Current Status of Diagnosis and Treatment of Pulmonary Sarcomatoid Carcinoma

Pulmonary sarcomatoid carcinoma (PSC) is a rare, poorly differentiated, subtype of non-small cell lung carcinoma (NSCLC) and constitutes approximately 0.1% to 0.5% of all lung malignancies. PSC can be divided into five subtypes based on the 2015 World Health Organization (WHO) classification of lung tumors: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma. Some imaging characteristics can be found for PSC although no special symptoms. The accurate pathological diagnosis of PSC can be a significant challenge, which depends on pathology and immunohistochemistry. PSC should be managed similar to other NSCLC, surgical resection is the standard management for early stage cases, moreover, multimodal treatment should be considered. However, PSC is insensitive to radiotherapy and chemotherapy, and has high rate of local and metastatic recurrence and poor prognosis. With the development of molecular pathology, targeted therapy and immunotherapy may have broad prospects

Macrophage Inhibitory Cytokine-1 (MIC-1) as A Biomarker for Diagnosis and Prognosis of Stage I-II Non-small Cell Lung Cancer

Background and objective Increased macrophage inhibitory cytokine-1 (MIC-1), member of transforming growth factor-β (TGF-β) superfamily, was found in patients serum with epithelial tumors. Therefore, our aim was to delineate the diagnostic and prognostic value of serum MIC-1 in patients with stage I-II non-small cell lung cancer (NSCLC). Methods A total of 152 consecutive patients with stage I–II NSCLC were prospectively enrolled and underwent follow up after total resection of tumor. Serum MIC-1 level was detected in lung cancer patients by ELISA, 48 benign pulmonary disease patients and 105 healthy controls, and was correlated with clinical features and prognosis of patients. Results The level of MIC-1 of NSCLC patients was significantly higher than that of controls (P<0.001) and benign pulmonary disease patients (P<0.001). A threshold of 1,000 pg/mL could be used to diagnose early-stage NSCLC with 70.4% sensitivity and 99.0% specificity. The level of MIC-1 was associated with elder age (P=0.001), female (P=0.03) and T2 (P=0.022). A threshold of 1,465 pg/mL could identify patients with early poor outcome with 72.2% sensitivity and 66.1% specificity. The overall 3-year survival rate in patients with high level of MIC-1 (≥1,465 pg/mL) was significantly lower than that of patients with low MIC-1 level (77.6% vs 94.8%). Multivariable Cox regression revealed that a high level of MIC-1 was an independent risk factor for compromised overall survival (HR=3.37, 95%CI: 1.09-10.42, P=0.035). Conclusion High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC

Association between radiotherapy and risk of second primary malignancies in patients with resectable lung cancer: a population-based study

Abstract Background The most common form of treatment for non-metastatic lung cancer is surgery-based combination therapy, which may also include adjuvant radiotherapy or chemotherapy. Second primary malignancies (SPMs) are uncommon but significant radiation side effects in patients with resectable lung cancer, and SPMs have not been adequately investigated. Our study aims to assess the correlations of radiotherapy with the development of SPMs in patients with resectable lung cancer. Methods We screened for any primary malignancy that occurred more than five years after the diagnosis of resectable lung cancer. Based on the large cohort of the Surveillance, Epidemiology and End Results database, radiotherapy-correlated risks were estimated using the Poisson regression analysis and the cumulative incidence of SPMs was calculated using Fine-Gray competing risk regression analysis. Results Among the 62,435 patients with non-metastatic lung cancer undergoing surgery, a total of 11,341 (18.16%) patients have received radiotherapy. Our findings indicated that radiotherapy was substantially related to a high risk of main second solid malignancies (RR = 1.21; 95%CI, 1.08 to 1.35) and a negligible risk of main second hematologic malignancies (RR = 1.08; 95%CI, 0.84 to 1.37). With the greatest number of patients, the risk of acquiring a second primary gastrointestinal cancer was the highest overall (RR = 1.77; 95 percent CI, 1.44 to 2.15). The cumulative incidence and standardized incidence ratios of SPMs revealed similar findings. Furthermore, the young and the elderly may be more vulnerable, and the highest risk of acquiring most SPMs was seen more than ten years after lung cancer diagnosis. Additionally, more attention should be paid to the second primary gastrointestinal cancer in young individuals with resectable lung cancer. Conclusion After receiving radiotherapy, an increased risk of developing second primary solid and gastrointestinal cancers was observed for patients with resectable lung cancer. The prevention of SPMs associated with radiotherapy requires further attention

