Clinical characteristics and influencing factors of chronic obstructive pulmonary disease in patients with non-small cell lung cancer in Hubei province / 公共卫生与预防医学

Objective To analyze the clinical characteristics and influencing factors of non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD) in Hubei province, and to provide a theoretical basis for the diagnosis and treatment of NSCLC patients with COPD. Methods A total of 246 NSCLC patients admitted to our hospital from 2018 to 2020 were selected and divided into control group (without COPD, n=125) and observation group (with COPD, n=121) according to COPD. The clinical characteristics of chest pain, hemoptysis, emasculation, atelectasis and pleural effusion were compared between the two groups. The values of FEV1/FVC, RV/TLC and DLCO in the two groups were measured by pulmonary function detector. The age, gender, smoking, smoking history, proportion of lung squamous cell carcinoma, TNM stage and other clinical data of all subjects were analyzed by self-made survey scale of our hospital. Univariate analysis and logistic regression were used to analyze the risk factors of COPD in NSCLC patients. Results Among 246 NSCLC patients, 121 patients (49.19%) were complicated with COPD, including 76 males and 45 females, and there was a statistical difference between the two groups (χ2=4.891, P>0.05). The average age of the observation group (61.02±4.82) was significantly higher than that of the control group (59.76±4.73) (t=2.069, P0.05). Male (OR=2.982), smoking history (OR=2.623) and lung squamous cell carcinoma (OR=3.147) were risk factors for COPD in NSCLC patients (P<0.05). Conclusions NSCLC patients with COPD are more common in male smokers in Hubei Province, often accompanied by pleural effusion , severe hemoptysis and other symptoms , and their lung function is decreased. Early detection and standardized treatment of COPD in the treatment of NSCLC can improve the prognosis of patients.

Buzhong Yiqitang Regulates Apoptosis via Nrf2/ROS Pathway to Alleviate Cisplatin Resistance in A549/DDP Cells / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Buzhong Yiqitang-containing serum in alleviating the cisplatin resistance in human non-small cell lung cancer （A549/DDP） cells via regulating the nuclear factor E2-related factor 2 （Nrf2）/reactive oxygen species （ROS） signaling pathway. MethodThe serum containing Buzhong Yiqitang was prepared and A549/DDP cells were cultured and randomly grouped： blank （10% blank serum）， cisplatin （10% blank serum+20 mg·L-1 cisplatin）， Buzhong Yiqitang （10% Buzhong Yiqitang-containing serum+20 mg·L-1 cisplatin）， ML385 （10% blank serum+5 μmol·L-1 ML385+20 mg·L-1 cisplatin）， Buzhong Yiqitang+ML385 （10% Buzhong Yiqitang-containing serum+5 μmol·L-1 ML385+20 mg·L-1 cisplatin）， tertiary butylhydroquinone （TBHQ） （10% blank serum+5 μmol·L-1 TBHQ+20 mg·L-1 cisplatin）， and Buzhong Yiqitang+TBHQ （10% Buzhong Yiqitang-containing serum+5 μmol·L-1 TBHQ+20 mg·L-1 cisplatin）. The median inhibitory concentration （IC50） of cisplatin in each group was determined by the cell counting kit-8 （CCK-8） method and the resistance index （RI） was calculated. The apoptosis rate was detected by flow cytometry. The ROS content of each group was determined with the DCFH-DA fluorescence probe. Western blot was employed to determine the protein levels of Nrf2， cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3）， cytochrome C （Cyt C）， and B-cell lymphoma-2 （Bcl-2）. ResultCompared with those in the cisplatin group， the IC50 and RI of A549/DDP cells to cisplatin in Buzhong Yiqitang， ML385， and Buzhong Yiqitang+ML385 groups decreased （P˂0.05）. Compared with the blank group， the cisplatin， Buzhong Yiqitang， ML385， and Buzhong Yiqitang+ML385 groups showed increased apoptosis rate of A549/DDP cells （P˂0.05）. Compared with the blank group， cisplatin promoted the expression of Nrf2 （P˂0.05）. Compared with the cisplatin group， Buzhong Yiqitang， ML385， and Buzhong Yiqitang+ML385 inhibited the expression of Nrf2 （P<0.05）， elevated the ROS level （P˂0.05）， up-regulated the protein levels of cleaved Caspase-3 and Cyt C， and down-regulated the protein level of Bcl-2 （P<0.05）， which were the most significant in the Buzhong Yiqitang+ML385 group. Compared with the cisplatin group， the TBHQ group showed increased IC50 and RI of cisplatin （P<0.05）， decreased apoptosis rate of A549/DDP cells （P<0.05）， up-regulated protein levels of Nrf2 and Bcl-2 （P<0.05）， lowered level of ROS （P˂0.05）， and down-regulated protein levels of cleaved Caspase-3 and Cyt C （P<0.05）. Compared with the TBHQ group， Buzhong Yiqitang+TBHQ decreased the IC50 and RI of cisplatin in A549/DDP cells （P<0.05）， increased the apoptosis rate （P<0.05）， down-regulated the protein levels of Nrf2 and Bcl-2 （P<0.05）， increased ROS （P˂0.05）， and up-regulated the protein levels of cleaved Caspase-3 and Cyt C （P<0.05）. ConclusionBuzhong Yiqitang induced apoptosis by inhibiting Nrf2/ROS pathway to alleviate cisplatin resistance in A549/DDP cells.

