Manejo intervencional del dolor torácico de origen oncológico: propuesta / Interventional management of chest pain cancer origin: proposal

El dolor es un síntoma frecuente de presentación en los casos de cáncer pulmonar y es un dolor refractario debido a la multiplicidad de generadores de dolor. Las presentaciones pueden ser una invasión pleural, metastasis costales, invasión mixta o síndrome costo-pleural, tumor de Pancoast, y metástasis vertebral con o sin invasion paravertebral. Se han desarrollado terapias intervencionales mínimamente invasivas para tratar el dolor, que en etapas tempranas en pacientes con dolor no controlado mejoran su condición de salud, mejoran su rendimiento para enfrentar la enfermedad y su tratamiento, y evitan o retrasan la escalada de opioides con sus efectos adversos asociados. Se requiere estandarizar las técnicas, mejorar la calidad de los ensayos clínicos y desarrollar guías de práctica clínica en un trabajo conjunto con oncología.

Pain is a frequent presenting symptom in cases of lung cancer and it is a refractory pain due to the multiplicity of pain generators. Clinical presentations may be pleural invasion, rib metastasis, mixed invasion or costo-pleural syndrome, Pancoast tumor, and vertebral metastasis with or without paravertebral invasion. Minimally invasive interventional therapies have been developed to treat pain, which in early stages in patients with uncontrolled pain improve their health condition, improve their performance in coping with the disease and its treatment, and prevent or delay the escalation of opioids with their associated side effects. It is necessary to standardize the techniques, improve the quality of clinical trials and develop clinical practice guidelines in a joint effort with oncology.

Comparative analysis of lung cancer incidence and mortality trends and risk factors in China and the United States based on GBD data / 国际肿瘤学杂志

Objective:To conduct comparative analysis of lung cancer incidence and mortality, as well as long-term trends in incidence and mortality rates and risk factors in China and the United States from 1990 to 2019 based on data from the Global Burden of Disease Study 2019 (GBD 2019) .Methods:The GBD 2019 database was used to extract new lung cancer cases, deaths, and age-standardized rate data for the analysis of lung cancer incidence and deaths in China and the United States based on different sex and age groups from 1990 to 2019. Joinpoint software was used to calculate and analyze annual percentage change (APC) and average annual percentage change (AAPC) of age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of lung cancer in China and the United States from 1990 to 2019, and to analyze the long-term trends. Risk factors associated with lung cancer mortality in China and the United States were analyzed using the disability-adjusted life years (DALYs) .Results:New cases of lung cancer in China increased from 257 000 cases in 1990 to 832 900 cases in 2019, and ASIR increased from 30.20/100 000 in 1990 to 41.71/100 000 in 2019; deaths increased from 256 300 cases in 1990 to 757 200 cases in 2019, and ASMR increased from 31.18/100 000 in 1990 to 38.70/100 000 in 2019. ASIR and ASMR for lung cancer in the United States showed a decreasing trend from 1990 to 2019, with ASIR decreasing from 58.87/100 000 in 1990 to 45.13/100 000 in 2019, and ASMR decreasing from 49.35/100 000 in 1990 to 36.11/100 000 in 2019. In terms of gender, the disease burden of lung cancer in Chinese males was higher than that of females in 1990 and 2019, with new cases of lung cancer in males rising from 179 000 in 1990 to 576 200 in 2019, and ASIR rising from 44.29/100 000 in 1990 to 61.74/100 000 in 2019, mortality rising from 177 900 in 1990 to 523 200 in 2019, and ASMR rising from 46.33/100 000 in 1990 to 58.10/100 000 in 2019. The number of new cases of lung cancer in Chinese females rose from 78 100 in 1990 to 256 700 in 2019, and ASIR rose from 18.01/100 000 in 1990 to 24.76/100 000 in 2019; the number of deaths rose from 78 400 in 1990 to 234 000 in 2019, and ASMR rose from 18.63/100 000 in 1990 to 22.86/100 000 in 2019. In 2019, lung cancer incidence rates for males and females in China and the United States showed an increasing and then decreasing trend with age, with incidence rates of lung cancer in Chinese males and females peaking in the age group of 85-89 years old; and in the United States, incidence rates of lung cancer in males peaked in the age group of 85-89 years old, and incidence rates of females peaked in the age group of 80-84 years old. In 2019, it was shown that mortality rate of lung cancer among males in China increased and then decreased with age, reaching a peak in the age group of 85-89 years old, and mortality rate of lung cancer among females increased with age, reaching a peak in the age group of ≥95 years old. In the United States, lung cancer mortality rate for males and females showed an increasing and then decreasing trend with age, peaking in the 85-89 and 80-84 age groups, respectively. Incidence and mortality rates were higher for males than females in all age groups in China and the United States in 1990 and 2019. The analysis results of Joinpoint software showed that ASIR and ASMR of lung cancer in China showed an overall increasing trend from 1990 to 2019, with an AAPC of 1.16% (95% CI: 0.93%-1.38%, P<0.001) for ASIR and 0.78% (95% CI: 0.56%-1.01%, P<0.001) for ASMR, with the most obviously increasing trend in ASIR and ASMR from 1997 to 2004, the APC were 2.84% and 2.58%, respectively. Lung cancer ASIR and ASMR in the United States population showed a decreasing trend, with an AAPC of -1.08% (95% CI: -1.20%-0.96%, P<0.001) for ASIR and -1.05% (95% CI: -1.24%--0.87%, P<0.001) for ASMR. In 1990 and 2019, the major mortality-related risk factor for lung cancer in China and the United States was smoking, and the major mortality-related risk factor for lung cancer in Chinese females was environmental particulate matter pollution. Conclusion:ASIR and ASMR of lung cancer in China show an increasing trend from 1990 to 2019, and ASIR and ASMR of lung cancer in the United States show a decreasing trend. In 2019, incidence rate of lung cancer in males and females in China show an increasing and then decreasing trend with age, mortality rate of lung cancer for males show an increasing and then decreasing trend with age, and mortality rate of lung cancer for females show an increasing trend with age. Lung cancer incidence and mortality rates for males and females in the United States in 2019 show an increasing and then decreasing trend with age. In both 1990 and 2019, incidence rates and mortality rates are higher for males than for females in all age groups in both China and the United States. Smoking is the major mortality-related risk factor for lung cancer in China and the United States, and environmental particulate matter pollution is the major mortality-related risk factor for lung cancer in Chinese females.

