Prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros / Smoking prevalence and lung cancer morbimortality in Brazilian states / Prevalencia del tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños

Introdução: O câncer de pulmão é uma doença grave, sendo a segunda maior causa de morte em todo o mundo, entretanto, em alguns países desenvolvidos, tornou-se já a primeira causa de morte. Cerca de 90% dos casos de neoplasia pulmonares são causados pela inalação da fumaça do cigarro. Objetivo: Correlacionar a prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, além de demonstrar a associação destes com sexo e faixa etária. Métodos: Estudo de caráter ecológico acerca da prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, nos períodos de 2013 e 2019, dividida por sexo e faixa etária. Foram utilizados bancos de coleta de dados como o Tabnet e Pesquisa Nacional de Saúde. Resultados: As maiores taxas de mortalidade e internações hospitalares foram do público masculino, em 2013, com taxa de 2,7 e 10, respectivamente, e em 2019 com 3,3 e 11,9, respectivamente. Ademais, a maior prevalência de tabagismo foi encontrada nos homens; entretanto seu índice tem caído, enquanto a quantidade de mulheres tabagistas tem aumentado. A Região Sul demonstrou maiores números de mortalidade em ambos os períodos estudados, com taxas de 4,9 e 5,8 por 100 mil habitantes, e morbidade hospitalar com 19,9 e 23,5 por 100 mil habitantes. Já a Região Norte se configurou com as menores prevalências: em 2013 apresentou taxa de óbito por câncer de pulmão de 1,0 e morbidade hospitalar de 3,5/100 mil habitantes, em 2019 apresentou taxa de mortalidade de 4,6 e internações de 1,6/100 mil habitantes. Os coeficientes de correlação de morbidade hospitalar e prevalência de tabagismo foram R2=0,0628, r=0,251 e p=0,042, enquanto os de mortalidade e prevalência de tabagismo foram R2=0,0337, r=0,183 e p=0,140. Conclusões: Na presente pesquisa, pode-se inferir que houve associação positiva na comparação entre taxa de morbidade hospitalar e prevalência de tabagismo; em contrapartida, não foi possível observar associação positiva na correlação da taxa de mortalidade por câncer de pulmão e prevalência de tabagismo.

Introduction: Lung cancer is a serious disease, being the second leading cause of death worldwide. Moreover, in some developed countries, it has already become the leading cause of death. About 90% of lung cancer cases are caused by cigarette smoking. Objective: To correlate the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states, and to demonstrate their association with sex and age group as well. Methods: An ecological study on the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states between 2013 and 2019, divided by sex and age group. The data collection databases Tabnet and National Health Survey were used. Results: The highest rates of mortality and hospital admissions were among men, in 2013 with a rate of 2.7 and 10, respectively, and in 2019 with 3.3 and 11.9, respectively. In addition, the highest prevalence of smoking was found in men, but this rate has fallen, while the number of women smokers has increased. The South region showed higher mortality rates in both periods studied, with rates of 4.9 and 5.8 per 100,000 inhabitants, and hospital morbidity with 19.9 and 23.5 per 100,000 inhabitants. The North region had the lowest prevalence, where in 2013, it had a death rate from lung cancer of 1.0 and hospital morbidity of 3.5/100 thousand inhabitants, and where in 2019, it had a mortality rate of 4.6 and hospitalizations of 1.6/100 thousand inhabitants. The correlation coefficients for hospital morbidity and smoking prevalence were R2=0.0628, r=0.251 and p=0.042, while for mortality and smoking prevalence, these were R2=0.0337, r=0.183 and p=0.140. Conclusions: In the present study, it can be inferred that there was a positive association between hospital morbidity rate and prevalence of smoking, while it was not possible to observe a correlation between lung cancer mortality rate and prevalence of smoking.

