1.Expert consensus on the diagnosis and treatment of advanced non-small cell lung cancer with EGFR PACC mutations (2025 edition).
Chinese Journal of Oncology 2025;47(9):811-829
Lung cancer is the malignancy with the highest incidence and mortality burden globally, ranking first in both morbidity and mortality among all types of malignant tumors. Pathologically, lung cancer is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer, with NSCLC accounting for approximately 85% of cases. Due to the often subtle or nonspecific clinical manifestations in early-stage disease, many patients are diagnosed at a locally advanced or metastatic stage, where treatment options are limited and prognosis remains poor. Therefore, molecular targeted therapy focusing on driver genes has become a key strategy to improve the survival outcomes of patients with advanced NSCLC. The epidermal growth factor receptor (EGFR) is one of the most common driver genes in NSCLC. While EGFR mutations occur in approximately 12% of advanced NSCLC patients globally, the incidence rises to 55.9% in Chinese patients. Among EGFR mutations, P-loop and αC-helix compressing (PACC) mutations account for about 12.5%. Currently, EGFR tyrosine kinase inhibitors (TKIs) have become the first-line standard treatment for advanced NSCLC patients with classical EGFR mutations, with efficacy well-established through clinical studies and real-world evidence. However, with rapid advancements in NSCLC precision medicine and deeper exploration of the EGFR mutation spectrum, EGFR PACC mutations have emerged as a key clinical focus. The structural characteristics of these mutations lead to significant variability in responses to EGFR TKIs, leaving therapeutic options still limited, while detection challenges persist due to the sensitivity constraints of current testing technologies, driving increasing demand for improved diagnostic and treatment approaches. The current clinical evidence primarily stems from retrospective analyses and small-scale exploratory studies, while prospective, large-scale, high-level evidence-based medical research specifically targeting this mutation subtype remains notably insufficient. This evidence gap has consequently led to the absence of standardized guidelines or expert consensus regarding optimal treatment strategies for advanced NSCLC with EGFR PACC mutations. As a clinical consensus specifically addressing EGFR PACC-mutant NSCLC, this document provides a comprehensive framework encompassing the clinical rationale for EGFR PACC mutation testing, therapeutic strategies for advanced-stage disease, management of treatment-related adverse events, and follow-up protocols. The consensus underscores the pivotal role of EGFR PACC mutation detection in precision medicine implementation while offering evidence-based recommendations to guide personalized therapeutic decision-making. By establishing clear clinical pathways encompassing molecular testing, therapeutic intervention, and long-term monitoring for EGFR PACC-mutant NSCLC, this consensus aims to meaningfully improve patient survival outcomes while serving as a robust, evidence-based foundation for developing personalized clinical management approaches.
Humans
;
Carcinoma, Non-Small-Cell Lung/pathology*
;
ErbB Receptors/antagonists & inhibitors*
;
Mutation
;
Lung Neoplasms/pathology*
;
Protein Kinase Inhibitors/therapeutic use*
;
Molecular Targeted Therapy
;
Consensus
2.Expert consensus on diagnosis and treatment of advanced non-small cell lung cancer with HER-2 alterations (2025 edition).
