Chinese medical journal pulmonary and critical care medicine最新文献

Background

The synergistic association between metformin and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has been confirmed in in vitro studies. It is still controversial which patients can benefit from metformin plus EGFR-TKIs treatment. Body mass index (BMI) was proved to be independently associated with prolonged progression-free survival (PFS) and overall survival (OS). This study aimed to investigate whether BMI is associated with the synergistic effect of metformin and EGFR-TKIs in advanced EGFR mutation (EGFRm)-positive non-small cell lung cancer (NSCLC) among nondiabetic Asian population.

Methods

We performed a post hoc analysis of a prospective, double-blind phase II randomized clinical trial (COAST, NCT01864681), which enrolled 224 patients without diabetes with treatment-naïve stage IIIB-IV EGFRm NSCLC. We stratified patients into those with a high BMI (≥24 kg/m²) and those with a low BMI (<24 kg/m²) to allow an analysis of the difference in PFS and OS between the two groups. The PFS and OS were analyzed using Kaplan–Meier curves, and the differences between groups were compared using log-rank test.

Results

In the univariate analysis, patients who had a high BMI (n = 56) in the gefitinib + metformin group (n = 28) did not have a better PFS (8.84 months vs. 11.67 months; P = 0.351) or OS (15.58 months vs. 24.36 months; P = 0.095) than those in the gefitinib + placebo group (n = 28). Similar results were also observed in the low-BMI groups. Strikingly, in the metformin plus gefitinib group, patients who had low BMI (n = 69) showed significantly better OS than those with high BMI (24.89 months [95% CI, 20.68 months–not reached] vs. 15.58 months [95% CI, 13.78–31.53 months]; P = 0.007), but this difference was not observed in PFS (10.78 months vs. 8.84 months; P = 0.285).

Conclusions

Our study showed that nondiabetic Asian advanced NSCLC patients with EGFR mutations who have low BMI seem to get better OS from metformin plus EGFR-TKI treatment.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease that affects the quality of life of nearly one-tenth of the global population. Due to irreversible airflow obstruction and progressive lung function decline, COPD is characterized by high mortality and disability rates, which imposes a huge economic burden on society. In recent years, the importance of intervention in the early stage of COPD has been recognized and the concept of early COPD has been proposed. Identifying and intervening in individuals with early COPD, some of whom have few or no symptoms, might halt or reverse the progressive decline in lung function, improve the quality of life, and better their prognosis. However, understanding of early COPD is not yet well established, and there are no unified and feasible diagnostic criteria, which complicates clinical research. In this article, we review evolution of the definition of early COPD over the past 20 years, describe the changes in awareness of this concept, and propose future research directions.

More peripheral pulmonary lesions (PPLs) are detected by low-dose helical computed tomography (CT) either incidentally or via dedicated lung cancer screening programs. Thus, using methods for safe and accurate diagnosis of these lesions has become increasingly important. Transthoracic needle aspiration (TTNA) and transbronchial lung biopsy (TBLB) are routinely performed during the diagnostic workup for PPLs. However, TTNA often carries the risk of pneumothorax, uncontrollable airway hemorrhage, and does not allow mediastinal staging in one procedure. In contrast, traditional TBLB often has a poorer diagnostic yield despite fewer complications. With the ongoing development of technology applied to bronchoscopy, guided bronchoscopy has become widely used and the diagnostic yield of TBLB has improved. Additionally, guided bronchoscopy continues to demonstrate a better safety profile than TTNA. In recent years, robotic-assisted bronchoscopy (RAB) has been introduced and implemented in the diagnosis of PPLs. At present, RAB has two platforms that are commercially available: Monarch™ and Ion™; several other platforms are under development. Both systems differ in characteristics, advantages, and limitations and offer features not seen in previous guided bronchoscopy. Several studies, including cadaveric model studies and clinical trials, have been conducted to examine the feasibility and performance of RAB using these two systems; large multicenter studies are underway. In this review, published experimental results, focusing on diagnostic yield and complications of RAB, are analyzed and the potential clinical application of RAB is discussed, which will enable the operators to have a clear overview of RAB.

