Fatores associados ao tempo para o início do tratamento do câncer de pulmão em Minas Gerais, Brasil / Factors associated with time to initiate lung cancer treatment in Minas Gerais, Brazil

Resumo O objetivo foi verificar a associação entre fatores individuais e organizativos do sistema de saúde com o tempo para o início do tratamento do câncer de pulmão pelo Sistema Único de Saúde (SUS) em Minas Gerais. Estudo de coorte retrospectiva com pacientes que iniciaram o tratamento para o câncer de pulmão pelo SUS de 2008 a 2015. Foram selecionadas variáveis sociodemográficas, clínicas e organizativas do sistema de saúde. O modelo de regressão logística avaliou a associação do desfecho do início do tratamento em até 60 dias após o diagnóstico com as variáveis explicativas selecionadas. Utilizou-se a odds ratio (OR) e o respectivo intervalo de confiança (95%) para mensurar a força de associação. A maioria dos tratamentos para o câncer de pulmão em Minas Gerais foram iniciados em até 60 dias após o diagnóstico, entretanto, ser do sexo masculino e diagnosticado em estadiamento IV aumentaram a chance de iniciar o tratamento em até 60 dias; todavia o aumento da idade, iniciar o tratamento por radioterapia, e o local de residência, diminuíram. O tempo para início do tratamento está associado a características individuais e à provisão de serviços nas macrorregiões, e as desigualdades observadas possivelmente se originam a partir do melhor ou pior acesso da população aos serviços prestados.

Abstract The aim was to verify the association of individual factors and healthcare system characteristics with time to initiate treatment of lung cancer by the Brazilian National Health System, in Minas Gerais state. A retrospective cohort study, with patients who initiated treatment for lung cancer by the SUS, from 2008 to 2015. Sociodemographic and clinical characteristics of patients, besides organizational variables of the healthcare system were selected. The logistic regression model evaluated the association of selected explanatory variables with the outcome of initiating treatment within 60 days after diagnosis. Odds ratio (OR) and respective 95% confidence interval were used to measure the power of association. Most treatments for lung cancer in the state of Minas Gerais initiated within 60 days after diagnosis. However, being male and diagnosed as stage IV increased the likelihood of starting treatment within 60 days. On the other hand, the patient's age, radiation therapy as first treatment, and the place of residence decreased such chance. Time to initiate treatment is associated with individual characteristics and provision of services in macroregions, and the observed inequalities possibly raised from the better or worse access of the population to the services provided by SUS.

Predictive Value of LIPI and iSEND Immune Scoring System in Immunotherapy of Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#This study retrospectively analyzed the application value of lung cancer immunotherapy prognostic index (LIPI) and iSEND immune scoring system in advanced non-small cell lung cancer (NSCLC) patients treated with immunotherapy in China, in order to find guidance for clinical development of NSCLC treatment plan.@*METHODS@#The clinical data of 178 patients with advanced NSCLC treated with immunotherapy were analyzed retrospectively. LIPI and iSEND immune scores were performed, receiver operating characteristic (ROC) curves were drawn, and the predictive values of two models for objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) were compared. Kaplan-Meier method was used for survival analysis, and Cox regression analysis method was used for univariate analysis and multivariate analysis.@*RESULTS@#The area under the curver (AUC) of ORR, DCR and PFS predicted by iSEND immune score were 0.616, 0.634 and 0.631 respectively; LIPI were 0.789, 0.750 and 0.732 respectively, which were higher than iSEND immune score (P<0.05). The median PFS of patients in LIPI score groups 0, 1 and 2 were 9.9 months, 6.1 mon and 3.7 mon respectively; The median PFS of patients with good, moderate and poor iSEND immune scores were 9.9 mon, 7.0 mon and 3.5 mon respectively, with statistically significant differences (P<0.001). In the immunotherapy subgroup, the median PFS of patients with different LIPI and iSEND immune scores was also statistically significant. Cox regression analysis showed that the derived neutrophil to lymphocyte ratio (dNLR), lactic dehydrogenase (LDH) and PFS were independently correlated (P<0.05).@*CONCLUSIONS@#LIPI and iSEND immune scoring system can effectively predict the efficacy and prognosis of advanced NSCLC treated with immunotherapy, and LIPI has higher predictive value than iSEND immune scoring system.

