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Lung cancer remains the leading cause of cancer-related deaths in men and women worldwide, and 85% of these patients have non-small cell lung cancer. In recent years, the clinical use of targeted drug therapy and immune checkpoint inhibitors has dramatically changed the treatment landscape for advanced NSCLC. The mechanism and the value of targeted therapies have been a hot topic of research, as KRAS is one of the earliest discovered and most frequently mutated oncogenes, which is activated by binding to GTP and triggers a series of cascade reactions in cell proliferation and mitosis. The KRAS protein acts as a molecular switch and is activated by binding to GTP, triggering a series of cascade responses in cell proliferation and mitosis. Clinically, patients with KRAS mutated NSCLC have poor response to systemic medical therapy and poor prognosis. Since the first report of KRAS gene in 1982, research on KRAS targeted therapeutics has been slow, and previous studies such as farnesyltransferase inhibitors and downstream protein inhibitors of KRAS signaling pathway have not achieved the expected results, making KRAS long defined as a "non-druggable target". The deeper understanding of the crystal structure of KRAS has led to the discovery of potential therapeutic sites for KRAS and the development of several drugs directly targeting KRAS, especially KRAS G12C inhibitors such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have shown encouraging results in clinical trials. In recent years, studies on the therapeutic efficacy of immune checkpoint inhibitors for KRAS-mutated NSCLC have made some progress. In this review, we systematically introduce the basic understanding of RAS gene and clinical characteristics of KRAS mutated NSCLC patients, summarize the medical treatments for KRAS mutated NSCLC, including chemotherapy, anti-vascular drug therapy and tumor immunotherapy, and focus on the review and outlook of the research progress of KRAS targeted therapy.
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Male , Humans , Female , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/genetics , Proto-Oncogene Proteins p21(ras)/therapeutic use , Genes, ras , Immune Checkpoint Inhibitors/therapeutic use , Guanosine Triphosphate/therapeutic use , MutationABSTRACT
The morbidity and mortality of non-small cell lung cancer(NSCLC)are among the highest of all malignancies.The mechanisms concerning metronomic chemotherapy include anti-angiogenesis, immune microenvironment regulation, and cytotoxic effects, among others.As an alternative to traditional chemotherapy, metronomic chemotherapy has shown promising outcomes in the treatment of advanced NSCLC.Several clinical trials have explored the application of metronomic chemotherapy in the treatment of advanced NSCLC, either as a monotherapy or in combination with chemotherapy, anti-angiogenic therapy, targeted therapy or immunotherapy.This paper mainly reviews the mechanisms underlying metronomic chemotherapy and its clinical application in advanced NSCLC, in order to provide more evidence for the optimization of NSCLC treatment regimens.
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Objective:To investigate the predictive value of the epithelial cell proliferation(ECP)pathway genes for the prognosis of elderly non-small cell lung cancer patients treated with immunotherapy.Methods:A total of 106 elderly patients aged 70 years and over receiving immunotherapy in the POPLAR and OAK clinical trials were retrospectively analyzed in October 2022.According to the mutation status, patients were divided into an ECP pathway-related gene mutation group(ECP mutation group, n=25)and an ECP pathway-related gene non-mutation group(ECP non-mutation group, n=81). The primary endpoints were overall survival(OS)and progression-free survival(PFS). Differences in survival and efficacy between the two groups were compared, and subgroup analysis was performed on clinical factors and genes involved in the pathway.Pyclone was used to calculate the distribution of major clones and subclones in each patient, and differences in survival were compared.Results:Survival outcomes were worse in the ECP(+ )group than in the ECP(-)group(mOS: 10.9 months vs.17.1 months, HR=1.84, 95% CI: 1.09-3.08, P<0.05; mPFS: 2.8 months vs.4.2 months, HR=1.58, 95% CI: 1.00-2.51, P<0.05). Of all mutations in ECP pathway-related genes, mutations in the RB1 gene had a significant prognostic effect on all patients, with the negative prognostic effect especially prominent in ECP(+ )patients.Compared with ECP(-)patients, ECP(+ )patients had a shorter mOS(6.9 months vs.12.6 months, HR=3.14, 95% CI: 1.10-8.97, P=0.024). Ten patients had clonal mutations and 15 patients had sub-clonal mutations in ECP pathway-related genes and the former had a shorter mPFS than the latter(1.3 months vs.5.3 months, HR=3.23, 95% CI: 1.25-8.37, P=0.011). Conclusions:Gene mutations in the epithelial cell proliferation pathway are a negative prognostic factor in elderly non-small cell lung cancer patients receiving immunotherapy, and mutations located in the clonal cluster have a stronger impact on the prognosis.
