results
We assessed the synergistic effects of PARP inhibitors and irinotecan in in vitro SCLC models, which revealed increased sensitivity, particularly in cells harboring BRCA mutations. However, even in cells lacking mutations in DDR pathway genes, the combination of the two drugs exhibited a synergistic effect. When treated with 50 nM irinotecan, the IC₅₀ fold changes for PARP inhibitors were as follows: olaparib, 1,649±4,049; talazoparib, 25±34.21; venadaparib, 336±596.01. This combination enhanced apoptosis signaling and increased p-chk1 and p-p53 protein levels. Additionally, the treatment of PARP inhibitor with irinotecan increased DNA damage, as visualized by the alkaline comet assay.
Conclusion
This study provides preclinical evidence of the potential clinical benefits of combining irinotecan with PARP inhibitors in SCLC. Further clinical investigations are warranted to validate these findings for the development of more effective and personalized therapeutic strategies for SCLC patients.

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