Research Progress on the Application of Liquid Biopsy in the Diagnosis and Treatment of Small Cell Lung Cancer / 中国肺癌杂志

Small cell lung cancer (SCLC) is a malignant tumor with strong invasiveness and high mortality. It has the characteristics of easy metastasis, fast growth, high degree of malignancy and strong invasiveness. The prognosis of patients is generally poor. The current clinical diagnosis of SCLC is mainly based on tissue biopsy, which is invasive, long cycle time and high cost. In recent years, liquid biopsy has been gradually applied because of its non-invasive, comprehensive and real-time characteristics that traditional tissue biopsy does not have. The main detection objects of liquid biopsy include circulating tumor DNA (ctDNA), circulating tumor cells (CTCs) and exosomes in peripheral blood. The application of liquid biopsy in the clinical treatment of SCLC will help clinicians to improve the detailed diagnosis of SCLC patients, as well as the timely control and response to the treatment response of patients.
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Advances in Diagnosis and Treatment of Leptomeningeal Metastasis of Lung Cancer / 中国肺癌杂志

Leptomeningeal metastases (LM), a special type of metastasis in advanced lung cancer, is known for its severe clinical symptoms, rapid progression and poor prognosis. LM used to be featured with low clinical diagnosis rate, limited treatment options, poor treatment efficacy, and very short survival if treatment not given. Though cerebrospinal fluid (CSF) cytology remains to be the gold standard for the diagnosis of LM, the positive rate of the first CSF cytology even in patients with suggestive clinical symptoms and positive imaging generally does not exceed 50%, leading to a delay in the diagnosis and treatment of patients with LM. With the progress of targeted therapy for driver gene-positive lung cancer and immunotherapy for driver gene-negative lung cancer, the overall survival of patients with lung cancer has been prolonged, meanwhile incidence of LM has been increasing year by year. Current clinical research in this field center around how to improve diagnosis rate and to find effective treatment approaches. This paper reviews advances in diagnosis and treatment of LM of lung cancer..
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Clinical practice guideline for multi-disciplinary team diagnosis and treatment of stage Ⅳ primary lung cancer in China / 中华肿瘤杂志

Although there are many treatment options for patients with stage Ⅳ primary lung cancer, the problems in the diagnosis and treatment process may involve multiple systems and organs due to their complex condition and heterogeneity. Therefore, cooperation between different disciplines is often required in the process of clinical practice. Multi-disciplinary team (MDT) refers to a fixed working group composed of more than two related disciplines, which puts forward the best treatment strategy for individual patient in the form of regular consultation for a certain system disease, and then the related disciplines implement the treatment strategy alone or jointly. MDT is widely used for disease diagnosis and treatment, and especially suitable for cancer patients. MDT has become a standard procedure for cancer treatment worldwide, including stage Ⅳ primary lung cancer. In order to promote the healthy development of MDT and generally improve the level of diagnosis and treatment of stage Ⅳ primary lung cancer in China, Chinese Association for Clinical Oncologists and Medical Oncology Branch of Chinese International Exchange and Promotion Association for Medical and Healthcare co-organized the national experts committee to formulate "Clinical practice guideline for multi-disciplinary team diagnosis and treatment of stage Ⅳ primary lung cancer in China" .

Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer (2022 edition) / 中华肿瘤杂志

Lung cancer is the most common malignancy with the highest incidence and mortality in China, which poses a major public health problem. To further standardize the prevention and treatment of lung cancer, improve the prognosis of patients, and provide professional evidence-based medical recommendations to medical professionals across China, the Oncology Society of Chinese Medical Association organized experts from departments of pulmonary medicine, oncology, thoracic surgery, radiotherapy, imaging, and pathology, based on indications approved by China Food and Drug Administration, domestically available drugs, recommendations of international guidelines and current clinical practice in China, integrated the latest evidence-based medical evidence of pathology, genetic testing, immune molecular biomarker detection and treatment methods of lung cancer in recent years. After consensus meetings, the Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer in China was formulated, which provided recommendations to clinicians, and imaging, laboratory, and rehabilitation professionals.

Practice of Palliative Care:Experience of a Patient with Advanced Lung Cancer at the End of Life / 中国医学科学院学报

Palliative care refers to the prevention and relief of physical and mental suffering through early recognition,active assessment,and management of pain and other painful symptoms to improve quality of life for both the patients with severe diseases and their families.A successful case of palliative care requires not only the establishment of correct concepts but also the team work and the improvement of the medical system.This paper introduced the end-of-life care experience for a patient with advanced lung cancer,showing the gains and deficiencies in the practice of palliative care.