Introducción: El cáncer de pulmón es una enfermedad grave, siendo la segunda causa de muerte en todo el mundo, sin embargo, en algunos países desarrollados, ya se ha convertido en la primera causa de muerte. Alrededor del 90% de los casos de neoplasias pulmonares están causados por la inhalación del humo del cigarrillo. Objetivo: Correlacionar la prevalencia de tabaquismo y la morbimortalidad por cáncer de pulmón en los estados brasileños, además de demostrar la asociación de estos con el género y el grupo de edad. Métodos: estudio ecológico sobre la prevalencia de tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños, dentro de los períodos 2013 y 2019, divididos por sexo y grupo de edad. Se utilizaron bancos de recogida de datos como Tabnet y la Encuesta Nacional de Salud. Resultados: las mayores tasas de mortalidad e ingresos hospitalarios se dieron en el público masculino, en 2013 con una tasa de 2,7 y 10, respectivamente, y en 2019 con 3,3 y 11,9, respectivamente. Además, la mayor prevalencia del tabaquismo se encontró en los hombres, sin embargo, su tasa ha disminuido, mientras que la cantidad de mujeres fumadoras ha aumentado. La región Sur presentó cifras más altas de mortalidad en ambos periodos estudiados, con tasas de 4,9 y 5,8 por 100.000 habitantes, y de morbilidad hospitalaria con 19,9 y 23,5 por 100.000 habitantes. Mientras que la región Norte se configuró con las prevalencias más bajas, en 2013 presentó una tasa de mortalidad por cáncer de pulmón de 1,0 y una morbilidad hospitalaria de 3,5/100.000 habitantes, en 2019 presentó una tasa de mortalidad de 4,6 y hospitalizaciones de 1,6/100.000 habitantes. Los coeficientes de correlación para la morbilidad hospitalaria y la prevalencia del tabaquismo fueron R2=0,0628, r=0,251 y p=0,042, mientras que para la mortalidad y la prevalencia del tabaquismo fueron R2=0,0337, r=0,183 y p=0,140. Conclusiones: En la presente investigación se puede inferir que existe una asociación positiva en la comparación entre la tasa de morbilidad hospitalaria y la prevalencia de tabagismo, en contrapartida, no fue posible observar una asociación positiva en la correlación de la tasa de mortalidad por cáncer de pulmón y la prevalencia de tabagismo.

Racial/ethnic disparities in curative-intent treatment for early-stage non-small cell lung cancer patients among heterogeneous Black populations: US-born Black, Afro-Haitian, West Indian Black, and Hispanic Black.

BACKGROUND: Heterogeneous Black populations encounter significant obstacles in accessing cancer care, yet research on lung cancer treatment disparities remains limited. This study investigates whether the disparity in receiving curative-intent treatment (curative-intent surgery and/or stereotactic body radiation therapy [SBRT]) for early-stage non-small cell lung cancer (NSCLC) between non-Hispanic Whites (NHWs) and total Blacks extends to diverse Black populations, including US-born, Afro-Haitian, West Indian Black, and Hispanic Black individuals. METHODS: This cross-sectional study included all Florida cancer registry early-stage NSCLC cases 2005-2017, linked to individual-level discharge data containing comorbidity and specific treatment details (surgery and/or SBRT). Multivariable logistic regression assessed the association between race/ethnicity and the receipt of curative-intent treatment, while accounting for sociodemographic factors (poverty, age, insurance, and smoking status) and clinical variables. RESULTS: Among 55,655 early-stage NSCLC patients, 71.1% received curative-intent treatment: 72.1% NHW and 59.7% Black (non-Hispanic and Hispanic) individuals. Black patients had 35% lower odds (ORadj, 0.65; 95% CI, 0.59-0.70) of receiving curative-intent treatment compared to NHW patients. ORs varied from 0.57 (95% CI, 0.59-0.70) for Hispanic Black to 0.76 (95% CI, 0.56-1.02) for West Indian Black. Remarkably, Black-White disparities persisted despite the availability of curative treatment options (SBRT) for both high Charlson Comorbidity Index (CCI) observed among US-born Blacks and surgery for low CCI patients among all other Black subgroups. CONCLUSIONS: Pronounced disparities in accessing curative-intent treatments for early-stage NSCLC were evident across all Black subgroups, regardless of treatment availability and comorbidity profile. These findings underscore the need to address Black heterogeneity and prompt further research to rectify treatment disparities in early-stage NSCLC.

Intratumoral and peritumoral radiomics model for the preoperative prediction of cribriform component in invasive lung adenocarcinoma: a multicenter study.