Chinese Journal of Oncology 2025;47(9):830-839
Mutations in the human epidermal growth factor receptor 2 (HER-2) gene are recognized as significant but relatively rare driver alterations in non-small cell lung cancer (NSCLC). These mutations predominantly manifest as gene mutation, amplification, and protein overexpression, with an estimated prevalence from 2.8% to 15.4% among NSCLC patients in China. Research indicates that HER-2 mutations, particularly exon 20 insertions (ex20ins), are strongly correlated with aggressive tumor biology, poor prognosis, and limited responsiveness to immunotherapy, thereby exhibiting characteristics of "cold tumors". Overexpression and amplification of HER-2 are also indicative of a heightened risk of chemotherapy resistance and unfavorable survival outcomes, suggesting a distinct molecular subtype with unique biological behaviors. In recent years, novel antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan (T-DXd), have demonstrated groundbreaking efficacy in HER-2-mutant advanced NSCLC patients. These ADCs have shown significant clinical benefits, including high objective response rates and progression-free survival advantages, making T-DXd the first targeted therapy approved for this patient population globally. Additionally, ADCs have exhibited therapeutic potential in patients with HER-2 overexpression, thus broadening the scope of their indications. To standardize the clinical diagnosis and treatment of HER-2 variant NSCLC, the Chinese Anti-cancer Association convened multidisciplinary experts from oncology, pulmonology, thoracic surgery, pathology, and molecular diagnostics to develop this consensus based on the latest evidences from both domestic and international studies, coupled with China's clinical practice experience. This consensus focuses on the molecular characteristics, clinical significance, diagnostic strategies, treatment options, and safety management of HER-2 alterations, addressing ten critical clinical questions in a systematic manner. It is recommended that HER-2 status be routinely tested at initial diagnosis, disease progression, or recurrence in NSCLC. Mutation detection should prioritize next-generation sequencing (NGS), while protein overexpression may be assessed using immunohistochemistry (IHC) standards for gastric cancer. Fluorescence in situ hybridization (FISH) is recommended for detecting HER-2 amplification. Regarding treatment, for HER-2-mutant patients, first-line therapy may involve chemotherapy with or without immune checkpoint inhibitors (ICIs), similar to treatment approaches for driver-gene negative populations. Upon failure of first-line treatment, trastuzumab deruxtecan, may be considered as alternative therapeutic options. For patients with HER-2 overexpression, ADCs should be considered after failure of standard systemic therapy. However, the management of HER-2 amplification remains insufficiently supported by evidence, necessitating a cautious, individualized approach. The consensus also includes detailed recommendations for screening and managing adverse effects associated with ADCs, such as interstitial lung disease (ILD), emphasizing the crucial role of safety management in ensuring treatment efficacy. The publication of this consensus aims to drive the standardization of molecular diagnosis and treatment pathways for HER-2 variant NSCLC, improve clinical outcomes and quality of life for patients, and facilitate the implementation of personalized precision treatment strategies.
Humans
;
Carcinoma, Non-Small-Cell Lung/pathology*
;
Lung Neoplasms/pathology*
;
Receptor, ErbB-2/metabolism*
;
Mutation
;
Immunoconjugates/therapeutic use*
;
Consensus
;
Trastuzumab/therapeutic use*
;
Camptothecin/analogs & derivatives*
3.Correlation between the skin surface temperature at the related back-shu points and the pulmonary ventilation function in patients with chronic persistent asthma based on the theory of "lung governing the skin and hair".
Shaoqian ZHAO ; Mengyu FU ; Nanxin HUANG ; Jipeng ZHOU ; Jinglin HUANG ; Wei LIU ; Hesheng WANG ; Lanying LIU
Chinese Acupuncture & Moxibustion 2025;45(3):274-279
OBJECTIVE:
To observe the skin surface temperature at the related back-shu points in the patients with the different levels of pulmonary ventilation function in chronic persistent asthma, and to explore the correlation between the skin temperature at the back-shu points and pulmonary ventilation function indexes based on "lung governing the skin and hair".
METHODS:
Sixty-one patients with chronic persistent asthma, based on the level of pulmonary ventilation function, were assigned into a reduced pulmonary ventilation function group (reduced function group, 32 cases) and a normal pulmonary ventilation function group (normal function group, 29 cases). In the two groups, the skin surface temperature was measured in the sites of bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23); and the pulmonary ventilation function indexes (the percentage of predicted value of forced vital capacity [FVC%pred], the percentage of predicted value of forced expiratory volume in the first second [FEV1%pred], the percentage of predicted value of FEV1/FVC [FEV1/FVC%pred] and the percentage of predicted value of the peak expiratory flow [PEF%pred]) were recorded. The correlation between the skin surface temperature of acupoints and pulmonary ventilation function was analyzed.
RESULTS:
Compared with the normal function group, the surface skin temperature at the bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23) was higher in the reduced function group (P<0.05, P<0.01). Compared with the normal function group, FEV1%pred, FEV1/FVC%pred and PEF%pred were decreased in the reduced function group (P<0.001). There was no significant difference in FVC%pred between the two groups (P>0.05). The skin surface temperature at the bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23) was negatively correlated with FVC%pred, FEV1%pred, FEV1/FVC%pred and PEF%pred in 61 patients with chronic persistent asthma (P<0.001, P<0.01, P<0.05).