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Objective:To investigate the efficacy and safety of recombinant human endostatin(Endostar)combined with platium-contained chemotherapeutic agents in advanced non-small cell lung cancer(NSCLC)patients over 60 years old.Methods:93 advanced NSCLC patients from January 2019 to June 2021 were selected as the research objects.The patients received three days of continuous intravenous infusion of Endostar(210 mg for 72 hours)combined with platinum-containing chemotherapy.The efficacy and toxicities were evaluated according to Response Evaluation Criteria in Solid Tumors(RECIST)version1.1 and National Cancer Institute Common Terminology Criteria for Adverse Events(NCI-CTCAE version 4.0), respectively.Follow-up data were obtained to perform the Kaplan-Meier survival analysis.Results:In our study, the objective remission rate(ORR)and disease control rate(DCR)were 38.7% and 78.5%, respectively.The median progression-free survival(PFS)and overall survival(OS)were 6.8 months and 16.5 months, respectively.A Multivariate analysis showed that tumor staging and TP53 mutation were independent prognostic factors related to PFS and OS in advanced NSCLC patients.Adverse reactions related to Endostar during treatment included arrhythmia in 2 cases(2.2%), myocardial ischemia in 1 case(1.07%)and bloody sputum in 1 case(1.07%), all of which were Grade 1 or Grade 2.Conclusions:The application of three days continuous intravenous infusion of Endostar combined with platium-contained chemotherapeutic agents is worthy to be recommended for clinical application in elderly patients with advanced NSCLC due to its high effective rate and survival advantage, as well as good safety.
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Objective:To investigate the value of pre-therapy 18F-FDG PET/CT radiomic models in differentiating epidermal growth factor receptor (EGFR) exon 19 deletion from exon 21 L858R missense in patients with non-small cell lung cancer (NSCLC). Methods:A total of 172 patients with EGFR mutant NSCLC (54 males, 118 females, age: (56.2±12.5) years) in the Fourth Hospital of Hebei Medical University between January 2015 and November 2019 were retrospectively included. Exon 19 mutation was found in 75 patients and exon 21 mutation was identified in 97 patients. The patients were divided into training set ( n=121) and validation set ( n=51) in a 7∶3 ratio by using random number table. The LIFEx 4.00 package was used to extract texture features of PET/CT images of lesions. The least absolute shrinkage and selection operator (LASSO) algorithm was used for feature screening. Three machine learning models, namely logistic regression (LR), random forest (RF), and support vector machine (SVM) models, were constructed based on the selected optimal feature subsets. The ROC curve analysis was performed to assess the predictive performance of those models. Finally, decision curve analysis (DCA) was used to evaluate the clinical value of the models. Results:Nine radiomics features, including 6 PET features (histogram (HISTO)_Kurtosis, SHAPE_Sphericity, gray level run length matrix (GLRLM)_ low gray-level run emphasis (LGRE), GLRLM_ run length non-uniformity (RLNU), neighborhood grey level different matrix (NGLDM)_Contrast, gray level zone length matrix (GLZLM)_ short-zone low gray-level emphasis (SZLGE)), and 3 CT features (gray level co-occurrence matrix (GLCM)_Correlation, GLRLM_ run percentage (RP), NGLDM_Contrast), were screened by LASSO algorithm. Three machine learning models had similar predictive performance in the training and validation sets: AUCs for the RF model were 0.79, 0.77, and those for the SVM model were 0.76, 0.75, for the LR model were 0.77, 0.75. The DCA showed that the 3 machine learning models had good net benefits and clinical values in predicting EGFR mutation subtypes.Conclusion:18F-FDG PET/CT radiomics provide a non-invasive method for the identification of EGFR exon 19 deletion and exon 21 L858R missense mutations in patients with NSCLC, which may help the clinical decision-making and the formulation of individualized treatment plan.
