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.

The Investigation of Quercus Infectoria Gall Aqueous Extract Effect on the Cell Proliferation, Apoptosis and Expression of CCND1, TP53, BCL2 and BAX Genes in Cell Line of Lung, Gastric and Esophageal Cancers.

Background: The therapeutic potential of Quercus infectoria (QI) gall, including its anti-inflammatory, antioxidant, and anticancer properties, is well-known. However, its impact on lung, gastric, and esophageal cancer cells remain unclear. This study aims to explore the effects of QI gall aqueous extract on cell viability, apoptosis, and gene expression in A549, BGC823, and KYSE-30 cell lines. Methods: A549, BGC823, and KYSE-30 cells were seeded in complete medium and incubated with different concentrations of QI gall extract for 24 hours. Cell viability was measured by an MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay. The induction of apoptosis was assessed through flow cytometric analysis after the adding FITC-conjugated Annexin V (Annexin V-FITC) and propidium iodide (PI). The mRNA expression levels of CCND1, TP53, BCL2 and BAX genes were determined using Real-time Quantitative Polymerase Chain Reaction analysis. Results: The MTT assay demonstrated that treatment with QI gall extract significantly reduced the number of viable cells in the A549, BGC823, and KYSE-30 cell lines at IC50 concentrations of 440.1, 437.1, and 465.2 mg/ml, respectively. Additionally, compared to untreated cell population, the percentages of early apoptosis, late apoptosis, and necrosis in the A549, BGC823, and KYSE-30 cells significantly increased following treatment with QI gall extract (P< 0.05). Also, the treatment with QI gall extract influenced the expression of CCND1, TP53, BCL2 and BAX genes. Conclusions: The present findings indicated that the gall extract of QI can inhibit the growth of A549, BGC823, and KYSE-30 cells by inducing apoptosis, which may be mediated via mitochondria-dependent pathway.

Pleuroparenchymal sarcoidosis: A rare manifestation mimicking metastatic lung cancer.

A 66-year-old male from Myanmar presented with 3 months of cough and constitutional symptoms. He was an ex-tobacco user with no significant medical or exposure history. Chest x-ray showed ill-defined bilateral opacities and a left pleural effusion. Chest CT revealed two right lower lobe masses, and a moderate-sized left pleural effusion. PET-CT demonstrated hypermetabolic uptake in the thickened nodular pleura, pericardium, and hilar/mediastinal lymph nodes. EBUS-TBNA of the right lower paratracheal node and TBLB of the right lower lobe mass yielded epithelioid granulomas comprising multinucleated giant cells, epithelioid histiocytes and lymphoplasmacytic cells. Thoracoscopy revealed hard, whitish mass-like parietal pleural plaques, and pleural biopsy revealed identical histopathologic results. His symptoms resolved quickly after commencing prednisolone 25 mg daily. Chest CT at 6 months demonstrated near complete resolution of the parenchymal masses and pleural effusion. We highlight this unique case of pleuroparenchymal sarcoidosis mimicking metastatic lung cancer in a tuberculosis-endemic region.

Advanced Lung Cancer Inflammation Index: A Novel Comprehensive Biomarker of Host Status for Patients with Metastatic Colorectal Cancer.

Numerous biomarkers that reflect host status have been identified for patients with metastatic colorectal cancer (mCRC). However, there has been a paucity of biomarker studies that comprehensively indicate body composition, nutritional assessment, and systemic inflammation status. The advanced lung cancer inflammation index (ALI), initially introduced as a screening tool for patients with non-small-cell lung cancer in 2013, emerges as a holistic marker encompassing all body composition, nutritional status, and systemic inflammation status. The index is calculated by the simple formula: body mass index × albumin value / neutrophil-to-lymphocyte ratio. Given its accessibility in routine clinical practice, the ALI has exhibited promising clinical utility in prognosticating outcomes for patients with multiple types of cancer. In this review, we focus on the significance of host status and the clinical applicability of the ALI in the treatment and management of patients with malignancies, including mCRC. We also suggest its potential in guiding the formulation of treatment strategies against mCRC and outline future perspectives.