CONCLUSION
The skin surface temperature at back-shu points is elevated in line with the the decline of pulmonary ventilation function in the patients with chronic persistent asthma, presenting a negative correlation with pulmonary ventilation function indexes. It is preliminarily verified that back-shu point is characterized by reflecting the visceral disorders.
Humans
;
Female
;
Male
;
Asthma/therapy*
;
Middle Aged
;
Adult
;
Skin Temperature
;
Lung/physiopathology*
;
Acupuncture Points
;
Pulmonary Ventilation
;
Aged
;
Chronic Disease/therapy*
;
Young Adult
;
Hair
4.SHI Xuemin's experience in treatment of stroke combined with obstructive sleep apnea hypopnea syndrome based on the theory of "stroke of lung qi exhaustion and snoring-like breathing".
Jiting LI ; Ziru YU ; Qian TIAN ; Zhe JI ; Peng ZHANG
Chinese Acupuncture & Moxibustion 2025;45(3):365-369
This article introduces the experience of Academician SHI Xuemin in treatment of stroke combined with obstructive sleep apnea hypopnea syndrome. It is believed that this disease is the syndrome of "stroke of lung qi exhaustion". It is rooted at the deficiency of primary qi, and lung qi declining; and characterized by phlegm stagnation, qi reversion and mind blockage. This disease is manifested as somnolence-like symptoms, snoring-like breathing and sawing-like expectorating. The therapeutic regimen focuses on "governing qihai (sea of qi ), regulating the spirit and adjusting the orifice closure". The main acupoints include Neiguan (PC6), Shuigou (GV26) and Sanyinjiao (SP6) to regain the consciousness and open the orifices. Besides, Renying (ST9) is added to regulate the respiration, Baihui (GV20) and Sishencong (EX-HN1) to harmonize the spirit, and Fengchi (GB20), Wangu (GB12) and Yifeng (TE17) to open the orifice for the treatment of symptoms. It provides a new idea for the clinical diagnosis and treatment of stroke with accompanying symptoms.
Humans
;
Sleep Apnea, Obstructive/complications*
;
Acupuncture Therapy
;
Stroke/physiopathology*
;
Male
;
Acupuncture Points
;
Female
;
Middle Aged
;
Qi
;
Aged
;
Lung/physiopathology*
;
Snoring/physiopathology*
;
Adult
;
Drugs, Chinese Herbal/administration & dosage*
5.Effect of electroacupuncture on intestinal flora in COPD rats based on gut-lung axis theory.
Daohong CHEN ; Ying CHEN ; Wenchuan QI ; Qian ZENG ; Ziyang ZHOU ; Ziwen WANG ; Yongjiang FANG ; Shuguang YU ; Ling ZHAO
Chinese Acupuncture & Moxibustion 2025;45(7):967-981
OBJECTIVE:
To observe the effect of electroacupuncture (EA) on the intestinal flora in rats with chronic obstructive pulmonary disease (COPD) and explore its possible mechanism based on the gut-lung axis theory.
METHODS:
A total of 30 male SD rats of SPF grade were randomly divided into a normal control (NC) group, a model group and an EA group, 10 rats in each one. In the model group and the EA group, COPD model was established by intratracheal instillation of lipopolysaccharide combined with cigarette fumigation. In the EA group, EA was applied at bilateral "Feishu" (BL13) and "Zusanli" (ST36), with disperse-dense waves, in frequency of 4 Hz/20 Hz, current of 1-3 mA, 20 min a time, once a day for 14 days continuously. Before and after modeling, as well as after intervention, body weight was observed; after intervention, the lung function indexes (forced expiratory volume in 0.1 second [FEV0.1], FEV0.1/forced vital capacity [FVC]%, forced expiratory volume in 0.3 second [FEV0.3] and FEV0.3/FVC%) were measured, serum levels of inflammatory factors (tumor necrosis factor-α[TNF-α], interleukin-6[IL-6], interleukin-1β[IL-1β] and interleukin-10[IL-10]) were detected by ELISA, histopathology of lung and colon tissues was observed by HE staining, the intestinal flora were analyzed by 16S rRNA, and the correlations between lung function and intestinal flora were analyzed.