Índice neutrófilo-linfocito e índice plaquetas-linfocito: herramientas pronósticas del cáncer de pulmón

El cáncer de pulmón es la neoplasia maligna que causa mayor mortalidad en el mundo. Dentro de los factores pronósticos de esta entidad, se encuentran el índice neutrófilo-linfocito y el índice plaquetas-linfocito, parámetros hematológicos que se utilizan para evaluar la inflamación y la respuesta inmunitaria en el cuerpo humano. Se realizó una revisión bibliográfica con el objetivo de exponer el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón, teniendo en cuenta la evidencia científica publicada hasta el momento. Se estudiaron 46 artículos, 28 de los cuales resultaron seleccionados para la elaboración de la investigación. Se emplearon como criterios de selección la calidad de los estudios, el nivel de actualización sobre el tema en cuestión, así como la fiabilidad de la fuente. Se usaron los recursos disponibles en la red Infomed para la selección de la información, entre ellos: PubMed, SciELO, EBSCO, Cumed, LILACS y Scopus, además de Medline, Academic Search Premier y MedicLatina. Se expuso el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón de células no pequeñas, en todos los estadios y con modalidades terapéuticas diferentes.

Lung cancer is the malignant neoplasm that causes higher mortality in the world. Among the prognostic factors of this entity are the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, hematological parameters that are used to assess inflammation and the immune response in the human body. A bibliographic review was carried out with the objective of exposing the value of the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool for lung cancer, taking into account the scientific evidence published to date. A total of 46 articles were studied, of which 28 were selected for the development of the research. The quality of the studies, the level of updating on the subject in question, as well as the reliability of the source was used as selection criteria. The resources available in the Infomed network were used to select the information, including PubMed, SciELO and EBSCO, Cumed, LILACS and Scopus, as well as Medline, Academic Search Premier and MedicLatina databases. The value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool in non-small cell lung cancer at all stages and with different therapeutic modalities was exposed.

Estadificación quirúrgica del cáncer de pulmón de células no pequeñas: ¿cuándo deberíamos realizar de rutina la resección de los ganglios supraclaviculares? / Surgical staging of non-small cell lung carcinoma: when should we routinely resect supraclavicular lymph nodes?