Effects of multi-disciplinary nutrition support team on nutritional status and quality of life in lung cancer patients undergoing chemotherapy / 中国实用护理杂志

Objective:To explore the effects of multi-disciplinary nutrition support team on nutritional status and quality of life in lung cancer patients undergoing chemotherapy, so as to provide reference for the formulation of nutritional intervention plans for lung cancer patients undergoing chemotherapy.Methods:This was a quasi experimental study. A total of 74 patients with lung cancer undergoing chemotherapy in Jinshan Hospital of Fudan University from February 2021 to July 2022 were selected as the research object by convenient sampling method. They were divided into two groups according to their admission time, 37 cases of patients from February to August 2021 for the control group, using conventional nursing interventions, 37 cases of patients from September 2021 to July 2022 for the observation group, with multi-disciplinary nutrition support team. A follow-up was conducted for three chemotherapy cycles, serum nutrition indicators and quality of life were compared between the two groups.Results:There were 27 males and 10 females in the control group, aged (68.14 ± 6.82) years old. There were 30 males and 7 females in the observation group, aged (65.92 ± 9.17) years old. There was no significant difference in the serum nutrition indicators and quality of life before intervention between the two groups (all P>0.05). The serum total protein, albumin and prealbumin levels in the observation group were (69.41 ± 5.87), (38.11 ± 4.04) g/L, and (243.57 ± 67.58) mg/L, which were higher than those in the control group (65.54 ± 8.33), (35.78 ± 5.39) g/L, and (200.84 ± 60.84) mg/L, the differences were statistically significant ( t=-2.31, -2.10, -2.86, all P<0.05). After intervention, the observation group showed higher scores for emotional function and overall health/life quality, with (88.29 ± 16.72), (60.36 ± 13.24) points, compared to the control group with (76.80 ± 17.58), (46.40 ± 16.38) points. The scores for fatigue, nausea/vomiting, insomnia, and loss of appetite were (34.53 ± 22.19), (11.26 ± 8.83), (20.72 ± 16.39), (24.32 ± 18.67) points in the observation group, which were lower than the scores in the control group (45.65 ± 22.95), (25.68 ± 18.67), (36.94 ± 23.29), (40.54 ± 22.41) points, all the differences were statistically significant ( t values were -4.03-4.24, all P<0.05). Conclusions:During chemotherapy in lung cancer patients, the multidisciplinary nutrition support team has been shown to significantly improve the patients′ nutritional status and enhance their quality of life.

The construction of a postoperative exercise management program for elderly lung cancer patients based on social cognitive theory / 中国实用护理杂志

Objective:To construct a postoperative exercise management program for elderly patients with lung cancer based on social cognitive theory, and to provide guidance for improving the postoperative exercise ability of elderly patients with lung cancer.Methods:Systematically searched UpToDate, PubMed, Web of Science, Cochrane Library, Medlive, Wanfang, CNKI and other databases for relevant literature on postoperative rehabilitation exercise for elderly patients with lung cancer, with the search time from the establishment of the database to February 13, 2023. Guided by social cognitive theory, a preliminary draft of the postoperative exercise management program for elderly patients with lung cancer was prepared based on the literature research, and the final draft was formed after revising the program content through expert meeting method.Results:The questionnaire recovery rate of expert meeting method was 12/12; the expert authority coefficient was 0.892; the importance coefficient of variation of each item was 0-0.150; the Kendall coordination coefficient was 0.262 ( P<0.001); the final exercise management program included 5 first-level items, 18 second-level items and 42 third-level items. Conclusions:The process of constructing the postoperative exercise management program for elderly patients with lung cancer has scientificity and reliability, and the content has rationality and comprehensiveness, which can provide guidance for improving the postoperative exercise rehabilitation of elderly patients with lung cancer.