Treatment Sequencing Strategies in Lung Cancer / 中国肺癌杂志

BACKGROUND@#The advances in the lung cancer screening methods and therapeutics, together with awareness towards deleterious habits, such as smoking, is increasing the overall survival with better quality of life for the patients. However, lung cancer is still one of the most common and fatal neoplasm with a high incidence and consequently burden to public health worldwide. Thus, based on guidelines and recent phases II and III clinical trials studies, this manuscript summarizes the current treatment sequencing strategies in lung cancer.@*METHODS@#A comprehensive search of related articles was performed focused on phases II and III clinical trials studies.@*RESULTS@#The lung cancer management should take into consideration the tumor characteristics, histology, molecular pathology and be discussed in a multidisciplinary team. Lung cancer treatment options comprises surgery whenever possible, radiotherapy associate with/or chemotherapy and immunotherapy as monotherapy, or combined with chemotherapy and best palliative care.@*CONCLUSIONS@#The screening predictability in more patients, smoking reduction, early diagnosis, better disease understanding and individualized, more effective and tolerable therapeutics are related to an increasing in overall survival and quality of life. In the near future improvement of personalized therapy in precision medicine is expected, enhancing new predictive biomarkers, optimal doses and optimal treatment sequencing as well as anti-cancer vaccines development.

Two Case Reports of Type 2 Diabetes Induced by Immune Checkpoint Inhibitors Combined with Chemotherapy / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) have become an important means of cancer treatment, and their application in the clinic is becoming more and more widespread. The adverse reactions caused by ICIs are gradually recognized. Among them, immunotherapy-related diabetes is a rare adverse reaction and type 1 diabetes mellitusis common. With the wide application of ICIs combined with chemotherapy in lung cancer patients, patients with type 2 diabetes mellitus have gradually been discovered during the treatment. However, the effect of continued use of ICIs maintenance therapy on blood glucose and ICIs treatment process in these patients is still unclear. This article reports two cases of type 2 diabetes mellitus induced by immune checkpoint inhibitor combined with chemotherapy, one of whom converted to type 1 diabetes mellitus, in order to increase the understanding of immunotherapy-related diabetes.
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Research Progress of Immunotherapy for Non-small Cell Lung Cancer with Drive Gene Mutation / 中国肺癌杂志

Lung cancer is the most lethal malignancy around the world and non-small cell lung cancer (NSCLC) accounts for 80% of all cases. Most of the NSCLC patients has "driver gene mutations" and targeted therapy achieved a relatively good efficacy, but some patients progressed or relapsed after treatment. Previous studies demonstrated that immune checkpoint inhibitor could improve the prognosis of advanced-stage NSCLC and prolong the survival time. However, the efficacy of immune therapy varies in NSCLC patients with different immune and molecular features. The efficacy of immune therapy was controversial in NSCLC patients with driver gene mutation. The present review will summarize the immune characteristics of NSCLC patients with driver mutation and the directions of immunotherapy for patients with driver mutation.
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Research Progress of Immunotherapy Biomarkers for Non-small Cell Lung Cancer / 中国肺癌杂志

Lung cancer is one of the most prevalent malignancies with the highest morbidity and mortality rates worldwide. In recent years, with the development of immune-oncology research and several therapeutic antibodies have reach the clinic, many breakthroughs have been made in immunotherapy. The advent of immunotherapy has revolutionized the treatment of NSCLC, but the response and durable clinical benefit are only observed in a small subset of patients. Therefore, strategies to screen the potential beneficial population and improve the efficacy of immunotherapy remain an essential topic. In the current article, the author review the biomarkers that have potential to better predict responders to immunotherapy and to provide ideas for the clinical application of immunotherapy.
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Advances in the Study of Tumor-associated Macrophages in Lung Cancer / 中国肺癌杂志