Anaplastic Lymphoma Kinase-Tyrosine Kinase Inhibitor Treatment for Metastatic Non-small Cell Lung Cancer Throughout the Entire Gestation Period.

Non-small cell lung cancer (NSCLC) occasionally develops in younger, fertile patients. This early-onset NSCLC tends to have more oncogenic driver mutations than in aged patients. Among early-onset NSCLC patients, pregnancy is very rare. However, there are some patients who were able to balance tyrosine kinase inhibitor (TKI) administration and pregnancy. Here, we report a case of a pregnancy under alectinib hydrochloride (a second-generation anaplastic lymphoma kinase (ALK)-TKI) administration throughout the entire gestational period for ALK-rearranged metastatic lung adenocarcinoma. The patient was an Asian female in her early 20s who became aware of her pregnancy after diagnosis and the start of alectinib administration. She intended to have the baby despite the necessity of continuing her treatment and the unknown risks involved. A multidisciplinary team (thoracic surgeon, obstetrics, pediatrics, and so on) was organized to support the patient, baby, and family. There were no obvious signs of tumor progression during pregnancy. She gave birth at 41 weeks and one day of gestation. There was no placental metastasis. Alectinib concentration at delivery was 155 ng/mL in maternal blood, 22.1 ng/mL in umbilical cord venous blood, 20.1 ng/mL in amniotic fluid, and 11.8 ng/mL in colostrum. The baby had been exposed to alectinib throughout the entire pregnancy; however, fetal growth curve parameters remained within the normal ranges and the baby developed without anatomical or neurodevelopmental anomalies or fetal metastasis for the first 13 months of age.

CBCT-based synthetic CT image generation using a diffusion model for CBCT-guided lung radiotherapy.

BACKGROUND: Although cone beam computed tomography (CBCT) has lower resolution compared to planning CTs (pCT), its lower dose, higher high-contrast resolution, and shorter scanning time support its widespread use in clinical applications, especially in ensuring accurate patient positioning during the image-guided radiation therapy (IGRT) process. PURPOSE: While CBCT is critical to IGRT, CBCT image quality can be compromised by severe stripe and scattering artifacts. Tumor movement secondary to respiratory motion also decreases CBCT resolution. In order to improve the image quality of CBCT, we propose a Lung Diffusion Model (L-DM) framework. METHODS: Our proposed algorithm is based on a conditional diffusion model trained on pCT and deformed CBCT (dCBCT) image pairs to synthesize lung CT images from dCBCT images and benefit CBCT-based radiotherapy. dCBCT images were used as the constraint for the L-DM. The image quality and Hounsfield unit (HU) values of the synthetic CTs (sCT) images generated by the proposed L-DM were compared to three selected mainstream generation models. RESULTS: We verified our model in both an institutional lung cancer dataset and a selected public dataset. Our L-DM showed significant improvement in the four metrics of mean absolute error (MAE), peak signal-to-noise ratio (PSNR), normalized cross-correlation (NCC), and structural similarity index measure (SSIM). In our institutional dataset, our proposed L-DM decreased the MAE from 101.47 to 37.87 HU and increased the PSNR from 24.97 to 29.89 dB, the NCC from 0.81 to 0.97, and the SSIM from 0.80 to 0.93. In the public dataset, our proposed L-DM decreased the MAE from 173.65 to 58.95 HU, while increasing the PSNR, NCC, and SSIM from 13.07 to 24.05 dB, 0.68 to 0.94, and 0.41 to 0.88, respectively. CONCLUSIONS: The proposed L-DM significantly improved sCT image quality compared to the pre-correction CBCT and three mainstream generative models. Our model can benefit CBCT-based IGRT and other potential clinical applications as it increases the HU accuracy and decreases the artifacts from input CBCT images.

Lung cancer caused by asbestos: What a reporting pathologist needs to know.