Effect of cold peppermint water spray on the thirst and oral comfort in patients undergoing thoracoscopic pulmonary lobectomy / 中国实用护理杂志

Objective:To investigate applications of cold peppermint water spray in patients undergoing thoracoscopic pulmonary lobectomy, so as to establish a effectively thirst management strategy for patients.Methods:By a randomized controlled study method, a total of 100 patients undergoing thoracoscopic pulmonary lobectomy in Xiaogan Central Hospital from May 2022 to May 2023 were convenient collected, they were assigned to experimental group and control group according to the random number table method, with 50 cases in each group. Both groups were implemented routine nursing care, in additional, cold pure water spray (6-10 ℃) was carried out in the control group, while cold peppermint water spray (6-10 ℃) therapy was implemented in the experimental group. The clinical effect was compared by thirst score, salivary flow rate, lip mucosa moistening degree and oral comfort score between the two groups.Results:There were 28 males and 22 females in the control group, aged (58.30 ± 16.64) years old; 30 males and 20 females in the experimental group, aged (58.66 ± 16.68) years old. At 1, 2, 4, 6 h after intervention, the thirst scores were (5.96 ± 1.58), (5.08 ± 1.37), (4.48 ± 1.18), (3.76 ± 0.72) points in the experimental group, lower than those in the control group (6.78 ± 1.04), (5.60 ± 1.09), (5.10 ± 1.16), (4.52 ± 1.09) points, the differences were statistically significant ( t values were 2.10-4.11, all P<0.05). At 2, 4, 6 h after intervention, the salivary flow rate were (0.21 ± 0.04), (0.23 ± 0.05), (0.30 ± 0.08) ml/min in the experimental group, higher than those in the control group (0.18 ± 0.06), (0.19 ± 0.06), (0.21 ± 0.08) ml/min, the differences were statistically significant ( t=2.31, 3.22, 6.57, all P<0.05). At 2, 4, 6 h after intervention, the lip mucosa moistening scores were (2.52 ± 0.93), (2.26 ± 0.75), (1.82 ± 0.83) points in the experimental group, lower than those in the control group (2.98 ± 0.84), (2.88 ± 0.85), (2.30 ± 0.76) points, the differences were statistically significant ( t=2.59, 3.87, 2.38, all P<0.05). At 3, 6 h after intervention, the oral comfort scores were (4.54 ± 0.39), (5.68 ± 1.67) points in the experimental group, higher than in the control group (3.62 ± 0.21), (4.76 ± 1.22) points, the differences were statistically significant ( t=3.19, 3.14, both P<0.05). Conclusions:Cold peppermint water spray can effectively improve the thirst of patients undergoing thoracoscopic pulmonary lobectomy, improve the oral comfort of patients, and provide new ideas for clinical medical staff to care for patients with thirst.

Effect of attachment on coping styles in patients with advanced lung cancer: the chain-mediated role of disease perception and hope / 中国实用护理杂志

Objective:To explore the mediating chain effect between attachment and coping style of disease perception and hope in patients with advanced lung cancer, and to provide theoretical basis for improving coping style in patients with advanced lung cancer.Methods:From October 2021 to June 2022, 354 patients with advanced lung cancer in the First and Second Affiliated Hospitals of Anhui Medical University were selected by convenience sampling. The general information questionnaire, the Experiences in Close Relationships Inventory, the Brief Illness Perception Questionnaire, the Herth Hope Index, and the Medical Coping Modes Questionnaire were used to conduct cross-sectional questionnaire survey. SPSS 25.0 software and Bootstrap method were used to construct and verify the chain mediation model.Results:Finally, 336 patients with advanced lung cancer were included, including 214 males and 122 females, aged 27-79(59.43 ± 8.61) years old. Attachment avoidance score was (3.31 ± 1.01) points, attachment anxiety score was (3.86 ± 1.17) points, illness perception score was (40.07 ± 12.01) points, hope score was (34.05 ± 5.87) points, and face coping score was (18.75 ± 5.34) points in patients with advanced lung cancer. The avoidance coping score was (15.47 ± 1.97) points, and the yielding coping score was (9.62 ± 3.85) points. In patients with advanced lung cancer, attachment avoidance and attachment anxiety were positively correlated with yield coping ( r=0.448, 0.747, both P<0.01), positively correlated with illness perception ( r=0.356, 0.627, both P<0.01), and negatively correlated with hope ( r=-0.406, -0.670, both P<0.01). Illness perception was positively correlated with yield coping ( r=0.744, P<0.01), and negatively correlated with hope ( r=-0.628, P<0.01). Hope was negatively correlated with yield response ( r=-0.769, P<0.01). The mediation model showed that the chain mediating effect of attachment avoidance, illness perception, hope and yield coping was significant in patients with advanced lung cancer, with an effect value of 0.009 and an effect size of 13.95%. The chain mediating effect of attachment anxiety, illness perception, hope and yield coping were significant, with an effect value of 0.010 and an effect size of 8.27%. Conclusions:Attachment can not only directly predict submission coping in advanced lung cancer patients, but also indirectly predict submission coping through the chain mediation of illness perception and hope.