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Objective:To explore the clinical efficacy of CT-guided 125I seed implantation in patients with oligometastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutations (EGFRm+ ) without progression after first-line EGFR-tyrosine kinase inhibitors (TKIs) treatment. Methods:From January 2015 to January 2019, 89 eligible patients (38 males, 51 females; age: (62±11) years) in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. They were divided into 2 groups according to different treatment methods. The 125I seeds were implanted for oligometastatic lesions and/or primary tumors without progression after first-line EGFR-TKIs therapy in local consolidation treatment group (Group A, n=32). The maintenance treatment group (Group B, n=57) only received EGFR-TKIs until disease progression. The progression-free survival (PFS) and overall survival (OS) of the 2 groups were estimated by Kaplan-Meier curves, and were compared by using log-rank test. Complications in Group A were observed. Results:The follow-up time of the group A and group B were 36.5(31.0, 43.3) months and 30.0(24.0, 35.0) months respectively. The median PFS and OS in group A were 15.0(95% CI: 12.8-17.2 ) months and 37.0(95% CI: 33.9-40.1) months, both of which were significantly longer than those in group B (12.0(95% CI: 10.9-13.1) months and 31.0(95% CI: 28.9-33.1) months; χ2 values: 8.80, 7.15, P values: 0.003, 0.007). In Group A, the total incidence of complications in CT-guided 125I seed implantation was 21.9%(7/32), and the common complications and adverse events were pneumothorax and hemoptysis. Only 1 patient underwent chest tube insertion, and the rest were treated with conservative treatment. No operation related death occurred. Conclusion:CT-guided 125I seed implantation is safe and feasible for patients with EGFRm+ oligometastatic NSCLC without progression after first-line EGFR-TKIs treatment, and can prolong the PFS and OS of patients.
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Objective:To assess the predictive efficacy of 18F-FDG PET/CT-based radiomics models for the mutation status of Kirsten rats sarcoma viral oncogene homolog (KRAS) in patients with non-small cell lung cancer (NSCLC). Methods:From January 2016 to January 2021, the 18F-FDG PET/CT images and KRAS testing of 258 NSCLC patients (180 males, 78 females; age: 33-91 years) in the First Affiliated Hospital of the Air Force Military Medical University were retrospectively analyzed. Patients were randomly divided into training set ( n=180) and validation set ( n=78) in the ratio of 7∶3. Tumor lesions on PET and CT images were drawn respectively, and the radiomics features of PET and CT lesions were extracted. The radiomics features were screened by least absolute shrinkage and selection operator (LASSO). CT radiomics score (RS) model, PET/CT RS model and composite models of PET/CT RS combined with screened clinical information were eventually developed. ROC curves were used to assess the predictive efficacy of these models. Results:The CT RS model included 4 radiomics features and the PET/CT RS model included 4 CT radiomics features and 8 PET radiomics features. The CT RS model and the PET/CT RS model both had significant differences in RS between KRAS mutant and wild-type patients in the training set and validation set ( z values: from -8.30 to -4.10, all P<0.001). In predicting KRAS mutations, the composite model of PET/CT RS combined with age showed AUCs of 0.879 and 0.852 in the training and validation sets respectively, which were higher than those of the CT RS model (0.813 and 0.770) and the PET/CT RS model (0.858 and 0.834). The accuracy of the composite model of PET/CT RS combined with age were 81.67%(147/180) and 79.49%(62/78) in the training set and validation set respectively, which were also higher than those of the CT RS model (75.00%(135/180) and 74.36%(58/78)) and the PET/CT RS model (78.89%(142/180) and 78.21%(61/78)). Conclusion:Models based on radiomics features can predict KRAS gene mutation status, and the composite model combining PET/CT RS and age can improve the prediction performance.
