Special Issue: Lung cancer
The wide application of lung CT scan and lung cancer screening significnatly improves the detection rate of multiple primary lung cancer (MPLC) , namely, lung cancer patients have two or more primaries at the same time. It is a tough problem all the time that how to distinguish between MPLC and intrapulmonary metastases (IM) . Although histological feature analysis is a good means to distinguish them in some circumstances, molecular analysis is also needed generally. Such as the application of next generation sequencing (NGS) is useful for the distinguish between MPLC and IM. For MPLC, surgery remains the main treatment modality. For inoperable MPLC, radiotherapy and local ablation are important treatments. NGS and new therapies such as targeted drug therapy and immune checkpoint inhibitors have become new altenatives for the diagnosis and treatment of MPLC. This article reviews recent advances in the diagnosis and treatment of MPLC.
In China, elderly patients with non-small cell lung cancer (NSCLC) accounts for the highest percentage of lung cancer patients, and most of them are found to have no surgical possibilities at the time of diagnosis. Moreover, these patients are increasing as aging advances. Increasing their survival rate will help to reduce the overall mortality of lung cancer patients. So identifying effective prognostic indicators in NSCLC patients with non-surgical treatment is of great significance in prognostic stratification, which also contributes to clinical studies aiming at improving the survival rate of such patients via prognostic stratification-based treatments.
To investigate the relationship between systemic immune-inflammatory-nutritional index (SIINI) and survival in non-surgically treated elderly patients with NSCLC.
Patients (n=231, ≥65 years old) with first treatment for NSCLC were retrospectively recruited from Hebei General Hospital from January 1, 2014 to June 30, 2018. Clinical characteristics were collected, mainly including age, sex, prevalence of smoking, baseline diseases, BMI, pathology, differentiation, and clinical stage of NSCLC. Some calculated data based on baseline routine blood test parameters, and/or serum albumin, and/or BMI using different approaches were also collected, including neutrophil to lymphocyte ratio (NLR) , derived NLR (dNLR) , platelet to lymphocyte ratio (PLR) , prognostic nutrition index (PNI) , systemic immune-inflammation index (SII) , advanced lung cancer inflammatory index (ALI) and SIINI 〔using a formula proposed in clinical retrospective studies, in which all variables are measured before treatment: (neutrophil count×platelet count×hemoglobin level) / (lymphocyte count×BMI×serum albumin level) 〕. Post-treatment follow-up was conducted till February 1, 2020 through outpatient reexamination, telephone or text messages with death as the endpoint. For assessing prognostic values of NLR, dNLR, PLR, PNI, SII, ALI and SIINI, ROC analysis was performed with defined optimal cut-off value and the area under the curve (AUC) for each indicator (if the AUC value is less than 0.5, then the optimal cut-off value is defined using the median value, by which the AUC value is defined as large or small when it is greater or less than the value) . The survival curves were comparatively analyzed by different patient characteristics. Cox regression analysis was applied to identify the influencing factors of survival. The survival rate curve was visualized using GraphPad Prism 8.0.2.
The optimal cut-off values using NLR, dNLR, PLR, PNI, SII, ALI and SIINI in assessing the prognosis were 3.30, 2.51, 179.99, 273.65, 736.54, 46.05 and 102.89, respectively. The survival curves varied significantly by age, sex, prevalence of smoking, pathology, differentiation, and clinical stage of NSCLC, NLR, dNLR, PLR, ALI, SII, PNI and SIINI (P<0.05) . Further analysis indicated that the difference between the survival curves of 65-70-year-olds and 76-and-over-year-olds was statistically significant (P<0.05) . The survival curves between those with low or moderate differentiation and those with high differentiation were significantly different (P<0.05) . The survival curves of patients with stageⅠ NSCLC were different from those of patients with stage Ⅱ, Ⅲ or Ⅳ NSCLC (P<0.05) . Cox regression analysis revealed that ≥76 years old (P<0.001) , highly differentiated NSCLC (P<0.001) , stage Ⅲ NSCLC (P=0.012) and Ⅳ NSCLC (P<0.001) and SIINI (P=0.001) were prognostic factors of patients. Moreover, there existed significant differences in survival curves by NLR, dNLR, PLR, ALI, SII, PNI, and SIINI (P<0.05) .