Asbestos is a carcinogen that can cause lung cancer. The suspicion that a lung cancer diagnosis may be associated with exposure to asbestos has no bearing on treatment. However, attributing an individual's lung cancer to asbestos exposure has important medicolegal implications and may impact public health measures and policy. Simultaneous exposure(s) to other carcinogens (such as tobacco smoke, silica and many others) adds complexity while trying to answer the causation question. The Helsinki criteria were formulated to assist attributing lung cancer to previous asbestos exposure. Surrogate markers can be used and include signs of asbestosis and pleural plaques. The most widely used criterion for the presence of asbestosis is interstitial fibrosis in conjunction with 2 or more asbestos bodies/1 cm2 tissue section by light microscopy. Identification of asbestos bodies ty light pr electron microscopy provides an important element for asbestos diagnosis. However, fibrosis may be subtle, and the distribution of asbestos bodies is not uniform throughout the lungs, some types of asbestos fibres have low biopersistence, and not all types of asbestos readily form asbestos bodies. Additional criteria require knowledge of exposure history, which is often unknown to pathologists, but reliance on morphology in isolation may lead to mis-classification of interstitial lung disease as idiopathic. While a smoking-related lung cancer signature has emerged, an asbestos-related lung cancer signature has not yet been identified. In this review we will discuss practice points for the surgical pathologist.

The experience of social alienation in elderly lung cancer patients: A Qualitative Study.

PURPOSE: To understand the experience of social alienation in elderly lung cancer patients, to explore its causes, and to propose targeted intervention strategies. METHODS: From July to August 2023, 16 elderly lung cancer patients attending the respiratory department of a tertiary hospital in Changsha City, Hunan Province, were selected for semi-structured interviews using a purposive sampling method. The Colaizzi 7-step method was used to analyze the data. RESULTS: A total of four themes were distilled: the experience of social alienation in elderly lung cancer patients (pessimistic feelings, inferiority complex, and heavy psychological burden), subjective causes (disease-included shame, avoidant social behavior, and stigmatized labels), objective causes (isolated social states, and reduced amount of socialization), and rehabilitation support. CONCLUSION: The causes of social alienation in elderly lung cancer patients include multiple aspects of personal, family, and social support, and symptom management and psychological guidance should be strengthened for this population to construct a hospital-society-family triple linkage care program to help patients recover.

Current Trial Report: A Multicenter Phase I/Ib study of Capmatinib Plus Trametinib in Patients With Metastatic Nonsmall Cell Lung Center Harboring MET Exon 14 Skipping Mutations and Other MET-Alterations.

INTRODUCTION: MET tyrosine kinase inhibitor (TKI) therapy is associated with improved outcomes in patients with nonsmall cell lung cancer (NSCLC) harboring a MET alteration, including MET exon 14 (METex14) skipping mutation, MET amplification, or MET fusion. However, primary or acquired resistance to TKI therapy ultimately develops. In preclinical models, hyperactivation of MAPK signaling was shown to promote resistance to MET TKI; resistance was overcome by co-treatment with a MET inhibitor and a MEK inhibitor. This phase I/Ib study offers a potential combination strategy simultaneously targeting MET (with capmatinib) and MEK signaling (with trametinib) to overcome resistance to MET inhibitor monotherapy in METex14 NSCLC. METHODS: In the dose escalation phase, a minimum of 6 and maximum of 18 patients will be enrolled using a conventional 3+3 design with the primary endpoint of identifying a recommended phase 2 dose (RP2D) of capmatinib in combination with trametinib. Once the RP2D is identified, patients will continue to enroll in a dose expansion phase to a total of 15 patients. The primary endpoint of the dose expansion phase is to further characterize the safety profile of the combination. CONCLUSION: This phase I/Ib clinical trial will assess the safety and efficacy of combination capmatinib and trametinib in NSCLC patients whose tumors harbor METex14 skipping mutations, MET amplification, or MET fusion and had developed progressive disease on single agent MET inhibitor therapy.

An ultrasensitive DNA-enhanced amplification method for detecting cfDNA drug-resistant mutations in non-small cell lung cancer with selective FEN-assisted degradation of dominant somatic fragments.