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The morbidity and mortality of lung cancer rank first in the world. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) can significantly prolong survival of patients with advanced non-small cell lung cancer (NSCLC). 18F-FDG PET/CT can evaluate EGFR mutation status and EGFR-TKI efficacy. This article reviews the role of 18F-FDG PET/CT in predicting EFGR mutation, the efficacy and survival prognosis evaluation of EGFR-TKI therapy, as well as the development of latest EGFR-TKI PET imaging agents.
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Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.
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Objective:To explore the values of dynamic 18F-FDG PET/CT semi-quantitative parameters in the differentiation of histological subtypes of non-small cell lung cancer (NSCLC) and the diagnosis of lymph node metastasis. Methods:Twenty-three patients (10 males, 13 females, age (61.5±8.1) years) with NSCLC in Shengjing Hospital of China Medical University were prospectively enrolled between October 2020 and June 2021. All patients underwent 40 min of dynamic PET/CT scan and static scan at 60 min post-injection of 18F-FDG. SUV max, SUV mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary lesions at different stages of PET/CT imaging were evaluated. SUV max of lymph nodes were also analyzed. The histopathological results were considered as the gold standard. Parameters of primary lesions and lymph nodes at different PET/CT imaging stages in different groups were compared by independent-sample t test or Mann-Whitney U test. The diagnostic efficiencies of those parameters were tested by ROC curve and compared by DeLong test. Results:A total of 24 lesions in 23 patients were pathologically confirmed as NSCLC, of which 11 were squamous cell carcinoma and 13 were adenocarcinoma. The SUV max (13.5±3.4 vs 9.6±5.1), SUV mean (8.1±2.2 vs 5.8±3.2) at the third stage of dynamic PET/CT (33-40 min) between squamous cell carcinoma and adenocarcinoma were both significantly different ( t values: 2.20, 2.10, P values: 0.039, 0.048). SUV max, TLG of static PET/CT between the 2 groups were also different ( t=2.22, P=0.037; z=-2.17, P=0.030). ROC curves of those parameters showed that AUCs were between 0.727 and 0.762. Fourteen patients underwent surgery and lymph node dissection. According to the pathological results, lymph nodes in 15 areas were metastatic, the rest in 70 areas were benign. There were significant differences in SUV max at the second stage of dynamic PET/CT (19-26 min) between metastatic and benign lymph nodes (4.0(2.8, 6.2) vs 2.3(1.8, 2.8); z=-4.31, P<0.001), as well as SUV max at the third stage of dynamic PET/CT and static PET/CT between the 2 groups ( z values: -4.59, -4.10, both P<0.001). ROC curves of those 3 parameters showed that the AUCs were 0.856, 0.879 and 0.838 respectively, with no significant differences ( z values: 0.78, 0.34, 1.27, P values: 0.434, 0.734, 0.205). The sensitivity, specificity, and accuracy of the SUV max of the third dynamic imaging stage were 13/15, 90.0%(63/70) and 89.4%(76/85), respectively. Conclusion:Dynamic 18F-FDG PET/CT semi-quantitative parameters have certain clinical significance in the identification of histological subtypes of NSCLC and the diagnosis of metastatic lymph nodes, especially the third stage dynamic imaging has a better diagnostic performance.
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The rapid progress on immunotherapy and targeted therapy has brought long-term survival benefits for locally advanced non-small cell lung cancer (NSCLC). The oncology community has also paid more attention to the local treatment for advanced NSCLC, especially for patients with limited metastatic lesions, also known as oligo-metastasis. Many studies have reported that oligo-metastatic NSCLC patients could benefit from the combination of local and systematic treatment, and even to be cured. In recent years, with the advances in radiation technology, stereotactic body radiation therapy (SBRT) has achieved precise high-dose radiotherapy for small target tumors. Currently, SBRT has been widely applied in the treatment of inoperable early lung cancer, and its application value and safety in patients with advanced lung cancer are also being actively explored. In this article, the research status, progress and future development direction of SBRT in the treatment of oligo-metastatic NSCLC were discussed.