Although the clinical efficacies of third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) such as osimertinib in the treatment of non-small cell lung cancer (NSCLC) with EGFR-activating mutations are promising, drug-acquired resistance inevitably occurs whether they are used as first-line or second-line treatment. Therefore, managing the acquired resistance to third-generation EGFR-TKIs is crucial in the clinic for improving patient survival. Great efforts have been made to develop potentially effective strategies or regimens for the treatment of EGFR-mutant NSCLC patients after relapse following these TKIs therapies with the hope that patients will continue to benefit from treatment through overcoming acquired resistance. Although this approach, which aims to overcome drug-acquired resistance, is necessary and important, it is a passive practice. Taking preventive action early before disease progression to manage the unavoidable development of acquired resistance offers an equally important and efficient approach. We strongly believe that early preventive interventions using effective and tolerable combination regimens that interfere with the process of developing acquired resistance may substantially improve the outcomes of EGFR-mutant NSCLC treatment with third-generation EGFR-TKIs. Thus, this review focuses on discussing the scientific rationale and mechanism-driven strategies for delaying and even preventing the emergence of acquired resistance to third-generation EGFR-TKIs, particularly osimertinib.

Background

Tracheal, bronchus, and lung (TBL) cancer imposes a high disease burden globally, and its pattern varies greatly across regions and countries. This study aimed to explore the global burden and temporal trends of TBL cancer from 1990 to 2019.

Methods

Data on incidence, mortality, and disability-adjusted life years (DALYs) metrics (number, crude rate, and age-standardized rates), and the attributable risk fraction of DALY of TBL cancer from 1990 to 2019 in 21 Global Burden of Disease (GBD) regions, four World Bank income regions, 204 countries and territories, and the globe were obtained from the up-to-date GBD 2019 study. We applied estimated annual percentage changes (EAPCs) to the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALY rate (ASDR) to quantify the temporal trends of the TBL cancer burden from 1990–2019. Associations of EAPC of age-standardized rates with universal health coverage (UHC) index at the national level were evaluated with Pearson correlation analysis.

Results

Globally, approximately 2,260,000 new TBL cancer cases, 2,042,600 deaths, and 45,858,000 DALYs were reported in 2019. Combination of all modifiable risk factors, behavioral, environmental, and metabolic risk factors accounted for 79.1%, 66.4%, 33.3%, and 7.9% of global lung cancer DALYs, respectively. The overall ASIR (EAPC: −0.1 [95% confidence interval [CI]: −0.2, −0.1]), ASMR (EAPC: −0.3 [95% CI: −0.4, −0.3]), and ASDR (EAPC: −0.7 [95% CI: −0.7, −0.6]) decreased from 1990 to 2019. The highest mortality rate of TBL cancer occurred in the >85-year-old age group for both sexes among high-income countries (HICs) and upper-middle-income countries (UMCs), and in males aged 80–84 years and females aged >85 years in lower middle-income countries (LMCs). HICs experienced the largest declines in ASIR (−12.6%), ASMR (−20.3%), and ASDR (−27.8%) of TBL cancer between 1990 and 2019, while UMCs had the highest increases in ASIR (16.7%) and ASMR (8.0%) over the period. Eleven (52.4%), 14 (66.7%), and 15 (71.4%) regions of the 21 GBD regions experienced descending trends in ASIR, ASMR, and ASDR of TBL cancer between 1990 and 2019, respectively, with the greatest mean decrease per year (EAPC: −1.7 [95% CI: −2.0, −1.5] for ASIR, −1.9 [95% CI: −2.2, −1.7] for ASMR, and −2.2 [95% CI: −2.5, −2.0] for ASDR) being observed in eastern Europe. The ASIR, ASMR, and ASDR of TBL cancer were deemed to be in decreasing trends in 85, 91, and 104 countries and territories, with the largest decrease in Bahrain (EAPC: −3.0 [95% CI: −3.3, −2.7] for ASIR, −3.0 [95% CI: −3.3, −2.6] for ASMR, and −3.4 [95% CI: −3.8, −3.1] for ASDR). ASIR (r=0.524), ASMR (r=0.411), and ASDR (r=0.353) of TBL cancer were positively associated with UHC index at the national level in 2019.

Conclusions

The TBL cancer burden shows a downward