Lung cancer is one of the malignant tumors with the highest morbidity and mortality in China. Therefore, the research on the treatment of lung cancer is also deepening. At present, there are mainly systemic chemotherapy, targeted therapy for positive driver genes, the application of immune checkpoint inhibitors, anti-tumor angiogenesis therapy and the combination of the different treatment methods mentioned above. The use of these regimens has significantly improved the prognosis of most lung cancer patients, but the prognosis of patients with advanced lung cancer remains unsatisfactory. Recently, more and more attention has been paid to the study of tumor microenvironment (TME). TME consists of immune cells, fibroblasts, vascular endothelial cells and other cellular components as well as related cytokines, which is the basis for the survival and development of tumor cells. As an important immune cell of TME, tumor-associated macrophages (TAMs) refer to macrophages infiltrating in tumor tissues, which can promote tumor cell proliferation, induce tumor immune tolerance, stimulate tumor angiogenesis, and increase the invasion and metastasis ability of tumor cells. Therefore, targeting TAMs has become a hot topic in lung cancer immunotherapy. In this review, the sources, phenotypes, mechanisms of TAMs in lung cancer, as well as future therapeutic targets of TAMs were reviewed to provide reference for optimal treatment of lung cancer.
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Molecular hydrogen is a promising therapeutic agent for pulmonary disease / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Molecular hydrogen exerts biological effects on nearly all organs. It has anti-oxidative, anti-inflammatory, and anti-aging effects and contributes to the regulation of autophagy and cell death. As the primary organ for gas exchange, the lungs are constantly exposed to various harmful environmental irritants. Short- or long-term exposure to these harmful substances often results in lung injury, causing respiratory and lung diseases. Acute and chronic respiratory diseases have high rates of morbidity and mortality and have become a major public health concern worldwide. For example, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. An increasing number of studies have revealed that hydrogen may protect the lungs from diverse diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, and pulmonary fibrosis. In this review, we highlight the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a focus on its roles in disease pathogenesis and clinical significance.

Caracterización clínica y marcadores de estrés oxidativo en pacientes con cáncer de pulmón tratados con poliquimioterapia / Clinical description and oxidative stress markers in patients with lung cancer treated with polychemotherapy

Introducción: Los tratamientos oncológicos aplicados en el cáncer de pulmón, en especial la poliquimioterapia, promueven en su mecanismo de acción citotoxicidad y liberación de ciertas especies reactivas del oxígeno. Objetivo: Caracterizar a pacientes con cáncer de pulmón según los marcadores de estrés oxidativo y de defensa antioxidante en el momento del diagnóstico y después de concluido el tratamiento con poliquimioterapia. Métodos: Se realizó un estudio analítico, prospectivo, en 86 casos divididos en dos grupos: casos diagnosticados con cáncer de pulmón (n= 52) y sanos (n= 34) en Hospital Neumológico Benéfico Jurídico en el período comprendido desde mayo de 2016 a mayo de 2018. Resultados: Predominó el sexo masculino (63,5 por ciento) y el 55,8 por ciento con más de 60 años. El tipo histológico más frecuente fue el adenocarcinoma (57,7 por ciento) y el 61,5 por ciento emplearon la modalidad de quimioterapia cisplatino y etopósido. Los pacientes con cáncer de pulmón mostraron un mayor daño oxidativo endógeno a lípidos y a proteínas (40,4 por ciento y 28,8 por ciento) respectivamente, mientras que el 63,5 por ciento mantienen la normalidad de concentraciones plasmáticas de peróxidos totales. En el 40,4 por ciento de los pacientes se incrementaron las actividades de defensa enzimáticas de la superóxido dismutasa, la catalasa y glutation peroxidasa, las cuales tuvieron una tendencia a la normalidad (63,5 por ciento y 48,0 por ciento) respectivamente. El 76,9 por ciento alcanzó niveles normales de glutation s-transferasa concluido el tratamiento oncoespecífico. Conclusiones: La quimioterapia se relaciona con una exacerbación del estrés oxidativo y una disminución del sistema de defensa antioxidante(AU)

Introduction: Oncological treatments used in lung cancer, particularly polychemotherapy, promote cytotoxicity and the release of certain reactive oxygen species in their mechanism of action. Objective: To describe patients with lung cancer according to oxidative stress and antioxidant defense markers at the time of diagnosis and after the end of treatment with polychemotherapy. Methods: An analytical, prospective study was carried out in 86 cases. They were distributed into two groups: subjects diagnosed with lung cancer (n= 52) and healthy subjects (n= 34) at the Pneumological Hospital from May 2016 to May 2018. Results: The male subjects predominated (63.5 percent) and 55.8 percent were over 60 years old. The most frequent histological type was adenocarcinoma (57.7 percent) and 61.5 percent used the cisplatin and etoposide chemotherapy modality. Lung cancer patients showed higher endogenous oxidative damage to lipids and proteins (40.4 percent and 28.8 percent) respectively, while 63.5 percent kept normal plasma concentrations of total peroxides. In 40.4 percent of the patients, the enzymatic defense activities of superoxide dismutase, catalase and glutathione peroxidase increased, which tended to normal (63.5 percent and 48.0 percent respectively. 76.9 percent reached normal levels of glutathione s-transferase after oncospecific treatment. Conclusions: Chemotherapy is related to exacerbation of oxidative stress and a decrease in the antioxidant defense system(AU)