RESUMEN Antecedentes: la evaluación precisa del estadio del carcinoma pulmonar luego del diagnóstico es esencial para la selección de una terapia apropiada. Objetivo: describir las características de los pacientes con carcinoma de pulmón de células no pequeñas en los cuales la resección ganglionar supraclavicular permitiría detectar metástasis ganglionares no palpables (N3-supraclavicular). Material y métodos: entre diciembre de 2016 y diciembre de 2019 se registraron los datos de pacientes a quienes se les realizó estadificación quirúrgica mediastinal para cáncer de pulmón de células no pequeñas mediante mediastinoscopia cervical y resección de los ganglios supraclaviculares. Resultados: fueron incluidos 60 pacientes, (hombres 76,7%). La media tumoral fue de 4,7 cm y la de estaciones ganglionares evaluadas fue de 2,37 ± 1,44 (DS). En todos se realizó la resección ganglionar supraclavicular y el resultado fue positivo para malignidad epitelial en 21 casos (35%). De los 21 casos N3-supraclavicular, 2 pacientes se registraron como skip metástasis; el resto se asoció a enfermedad mediastinal N2 (p=0,0424). Se observó una asociación significativa entre le presencia de tumor central y de N3-supraclavicular (p=0,0148). Conclusión: se sugiere realizar la resección ganglionar supraclavicular en pacientes con sospecha o confirmación de enfermedad ganglionar N2 y tumores centrales, antes de considerar un enfoque terapéutico multimodal que incluya la cirugía.

ABSTRACT Background: Accurate staging after the diagnosis of lung carcinoma is essential to select an appropriate therapy. Objective: The aim of the present study is to describe the characteristics of patients with non-small cell lung carcinoma in whom supraclavicular lymph node resection would detect non-palpable (N3 supraclavicular disease) lymph node metastases. Material and methods: Data from patients undergoing mediastinal surgical staging for non-small cell lung cancer using cervical mediastinoscopy and resection of supraclavicular lymph nodes were collected between December 2016 and December 2019. Results: A total of 60 patients were included; 76.6% were men. Mean tumor size was 4.7 cm ad mean lymph node stations evaluated by mediastinoscopy was 2.37 ± 1.44 (SD). All the patients underwent supraclavicular lymph node resection and the result was positive for epithelial carcinoma in 21 cases (35%). Of the 21 cases with N3 supraclavicular disease, 2 patients were recorded as skip metastases and the remaining cases were association with mediastinal N2 disease (p = 0.0424). There was a significant association between central tumor and N3 supraclavicular disease (p = 0.0148). Conclusion: Supraclavicular lymph node resection may be recommended in patients with suspected or confirmed N2 lymph node disease and central tumors, before considering a multimodal therapeutic approach including surgery.

Carcinoma tipo-linfoepitelioma pulmonar con expresión de virus de Epstein-Barr y PD-L1 / Pulmonary lymphoepithelioma-like carcinoma with ex pression of Epstein-Barr virus and PD-L1

Resumen El carcinoma tipo-linfoepitelioma pulmonar es una variante rara de carcinoma de células no pequeñas de pulmón, representa aproximadamente 0.7% de todos los casos. Está usualmente asociado con la infección por el virus de Epstein-Barr y es más prevalente en el Sureste de Asia; sin embargo, es extremadamente raro en Améri ca Latina. Informamos el caso de un hombre de 65 años de edad con un carcinoma tipo-linfoepitelioma pulmo nar, que se presentó con tos, disnea y pérdida de peso. La TAC de tórax mostró nódulo mal definido localizado en el pulmón derecho. Se realizó biopsia transtorácica de la lesión, y el estudio microscópico reveló células gran des poligonales dispuestas en mantos, infiltrados por abundantes linfocitos y células plasmáticas, alrededor del intersticio. Las células neoplásicas fueron positivas para citoqueratina 5/6 y p63, y negativas para Napsina A y el factor de transcripción tiroideo 1 (TTF-1). La expre sión de PD-L1 fue positivo (aproximadamente 100%) por inmunohistoquímica; así como el núcleo de las células neoplásicas mediante hibridación in situ para el RNA codificado por el virus de Epstein-Barr (EBER-ISH). El paciente recibió seis ciclos de un esquema combinado de quimioterapia basado en platino (gencitabina/cisplatino) más durvalumab. Presentó progresión de la enfermedad y finalmente murió 9 meses después del diagnóstico.