Summary of best evidence for preoperative prehabilitation for patients with lung cancer combined and chronic obstructive pulmonary disease / 中国实用护理杂志

Objective:To search and summarize the best evidence for preoperative prehabilitation in patients with lung cancer complicated by chronic obstructive pulmonary disease and to inform the management of preoperative prehabilitation in patients with lung cancer combined with COPD by clinical providers.Methods:Systematically guideline websites, professional society websites, evidence-based databases, and comprehensive databases were searched for types of literature including clinical decision making, guidelines, expert consensus, evidence summaries, systematic evaluations, Meta-analyses, and randomized controlled trials. The time for the retrieval was from the inception of databases until October 31th, 2023. And the quality of the included literature was evaluated and evidence was extracted, evaluated the quality of the included literature, and extracted evidence.Results:Finally, 18 articles were included, including 8 guidelines, 8 expert consensus, and 2 systematic reviews. Summarized the 30 best evidence in 4 areas of prerehabilitation: need, timing, location, content (including smoking cessation management, respiratory exercise, exercise, nutritional support, and medication management).Conclusions:This study summarizes the best evidence for preoperative prehabilitation in patients with lung cancer combined with chronic obstructive pulmonary disease, and healthcare professionals should be mindful of the need to develop preoperative prehabilitation protocols judiciously, taking into account the specific clinical context during the subsequent translation of the evidence to the clinic.

B1 corrected T1 mapping for distinguishing pathological types and differentiation degrees of lung cancers / 中国医学影像技术

Objective To observe the value of B1 corrected T1 mapping for distinguishing pathological types and differentiation degrees of lung cancers.Methods A total of 74 lesions in 65 patients with lung cancers were prospectively enrolled,including 49 poorly differentiated lesions and 25 moderately or well differentiated ones,i.e.42 adenocarcinomas,14 squamous cell carcinomas and 18 small cell lung cancers(all poorly differentiated).B1 corrected T1 mapping was performed,ROI(ROI1 and ROI2)were delineated using 2 methods,and T1 values of different pathological types and differentiation degrees lung cancers were compared.The receiver operating characteristic(ROC)curves were drawn,and the areas under the curve(AUC)were calculated.Results Significant differences of T1 values were found among different pathological types of lung cancer(all P＜0.05),as well as between small cell lung cancer and the rest 2 types of lung cancer(both P＜0.05).There were significant differences of T1 values between poorly differentiated and moderately well differentiated lung cancer(squamous cell carcinoma+adenocarcinoma)(both P＜0.05).Taken ROI1 T1 value=1 524.21 ms as the cut-off value,the AUC of T1 value for distinguishing poorly differentiated and moderately well differentiated lung cancer(squamous cell carcinoma+adenocarcinoma)was 0.698,with sensitivity of 64.50％and specificity of 76.00％.Taken ROI2 T1 value=1 630.68 ms as the cut-off value,the AUC of T1 value was 0.676,with sensitivity of 54.80％and specificity of 80.00％.Conclusion B1 corrected T1 mapping was helpful for distinguishing pathological types and differentiation degrees of lung cancers.

Research Progress of Spectral CT in Lung Cancer / 中国医学影像学杂志

Conventional CT is an important imaging modality for the evaluation of lung cancer,but it has a single imaging modality.At present,multiparametric imaging techniques of spectral CT(such as virtual monoenergetic imaging,spectral attenuation curves,material decomposition images and material effective atomic number)are valuable in improving the detection rate of lesions,differentiating benign and malignant of lung nodes,assessing lymph node metastasis,pathological staging,efficacy and prognosis of lung cancer.Here,this article summarizes and reviews spectral CT imaging methods and the results of studies related to the above four techniques in lung cancer.

Value of nomogram based on dual-layer detector spectral CT quantitative parameters and conventional CT features for evaluating high-grade pattern of pulmonary invasive non-mucinous adenocarcinoma / 中华放射学杂志

Objective:To explore the value of nomogram based on dual-layer detector spectral CT quantitative parameters and conventional CT feature in evaluating high-grade pattern (HGP) of pulmonary invasive non-mucinous adenocarcinoma.Methods:This study was a case-control study. A total of 71 patients with pathologically confirmed pulmonary invasive non-mucinous adenocarcinoma in the First Affiliated Hospital of Soochow University from February 2022 to May 2023 were retrospectively enrolled, which were divided into HGP and non-HGP groups according to pathological results. Conventional CT features were analyzed, including size, shape, density, internal signs, margins, and pleural retraction. The iodine concentration (IC), electron density (ED), and normalized iodine concentration (NIC) of the lesions in both the arterial phase (AP) and venous phase (VP) were measured. Differences between the two groups were analyzed using independent sample t-test, Mann-Whitney U test, or χ2 test. Multivariate logistic regression analysis was used to select the independent influencing factors of HGP in pulmonary invasive non-mucinous adenocarcinoma, and the conventional CT feature model, the spectral CT quantitative parameter model, and the combined model were constructed and expressed in a nomogram. The area under the curve (AUC) of receiver operating characteristic curve was used to assess the performance of each model, and was compared by DeLong test. Decision curves (DCA) was used to assess the clinical net benefit of the models. Results:There were significant differences between HGP group and non-HGP group in terms of density, lobulation, spiculation, IC AP, IC VP, NIC AP, ED AP and ED VP (all P<0.05). The multivariate logistic regression analysis showed that the solid nodule ( OR=15.452, 95% CI 4.246-56.235, P<0.001), lobulation ( OR=7.069, 95% CI 1.618-30.883, P=0.009), ED AP( OR=1.183, 95% CI 1.064-1.315, P=0.002) and IC VP ( OR=0.231, 95% CI 0.072-0.744, P=0.014) were independent influencing factors for predicting HGP in pulmonary invasive non-mucinous adenocarcinoma. The AUC of the conventional CT feature model, spectral CT quantitative parameter model, and the combined model were 0.835, 0.890, and 0.915, respectively. The AUC of the combined model was better than that of the conventional CT feature model ( Z=2.67, P=0.008). The DCA analysis demonstrated that the nomogram had higher clinical net benefit than the conventional CT feature model. Conclusions:The nomogram based on the quantitative parameters of dual-layer detector spectral CT and conventional CT features have favorable diagnostic efficacy in predicting HGP in pulmonary invasive non-mucinous adenocarcinoma, and can be used as a reliable tool for non-invasive diagnosis of HGP before surgery.