OBJECTIVES: Blood cell-free DNA (cfDNA) can be a new reliable tool for detecting epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. However, the currently reported cfDNA assays have a limited role in detecting drug-resistant mutations due to their deficiencies in sensitivity, stability, or mutation detection rate. METHODS: We developed an Archaeoglobus fulgidus-derived flap endonuclease (Afu FEN)-based DNA-enhanced amplification system of mutated cfDNA by designing a pair of hairpin probes to anneal with wild-type cfDNA to form two 5'-flaps, allowing for the specific cleavage of wild-type cfDNA by Afu FEN. When the dominant wild-type somatic cfDNA fragments were cleaved by structure-recognition-specific Afu FEN, the proportion of mutated cfDNA in the reaction system was greatly enriched. As the amount of mutated cfDNA in the system was further increased by PCR amplification, the mutation status could be easily detected through first-generation sequencing. RESULTS: In a mixture of synthetic wild-type and T790M EGFR DNA fragments, our new assay still could detect T790M mutation at the fg level with remarkably high sensitivity. We also tested its performance in detecting low variant allele frequency (VAF) mutations in clinical samples from NSCLC patients. The plasma cfDNA samples with low VAF (0.1 and 0.5 %) could be easily detected by DNA-enhanced amplification. CONCLUSIONS: This system with enhanced amplification of mutated cfDNA is an effective tool used for the early screening and individualized targeted therapy of NSCLC by providing a rapid, sensitive, and economical way for the detection of drug-resistant mutations in tumors.

Evaluation of radiofrequency identification tag accuracy using bronchoscopy with fluoroscopy and virtual navigation guidance before segmentectomy.

BACKGROUND: The use of sublobar resection has increased with advances in imaging technologies. However, it is difficult for thoracic surgeons to identify small lung tumours intraoperatively. Radiofrequency identification (RFID) lung-marking systems are useful for overcoming this difficulty; however, accurate placement is essential for maximum effectiveness. METHODS: We retrospectively reviewed patients who underwent RFID tag placement via fluoroscopic bronchoscopy under virtual bronchoscopic navigation (VBN) guidance before our institution's sublobar resection of lung lesions. Thirty-one patients with 31 lung lesions underwent RFID lung-marking with fluoroscopic bronchoscopy under VBN guidance. RESULTS: Of the 31 procedures, 26 tags were placed within 10 mm of the target site, 2 were placed more than 10 mm away from the target site, and 3 were placed in a different area from the target bronchus. No clinical complications were associated with RFID tag placement, such as pneumothorax or bleeding. The contribution of the RFID lung-marking system to surgery was high, particularly when the RFID tag was placed at the target site and tumour was located in the intermediate hilar zone. CONCLUSIONS: An RFID tag can be placed near the target site using fluoroscopic bronchoscopy in combination with VBN guidance. RFID tag placement under fluoroscopic bronchoscopy with VBN guidance is useful for certain segmentectomies.

Clinical significance of chronic pulmonary aspergillosis in lung cancer patients undergoing anticancer drug therapy.

BACKGROUND: Advances in anticancer drugs for lung cancer (LC) have improved the prognosis of LC. Chronic pulmonary aspergillosis (CPA) is a progressive and often exacerbating respiratory disease with a poor prognosis. To date, the prognosis of LC complicated by CPA has not been elucidated. This study investigated the clinical implications of concomitant CPA in patients with LC undergoing anticancer drug treatment. METHODS: Between January 2010 and May 2020, we consecutively enrolled patients with LC complicated with CPA at five different institutions in Japan. We analyzed patients with LC complicated by CPA who received anticancer drug treatment. RESULTS: A total of 10 patients with LC complicated by CPA received anticancer drug treatment. The median overall survival (OS) was 14.57 months (95% confidence interval [CI]: 5.37-21.67). The cause of death in all patients was LC. Six of the seven patients with LC did not show worsening pulmonary aspergillosis lesions during the anticancer drug treatment. Although two patients discontinued anticancer drug treatment due to pneumonitis, CPA complications did not interfere with the continuation of anticancer drug treatment. In univariate analyses, squamous histology (p = 0.01) and body mass index (<18.5 kg/m2) (p = 0.0008) were significantly associated with poorer OS. CONCLUSIONS: This study demonstrated that the cause of death in LC patients with concomitant CPA who received anticancer drug treatments and effective antifungal treatment was LC progression. Further large-scale studies are needed to identify the effect of CPA in patients with LC.

