Is cryoablation still suitable for advanced non-small cell lung cancer after failure of first-line chemotherapy? A multicenter, prospective, randomized-controlled trial of eighty-seven patients.

The aim of this study was to investigate the therapeutic effect of cryoablation treatment in advanced NSCLC patients who had failed first-line chemotherapy. Eighty-seven patients from ten hospitals in China were enrolled into the study, forty-four patients received cryoablation treatment plus basic treatment (experimental group), and forty-three patients had basic treatment alone (control group). Follow-up was performed once every three months until the end of the study or the death of the patient. The primary endpoints were overall and post-intervention survival; secondary endpoints included tumor markers, solid tumor efficacy, and symptom changes before and after treatment. There was no significant difference in median OS between the two groups of patients (9.0 months vs 11.2 months, P = 0.583). The disease control rate (DCR) and living quality of the experimental group was higher than that of the control group. In terms of OS, indiscriminate use of cryoablation for such patients was not beneficial, though it could improve symptoms of patients. Cryoablation had a significant effect on selected advanced NSCLC patients after the failure of first-line chemotherapy.

Prognostic significance of pyroptosis-related factors in lung adenocarcinoma.

Background: Numerous studies have revealed that the abnormal expression of pyroptosis-related genes is closely related to the prognosis of lung adenocarcinoma (LUAD); however, a comprehensive analysis has yet to be conducted. This study aimed to reveal the influence of pyroptosis-related genes on the prognosis of LUAD and establish a prognostic model based on those genes, in order to evaluate the prognosis of LUAD. Methods: The data of tumor and normal samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential analysis was used to identify pyroptosis-related genes (obtained from the GeneCards database) that were differentially expressed (DE) in TCGA database. Univariate and stepwise multivariate Cox proportional hazards regression analyses were used to screen feature genes related to LUAD overall survival (OS) and construct gene signature. Gene set enrichment analysis (GSEA) was then performed to reveal potential functions related to gene signature. Finally, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to reveal distinctions in each cell-subtype groups in the immune landscape of LUAD. Results: Overall, 26 DE genes (DEGs) associated with pyroptosis were obtained. Among them, 4 (MKI67, BTK, MST1, and TUBB6) were selected as prognostic genes and a 4-gene signature with a good prognostic performance in the TCGA and GEO was constructed. The gene signature was shown to be an independent prognostic factor of LUAD in subsequent analysis. Functional enrichment indicated that the 4-gene signature may participate in the tumorigenesis and development of LUAD through various pathways related to tumor progression to play a prognostic role in LUAD. Additionally, the results of the immune landscape indicated that the 4-gene signature may affect the prognosis of LUAD via cooperating with changes in the immune microenvironment. Conclusions: The key biomarkers and pathways identified in this study would deepen the comprehension of the molecular mechanism of pyroptosis in LUAD. More importantly, the 4-gene signature may serve as a novel potential prognostic model for LUAD.

Development and Validation of a Prognostic Model to Predict Overall Survival for Lung Adenocarcinoma: A Population-Based Study From the SEER Database and the Chinese Multicenter Lung Cancer Database.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small-cell lung cancer (NSCLC). The aim of our study was to determine prognostic risk factors and establish a novel nomogram for lung adenocarcinoma patients. Methods: This retrospective cohort study is based on the Surveillance, Epidemiology, and End Results (SEER) database and the Chinese multicenter lung cancer database. We selected 22,368 eligible LUAD patients diagnosed between 2010 and 2015 from the SEER database and screened them based on the inclusion and exclusion criteria. Subsequently, the patients were randomly divided into the training cohort (n = 15,657) and the testing cohort (n = 6711), with a ratio of 7:3. Meanwhile, 736 eligible LUAD patients from the Chinese multicenter lung cancer database diagnosed between 2011 and 2021 were considered as the validation cohort. Results: We established a nomogram based on each independent prognostic factor analysis for 1-, 3-, and 5-year overall survival (OS) . For the training cohort, the area under the curves (AUCs) for predicting the 1-, 3-, and 5-year OS were 0.806, 0.856, and 0.886. For the testing cohort, AUCs for predicting the 1-, 3-, and 5-year OS were 0.804, 0.849, and 0.873. For the validation cohort, AUCs for predicting the 1-, 3-, and 5-year OS were 0.86, 0.874, and 0.861. The calibration curves were observed to be closer to the ideal 45° dotted line with regard to 1-, 3-, and 5-year OS in the training cohort, the testing cohort, and the validation cohort. The decision curve analysis (DCA) plots indicated that the established nomogram had greater net benefits in comparison with the Tumor-Node-Metastasis (TNM) staging system for predicting 1-, 3-, and 5-year OS of lung adenocarcinoma patients. The Kaplan-Meier curves indicated that patients' survival in the low-risk group was better than that in the high-risk group (P < .001). Conclusion: The nomogram performed very well with excellent predictive ability in both the US population and the Chinese population.

