ObjectiveTo systematically review the efficacy and safety of crizotinib in the treatment of non-small cell lung cancer (NSCLC).MethodWe electronically searched databases including the Cochrane Library (Issue 5, 2017), PubMed, Embase, China Biology Medicine Database, China National Knowledge Internet Database, VIP Database and Wangfang Data from the establishment to May 2017. The randomized controlled trials (RCTs), non-RCTs, case series and case reports on crizotinib for NSCLC were included. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, assessed the methodological quality of included studies, then make Meta-analysis and descriptive analysis.ResultA total of 15 studies were included, including 4 RCTs, 1 non-RCT, 4 case series and 6 case reports. The results indicated that the progression-free survival time of crizotinib group was 8 months, which was better than chemotherapy group (4.6 months). The results of Meta-analysis showed that the response rate in the crizotinib group was higher than that in the chemotherapy group [RR=2.35, 95%CI (1.59, 3.46), P<0.000 1]. The one year survival rate in the crizotinib group was 74.5%-78.6%. The incidences of adverse reactions including dysopsia, dysgeusia, diarrhea, vomiting, constipation, transaminase lifts, upper respiratory tract infection, edema and dizziness in the crizotinib group were higher than those in the chemotherapy group (P<0.05), while the incidences of adverse reactions including leukopenia, thrombocytopenia, alopecia and fatigue in crizotinib group were lower than those in the chemotherapy group (P<0.05). Subgroup analysis under precision treatment showed the progression-free survival time of anaplastic lymphoma kinase (ALK)-positive group was 8 months, and it was longer than ALK-negative group of 4 months.ConclusionsBased on current evidence, crizotinib is better than chemotherapy for NSCLC. Due to limited quality of the included studies, the above conclusion needs to be verifed by more high quality studies.
Abstract: Objective To evaluate the significance of expression of vascular endothelial growth factor-C （VEGF-C） and cytokeratin 19 （CK19） in patients with stage I non-small cell lung cancer （NSCLC）. Methods A total of 269 patients with NSCLC who underwent standard lobectomy and lymph node dissection by the same surgical team in our hospital from January 2004 to June 2005 were included in this study. All the clinical data and follow-up results were complete, and all the pathological specimens were well kept. No preoperative or postoperative adjuvant therapy such as radiotherapy and chemotherapy was administered to those patients. Expressions of VEGF-C in cancer tissues was detected by immunohistochemical streptavidin-peroxidase （S-P） method, and CK19 was marked to examine micrometastasis in hilar and mediastinal lymph nodes. Clinical outcomes, pathological results and follow-up data were analyzed in combination with VEGF-C and CK19 expression. Results VEGF-C expression was not statistically different between different category in sex（Hc=1.722，P=0.084）, age （Hc=0.914，P=0.360）, smoking （Hc=2.440，P=0.295）, pathology type （Hc=5.668，P=0.058）or tumor size （Hc=0.165，P=0.920） . VEGF-C expression was statistically different between different groups of pathological differentiation （Hc=29.178，P=0.000). CK19 expression was not statistically different between different category in sex（χ2=0.000，P=0.999）, age （χ2=0.005，P=0.999）, smoking （χ2=2.294，P=0.317）, pathology type （χ2=0.573，P=0.289）, tumor size（χ2=0.006，P=0.999）, and pathological differentiation （χ2=2.927，P=0.231）. Five-year survival rate was statistically different between different grade of VEGF-C expression （χ2=37.318，P=0.000), and was also statistically different between positive group and negative group of CK19 （χ2=39.987，P=0.000). There was statistical difference between different grade of VEGF-C expression and positive rate of CK19 （χ2=25.954，P=0.000). Conclusion Expression of VEGF-C and CK19 is closely related to postoperative 5-year survival of patients with stage I NSCLC. Detection of VEGF-C and CK19 is of great clinical significance as it is helpful to predict patient prognosis and choose proper postoperative adjuvant therapy.