RESULTS:
Compared with the NC group, in the COPD group, the body weight and lung function indexes were reduced (P<0.01); the lung and colon tissues were damaged, the mean linear intercept (MLI) of alveolus and inflammatory cell numbers of 100 μm2 in lung tissue were increased (P<0.01); the serum levels of TNF-α, IL-6 and IL-1β were increased (P<0.01, P<0.05), and the serum level of IL-10 was decreased (P<0.01); α-diversity indexes of intestinal flora were increased (P<0.01); the relative abundance of Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus was increased (P<0.01), the relative abundance of Firmicutes, Actinobacteria, Tenericutes, TM7 and Lactobacillus, Allobaculum, Bifidobacterium, YRC22 was decreased (P<0.01, P<0.05); 31 different expressed metabolic pathways were identified between the two groups. Compared with the COPD group, in the EA group, the body weight and lung function indexes were increased (P<0.01); the damage of lung and colon tissues was improved, the MLI of alveolus was decreased (P<0.05); the serum levels of TNF-α, IL-6 and IL-1β were decreased (P<0.05), and the serum level of IL-10 was increased (P<0.05); α-diversity indexes of intestinal flora were decreased (P<0.01); the relative abundance of Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus was decreased (P<0.01, P<0.05), the relative abundance of Firmicutes, Actinobacteria, Tenericutes, TM7 and Lactobacillus, Allobaculum, Bifidobacterium, YRC22 was increased (P<0.01); 35 different expressed metabolic pathways were identified between the two groups. The lung function was positive related with Actinobacteria, Tenericutes, TM7 and YRC22, and was negative related with Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus.
CONCLUSION
EA may ameliorate lung function and tissue injury of COPD by regulating intestinal flora dysbiosis and inflammatory response, suggesting an anti-inflammatory effect mediated via "gut-lung" axis.
Animals
;
Pulmonary Disease, Chronic Obstructive/genetics*
;
Male
;
Electroacupuncture
;
Rats
;
Rats, Sprague-Dawley
;
Lung/metabolism*
;
Gastrointestinal Microbiome
;
Humans
;
Interleukin-6/immunology*
;
Tumor Necrosis Factor-alpha/immunology*
;
Intestines/microbiology*
;
Interleukin-10/immunology*
6.Acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux for gastroesophageal reflux cough: a randomized controlled trial.
Mingjie TANG ; Wen LU ; Xiaoni ZHANG ; Jiawei GAO ; Xinchang WEI ; Jin LU ; Jia ZHU ; Yulu FENG ; Lejing JIAO ; Xiaofang XIA ; Zhi ZHOU ; Zhaoming CHEN
Chinese Acupuncture & Moxibustion 2025;45(8):1047-1052
OBJECTIVE:
To observe the clinical efficacy of acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux for gastroesophageal reflux cough (GERC).
METHODS:
A total of 120 GERC patients were randomly assigned to an observation group (60 cases, 1 case dropped out) and a control group (60 cases, 1 case was eliminated). The observation group received acupoint thread-embedding treatment at positive response points of governor vessel. If no such points were detected, the following acupoints were used: Dazhui (GV14), Fenghu (Extra), Shendao (GV11), Lingtai (GV10), and Zhiyang (GV9). Treatment was administered once every two weeks. The control group received oral rabeprazole enteric capsules at 20 mg twice daily. All the treatment was given for 6 weeks. Clinical outcomes were assessed using cough symptom score, reflux disease questionnaire (RDQ) score, and Leicester cough questionnaire (LCQ) score before and after treatment in the two groups. Clinical efficacy was also compared between the two groups.
RESULTS:
After treatment, both groups showed decreased cough symptom scores and the each item scores and total scores of RDQ (P<0.001), and increased LCQ scores (P<0.001) compare with those before treatment. The observation group exhibited lower cough symptom score and chest pain, reflux and total score of RDQ, and higher LCQ score compared to those in the control group (P<0.05). The total effective rate in the observation group was 94.9% (56/59), which was higher than 84.7% (50/59) in the control group (P<0.05).
CONCLUSION
Acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux could effectively alleviate cough and reflux symptoms in patients with GERC and improve their quality of life.