Abstract Pulmonary lymphoepithelioma-like carcinoma is a rare type of non-small cell lung cancer, it accounts for approximately 0.7% of all cases. It is usually associated with Epstein-Barr virus infection and is more prevalent in Southeast Asia; however, it is extremely rare in Latin America. We present a 65-year-old man with a primary pulmonary lymphoepithelioma-like carcinoma, who presented with cough, dyspnoea and weight loss. Com puter tomographic scan of the thorax showed a nodule localized in the right lung. A transthoracic biopsy of the lung lesion was made and the microscopic obser vation revealed large polygonal cells that proliferated in a nest pattern with infiltration by lymphocytes and plasma cells around the interstitium. The tumour cells were positive for citokeratin 5/6 and p63, and negative for Napsin A and thyroid transcription factor 1 (TTF-1). PD-L1 expression was positive (approximately 100%) in the immunohistochemical study, and the nuclei of the tumour cells were positive for EBV-encoded small RNA in-situ hybridization (EBER-ISH). The patient underwent six cycles of platinum-based combination (gencitabine/ carboplatin) chemotherapy plus durvalumab. He pre sented progression of the disease and finally he died 9 months after diagnosis.

The prognostic value of decrease in prognostic nutritional index in stage III non-small cell lung cancer patients during curative thoracic radiotherapy

Background: Curative thoracic radiotherapy (CTRT) with concurrent chemotherapy has been considered as standard treatment approach for stage-III non-small cell lung cancer (NSCLC). The hematological and esophageal toxicities that have been encountered during CTRT would affect the immunonutritional status of the patients. The aim of this study is to evaluate the prognostic value of the change in pre- and post-treatment prognostic nutritional index (PNI) in stage-III NSCLC patients. Methods: Eighty seven consecutive stage III NSCLC patients� data were collected. Pre-radiotherapy (RT) and post-RT PNI values were calculated and the impact of prognostic value of PNI change on overall survival (OS) was evaluated by univariate and multivariate Cox regression analyses. A cutoff value of PNI change was obtained by receiver operator characteristic (ROC) curve analysis. Results: The cutoff value was found to be a 22% decrease in PNI by ROC curve analysis in terms of effect on OS. The median OS of low and high PNI decrease groups were 22.5 and 16.5 months respectively (P = 0,001). In univariate and multivariate analyses PNI decrease of ? 22% was found to be an independent poor prognostic factor for OS (P = 0.012) and hazard ratio (95% confidence interval)= 2.05 (1.16�62). Conclusion: The PNI change would be a convenient parameter to assess the immunonutrition

Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer / 中华肿瘤杂志

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

Progress of Research on Immune-related Pneumonia in Non-small Cell Lung Cancer / 肿瘤防治研究

In recent years, immunotherapy has made a breakthrough in the field of non-small cell lung cancer, reshaping the pattern of lung cancer treatment. However, with the wide application of immunotherapy in clinical practice, immune-related adverse events have attracted increasing attention. Immune pneumonia, as one of the immune-related toxic side effects of greatest concern, affects the treatment process and curative effect and can be a threat to life in serious cases. Given that immune pneumonia has a complicated pathogenesis and diverse clinical manifestations, strengthening the understanding of immune pneumonia is urgently needed. The treatment of immune pneumonia is limited, and additional therapeutic medicines are still awaiting exploration. Therefore, this paper summarizes the progress of the research on immune pneumonia in the treatment of non-small cell lung cancer.

Predictive Value of Lymphocyte Count Changes on Checkpoint-inhibitor-related Pneumonitis in Patients with Non-small Cell Lung Cancer / 肿瘤防治研究