ObjectiveTo analyze the correlation between folate receptor-positive circulating tumor cells (FR+CTC) and the benign or malignant lesions of the lung, and to establish a malignant prediction model for pulmonary neoplasm based on clinical data, imaging and FR+CTC tests.MethodsA retrospective analysis was done on 1 277 patients admitted to the Affiliated Hospital of Qingdao University from September 2018 to December 2019, including 518 males and 759 females, with a median age of 57 (29-85) years. They underwent CTC examination of peripheral blood and had pathological results of pulmonary nodules and lung tumors. The patients were randomly divided into a trial group and a validation group. Univariate and multivariate analyses were performed on the data of the two groups. Then the nomogram prediction model was established and verified internally and externally. Receiver operating characteristic (ROC) curve was used to test the differentiation of the model and calibration curve was used to test the consistency of the model.ResultsTotally 925 patients suffered non-small cell lung cancer and 113 patients had benign diseases in the trial group; 219 patients suffered non-small cell lung cancer and 20 patients had benign diseases in the verification group. The FR+CTC in the peripheral blood of non-small cell lung cancer patients was higher than that found in the lungs of the patients who were in favorite conditions (P<0.001). Multivariate analysis showed that age≥60 years, female, FR+CTC value>8.7 FU/3 mL, positive pleural indenlation sign, nodule diameter, positive burr sign, consolidation/tumor ratio<1 were independent risk factors for benign and malignant lung tumors with a lesion diameter of ≤4 cm. Thereby, the nomogram prediction model was established. The area under the ROC curve (AUC) of the trial group was 0.918, the sensitivity was 86.36%, and the specificity was 83.19%. The AUC value of the verification group was 0.903, the sensitivity of the model was 79.45%, and the specificity was 90.00%, indicating nomogram model discrimination was efficient. The calibration curve also showed that the nomogram model calibration worked well.ConclusionFR+CTC in the peripheral blood of non-small cell lung cancer patients is higher than that found in the lungs of the patients who carry benign pulmonary diseases. The diagnostic model of clinical stage Ⅰ non-small cell lung cancer established in this study owns good accuracy and can provide a basis for clinical diagnosis.
Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.
Objective To evaluate the safety and efficacy of gefitinib in comparison with platinum-based doublets chemotherapy as a first-line precision treatment for advanced non-small cell lung cancer (NSCLC), and find the benefit population of gefitinib. Methods The Cochrane Library, PubMed, Embase, China National Knowledge Internet, VIP database and China Biology Medicine database were searched to collect the randomized contolled trials (RCTs) of gefitinib vs. platinum-based doublets chemotherapy for advanced NSCLC from inception to November, 2017. The data in the included RCTs were extracted, and the qualities were assessed in accordance with Cochrane Collaboration, and a Meta-analysis was conducted with RevMan 5.3 software. Results Four trials were included, including 968 subjects in the gefitinib group and 968 subjects in the chemotherapy group, and a majority of the subjects were diagnosed advanced adenocarcinoma, and all of the subjects were East Asians. The results of Meta-analysis showed that in all population or patients with epidermal growth factor receptor (EGFR) mutation-positive, gefitinib was better than chemotherapy in progression-free survival (PFS) [in all population: hazard ratio (HR)=0.76, 95% confidence interval (CI) (0.67, 0.85), P<0.000 01; in patients withEGFR mutation-positive: HR=0.42, 95%CI (0.35, 0.50), P<0.000 01] and objective response rate (ORR) [in all population: risk ratio (RR)=1.30, 95%CI (1.15, 1.47), P<0.000 1; in patients withEGFR mutation-positive: RR=1.92, 95%CI (1.46, 2.52), P<0.000 01], and there was no significant difference between the two groups in overall survival (OS) (P>0.05); but inEGFR mutation-negative, chemotherapy was better than gefitinib in PFS [HR=2.09, 95%CI (1.05, 4.13), P=0.03]. Subgroup analysis showed that in female patients, for patients with Performance Status (PS) score 0 or 1, and the ones who never smoked, gefitinib was better than chemotherapy in PFS (P<0.05); but there was no significant difference between the two groups in OS (P>0.05). The incidences of rash, itching, dry skin, paronychia, diarrhea, aminotransferase abnormality were higher in the gefitinib group (P<0.05), while the incidences of hair loss, vomiting, nausea, constipation, anorexia, leukopenia, thrombocytopenia, and neutropenia, anemia, fatigue, nerve toxicity reaction were higher in the chemotherapy group (P<0.05). Conclutions Based on the current evidence, in patients with adenocarcinoma of East Asians, the benefit population are those with the characteristics of EGFR mutation-positive, female, never smoking, and PS 0 or 1. In the aspect of safety, the common adverse drug events in subjects treated with gefitinib are the damage of skin mucous membrane, but the incidences of digestive system diseases and the blood system diseases are less in patients treated with gefitinib than those with chemotherapy.