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Objective:To conduct meta analysis to compare the effect of complete resection with or without postoperative radiotherapy (PORT) on survival in stage Ⅲ(N 2) non-small cell lung cancer (NSCLC). Methods:Relevant studies of the efficacy of PORT for stage Ⅲ(N 2) NSCLC were searched from Wanfang Data, PubMed, and Cochrane Library from January 2006 to January 2022. Literature screening, extraction of information and assessment of the risk of bias of the included literature was carried out by two independent researchers. Meta analysis was performed using R4.0.3 software. Results:A total of 12 publications consisting of 2992 patients were included, 1479 cases in the PORT group and 1513 cases in the control group. PORT improved the overall survival (OS) and disease free survival (DFS) compared to the control group. Fixed-effects model meta analysis of 6 randomized controlled trials showed that PORT did not significantly reduce the risk of death ( HR=0.98, 95% CI: 0.80-1.20). Fixed-effects model meta analysis of 6 retrospective studies showed that PORT improved prognosis ( HR=0.68, 95% CI: 0.59-0.79). PORT could improve OS of patients with multiple (station) metastasis of ipsilateral mediastinum and / or submandibular lymph nodes ( HR=0.89, 95% CI: 0.80-0.99). Conclusions:PORT could improve OS and DFS in stage Ⅲ(N 2) NSCLC. A trend towards benefit can be observed in the subgroup with multiple/multi-station N2 metastasis.
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Objective:To compare the adverse reactions, efficacy and survival rate of carbon ion beam irradiation in the elective lymph node (ENI) drainage area of locally advanced non-small cell lung cancer (LA-NSCLC) with relative biological effect (RBE) dose of 48 Gy using 16 and 12 fractions.Methods:A total of 72 patients with pathologically confirmed LA-NSCLC admitted to Wuwei Heavy Ion Center of Gansu Wuwei Tumor Hospital from June 2020 to December 2021 were enrolled and simple randomly divided into groups A and B, with 36 patients in each group. Patients in groups A and B were treated with carbon ion beam irradiation to the lymph node drainage area with 48 Gy (RBE) using 16 and 12 fractions. The acute and chronic adverse reactions, efficacy and survival rate were observed. The survival curve was drawn by Kaplan-Meier method. Difference test was conducted by log-rank test.Results:The median follow-up time was 13.9 (8.8-15.7) months in group A and 14.6 (6.3-15.9) months in group B. Sixteen (44.4%) patients were effectively treated in group A and 9 (25%) patients in group B. Thirty-four (94.4%) cases achieved disease control in group A and 30 (83.3%) cases in group B. Statistical analysis showed that the overall survival rate in group B was similar to that in group A ( χ2=1.192, P=0.275). Comparison of planning parameters between two groups showed CTV volume, D mean, V 5 Gy(RBE), V 20 Gy(RBE) and V 30 Gy(RBE) of the affected lung, cardiac V 20 Gy(RBE), V 30 Gy(RBE) and D mean, esophageal V 30 Gy(RBE), V 50 Gy(RBE), D max and D mean, D max of the trachea and spinal cord had no significant difference (all P>0.05). No grade 3 or 4 adverse reactions occurred in the enrolled patients during treatment and follow-up. No statistical differences were observed in the acute radiation skin reaction ( χ2=5.134, P=0.077), radiation esophagitis ( χ2=1.984, P=0.371), and advanced radiation pneumonia ( χ2=6.185, P=0.103) between two groups. Conclusions:The two dose fractionation modes of carbon ion therapy system are equally safe in the mediastinal lymphatic drainage area of LA-NSCLC, and the adverse reactions are controllable. The long-term efficacy still needs further observation.