The Role of TGFBR3 in the Development of Lung Cancer.

The Transforming Growth Factor-ß (TGF-ß) mediates embryonic development, maintains cellular homeostasis, regulates immune function, and is involved in a wide range of other biological processes. TGF-ß superfamily signaling pathways play an important role in cancer development and can promote or inhibit tumorigenesis. Type III TGF-ß receptor (TGFBR3) is a co-receptor in the TGF-ß signaling pathway, which often occurs with reduced or complete loss of expression in many cancer patients and can act as a tumor suppressor gene. The reduction or deletion of TGFBR3 is more pronounced compared to other elements in the TGF-ß signaling pathway. In recent years, lung cancer is one of the major malignant tumors that endanger human health, and its prognosis is poor. Recent studies have reported that TGFBR3 expression decreases to varying degrees in different types of lung cancer, both at the tissue level and at the cellular level. The invasion, metastasis, angiogenesis, and apoptosis of lung cancer cells are closely related to the expression of TGFBR3, which strengthens the inhibitory function of TGFBR3 in the evolution of lung cancer. This article reviews the mechanism of TGFBR3 in lung cancer and the influencing factors associated with TGFBR3. Clarifying the physiological function of TGFBR3 and its molecular mechanism in lung cancer is conducive to the diagnosis and treatment of lung cancer.

Auriculasin induces mitochondrial oxidative stress and drives ferroptosis by inhibiting PI3K/Akt pathway in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for the majority of cases of lung cancer with poor outcomes. Auriculasin is a prenylated isoflavone abundant in the root of F. philippinensis with multiple pharmacological effects, including anticancer role. However, its roles in NSCLC remain largely unknown. NSCLC A549 cells were treated with auriculasin in vitro, and used to induce xenograft models. Cell viability was detected via CCK-8 assay. Mitochondrial oxidative stress was analyzed by JC-1 staining, ROS staining, and levels of MDA, SOD and GSH. Ferroptosis was assessed via iron content, and levels of ACSL4, PTGS2, FSP1 and GPX4. The phosphorylation levels of PI3K and Akt were measured by western blot. Auriculasin reduced NSCLC cell viability. Auriculasin promoted mitochondrial oxidative stress by reducing mitochondrial membrane potential, SOD and GSH levels, and enhancing ROS and MDA contents. In addition, auriculasin induced ferroptosis via increasing iron, ACSL4 and PTGS3 levels, and decreasing FSP1 and GPX4 levels. Furthermore, the potential targets of auriculasin in NSCLC were enriched in PI3K/Akt signaling. Auriculasin blunted PI3K/Akt pathway activation by blocking the phosphorylation. Activated PI3K/Akt signaling by activator 740Y-P reversed the effects of auriculasin on mitochondrial oxidative stress and ferroptosis. Finally, auriculasin reduced NSCLC cell growth in xenograft models. Auriculasin facilitates mitochondrial oxidative stress and induces ferroptosis through inhibiting PI3K/Akt pathway in NSCLC.

EGFR-mutated lung cancer as a secondary neoplasm in a patient with Li-Fraumeni syndrome: case report.