PURPOSE: This study aimed to investigate the predictive value of intratumoral and peritumoral radiomics model for the cribriform component (CC) of invasive lung adenocarcinoma (LUAD). MATERIALS AND METHODS: The 144 patients with invasive LUAD from our center were randomly divided into training set (n = 100) and internal validation set (n = 44) in a ratio of 7:3, and 75 patients from center 2 were regarded as the external validation set. Clinical risk factors were examined using univariate and multivariate logistic regression to construct the clinical model. We extracted radiomics features from gross tumor volume (GTV), gross and peritumoral volume (GPTV), and peritumoral volume (PTV), respectively. Radiomics models were constructed with selected features. A combined model based on the optimal Radscore and clinically independent predictors was constructed, and its predictive performance was assessed by receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: The area under curves (AUCs) of the GTV model were 0.882 (95% CI 0.817-0.948), 0.794 (95% CI 0.656-0.932), and 0.766 (95% CI 0.657-0.875) in the training, internal validation, and external validation sets, and the PTV model had AUCs of 0.812 (95% CI 0.725-0.899), 0.749 (95% CI 0.597-0.902), and 0.670 (95% CI 0.543-0.798) in the training, internal validation, and external validation sets, respectively. However, the GPTV radiomics model showed better predictive performance compared with the GTV and PTV radiomics models, with the AUCs of 0.950 (95% CI 0.911-0.989), 0.844 (95% CI 0.728-0.959), and 0.815 (95% CI 0.713-0.917) in the training, internal validation and external validation sets, respectively. In the clinical model, tumor shape, lobulation sign and maximal diameter were the independent predictors of CC in invasive LUAD. The combined model including independent clinical predictors and GPTV-Radscore show the considerable instructive to clinical practice, with the AUCs of 0.954(95% CI 0.918-0.990), 0.861(95% CI 0.752-0.970), and 0.794(95% CI 0.690-0.898) in training, internal validation, and external validation sets, respectively. DCA showed that the combined model had good clinical value and correction effect. CONCLUSION: Radiomics model is a very powerful tool for predicting CC growth pattern in invasive LUAD and can help clinicians make the strategies of treatment and surveillance in patients with invasive LUAD.

Scoping review of anticancer drug utilization in lung cancer patients at the end of life.

PURPOSE: This scoping review aims to deepen the understanding of end-of-life anticancer drug use in lung cancer patients, a disease marked by high mortality and symptom burden. Insight into unique end-of-life treatment patterns is crucial for improving the appropriateness of cancer care for these patients. METHODS: Comprehensive searches were carried out in Medline and Embase to find articles on the utilization of anticancer drugs in the end of life of lung cancer patients. RESULTS: We identified 68 publications, highlighting the methodological characteristics of studies including the timing of the research, disease condition, treatment regimen, type of treatment, and features of the treatment. We outlined the frequency of anticancer drug use throughout different end-of-life periods. CONCLUSION: This review provides a comprehensive overview of primary studies exploring end-of-life treatments in lung cancer patients. Methodological inconsistencies pose many challenges, revealing a notable proportion of patients experiencing potential overtreatment, warranting more standardized research methods for robust evaluations.

MicroRNAs in Lung Cancer Brain Metastasis.

Brain metastasis is a significant clinical challenge for patients with advanced lung cancer, occurring in about 20-40% of cases. Brain metastasis causes severe neurological symptoms, leading to a poor prognosis and contributing significantly to lung cancer-related mortality. However, the underlying molecular mechanism behind brain metastasis remains largely unknown. MicroRNAs (miRNAs) are small, non-coding RNAs linked to several aspects of cancer progression, including metastasis. In the context of lung cancer, significant research has shown the involvement of miRNAs in regulating critical pathways related to metastatic spread to the brain. This review summarizes the scientific evidence regarding the regulatory roles of intra- and extracellular miRNAs, which specifically drive the spread of lung cancer cells to the brain. It also revises the known molecular mechanisms of brain metastasis, focusing on those from lung cancer as the primary tumor to better understand the complex mechanisms underlying this regulation. Understanding these complex regulatory mechanisms holds promise for developing novel diagnostic biomarkers and potential therapeutic strategies in brain metastasis.

Pemetrexed and platinum with or without pembrolizumab for advanced non-small-cell lung cancer (NSCLC): a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to evaluate the efficacy and safety of combining pemetrexed and platinum with or without pembrolizumab for the treatment of advanced non-small-cell lung cancer (NSCLC). METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web Of Science databases was conducted to identify studies comparing pemetrexed and platinum with or without pembrolizumab in advanced NSCLC. Raw data were extracted from eligible studies to calculate Hazard Ratios (HR) for Progression-Free Survival (PFS) and Overall Survival (OS), as well as rates of adverse events of all grades and those of Grade 3 or higher. RESULTS: Eight studies with 1639 patients occurred advanced NSCLC included. The group receiving pembrolizumab in combination with pemetrexed and platinum showed significant benefits in terms of OS (HR 0.63; 95% CI 0.54-0.73; p < 0.00001) and PFS (HR:0.64; 95% CI 0.48-0.85; p = 0.002) compared to the group receiving pemetrexed and platinum alone. However, this benefit was accompanied by a higher incidence of Grade 3 or higher adverse events (OR: 1.55; 95% CI 1.24-1.95; p = 0.0001). CONCLUSION: The combination of pemetrexed and platinum with pembrolizumab is recommended as a first-line treatment option for advanced NSCLC due to its significant efficacy benefits. However, the increased risk of Grade 3 or higher adverse events suggests the need for careful consideration and assessment when considering this regimen for second-line or subsequent therapy.