Humans
;
Acupuncture Points
;
Gastroesophageal Reflux/physiopathology*
;
Male
;
Female
;
Cough/physiopathology*
;
Middle Aged
;
Aged
;
Acupuncture Therapy
;
Adult
;
Treatment Outcome
;
Lung/physiopathology*
;
Meridians
7.Xujiang Xie's bloodletting therapy combined with Qingyan Lige decoction for acute pharyngitis with lung-stomach heat accumulation: a randomized controlled trial.
Xinhua FAN ; Minfang YUAN ; Guohua LI ; Tingting KANG ; Peiling LI ; Qiang XIE
Chinese Acupuncture & Moxibustion 2025;45(11):1565-1570
OBJECTIVE:
To observe the clinical efficacy of Xujiang Xie's bloodletting therapy combined with Qingyan Lige decoction on acute pharyngitis with lung-stomach heat accumulation.
METHODS:
A total of 88 patients with acute pharyngitis of lung-stomach heat accumulation were randomly divided into an observation group (44 cases, 4 cases dropped out) and a control group (44 cases, 4 cases dropped out). The control group was treated with oral Qingyan Lige decoction, 150 mL each time, twice a day for 6 continuous days. On the basis of the treatment in the control group, Xujiang Xie's bloodletting therapy was applied at bilateral Shaoshang (LU11), Shangyang (LI1), and Erjian (EX-HN6) in the observation group, 0.1-0.5 mL of bloodletting per site, once every other day for 3 times in total. The TCM symptom and sign score, complete blood count (white blood cell [WBC] count, neutrophilic granulocyte percentage [NE%]), inflammation indexes (serum levels of C-reactive protein[CRP], interleukin[IL]-1β, IL-6, tumor necrosis factor [TNF]-α) and immune indexes (??, ??, ??) of the two groups were observed before treatment and after 6 days of treatment, and the clinical efficacy was evaluated.
RESULTS:
After 6 days of treatment, the sore throat scores, redness and swelling scores of pharyngeal mucosa and uvula, pharyngeal dry and burning scores, hyperemia scores of posterior pharyngeal lymphoid follicles, chill and fever scores, total scores of TCM symptom and sign, WBC count, NE%, CRP, IL-1β, IL-6, TNF-α and ?? in both groups were decreased compared with those before treatment (P<0.05), the above indexes in the observation group were lower than those in the control group (P<0.01, P<0.05, P<0.001). After 6 days of treatment, the levels of ?? and ?? in both groups were increased compared with those before treatment (P<0.05), and the above indexes in the observation group were higher than those in the control group (P<0.001). The total effective rate of the observation group was 95.0% (38/40), which was higher than 90.0% (36/40) in the control group (P<0.001).
CONCLUSION
Xujiang Xie's bloodletting therapy combined with Qingyan Lige decoction could improve the symptoms in patients with acute pharyngitis of lung-stomach heat accumulation, inhibit inflammatory response and improve immune function.
Humans
;
Drugs, Chinese Herbal/administration & dosage*
;
Male
;
Female
;
Pharyngitis/drug therapy*
;
Adult
;
Middle Aged
;
Bloodletting
;
Young Adult
;
Lung/drug effects*
;
Combined Modality Therapy
;
Interleukin-6
;
Adolescent
;
Tumor Necrosis Factor-alpha
;
Acute Disease/therapy*
;
Treatment Outcome
8.Effect of governor vessel moxibustion on cardiopulmonary fitness in stable chronic obstructive pulmonary disease with qi deficiency of lung and kidney.
Hongxin CHEN ; Lixia CHEN ; Jing XU ; Mengting CHANG ; Xirong CHENG
Chinese Acupuncture & Moxibustion 2025;45(12):1717-1722
OBJECTIVE:
To observe the effect of governor vessel moxibustion on improving cardiopulmonary fitness in patients with stable chronic obstructive pulmonary disease (COPD) of qi deficiency of lung and kidney.
METHODS:
A total of 40 patients with stable COPD of qi deficiency of lung and kidney were randomized into an observation group (20 cases) and a control group (20 cases). The routine basic treatment and nursing were adopted in the control group. In the observation group, on the basis of the treatment in the control group, governor vessel moxibustion was applied at the area from Dazhui (GV14) to Yaoshu (GV2) of the governor vessel, 1 hour a time, once a week. Both groups were treated for 8 weeks consecutively. The maximal oxygen uptake (VO2max), 6-minute walking test (6MWT) and Borg score, pulmonary function indexes (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC] and ratio of FEV1 and FVC [FEV1/FVC]), chronic obstructive pulmonary disease assessment test (CAT) score, and TCM syndrome score were observed in the two groups before and after treatment respectively.