Background: Li-Fraumeni syndrome (LFS) is a rare hereditary disorder caused by mutations in the tumor protein p53 (TP53). It causes a predisposition for the development of multiple malignancies, primarily including breast cancers, sarcomas, and central nervous system tumors. There are a few cases reported in the literature of patients with LFS presenting with an epidermal growth factor receptor (EGFR) mutated lung cancer. Still, it has been suggested that there may be an association between the TP53 pathogenic variant and lung cancer with EGFR mutation in somatic cells. Case Description: A 47-year-old non-smoker woman with LFS with a history of multiple tumors, including bilateral breast cancer, pecoma, and sarcoma. In one of her computed tomography, a lesion in the lingula of the lung was detected. It was biopsied, which diagnosed lung adenocarcinoma, and genetic studies detected an EGFR exon 19 deletion. She was treated with a left inferior lobectomy, followed by pemetrexed and cisplatin. Conclusions: The association between TP53 and lung cancer with EGFR mutation has been suggested in case reports. Studies in lung cancer cell lines have shown a link between TP53 mutation and EGFR overexpression. Nonetheless, as more cases are reported, further research is needed to comprehend the interrelation between these two pathologies and the risk posed by LFS to the emergence of EGFR-mutated lung cancer.

A case report of synchronous breast and lung cancer with three different pathologic diagnoses.

Background: Multiple primary malignant tumors (MPMTs) pose a significant clinical challenge, denoting the occurrence of two or more distinct malignant tumors with differing histological characteristics, all diagnosed within a 6-month timeframe. MPMT is a rare condition and due to the unique treatment requirements for each specific cancer type, it is crucial for healthcare professionals to accurately differentiate between metastatic growth and distinct primary tumors. Case Description: In this case report, we present a 41-year-old female patient who received diagnoses of three separate synchronous primary tumors. The patient presented for evaluation of a right breast mass that had been present for 1 year. Initial diagnostic tests, including mammography and ultrasound, did not provide any conclusive results. Subsequent magnetic resonance imaging (MRI) of the breast prompted an ultrasound-guided biopsy which confirmed moderately differentiated invasive ductal carcinoma (IDC). During pre-surgical testing, a suspicious opacity was detected on a chest X-ray, prompting further investigation with a computed tomography (CT) scan of the chest to distinguish between metastatic disease and a potential new primary tumor. Clinical and pathological examinations revealed the presence of bilateral masses originating from two different origins: invasive mucinous pulmonary adenocarcinoma in the left lower lobe and a neuroendocrine carcinoma in the right middle lobe of the lung. Conclusions: Cases of this nature present a complex challenge to physicians and underscore the critical importance of maintaining a high level of clinical suspicion to ensure the delivery of high-quality care. Effective management of such patients requires a multidisciplinary collaboration among breast surgeons, thoracic surgeons, and medical and radiation oncologists.

Real-World Pharmacokinetics, Effectiveness, and Safety of Atezolizumab in Patients With Unresectable Advanced or Recurrent NSCLC: An Exploratory Study of J-TAIL.

Introduction: This study validated real-world pharmacokinetic (PK) data using an established population PK (PopPK) model for atezolizumab in Japanese patients with NSCLC and explored the relationship between PK parameters, effectiveness, and adverse events (AEs) for the 1200 mg once every three weeks regimen. Methods: A subgroup of 262 of 1039 patients from J-TAIL consented to this exploratory research for PK evaluation of atezolizumab monotherapy for unresectable advanced/recurrent NSCLC (August 2018 to October 2019; 197 institutions). We evaluated plasma concentrations before the start of the third cycle of atezolizumab infusion classified into quartiles 1 to 4, their association with effectiveness, and the association between atezolizumab maximum plasma concentrations (Cmax) calculated using the existing PopPK model and AEs of special interest (AESIs). Results: Overall, 175 of 262 patients were included; baseline characteristics were similar to those of patients enrolled in J-TAIL (Eastern Cooperative Oncology Group performance status ≥ 2, 12.0%; age ≥ 75 y, 28.9%; atezolizumab as more than or equal to third-line treatment, 57.5%). Atezolizumab plasma concentrations were similar to previously reported data among Japanese/non-Japanese patients. The overall survival was significantly shorter in patients with lower atezolizumab plasma concentrations in Q1 versus Q2 to Q4, although progression-free survival remained the same. The PK data adequately fit the PopPK model, with the frequency of AESIs increasing as the calculated Cmax at cycle 1 increased. Conclusions: In real-world Japanese patients with unresectable advanced/recurrent NSCLC, PKs were similar to previous reports. Certain patient populations had shorter overall survival, and atezolizumab plasma concentrations in cycle 3 were lower in this population. Elevated Cmax at cycle 1 may be associated with an increased frequency of AESIs.