Objective To investigate the correlation of peripheral blood lymphocyte, T-cell, Th-cell, and Ts-cell counts with the development of checkpoint-inhibitor-related pneumonitis in NSCLC. Methods The clinical data of 85 patients with NSCLC treated with immune checkpoint inhibitors (ICIs) were retrospectively analyzed.Paired t-test was used to analyze lymphocyte changes.ROC curves were utilized to analyze predictive performance.The Spearman correlation coefficient test was conducted to analyze the linear relationship between lymphocyte changes and CIP grade. Results A statistically significant decrease in lymphocyte, T-cell, Th-cell, and Ts-cell counts from the baseline was observed in patients at the onset of CIP (P < 0.05), whereas no such change was observed in the control group.ROC curve analysis revealed AUCs of 0.867, 0.843, 0.865, and 0.843 for lymphocyte, T-cell, Th-cell, and Ts-cell counts, respectively.A linear relationship was found between the percentage decrease in lymphocyte, T-cell, and Ts-cell counts from the baseline and the severity of CIP (P < 0.05). Conclusion Decreased lymphocyte, T-cell, Th-cell, and Ts-cell counts have a predictive value for the development of CIP, and the lymphocyte count change has the greatest predictive value.The percentage decrease in lymphocyte, T-cell, and Ts-cell counts from the baseline is correlated with the severity of CIP.

New Thoughts on Surgical Principles of Non-Small Cell Lung Cancer / 肿瘤防治研究

Non-small cell lung cancer (NSCLC) is an important malignancy. Surgery is the earliest treatment and still the main strategy for lung cancer at present. Recently, significant progress has been made in the diagnosis and treatment of lung cancer, covering new theories, knowledge, and methods that urgently require the attention and learning of surgeons. Only by following the new situation and strategies of oncology and making corresponding changes can surgical techniques be perfectly combined with the new developments in oncology, avoiding over-diagnosis/underdiagnosis and over-treatment/undertreatment of lung cancer, and ultimately creating new achievements for patients' long-term cure.

Clinical application and prospect of SBRT in treatment of oligo-metastatic NSCLC / 中华放射肿瘤学杂志

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.

The efficacy of postoperative radiotherapy in stage Ⅲ(N 2) non-small cell lung cancer: a meta analysis / 中华放射肿瘤学杂志

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.

Clinical report of two dose fractionation modes using carbon ion beam therapy in the lymph node drainage area for lung cancer / 中华放射肿瘤学杂志

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.

Clinical efficacy and toxic effects of prophylactic cranial irradiation in non-small cell lung cancer: a meta-analysis / 中华放射肿瘤学杂志

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.

Prediction of EGFR mutant subtypes in patients with non-small cell lung cancer by pre-treatment CT radiomics and machine learning / 中华放射医学与防护杂志

Objective:To evaluate the feasibility and clinical value of pre-treatment non-enhanced chest CT radiomics features and machine learning algorithm to predict the mutation status and subtype (19Del/21L858R) of epidermal growth factor receptor (EGFR) for patients with non-small cell lung cancer (NSCLC).Methods:This retrospective study enrolled 280 NSCLC patients from first and second affiliated hospital of University of South China who were confirmed by biopsy pathology, gene examination, and have pre-treatment non-enhanced CT scans. There are 136 patients were confirmed EGFR mutation. Primary lung gross tumor volume was contoured by two experienced radiologists and oncologists, and 851 radiomics features were subsequently extracted. Then, spearman correlation analysis and RELIEFF algorithm were used to screen predictive features. The two hospitals were training and validation cohort, respectively. Clinical-radiomics model was constructed using selected radiomics and clinical features, and compared with models built by radiomics features or clinical features respectively. In this study, machine learning models were established using support vector machine (SVM) and a sequential modeling procedure to predict the mutation status and subtype of EGFR. The area under receiver operating curve (AUC-ROC) was employed to evaluate the performances of established models.Results:After feature selection, 21 radiomics features were found to be efffective in predicting EGFR mutation status and subtype and were used to establish radiomics models. Three types models were established, including clinical model, radiomics model, and clinical-radiomics model. The clinical-radiomics model showed the best predictive efficacy, AUCs of predicting EGFR mutation status for training dataset and validation dataset were 0.956 (95% CI: 0.952-1.000) and 0.961 (95% CI: 0.924-0.998), respectively. The AUCs of predicting 19Del/L858R mutation subtype for training dataset and validation dataset were 0.926 (95% CI: 0.893-0.959), 0.938 (95% CI: 0.876-1.000), respectively. Conclusions:The constructed sequential models based on integration of CT radiomics, clinical features and machine learning can accurately predict the mutation status and subtype of EGFR.