Combining serum CDK1 with tumor markers for the diagnosis of small cell lung cancer.

OBJECTIVE: An investigation of the diagnostic and clinical value of cell cycle-dependent kinase 1 (CDK1) in small cell lung cancer (SCLC). METHODS: A large tertiary hospital in Jiangxi Province enrolled 80 SCLC cases, 105 cases of non-small cell lung cancer (NSCLC), 114 cases of pulmonary nodule (PN) and 60 control cases from December 2022 to December 2023. ELISA was used to measure CDK1 levels in serum. The expression levers of neuron-specific enolase (NSE), Pro gastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCA), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and cytokeratin 19 fragment (YFRA21-1) were detected by electrochemiluminescence immunoassay. RESULTS: ①CDK1, ProGRP, NSE, and CA199 expressions were significantly higher in the SCLC group compared to the NSCLC, PN and Control groups (P < 0.01). ②Spearman correlation analysis showed that serum levels of CDK1, NSE, and ProGRP were associated with clinical staging and lymph node metastasis in SCLC patients (P < 0.05). ③The serum levels of CDK1, NSE, and ProGRP in patients with extensive-disease (ED) SCLC were higher than those in patients with limited-disease (LD) SCLC (P < 0.05), and the serum levels of CDK1, NSE, and ProGRP in SCLC patients with lymph node metastasis were higher than those without lymph node metastasis (P < 0.05). ④Compared with the NSCLC group, the AUC of subjects diagnosed with SCLC by CDK1 was the largest and the sensitivity was the highest, 0.831 and 72.50%, the specificity of ProGRP in diagnosing SCLC is the highest, at 95.20% (P < 0.01). Compared with the PN group, CDK1 had the highest AUC, sensitivity, and specificity in diagnosing SCLC, with values of 0.93%, 88.80%, and 94.70%, respectively (P < 0.01). ⑤The combination of CDK1, ProGRP and NSE had the highest AUC and sensitivity of 0.903 and 86.30% for the diagnosis of SCLC (P < 0.01). CONCLUSION: CDK1 not only plays an important role in assisting the diagnosis of SCLC but also in the differential diagnosis between SCLC and NSCLC. The combination of CDK1 and NSE and ProGRP can significantly improve the diagnostic performance and provide new ideas for the clinical diagnosis of SCLC.

Development of a Second Primary Lung Cancer Following a Primary Breast Cancer: A Case Series.

Breast cancer (BC) accounts for 24.2% of all women's malignant tumors, with rising survival rates due to advancements in chemotherapy and targeted treatments. However, second primary cancers, particularly lung cancer (LC), have become more prevalent, often emerging approximately 10 years after BC treatment. This study presents a case series of 9 women diagnosed with second primary LC following BC, treated at a high-complexity hospital in Colombia between 2014 and 2019. All initial BCs were ductal carcinomas, 7 were triple negative, 1 was human epidermal growth factor receptor 2 positive, and 1 was estrogen and progesterone positive. Each patient had undergone radiation therapy, and 7 had received chemotherapy, increasing their LC risk. The second primary LCs, all adenocarcinomas, were confirmed using immunohistochemical stains for thyroid transcription factor-1 (TTF-1), Napsin A, and estrogen receptor (ER) status. The interval between treatments and LC detection ranged from 1 to 17 years, with 4 cases identified after 10 years and 3 within 1 to 3 years, underscoring the need for prolonged surveillance. Seven LCs were ipsilateral to the BC and radiation site, while 2 were contralateral, highlighting the necessity of monitoring both sides for potential LC development. This case series enhances the local epidemiological understanding, showing that prior radiotherapy for BC and histological analysis are key in characterizing second primary LC patients. The study emphasizes the critical role of accurate histological diagnosis in guiding treatment approaches for lung lesions in BC survivors.

Certification system for multidisciplinary thoracic tumour boards.