ObjectiveTo evaluate the survival results of surgical resection (SR) and CT-guided percutaneous ablation (PA) for stageⅠnon-small cell lung cancer (NSCLC).MethodsThe PubMed, Web of Science, EMbase, The Cochrane Library, CNKI, VIP, Wanfang databases from inception to June 2021 were searched to collect comparative studies on the survival results between SR and CT-guided PA treatment for stageⅠNSCLC. RevMan 5.3 software was used for statistical analysis of data.ResultsA total of 3 114 patients were included in 11 studies. The results of meta-analysis showed that compared with the PA group, the SR group had a higher 2-year postoperative overall survival (OS) rate (OR=1.44, 95%CI 1.00-2.06, P=0.05), 3-year postoperative OS rate (OR=2.37, 95%CI 1.47-3.81, P<0.001), 5-year OS rate (OR=1.64, 95%CI 1.19-2.28, P<0.01), 5-year progression-free survival rate after operation (OR=2.43, 95%CI 1.54-3.82, P<0.001) and lower local recurrence rate (OR=0.26, 95%CI 0.13-0.54, P<0.001). There were no statistical differences between the two groups in terms of 1-year postoperative OS rate, 1-year, 2-year, and 3-year tumor-related survival rates, 1-year, 2-year tumor-free survival rates, or distant postoperative recurrence rate (P>0.05).ConclusionFor patients with stageⅠNSCLC with optimal basic conditions, surgery is a more appropriate treatment. For patients who cannot withstand surgical injuries or refuse surgery, CT-guided PA is also a potential alternative treatment. However, this conclusion needs to be verified by prospective controlled trials with larger sample sizes and a more rigorous design.
Medical studies have found that tumor mutation burden (TMB) is positively correlated with the efficacy of immunotherapy for non-small cell lung cancer (NSCLC), and TMB value can be used to predict the efficacy of targeted therapy and chemotherapy. However, the calculation of TMB value mainly depends on the whole exon sequencing (WES) technology, which usually costs too much time and expenses. To deal with above problem, this paper studies the correlation between TMB and slice images by taking advantage of digital pathological slices commonly used in clinic and then predicts the patient TMB level accordingly. This paper proposes a deep learning model (RCA-MSAG) based on residual coordinate attention (RCA) structure and combined with multi-scale attention guidance (MSAG) module. The model takes ResNet-50 as the basic model and integrates coordinate attention (CA) into bottleneck module to capture the direction-aware and position-sensitive information, which makes the model able to locate and identify the interesting positions more accurately. And then, MSAG module is embedded into the network, which makes the model able to extract the deep features of lung cancer pathological sections and the interactive information between channels. The cancer genome map (TCGA) open dataset is adopted in the experiment, which consists of 200 pathological sections of lung adenocarcinoma, including 80 data samples with high TMB value, 77 data samples with medium TMB value and 43 data samples with low TMB value. Experimental results demonstrate that the accuracy, precision, recall and F1 score of the proposed model are 96.2%, 96.4%, 96.2% and 96.3%, respectively, which are superior to the existing mainstream deep learning models. The model proposed in this paper can promote clinical auxiliary diagnosis and has certain theoretical guiding significance for TMB prediction.