We found that SIINI, a new indictor calculated based on immunity, inflammation and nutrition factors, is effective in predicting the overall survival in non-surgically treated elderly patients with NSCLC, and it may be superior to NLR, dNLR, PLR, PNI, SII, ALI in terms of survival prediction-related application and in-depth research.
Immunotherapy represented by programmed death protein-1 (PD-1) inhibitors has gradually become the standard treatment of advanced non-small cell lung cancer (NSCLC) in recent years, changing the treatment landscape of advanced NSCLC. However, most PD-1-related studies excluded patients with NSCLC more than 70 or 75 years, resulting in relatively limited data about the efficacy and safety of PD-1 inhibitors in elderly patients.
This study aims to evaluate the efficacy and safety of PD-1 inhibitors in elderly patients with advanced NSCCL.
This study selected elderly patients with advanced NSCLC over 65 years who received PD-1 inhibitors monotherapy in Department of Thoracic Surgery and Oncology of the Fourth Affiliated Hospital of Gansu University of Traditional Chinese Medicine from October 2018 to November 2021. A total of 63 elderly patients with NSCLC were included. The PD-1 inhibitors of the study were approved in Chinese market, including camrelizumab, sintilimab and pembrolizumab. The data about efficacy and safety of PD-1 inhibitors were collected in the hospital electronic medical record system. All patients were followed up regularly to obtain the long-term prognostic data until 2022-03-15. The efficacy data of PD-1 inhibitors, the prognosis of elderly patients with advanced NSCLC and the toxicity and side effects of PD-1 inhibitors were collected. Cox comparative risk model was used to explore the influencing factors of the prognosis of elderly patients with advanced NSCLC.
The median age of the 63 elderly patients with advanced NSCLC was 71 (65, 89) years. The best response assessment during PD-1 inhibitors therapy showed that no patients had complete response, 14 patients had partial responses, 21 patients had stable status, and 28 patients had progressive status. The objective response rate (ORR) of patients with advanced NSCLC treated with PD-1 inhibitors monotherapy was 22.2% (14/63) , and the disease control rate (DCR) was 66.7% (14/21) . Prognostic data showed that the median progression free survival (PFS) of the 63 patients with advanced NSCLC was 3.3 (2.0, 4.6) months and the median overall survival (OS) was 10.2 (6.1, 14.3) months. Among 63 elderly patients with NSCLC, 46 of them (73.0%) had treatment related adverse reaction during PD-1 inhibitors monotherapy, and the rate of grade 3 or above adverse reactions was 14.3%. The most common adverse reactions were fatigue, diarrhea, rash and abnormal liver function with the rates of 23.8% (15/63) , 19.1% (12/63) , 15.9% (10/63) and 14.3% (9/63) , respectively. Cox comparative risk model analysis suggested that ECOG performance status and number of metastatic lesions might be independent factors of PFS in patients with advanced NSCLC treated with PD-1 inhibittors.
PD-1 blockades monotherapy demonstrated potential efficacy and acceptable safety for elderly patients with NSCLC. ECOG performance status and number of metastatic lesions might be potential risk factors that predict the PFS of the patients.
Post-treatment recurrence is a major difficulty in the treatment of lung cancer, one of the deadliest cancers worldwide. Minimal residual disease (MRD) as a "bridgehead" for the recurrence of solid tumors, is described as the presence of free circulating tumor cells or other tumor cell derivatives in the biological fluid of patients without any clinical cancer symptoms after the primary tumor treatment. China recently issued its first Consensus on the Detection and Clinical Application of MRD in Lung Cancer, aiming at improving the postoperative individualized treatment for lung cancer patients in accordance with the MRD status detected by the liquid biopsy. We reviewed the latest advances in the use of several most widely used body fluids (peripheral blood, urine, saliva, sputum and pleural effusion) in the detection of MRD in lung cancer, and discussed their values in guiding the precise treatment of MRD in lung cancer.