In Spain, lung cancer (LC) is the fourth most common cancer. Managing LC involves different professionals, and cooperative and coordinated work is crucial. Therefore, important decisions are better made by Multidisciplinary Thoracic Tumour Boards (MTTBs). On the other hand, certification systems have proven to improve the structure of care, ultimately having a positive impact on patient survival. Herein, a multidisciplinary working group of 11 experts (a Radiologist, a Thoracic Surgeon, a Pulmonologist, a Radiotherapy Oncologist, four Medical Oncologists, a Hospital Managing Director, a Cytologist, and a Molecular Biologist specialist) proposed a standard to certify and evaluate MTTBs. The following components were suggested for the standard: minimum requirements for the MTTB, a mixed model developed in two stages (preparation and audit), a structure comprising three groups of indicators (Strategic and Management, Support, and Operational), three certification levels, and an audit process. In our opinion, certifying MTTBs is critical to improve the standard of care for LC patients.

Dendritic cell-based immunotherapy in non-small cell lung cancer: a comprehensive critical review.

Despite treatment advances through immunotherapies, including anti-PD-1/PD-L1 therapies, the overall prognosis of non-small cell lung cancer (NSCLC) patients remains poor, underscoring the need for novel approaches that offer long-term clinical benefit. This review examined the literature on the subject over the past 20 years to provide an update on the evolving landscape of dendritic cell-based immunotherapy to treat NSCLC, highlighting the crucial role of dendritic cells (DCs) in immune response initiation and regulation. These cells encompass heterogeneous subsets like cDC1s, cDC2s, and pDCs, capable of shaping antigen presentation and influencing T cell activation through the balance between the Th1, Th2, and Th17 profiles and the activation of regulatory T lymphocytes (Treg). The intricate interaction between DC subsets and the high density of intratumoral mature DCs shapes tumor-specific immune responses and impacts therapeutic outcomes. DC-based immunotherapy shows promise in overcoming immune resistance in NSCLC treatment. This article review provides an update on key clinical trial results, forming the basis for future studies to characterize the role of different types of DCs in situ and in combination with different therapies, including DC vaccines.

Analysis of genomic alternations in epidermal growth factor receptor (EGFR)-T790M-mutated non-small cell lung cancer (NSCLC) patients with acquired resistance to osimertinib therapy.

BACKGROUND AND OBJECTIVES: Genomic alterations after resistance to osimertinib therapy in advanced T790M-mutated non-small cell lung cancer (NSCLC) are complex and poorly understood. In this study, we aimed to detect these genomic alternations via comprehensive next-generation sequencing (NGS) of tissue and liquid biopsies. PATIENTS AND METHODS: From September 2020 to June 2021, 31 stage IIIB/IV T790M-mutated NSCLC patients who exhibited progressive disease after osimertinib therapy and provided written informed consent were recruited. Liquid and tissue biopsy samples for NGS testing were collected from 31 and 18 patients, respectively. Eighteen study patients had paired NGS data from tissue and liquid biopsies. RESULTS: With respect to the T790M mutation status, the preservation and loss rates were 33% and 67%, respectively, in both liquid and tissue biopsy samples. Five patients (16.1%) had the C797S mutation (4 liquid samples and 1 tissue sample). Two (6.5%) had MET mutations, 3 (9.7%) had BRAF-V600E mutations, and 1 (3.2%) had a KRAS-G12C mutation. Among the 18 patients who underwent tissue rebiopsies, those with preserved T790M mutation had significantly longer progression-free survival (PFS) with osimertinib therapy than those with T790M mutation loss (10.8 vs. 5.0 months, P = 0.045). Among all patients, those with T790M mutation loss in liquid biopsy samples had longer PFS after osimertinib therapy (10.8 vs. 7.5 months, P = 0.209) and postprogression survival (17.7 vs. 9.6 months, P = 0.132) than those with preserved T790M mutation based on liquid biopsies. CONCLUSIONS: NGS using either tissue or liquid biopsy samples from advanced T790M-mutated NSCLC patients with acquired resistance to osimertinib therapy can detect various genomic alternations. Future studies focusing on subsequent tailored therapies on the basis of NGS results are warranted.

STAS: New explorations and challenges for thoracic surgeons.

Spread through air spaces (STAS) represents a relatively novel concept in the pathology of lung cancer, and it specifically refers to the dissemination of tumour cells into the parenchymal air spaces adjacent to the primary tumour. In 2015, the World Health Organization (WHO) classified STAS as a new invasive form of lung adenocarcinoma (LUAD). Many studies investigated the role of STAS and revealed its association with the prognosis of LUAD and its influence on the outcomes of other malignant pulmonary neoplasms. Additionally, the underlying mechanisms and predictive models of STAS have received considerable attention in recent years. This paper provides a comprehensive overview of the research advancements and prospects of STAS by examining it from multiple perspectives.