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Objective:To investigate the role of prophylactic cranial irradiation (PCI) in non-small cell lung cancer (NSCLC) by meta-analysis.Methods:Studies published from January 1, 1980 to August 30, 2021 were searched systematically in PubMed, Embase, Cochrane Systematic Review database and China National Knowledge Infrastructure Database. The searching keywords included "non-small cell lung cancer", "randomized controlled trial", "prophylactic cranial irradiation" and "clinical trial". The data extracted from the above studies were analyzed using Review Manager 5.3 and Stata 12.0 software. Outcomes included the development of brain metastases (BM), overall survival (OS), disease-free survival (DFS), toxicity, and quality of life (QoL).Results:Ten trials, including 2005 NSCLC patients, met the inclusion criteria. Patients who underwent PCI had a significantly lower risk of BM than those who did not ( OR=0.29, 95% CI: 0.22-0.40, P<0.001). Compared with non-PCI group, DFS in PCI group was significantly increased ( HR=0.75, 95% CI: 0.63-0.89, P=0.001). However, there was no significant difference in OS ( OR=0.90, 95% CI: 0.69-1.18, P=0.45). In addition, the incidence of fatigue was significantly increased in the PCI group ( OR=2.64, 95% CI: 1.58-4.40, P<0.001). There was no significant difference in cognitive impairment between the PCI and non-PCI groups ( OR=3.60, 95% CI: 0.97-13.32, P=0.06). Conclusions:PCI is the standard treatment for NSCLC. Compared with non-PCI, PCI significantly reduces the incidence of BM and prolongs the DFS of NSCLC patients. The effect of PCI-related toxicity on the QoL and long-term OS needs further study.
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Objective:To investigate the value of preoperative enhanced CT combined with serum cytokeratin fragment 19 (CYFER21-1) and neuron-specific enolase (NSE) in the diagnosis of lymph node metastasis in patients with non-small cell lung cancer (NSCLC).Methods:160 patients with NSCLC admitted to Linyi Cancer Hospital from October 2018 to October 2021 were retrospectively selected. All patients received surgical treatment in our hospital, and 84 patients with lymph node metastasis (metastatic group) and 76 patients without lymph node metastasis (non-metastatic group) were confirmed after surgery. The features of enhanced CT images and serum CYFER21-1 and NSE levels were compared between the two groups before operation, and the value of each index in the diagnosis of lymph node metastasis in patients with NSCLC alone and in combination was analyzed by receiver operating characteristic (ROC) curve.Results:The proportions of patients with lesion diameter ≥3.0 cm, pleural depression, lymph node enlargement shown by CT, lymph node short diameter ≥10 mm, lymph node boundary ambiguity and lymph node enhancement in metastatic group were significantly higher than those in non-metastatic group, with statistical significance (all P<0.05). Serum CYFER21-1 and NSE levels in metastatic group were significantly higher than those in non-metastatic group, with statistical significance (all P<0.05). The area under curve (AUC) of CYFER21-1 and NSE levels in the diagnosis of lymph node metastasis in NSCLC patients were 0.652 and 0.845, respectively, and the diagnostic cut-off values were 4.81 ng/ml and 24.14 ng/ml, respectively. The sensitivity and specificity of CYFER21-1+ NSE+ enhanced CT in the diagnosis of lymph node metastasis in NSCLC patients were 91.67% and 94.74%. Conclusions:Preoperative enhanced CT is of certain clinical value in the diagnosis of lymph node metastasis in NSCLC patients. Combined with serum CYFER21-1 and NSE levels, enhanced CT can further improve the sensitivity and specificity of diagnosis.