Successful Lorlatinib Rechallenge After Severe Drug-Induced Psychosis in ALK-Positive Metastatic NSCLC: A Case Report.

Neurocognitive adverse events (NAEs) have been reported in up to 60% of patients on lorlatinib, a potent central nervous system-active ALK inhibitor. Manifestations may include psychotic, mood, speech, and cognitive symptoms. Current guidance recommends permanent discontinuation of lorlatinib in cases of grade IV NAEs. Here, we report a case of successful rechallenge of dose-reduced lorlatinib after recovery of grade IV psychosis in a patient with ALK-positive NSCLC.

Analysis of surgical complexity and short-term prognostic indicators in NSCLC patients: neoadjuvant targeted therapy versus neoadjuvant chemoimmunotherapy.

Background: Neoadjuvant therapy improves survival benefits in patients with locally advanced non-small cell lung cancer but increases tissue density, presenting challenges for surgeons. Objectives: To compare the differences in surgical complexity and short-term prognostic outcomes between neoadjuvant targeted therapy (NTT) and neoadjuvant chemoimmunotherapy (NCI). Design/methods: This study enrolled 106 patients underwent curative surgery after neoadjuvant therapy between January 2020 and December 2023 at the National Cancer Center of China. Differences in surgical complexity and short-term prognostic outcomes between the two neoadjuvant therapy cohorts were evaluated. The pathological indicators such as pathological response rate and lymph node upstaging/downstaging were then analyzed. Results: In total, 33 patients underwent NTT and 73 underwent NCI preoperatively. Patients who received NTT showed a higher minimally invasive surgery rate (84.8% versus 53.4%, p < 0.01), shorter operative time (144 versus 184 min, p < 0.01), lower conversion rate (3.3% versus 17.8%, p = 0.03), less postoperative drainage (day 3: 140 versus 200 mL, p = 0.03), and lower incidence of postoperative complications including arrhythmias (6.1% versus 26%, p = 0.02). The pathological response rate in the NTT and NCI groups was 70% and 75%, respectively, with the latter group showing a higher complete pathological response rate. The two groups had no significant differences in major pathological response and lymph node pathological response rate. Conclusion: Patients who received NTT presented fewer surgical challenges for surgeons and had better surgical outcomes than those who received NCI therapy, with comparable pathological response rates between the two cohorts. Accordingly, NTT is the preferred induction regimen for patients harboring mutation status.

Combination of anlotinib and second-line chemotherapy as surrogate to reduce immunosuppression in patients with advanced non-small cell lung cancer.

Objective: To study the clinical effects of anlotinib combined with second-line chemotherapy (SLC) on immunosuppression in patients with advanced non-small cell lung cancer (NSCLC). Methods: In this retrospective study, the medical records of 106 patients with advanced NSCLC admitted to the Lianyungang First People's Hospital from November 2020 to March 2022 were retrospectively analyzed. Amongst 106 patients, 53 patients received second-line single-agent chemotherapy regimens (SLC group), and 53 patients received anlotinib combined with SLC (ASLC group). Prognosis, levels of immune cells and inflammatory cytokine, and adverse reactions were analyzed. Results: Clinical efficacy of the ASLC group was significantly higher than the SLC group (p<0.05). After treatment, patients in the ASLC group exhibited significantly higher levels of CD4+/CD8+ and CD4+ compared to those in the SLC group (p<0.05), while the difference in CD8+ level between the two groups was not statistically significant (p>0.05). After treatment, levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-8 (IL-8), interleukin-6 (IL-6) in the ASLC group were lower compared to the SLC group (p<0.05). Conclusion: In patients with advanced NSCLC, anlotinib combined with SLC is associated with higher levels of immune cells and reduced inflammatory factors. This treatment regimen, thus, can reduce immunosuppression and improve the prognosis of NSCLC patients.