The efficacy and safety of neoadjuvant immunochemotherapy in resectable stage I-III non-small cell lung cancer: a systematic review and network meta-analysis.

BACKGROUND: Neoadjuvant immunochemotherapy (NICT) is a new treatment method for resectable non-small-cell lung cancer (NSCLC). Network meta-analysis assessed efficacy, safety, and optimal treatment. METHODS: We searched for randomized controlled trials (RCTs) comparing NICT with neoadjuvant chemotherapy (NCT) in PubMed, Embase, Web of Science, Cochrane Library, and international conferences. Outcomes were surgical resection rate, pathological complete response(pCR),event-free survival (EFS), and Grade 3-5 treatment-related adverse events (TRAEs). RESULTS: RCTs of 3,387 patients, six treatment combinations, and two modalities were included. Meta-analysis showed that NICT yielded higher pCR and EFS rates than NCT. The toripalimab-chemotherapy combination had the highest surgical resection rate (OR = 1.68, 95% CI: 1.05-2.73), pCR (OR = 38.84, 95% CI: 11.05-268.19) and EFS (HR = 0.40, 95% CI: 0.28-0.58).This regimen worked well for patients with low programmed death-ligand 1 (PD-L1) expression or squamous cell pathology. For high PD-L1 expression and patients with NSCLC, neoadjuvant nivolumab with chemotherapy had the most efficacy. The incidence of treatment-related adverse events increased with longer treatment cycles, with perioperative nivolumab combined with chemotherapy showing the worst safety profile (RR = 1.32, 95% CI: 1.00-1.76), while neoadjuvant nivolumab combined with chemotherapy alone had the best safety profile (RR = 0.91, 95% CI: 0.68-1.21). Indirect comparison showed no survival benefit for neoadjuvant-adjuvant immunotherapy (HR = 0.93, 95% CI: 0.65-1.35). In the indirect comparison between the two immune checkpoint inhibitors(ICIs), although there was no significant difference in EFS (HR = 0.81, 95% CI: 0.61-1.08), PD-1 inhibitors may still be the most effective treatment option. CONCLUSIONS: NICT effectively and safely treats resectable NSCLC. The optimal treatment combination is typically toripalimab and chemotherapy. Treatment based on PD-L1 expression and pathological type is recommended.

Identifying patients who benefit more from perioperative immunotherapy combinations for resectable non-small cell lung cancer based on clinical and molecular characteristics: a meta-analysis of randomized clinical trials.

PURPOSE: This study aims to identify patient subgroups who benefit more from perioperative immunotherapy combined with chemotherapy (IO-CT) based on clinical and molecular characteristics in resectable non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials (RCTs) on perioperative IO-CT were searched. Beneficial differences of IO-CT regimens across different patient subgroups were assessed by pooling trial-specific ratios in event-free survival (EFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR). RESULTS: Six studies (n = 3003) involving five IO-CT regimens were included. Compared to CT alone, all IO-CT regimens significantly improved EFS, OS, MPR, and pCR, but increased toxicity. Toripa-chemo showed the best EFS and nivo-chemo showed the best OS. Patients with PD-L1 ≥ 1% had more EFS benefits compared to those with PD-L1 < 1% (HR [hazard ratio]: 1.55, 95% CI 1.17-2.04). Squamous NSCLC patients had significantly more pCR and MPR benefits than non-squamous NSCLC patients (pCR: OR [odds ratio] 0.68, 95% CI 0.49-0.95; MPR: OR 0.61, 95% CI 0.45-0.82). Former smokers had significantly higher pCR benefits than non-smokers (OR: 2.18; 95% CI 1.21-3.92). Additionally, OS benefit was significantly higher in patients < 65 years compared to those ≥ 65 years (HR ratio: 0.59, 95% CI 0.36-0.95). For MPR, males benefited significantly more from IO-CT compared to females (OR: 1.69, 95% CI 1.18-2.42). CONCLUSION: Perioperative IO-CT is more effective but more toxic than CT alone in resectable NSCLC. Patients with PD-L1 ≥ 1%, squamous NSCLC, a history of smoking, age < 65 years and male gender may experience greater benefits from perioperative IO-CT.

Proceedings from the First Onco Summit: LATAM Chapter, 19-20 May 2023, Rio de Janeiro, Brazil.