Objective To evaluate the clinical effectiveness and safety of radiotherapy (RT) combined with hyperthermia (HT) for locally-advanced non-small cell lung cancer (NSCLC). Methods The randomized controlled trials (RCTs) on RT plus HT vs. RT alone for locally-advanced NSCLC were searched in PubMed, The Cochrane Library, EMbase, VIP, CNKI, CBM and other electronic databases from inception to November 2011. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and assessed quality of the included studies independently. Then meta-analyses were performed using RevMan 5.0.2. Results A total of 9 RCTs involving 527 cases were included. The results of meta-analyses showed that compared with the RT alone group, the RT plus HT group could increase the total effective rate (OR=2.08, 95%CI 1.44 to 3.02, P=0.000 1) and the progression-free survival rate (OR=4.85, 95%CI 1.88 to 12.48, P=0.001). However, there were no significant differences between the two groups in the overall survival rate (OR=1.13, 95%CI 0.64 to 1.98, P=0.68), symptoms improve rate (OR=3.37, 95%CI 1.68 to 6.78, P=0.000 6), and other acute adverse reactions. Conclusion Current results of systematic review show that radiotherapy combined with hyperthermia can obviously increase the total effective rate and improve the progression-free survival rate for locally-advanced NSCLC, and doesn’t increase the incidence of adverse reaction. Therefore, radiotherapy combined with hyperthermia is a fairly reasonable and effective treatment method for locally-advanced NSCLC.
Non-small cell lung cancer is one of the primary types of cancer that leads to brain metastases. Approximately 10% of patients with non-small cell lung cancer have brain metastases at the time of diagnosis, and 26%-53% of patients develop brain metastases during the progression of their disease. However, the underlying mechanisms of lung cancer brain metastasis have not been fully elucidated. With the continuous development of single-cell and spatial transcriptomics, the genomic and transcriptomic characteristics of lung cancer brain metastasis are gradually being revealed. In February 2025, the journal Nature Medicine published an article titled "Single-cell and spatial genomic landscape of non-small cell lung cancer brain metastases". This article aims to provide a brief interpretation of the paper for colleagues in research and clinical practice.
Objective To evaluate the clinical efficacy and safety of hyperthermia combined with radiotherapy and chemotherapy (HRCT) for non-small cell lung cancer (NSCLC), so as to provide references for further clinical practice and research. Methods The databases such as The Cochrane Library, PubMed, EMbase, CBM, CNKI, VIP and WanFang Data were searched on computer from the date of their establishment to May 1st of 2011, and other sources as supplied were also retrieved to collect all the relevant randomized controlled trials (RCTs) on comparing HRCT with non-HRCT. The quality of the included trials was assessed according to the Cochrane Handbook 5.1 for Systematic Review and the features of this study as well. Meta-analyses were conducted by using RevMan 5.1 software. Results A total of eight RCTs involving 546 patients were included. The results of meta-analyses showed that: a) Total effective rate: The total effective rate of HRCT was higher than other non-HRCT therapies, and there were significant differences in HRCT compared with radio-chemotherapy, hyperthermia plus chemotherapy, and pure chemotherapy, the OR and 95%CI were 2.05 (1.18, 3.56), 3.41 (1.12, 10.38), and 6.11 (1.20, 31.16), respectively; and b) Safety evaluation: The incidence rates of radiation pneumonitis, radiation esophagitis and granulocytopenia were all lower in the HRCT group than that in the radio-chemotherapy group, but the significant differences were only found in the incidence rate of granulocytopenia (OR=0.34 (0.19, 0.59). Conclusion Compared with other therapies, HRCT tends to improve the clinical efficacy and safety for NSCLC, but this result needs to be proved by more clinical trials. HRCT is superior to the routine radio-chemotherapy in both efficacy and safety, but the relevant evidence for proving its long-term efficacy and safety is still required.