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Objective:To analyze the effects of apatinib on quality of life and immune function in older adult patients with advanced non-small cell lung cancer.Methods:A total of 187 older adult patients with advanced non-small cell lung cancer admitted to Taizhou Cancer Hospital from January 2017 to January 2021 were included in this study. They were divided into the control group ( n = 93) and the observation group ( n = 94). The control group was treated with carboplatin combined with pemetrexed and the observation group was treated with apatinib based on carboplatin and pemetrexed. Sign and symptoms remission was compared between the observation and control groups. The levels of tumor markers, immune function, and quality of life score were compared between the two groups before and after treatment. Results:Total remission rate in the observation group was significantly higher than that in the control group (88.30% vs. 69.89%, χ2 = 9.59, P < 0.05). After treatment, carbohydrate antigen 125, carbohydrate antigen 50, and carcinoembryonic antigen in the observation group were (16.25 ± 5.47) μg/L, (15.23 ± 3.27) μg/L and (5.91 ± 2.66) mg/L, respectively, which were significantly lower than (21.49 ± 6.61) μg/L, (19.11 ± 3.48) μg/L and (10.14 ± 2.73) mg/L in the control group ( t = 5.91, 7.86, 10.73, all P < 0.05). The percentage of CD3 + and CD4 + cells, and the ratio of CD4 +/CD8 + cells in the observation group were (69.34 ± 8.85)%, (38.15 ± 6.52)%, (1.40 ± 0.33), respectively, which were significantly higher than (64.51 ± 8.74)%, (33.55 ± 6.33)%, (1.23 ± 0.25) in the control group ( t = -3.75, -5.36, -3.97, all P < 0.05). Quality of life score was increased in each group ( P < 0.001). The amplitude of increase in quality of life score was greater in the observation group compared with the control group ( P < 0.001). Conclusion:Apatinib can effectively reduce the level of tumor markers and improve immune function in older adult patients with advanced non-small cell lung cancer and improve quality of life.
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Objective:To investigate the risk factors of moderate to severe pain in patients with non-small cell lung cancer within 3 days after lobectomy.Methods:The clinical data of 297 patients with non-small cell lung cancer who underwent lobectomy in the Department of Thoracic Surgery, Sun Yat-sen University Cancer Center from December 2020 to June 2021 were retrospectively analyzed. A numerical rating scale was used to score the most severe pain within 3 days after surgery. Pain score ≥ 4 was defined as moderate to severe pain. The risk factors for moderate to severe pain were analyzed by binary Logistic regression. General linear model repeated measures and linear mixed models were used to analyze the trend of risk factors influencing postoperative pain with time.Results:The incidence of moderate to severe pain was 34.2% (102/297), 59.8% (178/297), 66.4% (198/297), and 28.2% (84/297) on days 0, 1, 2, and 3 after surgery respectively. The risk for moderate to severe pain was significantly higher in patients undergoing thoracotomy than patients undergoing thoracoscopic surgery on days 1 ( OR = 1.99, P = 0.009), 2 ( OR = 3.08, P < 0.001), and 3 ( OR = 3.88, P < 0.001) after surgery. However, the risk for moderate to severe pain in patients undergoing thoracotomy was slightly, but not significantly, higher than that in patients undergoing thoracoscopic surgery ( OR = 1.53, P = 0.087). The risk for moderate to severe pain was higher in female patients than male patients on day 2 ( OR = 1.62, P = 0.077), and in particular on day 3 after surgery ( OR = 2.39, P = 0.002). Prophylactic use of parecoxib significantly reduced the risk of moderate to severe pain on day 0 ( OR = 0.32, P = 0.004), 1 ( OR = 0.20, P < 0.001), 2 ( OR = 0.36, P < 0.001) and 3 ( OR = 0.56, P = 0.047). Conclusion:The incidence of moderate to severe pain on days 1 and 2 after lobectomy was relatively high in patients with non-small cell lung cancer. Patients undergoing thoracotomy have a higher risk of moderate to severe pain than those who underwent thoracoscopic surgery. Female patients have a higher risk for moderate to severe pain on days 2 and 3 after surgery than male patients. Prophylactic use of parecoxib can decrease the risk for moderate to severe pain in patients with non-small cell lung cancer.
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Objective:To investigate the prognostic value of urinary interleukin(IL)-8 in elderly patients with non-small cell lung cancer (NSCLC).Methods:The clinical data of 110 elderly patients with NSCLC treated in Beijing Hepingli Hospital from January 2018 to January 2019 were collected, and the relationship between urinary IL-8 and clinicopathological characteristics were analyzed. The best cut-off value was determined by receiver operating characteristic (ROC) curve. The factors affecting the survival and prognosis of elderly patients with NSCLC were determined by univariable and multivariable Cox proportional hazards regression models.Results:The best cut-off value of urine interleukin-8 for predicting prognostic of elderly patients with NSCLC was 26.08 ng/L, the specificity was 80.00%, the sensitivity was 84.60%. The level of urine IL-8 was related to neutrophil cell count, clinical stage and serum IL-8 level ( P<0.05). The results of Cox multivariate analysis showed that the age ( HR = 4.810, P = 0.000), serum soluble fragment of cytokeratin 19(CYFRA211) ( HR = 2.728, P = 0.017), clinical stage ( HR = 2.090, P = 0.014), urine IL-8 ( HR = 4.451, P = 0.000) were independent risk factors for survival of elderly patients with NSCLC. Conclusions:Urine IL-8 is an independent prognostic risk factor of survival of elderly patients with NSCLC, it can be used as one of the indicators to evaluate the survival prognosis of patients.