Long-term survival patients with advanced non-small cell lung cancer receiving thoracic radiotherapy: clinical characteristics and the construction of a nomogram prognostic model / 中华放射医学与防护杂志

Objective:To analyze the clinical characteristics of long-term survival patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy combined with primary tumor radiotherapy, and to establish a Nomogram prognostic model, aiming to provide a certain reference for making a decision about the treatment of advanced NSCLC.Methods:A retrospective analysis was made on the data of 260 NSCLC patients who participated in two prospective clinical studies from January 2003 to May 2012 and the data of 138 NSCLC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from January 2014 to August 2020. The former 260 cases were used as a training set and the latter 138 cases were used as the validation set. The overall survival (OS) of ≥ 18 months was defined as long-term survival (LTS). The clinical characteristics of LTS patients were compared with those with OS less than 18 months. The clinical characteristics and treatment-related parameters between the two types of patients were compared using the χ2 test. A multivariate analysis was made using logistic regression, and a nomogram model was built using RStudio. Results:The median OS of the training set was 13.4 months (95% CI: 11.9-14.9), with 1-, 2-, and 3-year OS rates of 55.4%, 19.1%, and 11.9%, respectively. In the training set, 87 cases had LTS and were classified as the LTS group, while 173 cases had OS less than 18 months and were classified as the non-LTS group. The univariate analysis showed that the prognostic factors affecting LST included the KPS score, T status, the number of metastatic organs, the number of metastatic lesions, brain metastasis, bone metastasis, the number of chemotherapy cycles, the biologically effective dose (BED) to the primary tumor, hemoglobin level, platelet count, plasma D-dimer, fibrinogen level, lactate dehydrogenase, and lung immune prognostic index (LIPI; χ2=4.72-12.63, P < 0.05). The multivariable analysis showed that the independent prognostic factors of LTS included a number of chemotherapy cycles ≥ 4, BED ≥ 70 Gy, platelets ≤ 220×10 9/L, D-dimer ≤ 0.5 mg/L, and a good LIPI score ( P= 0.002, 0.036, 0.005, 0.008, and 0.002). A nomogram model was established using the meaningful parameters obtained in the multivariable analysis, determining that the training and validation sets had a consistency index (C-index) of 0.750 and 0.727, respectively. As shown by the analytical result of the corrected curves, for the advanced NSCLC patients treated with thoracic radiotherapy, their LTS probability predicted using the nomogram prognostic model was highly consistent with their actual LTS probability. Both the analytical result of the receiver operating characteristic (ROC) curves and the decision curve analysis (DCA) result showed that the composite prediction model was more beneficial than a single prediction model. Conclusions:For patients with advanced NSCLC treated with thoracic radiotherapy, the independent prognostic factors of LTS included the number of chemotherapy cycles, BED, platelet count, pre-chemotherapy D-dimer, and LIPI score. The Nomogram prognostic model built based on these prognostic factors is a convenient, intuitive, and personalized prediction model used to screen patients who can benefit from thoracic radiotherapy.

Interpretation of CT images of pulmonary mucinous adenocarcinoma / 中国综合临床

Pulmonary mucinous adenocarcinoma (PMA) is relatively rare. On chest CT, it can be divided into two types: mass type and pneumonia type. Mass type PMA is more common and is difficult to distinguish from other nonsmall cell lung cancer. It is a solid or partial solid nodule or mass, predominantly located in the peripheral field of the lung with lobulation, spiculation, and more prone “vacuole sign”. Pneumonia type PMA has a poor prognosis and is more likely to develop into diffuse, multifocal and multilobular lesions similar to inflammatory manifestations, indicating dissemination along the airway. Typical signs include large areas of low density, low enhancement consolidation, and “dead tree sign”.

The value of enhanced CT combined with serum CYFER21-1 and NSE in the diagnosis of lymph node metastasis in patients with NSCLC / 中国医师杂志

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.

Effects of apatinib on quality of life and immune function in older adult patients with advanced non-small cell lung cancer / 中国基层医药

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.

Risk factors of moderate to severe pain in patients with non-small cell lung cancer within 3 days after lobectomy / 中国基层医药

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.