The level of exercise self-efficacy of lung cancer patients affects the establishment of exercise goals and the belief of overcoming difficulties. Understanding the current situation has a good predictive effect on the exercise behavior of lung cancer patients, but there is no norm for exercise self-efficacy assessment tools for lung cancer patients in China, which makes the measurement results lack of reference standards.
To establish the norm of Exercise Self-efficacy Scale for lung cancer patients in Anhui Province.
Anhui Province was divided into northern, central and southern regions according to its geographical location. A total of 1 600 lung cancer patients were selected by regional stratified random sampling from January to August in 2021, and Exercise Self-efficacy Scale was used to investigate them, the mean, percentile and demarcation norm of the scale were established.
A total of 1 600 questionnaires were distributed, 1 459 valid questionnaires were recovered, with an effective recovery rate of 91.19%. The total score of Exercise Self-efficacy Scale for lung cancer patients in Anhui Province was (67.66±14.90) , and the score of efficacy expectation dimension was (63.09±18.13) , the outcome expectation dimension score was (73.48±14.10) . In this study, the mean norm of Exercise Self-efficacy Scale for lung cancer patients in Anhui Province was established according to gender and age groups (young group of 19-35 years old, middle-aged group of 36-59 years old, and elderly group of ≥60 years old) . The results of multiple linear regression analysis showed that gender, age, education level, occupation, regular exercise habits, concomitant diseases, hospital level, department, BMI and regional division were the influencing factors for the total score of exercise self-efficacy in lung cancer patients (P<0.05) . Therefore, the classification norm was established based on the above variables. With 5% as the interval, the percentile norm of the Exercise Self-efficacy Scale for lung cancer patients from 5 to 95 was established. With (-s) , (-0.5s) , (+0.5s) , (+s) as the boundary point, the exercise self-efficacy level of lung cancer patients was divided into five states according to the total score of the scale from low to high: very low, low, medium, high and very high.
This study preliminarily constructed the norm of Exercise Self-efficacy Scale for lung cancer patients in Anhui Province, which can provide a reference standard for the study of exercise self-efficacy level of this population, and also provide a theoretical basis for further exploring the influencing factors of exercise self efficacy in lung cancer patients.
Curative Effect of EGFR-TKIs with Anti-angiogenic Drugs as the Treatment for Patients with Advanced EGFR-mutant Non-small Cell Lung Cancer：a Meta-analysis
Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) will eventually occur in almost all advanced EGFR-mutant non-small cell lung cancer (EGFR-mutant NSCLC) patients although the therapy has been a standard treatment for such patients. But EGFR-TKIs in combination with anti-angiogenic drugsmay prolong the survival time of these patients.
To explore the efficacy and safety of EGFR-TKIs with anti-angiogenic drugs as the treatment for patients with advanced EGFR-mutant NSCLC.
Databases including CNKI, CQVIP, Wanfang Data Knowledge Service Platform, PubMed, EMBase, and The Cochrane Library were searched from inception to July 2021 using subject headings with free-text words, for randomized controlled trials (RCTs) about the first-line treatment of advanced EGFR-mutant NSCLC patients with EGFR-TKIs in combination with anti-angiogenic drugs (combination therapy group) versus EGFR-TKIs alone (monotherapy group) . Two researchers performed literature screening, data extraction (the first author, publication time, the country where the author coming from, study type, sample size, stage of NSCLC, sex, average age, treatment regimen, ECOG PS score, median follow-up time, pathological type, gene mutation type, outcome indicators) , separately, and assessed risk of bias in the included RCTs. STATA 15.0 was used formeta-analysis.
Nine RCTs were included, involving 1 553 patients. Meta-analysis results showed that the combination therapy was associated with longer progression-free survival (PFS) 〔HR=0.61, 95%CI (0.54, 0.70) , P<0.001〕. Further analysis based on PFS revealed that the combination therapy did not significantly prolong the PFS in those aged ≥65 yearsand in those with brain metastases (P>0.05) . Moreover, the combination therapy was not superior to monotherapy in terms of prolonging the overall survival, and improving the objective response rate, and disease control rate (P>0.05) . However, the rate of adverse eventsabove grade 3〔RR=1.77, 95%CI (1.62, 1.94) , P<0.001〕was significantly increased.