A multicenter randomized controlled trial to assess the efficacy of cancer green therapy in treatment of stage IIIb/IV non-small cell lung cancer.

BACKGROUND: Chemotherapy is the main therapy for stage IIIB/IV non-small cell lung cancer (NSCLC). However, the 5-year survival rate is 6%. Cancer Green Therapy is a novel therapy in China, which refers to cryoablation combined with traditional Chinese medicine (TCM) formula. Our previous retrospective analysis showed that patients with NSCLC had longer survival time and better quality of life after receiving cryoablation combined with TCM formula, compared with patients who received chemotherapy alone. METHODS: This study is a multicenter, randomized, controlled clinical study. The experiment will be carried out in 6 hospitals at the same time, and a total of 450 cases of participants will be randomly assigned to the experimental group and the control group (n = 225). The experimental group will be given cryoablation and 28-days TCM formula, and the control group will be given 4 cycles chemotherapy. After 30 months of follow-up, the efficacy and safety of cryoablation combines with TCM formula in patients with stage IIIB/IV NSCLC will be observed. The primary outcome is overall survival. The secondary outcomes include progression-free survival, objective response rate, and quality of life. We will also conduct a safety evaluation of the treatment at the end of the trial. DISCUSSION: This multicenter, randomized, controlled clinical study not only provides data on the efficacy and safety of cryoablation combined with TCM formula, but also provides a novel treatment strategy for clinicians and advanced NSCLC patients.

Cryoablation for advanced non-small cell lung cancer: a protocol for a systematic review.

INTRODUCTION: National Comprehensive Cancer Network has recommended cryoablation to replace the resection in the treatment of medically operable non-small cell lung cancer (NSCLC). Cryoablation also has been used for the advanced NSCLC in randomised controlled trials. However, they have not been systematically reviewed. Here, we provide a protocol to evaluate the effectiveness and safety of cryoablation in the treatment of advanced NSCLC. METHODS AND ANALYSES: We will search PubMed, Embase, the Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database without language restrictions from inception until 1 February 2020. Trial registers (International Clinical Trials Registry platform, the US National Institutes of Health Ongoing Trials Register and the ISRCTN registry) and reference lists of retrieved articles will also be searched. Two reviewers will independently extract data on participants, interventions, comparisons, outcomes and assess the methodological quality by the Cochrane risk of bias tool. The strength of evidences will be evaluated according to the Grading of Recommendations Assessment, Development and Evaluation approach. Review Manager V.5.3 software will be used for data analyses. Meta-analyses will be performed if the data are sufficiently homogeneous. The primary outcomes will be objective response rate and overall survival. The secondary outcomes will be adverse effects, health-related quality of life, changes of immune indicators and surrogate outcomes (disease control rate, progression-free survival and survival rate). ETHICS AND DISSEMINATION: Ethics approval is not required, as this study will not involve patients. The results of this study will be submitted to a peer-reviewed journal for publication, to inform both clinical practice and further research. PROSPERO REGISTRATION NUMBER: CRD42019138660.