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Objective:To explore the efficacy of sequential and concurrent chemoradiotherapy in the treatment of advanced non-small cell lung cancer (NSCLC) in the elderly, and to analyze the influencing factors of prognosis and outcome.Methods:The clinical data of 195 elderly patients with advanced NSCLC admitted to Beijing Shijingshan Hospitaland and Beijing Shijitan Hospital from March 2015 to March 2018 were retrospectively analyzed. They were divided into the concurrent chemoradiotherapy (100 cases) and the sequential chemoradiotherapy (95 cases) according to different chemoradiotherapy regiments. The short-term efficacy, 3-year survival, influencing factors of prognosis and toxic and adverse effects of the two groups were compared.Results:The objective response rate in the concurrent chemoradiotherapy group was significantly higher than that in the sequential chemoradiotherapy group: 61.00%(61/100) vs. 44.21%(42/95), there was statistically difference ( χ2 = 5.51, P<0.05). The 2-year and 3-year survival rate in the concurrent chemoradiotherapy group were 52.00% and 23.00%, which were significantly higher than those in the sequential chemoradiotherapy group: 32.60%, 11.60%, there were statistically differences ( P<0.05). Multivariate analysis results showed that smoking, Karnofsky score<70, TNM stage Ⅲb, short-term efficacy and treatment methods/sequential chemoradiotherapy were independent risk factors ( P<0.05). The incidence of radiation esophagitis, bone marrow suppression and lung function damage in the concurrent chemoradiotherapy group were higher than those in the sequential chemoradiotherapy group: 45.00%(45/100) vs. 27.37% (26/95), 36.00%(36/100) vs. 22.11%(21/95), 48.00%(48/100) vs. 26.32%(25/95), there were statistically differences ( χ2 = 6.54, 4.55, 9.78; P<0.05). Conclusions:Concurrent chemoradiotherapy can improve the short-term efficacy, and improve the 2-year and 3-year survival rates in advanced NSCLC in elderly patients, but the adverse effects are significantly enhanced.
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Objective:To explore the potential categories of post-operative supportive care demand trajectory for patients with non-small cell lung cancer (NSCLC), analyze the influencing factors, and propose targeted interventions.Methods:This was a prospective observational study. A convenient sampling method was used to select 177 NSCLC patients who received surgical treatment in Shanghai Lung Hospital Affiliated to Tongji University from January 2021 to February 2022. The Supportive Care Demand Scale for cancer patients was used to investigate the level of patients′supportive care demand 1 day before operation, 3 days after operation, 1 day before discharge, 1 week after discharge, 1 month after discharge, and 3 months after discharge, and the potential growth model was used to identify the trajectory category and multi category Logistic regression analysis was used to explore the influencing factors.Results:Three supportive care demand trajectories were fitted out in this study, which were the continuous high demand group (46.33%), the slowly decreasing demand group (30.51%), and the low decreasing demand group (23.16%). With the potential category group 3, low demand reduction group as the reference category, Logistic regression analysis showed that high psychological distress, low social support, high disease stage, high comorbidities were more likely to enter the continuous high demand group ( OR = 0.826 to 18.526, all P<0.05), and high education level (college education and above and high school) were more likely to enter the slowly decreasing demand group ( OR = 6.076, 4.199, both P<0.05). Conclusions:The demand track of NSCLC patients for supportive care after surgery has population heterogeneity. Clinical medical staff should provide personalized social support and emotional support for patients with high disease stage, more complications and low education level in the early postoperative period.