Clinical analysis of 54 cases of lung cancer treated by domestic carbon ion system / 中华放射肿瘤学杂志

Objective:To evaluate clinical prognosis and prognostic factors of patients with early stage (Ⅰ stage) and locally advanced (Ⅱ/Ⅲ stage) lung cancer treated with carbon ion radiotherapy (CIRT).Methods:Clinical data, treatment, adverse reactions, survival and so on of 54 lung cancer patients who received CIRT and follow-up in the Heavy Ion Center of Wuwei Cancer Hospital of Gansu Province from March 2020 to September 2022 were retrospectively analyzed. The survival curve was plotted using Kaplan-Meier method. Difference tests were performed using log-rank test. Logistic regression analysis was used to identify prognostic factors.Results:According to inclusion and exclusion criteria, 54 patients were enrolled in the study, including 10 patients with early stage lung cancer and 44 patients with locally advanced lung cancer. The median follow-up time for 10 patients with early stage lung cancer was 11.0 (6.75, 17.25) months, and the median dose of irradiation was 60 Gy [relative biological effect (RBE)]. Upon the last follow-up, 3 patients had complete response (CR) and 3 patients had partial response (PR). Four patients had stable disease (SD) and no progressive disease (PD). The 1-year and 2-year local control rates (LCR), progression-free survival (PFS) rates and overall survival (OS) rates were 100%. During treatment and follow-up, 2 patients developed grade 1 radiation pneumonia, 1 case of grade 2 radiation pneumonia, 1 case of chest wall injury (chest wall pain), and there were no adverse reactions greater than grade 2. The median follow-up time of 44 patients with locally advanced stage was 12.5 (4.25, 21.75) months, and the median irradiation dose was 72 Gy (RBE). Thirty-two (73%) patients received concurrent chemotherapy during treatment, 20 (45%) patients received sequential chemotherapy after treatment, 14 (32%) patients received immune maintenance therapy and 3 (7%) patients obtained PD and received targeted drugs. Upon the last follow-up, 3 (7%) patients had CR, 17 (39%) patients had PR, 19 (43%) patients obtained SD, and 5 (11%) patients had PD. The 1-year and 2-year LCR were 96.0% and 87.3%, 90.9% and 84.1% for the 1-year and 2-year PFS rates, and 93.2% and 86.4% for the 1-year and 2-year OS rates, respectively. The median OS and PFS of patients were not reached. Multivariate logistic regression analysis showed that maintenance therapy after radiotherapy ( P=0.027) and clinical target volume (CTV) irradiation volume ( P=0.028) were the factors affecting PFS. Simultaneous chemoradiotherapy ( P=0.042) and maintenance therapy after radiotherapy ( P=0.020) were the factors affecting OS. And gross tumor volume (GTV) ≥215 ml ( P=0.068) might be an independent risk factor for grade 2 and above radiation pneumonia. Conclusions:The domestic carbon ion system has definite clinical effect and controllable toxic and side effects in the treatment of early stage and locally advanced lung cancer. The combination of synchronous chemotherapy and further maintenance treatment can significantly improve clinical prognosis of patients without significantly increasing the risk of toxic and side effects.

Predictive value of intratumoral heterogeneity measured by 18F-FDG PET/CT for EGFR mutation of adenocarcinoma / 中华核医学与分子影像杂志