The Onco Summit 2023: The Latin American (LATAM) Chapter took place over two days, from 19-20 May 2023, in Brazil. The event aimed to share the latest updates across various oncology disciplines, address critical clinical challenges, and exchange best practices to ensure optimal patient treatment. More than 30 international and regional speakers and more than 300 oncology specialists participated in the Summit. The Summit discussions centered on common challenges and therapeutic advances in cancer care, with a specific focus on the unique obstacles faced in LATAM and examples of adaptable strategies to address these challenges. The Summit also facilitated the establishment of a network of oncologists, hematologists, and scientists in LATAM, enabling collaboration to improve cancer care, both in this region and globally, through drug development and clinical research. This report summarizes the key discussions from the Summit for the global and LATAM oncology community.

Global transcriptomic network analysis of the crosstalk between microbiota and cancer-related cells in the oral-gut-lung axis.

Background: The diagnosis and treatment of lung, colon, and gastric cancer through the histologic characteristics and genomic biomarkers have not had a strong impact on the mortality rates of the top three global causes of death by cancer. Methods: Twenty-five transcriptomic analyses (10 lung cancer, 10 gastric cancer, and 5 colon cancer datasets) followed our own bioinformatic pipeline based on the utilization of specialized libraries from the R language and DAVID´s gene enrichment analyses to identify a regulatory metafirm network of transcription factors and target genes common in every type of cancer, with experimental evidence that supports its relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during the tumoral process. The network's regulatory functional and signaling pathways might depend on the constant crosstalk with the microbiome network established in the oral-gut-lung axis. Results: The global transcriptomic network analysis highlighted the impact of transcription factors (SOX4, TCF3, TEAD4, ETV4, and FOXM1) that might be related to stem cell programming and cancer progression through the regulation of the expression of genes, such as cancer-cell membrane receptors, that interact with several microorganisms, including human T-cell leukemia virus 1 (HTLV-1), the human papilloma virus (HPV), the Epstein-Barr virus (EBV), and SARS-CoV-2. These interactions can trigger the MAPK, non-canonical WNT, and IFN signaling pathways, which regulate key transcription factor overexpression during the establishment and progression of lung, colon, and gastric cancer, respectively, along with the formation of the microbiome network. Conclusion: The global transcriptomic network analysis highlights the important interaction between key transcription factors in lung, colon, and gastric cancer, which regulates the expression of cancer-cell membrane receptors for the interaction with the microbiome network during the tumorigenic process.

Lung immune prognostic index (LIPI) as a prognostic factor in patients with extensive-stage small cell lung cancer treated with first-line chemoimmunotherapy.

INTRODUCTION: The lung immune prognostic index (LIPI) is a biomarker that combines the lactate dehydrogenase (LDH) value and the derived neutrophil/lymphocyte ratio (dNLR). Its prognostic ability has been reported in non-small cell lung cancer (NSCLC) with immunotherapy. In the context of extensive-stage small cell lung cancer (ES-SCLC) with chemoimmunotherapy, its role remains to be determined. METHODS: A retrospective, multicenter study of patients with ES-SCLC who received atezolizumab plus chemotherapy as first-line treatment was conducted. 101 patients were divided into three groups: LIPI good (n = 33), LIPI intermediate (n = 41), and LIPI poor (n = 27). The Kaplan-Meier method was used for analysis of overall survival (OS) and progression-free survival (PFS), using the log-rank test for comparisons. Univariate and multivariate Cox models were developed to assess the LIPI as an independent predictor of survival. RESULTS: The good LIPI group had a significantly longer median PFS than the intermediate and poor LIPI groups: 9.6 vs 5.4 vs 5.2 months, respectively (p < 0.001). Significant differences in OS between good, intermediate, and poor LIPI were also observed, with median OS of 23.4 vs 9.8 vs 6.0 months, respectively (p < 0.001). Multivariate Cox regression analysis for PFS identified liver metastases and intermediate and poor LIPI as worse prognostic factors (p < 0.050). For OS, a worse prognosis was confirmed in both the intermediate LIPI group (HR: 2.18, 95% CI: 1.07-4.41, p = 0.031) and the poor LIPI group (HR: 5.40, 95% CI: 2.64-11.07, p < 0.001). CONCLUSIONS: In patients with ES-SCLC treated with chemoimmunotherapy, an intermediate and poor pretreatment LIPI score was associated with worse PFS and OS prognosis.

Circulating Polyploid Giant Cancer Cells, a Potential Prognostic Marker in Patients with Carcinoma.