By using the combination therapy, advanced EGFR-mutant NSCLC patients may obtain a prolonged PFS, but with increased risk of serious adverse events. In addition, the patients could not obtain a prolonged overall survival, higher objective response rate and disease control rate.
Myelosuppression is one of the most common adverse effects of chemotherapy for lung cancer, in response to chemotherapy-related myelosuppression, modern medicine mostly adopts symptomatic treatment, but there are many limitations.
To investigate the effects of press-needle therapy on pevention of myelosuppression after chemotherapy of lung cancer patients based on the midnight-noon ebb-flow point selection theory.
A total of 142 non-small cell lung cancer (NSCLC) patients during first chemotherapy hospitalized in the respiratory department of Northern Jiangsu People's Hospital from July 2020 to June 2022 were selected and randomly divided into the control group (n=47) , press-needle group (n=48) and timing group (n=47) according to a prior computer-generated random number table and the developed allocation scheme. The control group received routine care measures, the press-needle group received press-needle therapy at acupoints such as Geshu acupoint, Pishu acupoint and Weishu acupoint on the basis of routine care measures, the timing group received press-needle therapy between 7 a.m. and 11 a.m on the day using midnight-noon ebb-flow method on the basis of routine care measures. The changes of blood routine indicators reflecting myelosuppression and the comfort scores before chemotherapy and 3rd, 7th, 14th, 21st days of chemotherapy were observed in the three groups.
The white blood cell count and neutrophil count in the press needle group and timing group were higher than the control group, and the white blood cell count and neutrophil count in the timing group were higher than the press needle group on the 7th and 14th days of chemotherapy (P< 0.05) ; the platelet count in the press needle group and timing group were higher than the control group on the 7th and 14th days of chemotherapy (P< 0.05) . The comfort scores in the press needle group and timing group were higher than the control group on the 7th and 14th days of chemotherapy (P< 0.05) , the comfort scores in the timing group were higher than the press needle group on the 14th day of chemotherapy (P< 0.05) .
The timing press-needle therapy based on the midnight-noon ebb-flow point selection theory can effectively prevent myelosuppression, improve blood routine indicators including white blood cell count, neutrophil count and platelet count, and promot comfort in NSCLC patients after chemotherapy.
Perioperative acute ischemic stroke (POAIS) is a severe complication of surgery, which can increase surgical mortality and reduce patients' quality of life. The pathogeneses are complex and rarely explored, especially in patients with non-small cell lung cancer (NSCLC) .
To investigate the influencing factors of POAIS in NSCLC patients and the predictive value of serum uric acid (SUA) on the occurrence of POAIS in NSCLC patients.
A total of 25 NSCLC patients admitted to the Fourth Hospital of Hebei Medical University from July 2014 to April 2022, who suffered from POAIS following lung resection were selected as the case group, while 126 patients without POAIS were randomly selected as the control group after matching by age and gender. The preoperative baseline data, intraoperative data and postoperative pathology-related data of all patients were collected. Multivariate Logistic regression analysis was performed to explore the influencing factors of POAIS in the NSCLC patients, and the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of preoperative SUA on the development of POAIS in NSCLC patients.
The average age of the 151 patients was (64±7) years, 57.62% (87/151) of whom were male. The multivariate Logistic regression analysis showed that SUA was an influencing factor of POAIS in NSCLC patients〔OR=0.990, 95%CI (0.982, 0.998) , P=0.019〕. The ROC curve indicated that the area under the curve (AUC) of SUA to predict POAIS in NSCLC patients was 0.64, with an optimal threshold value of 307.40 μmol/L, sensitivity and specificity of 58.7% and 76.0%, respectively.
Preoperative SUA level can serve as an independent predictor of POAIS incidence in NSCLC patients. Higher SUA levels at baseline may predict a lower risk of POAIS.
Special Issue: Lung cancer