Objective:To investigate the value of traditional metabolic parameters, CT features and intratumoral heterogeneity parameters measured by 18F-FDG PET/CT in predicting the mutation status of the epidermal growth factor receptor (EGFR) gene in patients with adenocarcinoma. Methods:A total of 147 patients (73 males, 74 females, age (59.8±10.2) years) with pathological confirmed adenocarcinoma between January 2016 and June 2020 in the Affiliated Hospital of Jining Medical University were retrospectively included. The differences of clinical data (smoking history, tumor location and clinical stage), CT features (maximum diameter, ground-glass opacity content, lobulation, speculation, cavitation, air-bronchogram, pleural retraction and bronchial cut-off sign), 18F-FDG PET/CT traditional metabolic parameters (SUV max, SUV mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)) and intratumoral heterogeneity parameters ( CV, heterogeneity index (HI)) were analyzed between patients with EGFR mutation and patients with EGFR wild-type. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Multivariate logistic regression was used to analyze the predictors of EGFR mutation. ROC curve analysis was used to evaluate the predictive value of clinical and PET/CT information. Results:Among 147 patients, 87 were with EGFR mutation and 60 were with EGFR wild-type. There were significant differences in gender (male/female), smoking history (with/without), location (peripheral lesion/central lesion), pleural retraction (with/without), SUV max, SUV mean, TLG, CV and HI ( χ2 values: 4.72-23.89, z values: from -2.31 to 5.74, all P<0.05). Multivariate logistic regression analysis showed that smoking history (odds ratio ( OR)=0.167, 95% CI: 0.076-0.366; P<0.001), pleural retraction ( OR=1.404, 95% CI: 1.115-3.745; P=0.012), SUV max ( OR=0.922, 95% CI: 0.855-0.995; P=0.003), TLG ( OR=0.991, 95% CI: 0.986-0.996; P=0.001) and HI ( OR=0.796, 95% CI: 0.700-0.859; P<0.001) were predictors of EGFR mutation. ROC curve analysis showed the AUC of HI was 0.779, with the sensitivity of 76.67%(46/60) and the specificity of 79.31%(69/87). The predictive model was constructed by combining smoking history, pleural retraction, TLG, SUV max and HI, and the AUC was 0.908, with the sensitivity of 88.33%(53/60) and the specificity of 68.97%(60/87). The difference of AUCs between HI and the predictive model was statistically significant ( z=3.71, P<0.001). Conclusion:HI can predict EGFR mutations better, and the predictive value for EGFR mutations can be enhanced when combining HI with smoking history, pleural retraction, TLG and SUV max.

Preoperative prediction of lymphovascular and visceral pleural invasion of lung adenocarcinoma based on 18F-FDG PET radiomics / 中华核医学与分子影像杂志

Objective:To evaluate the predictive value of 18F-FDG PET-based radiomics models for lymphovascular invasion (LVI) and visceral pleural invasion (VPI) in lung adenocarcinoma (LAC) prior to surgery. Methods:Eighty-seven patients with LAC (42 males, 45 females, age: (64.6±9.0) years; 90 lesions) pathologically confirmed in the Affiliated Taizhou People′s Hospital of Nanjing Medical University between August 2018 and August 2022 were retrospectively included. Based on the radiomics features extracted from PET images, the machine learning models were constructed by using the support vector machine (SVM), logical regression (LR), decision tree (DT), and K-nearest neighbor (KNN) algorithm. Stratified sampling (Python′s StratifiedkFold function) was employed to divide the data into training set and test set at a ratio of 8∶2. The model stability was assessed using the 50% discount cross-validation. The ROC curve was drawn, and the AUC was calculated to evaluate the value of radiomics models in predicting LVI and VPI in LAC. Delong test was used to compare AUCs of different models.Results:The radiomics models (SVM, LR, DT, KNN) based on PET images showed good predictive value for LVI and VPI in patients with LAC. For LVI, the AUCs were 0.91, 0.90, 0.91, 0.91 in the training set, and were 0.85, 0.87, 0.77, 0.78 in the test set; for VPI, the AUCs were 0.86, 0.86, 0.84, 0.81 in the training set, and were 0.82, 0.80, 0.69, 0.78 in the test set. The F1 scores of the SVM model were the best (0.59 and 0.66 for predicting LVI and VPI respectively). The Delong test showed that there were no significant differences in AUCs among the four models ( z values: from -1.46 to 1.71, all P>0.05). Conclusions:The machine learning models based on 18F-FDG PET radiomics features are effective in predicting LVI and VPI in patients with LAC prior to surgery. These models can assist clinicians in stratifying the risk of LAC and making informed clinical decisions. The SVM model has the best performance in predicting LVI and VPI.

The role of DNA methylation detection in the early diagnosis and prognosis of lung cancer / 中华检验医学杂志

Lung cancer is the leading type of cancer death, and most patients with lung cancer are diagnosed at an advanced stage and have a very poor prognosis. Although low-dose computed tomography (LDCT) has entered the clinic as a screening tool for lung cancer, its false-positive rate is more than 90%. As one of the epigenetic modifications of research hotspots, DNA methylation plays a key role in a variety of diseases, including cancer.Hypermethylation of tumor suppressor genes and hypomethylation of proto-oncogenes are important events in tumorigenesis and development. Therefore, DNA methylation analysis can provide some useful information for the early screening, diagnosis, treatment and prognosis of lung cancer. Although invasive methods such as tissue biopsy remain the gold standard for tumor diagnosis and monitoring, they also have limitations such as inconvenience in sampling. In recent years, there has been a rapid development of liquid biopsy, which can detect primary or metastatic malignancies and reflect the heterogeneity of tumors. In addition, the blood sample can be collected in a minimally invasive or non-invasive format and is well tolerated in older and frail patients. This article explores some of the emerging technologies for DNA methylation analysis and provides an overview of the application of DNA methylation in the diagnosis and treatment of lung cancer.