RESULTS:
After treatment, the VO2max, 6MWT, FEV1, FVC and FEV1/FVC were increased compared with those before treatment in the two groups (P<0.001, P<0.05), the above indexes in the observation group were higher than those in the control group (P<0.05, P<0.01). After treatment, the Borg, CAT and TCM syndrome scores were decreased compared with those before treatment in the two groups (P<0.05, P<0.001), the above indexes in the observation group were lower than those in the control group (P<0.05).
CONCLUSION
Governor vessel moxibustion can effectively improve the cardiopulmonary fitness, clinical symptoms and the quality of life in patients with stable COPD of qi deficiency of lung and kidney.
Humans
;
Moxibustion
;
Pulmonary Disease, Chronic Obstructive/physiopathology*
;
Male
;
Female
;
Middle Aged
;
Aged
;
Qi
;
Lung/physiopathology*
;
Kidney/physiopathology*
;
Acupuncture Points
9.Advancing breast cancer and lung cancer screening: Expert perspectives to advance programmes in Singapore.
Clive TAN ; Ern Yu TAN ; Geak Poh TAN ; Ravindran KANESVARAN
Annals of the Academy of Medicine, Singapore 2025;54(8):498-504
INTRODUCTION:
The high prevalence and mortality rates of breast cancer and lung cancer in Singapore necessitate robust screening programmes to enable early detection and intervention for improved patient outcomes, yet 2024 uptake and coverage remain suboptimal. This narrative review synthesises expert perspectives from a recent roundtable discussion and proposes strategies to advance breast cancer and lung cancer screening programmes.
METHOD:
A 2024 roundtable convened clinical practitioners, health policymakers, researchers and patient advocates discussed current challenges and opportunities for improving cancer screening in Singapore. Perspectives and insights were analysed to identify themes related to existing programme gaps, opportunities for innovation and implementation challenges.
DISCUSSION:
Singapore's national breast cancer screening programme has been in place for over 2 decades, yet screening uptake remains suboptimal. A national lung cancer screening programme, in contrast, is still in its early stages of implementation. Regardless, employment of risk stratification approaches that integrate genetic, demographic and lifestyle factors could enhance screening effectiveness by identifying high-risk indivi-duals, while also taking local epidemiological trends into consideration. Integration of digital health technologies, artificial intelligence and behavioural change models can enhance cancer screening uptake and accuracy to overcome barriers such as low awareness, cultural beliefs and socioeconomic factors that contribute to low participation rates.
CONCLUSION
Key recommendations include enhancing public awareness, refining screening guidelines, expanding access and applying innovative technologies. A coordinated effort among stakeholders is crucial to continually assess and enhance screening programmes to narrow the practice-policy gap and ultimately reduce breast cancer and lung cancer burden in Singapore.
Humans
;
Singapore/epidemiology*
;
Lung Neoplasms/epidemiology*
;
Breast Neoplasms/epidemiology*
;
Early Detection of Cancer/methods*
;
Female
;
Mass Screening/organization & administration*
10.Circulating tumor DNA- and cancer tissue-based next-generation sequencing reveals comparable consistency in targeted gene mutations for advanced or metastatic non-small cell lung cancer.
Weijia HUANG ; Kai XU ; Zhenkun LIU ; Yifeng WANG ; Zijia CHEN ; Yanyun GAO ; Renwang PENG ; Qinghua ZHOU
Chinese Medical Journal 2025;138(7):851-858
BACKGROUND:
Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing.
METHODS:
Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS.
RESULTS:
A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS.
CONCLUSION
ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.
Humans
;
Carcinoma, Non-Small-Cell Lung/pathology*
;
Circulating Tumor DNA/blood*
;
High-Throughput Nucleotide Sequencing/methods*
;
Female
;
Male
;
Lung Neoplasms/pathology*
;
Middle Aged
;
Mutation/genetics*
;
Aged
;
Adult
;
Aged, 80 and over

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