Polyploid Giant Cancer Cells (PGCCs) have been recognized as tumor cells that are resistant to anticancer therapies. However, it remains unclear whether their presence in the bloodstream can be consistently detected and utilized as a clinical marker to guide therapeutic anticancer regimens. To address these questions, we conducted a retrospective study involving 228 patients diagnosed with six different types of carcinomas (colon, gastric, NSCLC, breast, anal canal, kidney), with the majority of them (70%) being non-metastatic. Employing a highly sensitive liquid biopsy approach, ISET®, and cytopathological readout, we isolated and detected circulating PGCCs in the patients' blood samples. PGCCs were identified in 46 (20.18%) out of 228 patients, including in 14.47% of 152 non-metastatic and 29.85% of 67 metastatic cases. Patients were subsequently monitored for a mean follow up period of 44.74 months (95%CI: 33.39-55.79 months). Remarkably, the presence of circulating PGCCs emerged as a statistically significant indicator of poor overall survival. Our findings suggest that circulating PGCCs hold promise as a reliable prognostic indicator. They underscore the importance of further extensive investigations into the role of circulating PGCCs as a prognostic marker and the development of anti-PGCC therapeutic strategies to improve cancer management and patient survival.

Prognostic impact of nectin-like molecule-5 (CD155) expression in non-small cell lung cancer.

BACKGROUND: CD155 is a transmembrane protein that inhibits antitumor immune response and represents a predictor of worse prognosis in non-small-cell lung cancer (NSCLC). However, it remains unexplored its association with clinical characteristics and genomic status of Latin American patients. This study characterizes the CD155 expression and its clinical implications in this population. METHODS: Tissue biopsies from 86 patients with locally-advanced or metastatic NSCLC were assessed for CD155 protein expression, ALK rearrangements and EGFR mutations. Cutoff values for high CD155 expression (CD155high) were determined from receiver operating characteristic (ROC) curves according to 2-year survival. It was evaluated its association with clinicopathological features, median progression-free survival (mPFS) and overall survival (mOS). RESULTS: the cutoff score for CD155high was 155 in the entire cohort and in patients without oncogenic alterations, and it was 110 in patients with oncogenic alterations. Eighty-four patients (97.7%) were CD155 positive, of which fifty-six (65.0%) had CD155high. EGFR L858R mutation related to lower CD155 IHC score than exon 19 deletion. Individuals with CD155high showed a shorter mOS (13.0 vs. 30.8 months; HR: 1.96 [95% CI, 1.15-3.35]; p = 0.014). Patients without oncogenic alterations having a CD155high displayed shorter mPFS (1.6 vs. 6.4 months, HR: 2.09 [95% CI, 1.06-4.20]; p = 0.034) and mOS (2.9 vs. 23.1 months; HR: 1.27 [95% CI, 1.07- 4.42]; p = 0.032). Patients with oncogenic alterations having CD155high only showed a trend to shorter mOS (26.3 vs. 52.0 months; HR: 2.39 [95% CI, 0.98-5.83]; p = 0.058). CONCLUSION: CD155high is a predictor of worse outcomes in patients with advanced NSCLC, predominantly among those without oncogenic alterations. CD155 could be a potential biomarker and a molecular target in patients with poor responses to current therapies.

Application of random survival forest to establish a nomogram combining clinlabomics-score and clinical data for predicting brain metastasis in primary lung cancer.

PURPOSE: To establish a nomogram for predicting brain metastasis (BM) in primary lung cancer at 12, 18, and 24 months after initial diagnosis. METHODS: In this study, we included 428 patients who were diagnosed with primary lung cancer at Harbin Medical University Cancer Hospital between January 2020 and January 2022. The endpoint event was BM. The patients were randomly categorized into two groups in a 7:3 ratio: training (n = 299) and validation (n = 129) sets. Least absolute shrinkage and selection operator was utilized to analyze the laboratory test results in the training set. Furthermore, clinlabomics-score was determined using regression coefficients. Then, clinlabomics-score was combined with clinical data to construct a nomogram using random survival forest (RSF) and Cox multivariate regression. Then, various methods were used to evaluate the performance of the nomogram. RESULTS: Five independent predictive factors (pathological type, diameter, lymph node metastasis, non-lymph node metastasis and clinlabomics-score) were used to construct the nomogram. In the validation set, the bootstrap C-index was 0.7672 (95% CI 0.7092-0.8037), 12-month AUC was 0.787 (95% CI 0.708-0.865), 18-month AUC was 0.809 (95% CI 0.735-0.884), and 24-month AUC was 0.858 (95% CI 0.792-0.924). In addition, the calibration curve, decision curve analysis and Kaplan-Meier curves revealed a good performance of the nomogram. CONCLUSIONS: Finally, we constructed and validated a nomogram to predict BM risk in primary lung cancer. Our nomogram can identify patients at high risk of BM and provide a reference for clinical decision-making at different disease time points.