Efficacy comparison of simultaneous and staged video-assisted thoracoscopic surgery anatomic segmentectomy for bilateral double primary lung cancer / 肿瘤研究与临床

Objective:To explore the clinical efficacy of simultaneous or staged video-assisted thoracoscopic surgery (VATS) anatomic segmentectomy for bilateral double primary lung cancer (DPLC).Methods:A retrospective cohort study was conducted. The clinical data of 76 patients with bilateral DPLC who underwent VATS anatomic segmentectomy in Luzhou Traditional Chinese Medicine Hospital from February 2020 to August 2022 were retrospectively analyzed, and they were classified into the simultaneous bilateral thoracoscopic surgery group (the simultaneous group, 44 cases) and the staged thoracoscopic surgery group (the staged group, 32 cases) on the basis of the surgical methods. The intraoperative conditions, perioperative indexes and postoperative complications of the two groups were compared.Results:There were no statistically significant differences in the gender, age, pathological type,postoperative TNM staging of both groups (all P > 0.05). The anesthesia awakening time of the first and second stages of surgery in the staged group was (11±3) min and (13±4) min, which was shorter than that in the simultaneous group [(16±4) min] ( t values were 5.27 and 3.51, both P < 0.05). The number of drainage tubes placed in the simultaneous group was less than that in the sum of two stages of the staged group [(1.9±0.5) tubes vs. (2.2±0.5) tubes, t = 3.40, P = 0.001]. The duration of thoracic drainage tube retention, the postoperative total drainage flow, the days of hospitalization, the first postoperative landing time, and the total treatment cost in the first and second stages of surgery in the staged group were lower than those in the simultaneous group (all P < 0.05), while the postoperative total drainage flow, the days of hospitalization, and the total treatment cost in the sum of two stages of the staged group were higher than those in the simultaneous group (all P < 0.05). The total incidence of complications in the simultaneous group was higher than that in the staged group 1 month after surgery [18.18% (8/44) vs. 3.13% (1/32)], and the difference was statistically significant ( χ2 = 4.02, P = 0.045). The scores of activities of daily living, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, and blood oxygen saturation in the simultaneous group were lower than those in the staged group (all P < 0.05). Conclusions:Staged VATS anatomic segmentectomy for bilateral DPLC has few complications and good ability to perform activities of daily living, whereas the treatment cost of simultaneous bilateral thoracoscopic surgery is low. Clinicians may recommend prioritizing simultaneous bilateral thoracoscopic surgery after comprehensively considering the patients ' physical and economic conditions.

Factors influencing the prognosis of patients with laryngeal cancer combined with simultaneous lung cancer based on the SEER database / 肿瘤研究与临床

Objective:To explore the prognostic factors and the relationship between the disease type at initial diagnosis and the disease type causing death in patients with laryngeal cancer combined with simultaneous lung cancer.Methods:The clinicopathological data of 240 patients diagnosed with laryngeal cancer combined with simultaneous lung cancer between January 2004 and December 2015 in the Surveillance, Epidemiology and End Results (SEER) database were retrospectively analyzed. Chi-square test was used to evaluate the relationship between the disease type at initial diagnosis and the disease type causing death in patients with laryngeal cancer combined with simultaneous lung cancer. Kaplan-Meier method was used for survival analysis, and Cox proportional risk model was used to make univariate and multivariate analysis of the factors influencing the overall survival of patients.Results:A total of 240 cases with laryngeal cancer combined with simultaneous lung cancer included 222 males and 18 females, and there were 141 cases aged over 65 years. The disease type at initial diagnosis was not correlated with the disease type causing death of patients ( χ2 = 3.31, P = 0.191). The 1-year, 3-year, and 5-year overall survival rates of these patients were 62.1%, 31.5%, and 16.4%, respectively. Univariate analysis showed that the primary location of laryngeal cancer, primary location of lung cancer, histological grade of lung cancer, pathological type, clinical staging, surgical condition, and radiotherapy influenced the overall survival of patients (all P < 0.05); multivariate analysis showed that the primary location of laryngeal cancer, primary location of lung cancer, histological grade of lung cancer, pathological type, clinical stage, and surgical condition were independent influencing factors for overall survival of patients with laryngeal cancer combined with simultaneous lung cancer (all P < 0.05). Conclusions:The independent factors influencing the prognosis of laryngeal cancer with simultaneous lung cancer patients include the primary focus of laryngeal cancer, the primary focus of lung cancer, the histological grade of lung cancer, the pathological type, the clinical stage, and the surgical condition. And there is no correlation between the disease type at initial diagnosis and the disease type causing death.

Clinical diagnostic value of bronchoscopic narrow band imaging combined with serum HSP70 and Ntn1 for bronchogenic carcinoma / 肿瘤研究与临床