Chinese guideline for clinical diagnosis and treatment of malignant pleural mesothelioma (2021 Edition) / 中华肿瘤杂志

Malignant pleural mesothelioma (MPM) is a pleura-derived malignant tumor, with a gradually increasing incidence in recent years based on domestic and foreign epidemiologic data. Most patients with MPM are diagnosed at an advanced stage due to its insidiousness and aggressiveness. The therapeutic strategies of MPM mainly include surgery, chemotherapy and radiotherapy. Recently, the immunotherapy has altered the treatment pattern and further improved the survival of these patients. In order to timely present the domestic and foreign progress in the diagnosis and treatment of MPM, and to further improve the level of standardized diagnosis and treatment in MPM in China, this guideline was formulated on the basis of existing clinical research evidence combined with experts' opinions. The guideline covers the epidemiology, diagnosis, pathology, treatment and follow-up of MPM.

Clinical practice guideline for stage Ⅳ primary lung cancer in China(2021 version) / 中华肿瘤杂志

Primary lung cancer is the most common malignancy and the leading cause of cancer death in China, with an estimated 787 thousands incident cases and 631 thousands deaths in 2015. Due to its aggressive behavior and the absence of effective early screening methods, most patients with lung cancer in China are in stage Ⅳ when diagnosed. Chemotherapy is the cornerstone of stage Ⅳ lung cancer, but its efficacy is unsatisfactory. In recent years, with the rapid development of molecular targeted therapy and immunotherapy, the treatment concept has continuously changed and survival for patients has also been greatly improved. In order to update the progress in the treatment of stage Ⅳ lung cancer worldwide timely, and further improve the level of standardized diagnosis and treatment of stage Ⅳ lung cancer in China, Chinese Association for Clinical Oncologists and Medical Oncology Branch of Chinese International Exchange and Promotion Association for Medical and Healthcare organized experts to formulate "Clinical Practice Guideline for Stage Ⅳ Primary Lung Cancer in China(2021 version)" .

Oncology Society of Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer (2021 edition) / 中华肿瘤杂志

In China, the incidence and mortality of lung cancer are ranked the first among malignant tumors. In order to further standardize the prevention and treatment measures of lung cancer, improve the prognosis of patients, and provide professional evidence-based medical recommendations to clinical medical staffs, Oncology Society of Chinese Medical Association organized experts from departments of pulmonary medicine, oncology, thoracic surgery, radiotherapy, imaging and pathology, based on the international guidelines and clinical practices in China, integrated the latest evidence-based medical evidences in lung cancer pathology, genetic testing, immune molecular marker detection and treatment methods in recent years. After consensus meetings, the Oncology Society of Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer in China was conducted, which provided recommendations of lung cancer screening, diagnosis, pathology, treatment and follow-up to clinicians, imaging, laboratory, and rehabilitation professionals.

Research Progress of Circular RNAs in Tumor Immunotherapy / 中国肺癌杂志

Tumor immunotherapy is a new therapy which developed in recent years, it has greatly changed the therapeutic schedules and brought new options for patients. However, not all patients can have obvious therapeutic effects after using immunotherapy. So selecting more suitable patients and raising immunotherapy effect are worthy to discuss. With the research of circular RNAs (circRNAs), circRNAs have been found that they not only play a significant role in the field of tumor markers, tumor progression and prognosis, but also can abnormally express in a variety of tumors and affect tumor immunity. Therefore, the circRNAs expression may not only can be used as a supplementary method for selecting patients, but also can be used to predict the efficacy of tumor immunotherapy. In this article, we summarize current knowledge on circRNAs abnormally expressed in many cancers, especially lung cancer which can affect tumor immunity, and discuss its potential effects in tumor immunotherapy, and we hope to provide more references for the clinical practice of circRNAs.
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Advances in Biomarkers for Immunotherapy of Non-small Cell Lung Cancer / 中国肺癌杂志

Lung cancer is a malignant tumor with the highest mortality in the world. The most common pathological type of lung cancer is non-small cell lung cancer (NSCLC). In recent years, immunotherapy has brought about epoch-making changes in the treatment of NSCLC. In particular, immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) have been approved for first-line and second-line treatment in patients with metastatic NSCLC. However, only 15% to 30% of patients with advanced NSCLC can achieve sustained remission and long-term survival from immunotherapy. Therefore, biomarker for predicting the efficacy of immunotherapy is particularly important. This article reviews the relevant literatures on predictive biomarkers for immunotherapy of NSCLC and provides direction for future research.
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