Objective:To investigate the clinical value of bronchoscopic narrow band imaging combined with serum heat shock protein family 70 (HSP70) and netrin-1 (Ntn1) in the diagnosis of bronchogenic carcinoma.Methods:A retrospective cohort study was conducted. A total of 96 patients with suspected central lung cancer combined with airway obstruction admitted to Shanxi Province Cancer Hospital from January 2021 to January 2022 were retrospectively analyzed. Bronchoscopy and narrow band imaging were performed in all patients. Serum HSP70 and Ntn1 levels were measured by using enzyme-linked immunosorbent assay (ELISA). Pathological biopsy was taken as the gold standard. Receiver operating characteristic (ROC) curves were used to analyze the value of bronchoscopic narrow band imaging combined with serum HSP70 and Ntn1 in the diagnosis of bronchogenic carcinoma.Results:There were 70 males and 26 females in 96 suspected patients, with the age of (46±5) years. According to the pathological results, 72 were diagnosed with central lung cancer, including 43 cases of squamous cell carcinoma, 24 cases of adenocarcinoma, 3 cases of small cell carcinoma, 2 undifferentiated cases,and 24 cases of benign lesions in lung. The sensitivity, specificity, and accuracy of bronchoscopic narrow band imaging in the diagnosis of bronchogenic carcinoma were 90.3%, 79.2% and 87.5%, respectively. The serum HSP70 and Ntn1 levels in patients with lung cancer were higher than those in benign patients (all P < 0.05). ROC curves showed that the optimal cut-off values of HSP70 and Ntn1 in the diagnosis of bronchogenic carcinoma were 10.08 ng/ml and 562.82 pg/ml, respectively. The sensitivity, specificity, and accuracy of serum markers (HSP70 + Ntn1) in the detection of bronchogenic carcinoma were 93.1%, 58.3% and 84.4%, respectively. The sensitivity, specificity, and accuracy of bronchoscopic narrow band imaging combined with serum markers in the diagnosis of bronchogenic carcinoma were 98.6%, 87.5% and 95.8%, respectively; and the diagnostic accuracy of the combined method was higher than that of a single detection method such as bronchoscopic narrow band imaging or serum indexes ( χ2 values were 4.36, 7.07, all P < 0.05). Conclusions:Bronchoscopic narrow band imaging has a good diagnostic value for bronchogenic carcinoma, and the combination of serum HSP70 and Ntn1 can further improve the clinical diagnostic efficacy.

Global Landscape of Clinical Trials in Lung Cancer / 肿瘤防治研究

Lung cancer, the second most prevalent cancer in the world with a persistently high mortality rate, threatens the life and health of all humanity. With the development of clinical trials, the treatment options for lung cancer have been enriched, and the understanding of the timing of intervention has become more explicit than before. Thus, the prognosis of lung cancer has significantly improved. However, unmet clinical needs still exist. This review provides the global trend of clinical research in lung cancer treatment and describes the evolution of clinical trials in terms of design, implementation, and regulation. The change in study endpoints is conducive to shortening the research and development cycle and accelerating the launch of drugs. The refinement of study populations and therapeutic targets facilitates the realization of the maximum efficacy of precision treatment. The integration of comprehensive and diversified therapeutic strategies and the combination of prevention and treatment further promote the improvement of survival and the alleviation of social burden. This review also proposes a prospective direction for future development of clinical research in lung cancer.

Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities / 中国肺癌杂志

BACKGROUND@#In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.@*METHODS@#A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.@*RESULTS@#MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).@*CONCLUSIONS@#The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.

Impact of Folic Acid on the Resistance of Non-small Cell Lung Cancer Cells to Osimertinib by Regulating Methylation of DUSP1 / 中国肺癌杂志

BACKGROUND@#Drug resistance is the main cause of high mortality of lung cancer. This study was conducted to investigate the effect of folic acid (FA) on the resistance of non-small cell lung cancer (NSCLC) cells to Osimertinib (OSM) by regulating the methylation of dual specificity phosphatase 1 (DUSP1).@*METHODS@#The OSM resistant NSCLC cell line PC9R was establishd by gradually escalation of OSM concentration in PC9 cells. PC9R cells were randomly grouped into Control group, OSM group (5 μmol/L OSM), FA group (600 nmol/L FA), methylation inhibitor decitabine (DAC) group (10 μmol/L DAC), FA+OSM group (600 nmol/L FA+5 μmol/L OSM), and FA+OSM+DAC group (600 nmol/L FA+5 μmol/L OSM+10 μmol/L DAC). CCK-8 method was applied to detect cell proliferation ability. Scratch test was applied to test the ability of cell migration. Transwell assay was applied to detect cell invasion ability. Flow cytometry was applied to measure and analyze the apoptosis rate of cells in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) method was applied to detect the expression level of DUSP1 mRNA in cells. Methylation specific PCR (MSP) was applied to detect the methylation status of the DUSP1 promoter region in each group. Western blot was applied to analyze the expression levels of DUSP1 protein and key proteins in the DUSP1 downstream mitogen-activated protein kinase (MAPK) signaling pathway in each group.@*RESULTS@#Compared with the Control group, the cell OD450 values (48 h, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of extracellular regulated protein kinases (ERK) were obviously increased (P<0.05); the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the DAC group were obviously increased (P<0.05); the apoptosis rate, the expression of p38 MAPK protein, the phosphorylation level of ERK, and the methylation level of DUSP1 were obviously reduced (P<0.05). Compared with the OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously increased (P<0.05). Compared with the FA+OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM+DAC group were obviously increased; the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously reduced (P<0.05).@*CONCLUSIONS@#FA may inhibit DUSP1 expression by enhancing DUSP1 methylation, regulate downstream MAPK signal pathway, then promote apoptosis, inhibit cell invasion and metastasis, and ultimately reduce OSM resistance in NSCLC cells.