Global burden and temporal trends in incidence and mortality of oesophageal cancer

Introduction: Oesophageal cancer is a prevalent and deadly cancer around the world. Objectives: We aimed to present a comprehensive analysis of the global geographic patterns and temporal trends in the mortality and incidence of oesophageal cancer. Methods: The mortality and incidence data of oesophageal cancer in 2020 were obtained from the GLOBOCAN database. Based on World Health Organization (WHO) mortality database and the Cancer Incidence in Five Continents (CI5), we also retrieved the mortality and incidence age-standardized rates (ASRs) of oesophageal cancer. The average annual percentage changes (AAPCs) of mortality and incidence were calculated using the joinpoint regression analysis. Results: Globally, 0.54 million deaths and 0.6 million new cases were identified in 2020. In the majority of countries of South America and Asia, the mortality and incidence trends have substantially decreased, but trends in European countries have varied. The prevalence in European nations varied, but the incidence in most other continents decreased dramatically. In terms of mortality, the global average rate was 5.6 per 100000, ranging from 16.7 (Malawi) to 0.28 (Belize). European countries varied in mortality, such as Norway (AAPC, male: 0.68; female: 0.89) and Ireland (AAPC, male: −0.96; female: −1.52). Most non-European countries saw large decreases in mortality, such as Singapore (AAPC, male: −4.78; female: −6.89). The elderly had more noticeable trends in mortality and incidence in most countries. Conclusions: We have identified different trends in mortality and incidence among European countries, whereas declining trends were identified in most non-European countries. However, increasing trends were identified in specific subgroups of some countries, such as men in Thailand. For populations with rising mortality and incidence trends, more preventative efforts are required

Utility of 18F-FDG uptake in predicting major pathological response to neoadjuvant immunotherapy in patients with resectable non‑small cell lung cancer

Purpose: The aim of present study was to investigate the efficiency of 18F-FDG uptake in predicting major pathological response (MPR) in resectable non-small cell lung cancer (NSCLC) patients with neoadjuvant immunotherapy. Methods: A total of 104 patients with stage I-IIIB NSCLC were retrospectively derived from National Cancer Center of China, of which 36 cases received immune checkpoint inhibitors (ICIs) monotherapy (I-M) and 68 cases with ICI combination therapy (I-C). 18F-FDG PET-CT scans were performed at baseline and after neoadjuvant therapy (NAT). Receiver‐operating characteristic (ROC) curve analyses were conducted and area under ROC curve (AUC) was calculated for biomarkers including maximum standardized uptake value (SUVmax), inflammatory biomarkers, tumor mutation burden (TMB), PD-L1 tumor proportion score (TPS) and iRECIST. Results: Fifty-four resected NSCLC tumors achieved MPR (51.9%, 54/104). In both neoadjuvant I-M and I-C cohorts, post-NAT SUVmax and the percentage changes of SUVmax (ΔSUVmax%) were significantly lower in the patients with MPR versus non-MPR (p < 0.01), and were also negatively correlated with the degree of pathological regression (p < 0.01). The AUC of ΔSUVmax% for predicting MPR was respectively 1.00 (95% CI: 1.00–1.00) in neoadjuvant I-M cohort and 0.94 (95% CI: 0.86–1.00) in I-C cohort. Baseline SUVmax had a statistical prediction value for MPR only in I-M cohort, with an AUC up to 0.76 at the threshold of 17.0. ΔSUVmax% showed an obvious advantage in MPR prediction over inflammatory biomarkers, TMB, PD-L1 TPS and iRECIST. Conclusion: 18F-FDG uptake can predict MPR in NSCLC patients with neoadjuvant immunotherapy

Ten-Year Trends of Clinicopathologic Features and Surgical Treatment of Lung Cancer in China

BACKGROUND: Lung cancer has changed significantly during the past 2 decades in its epidemiology and treatment. This retrospective analysis used data from 7 major areas of China over 10 years to evaluate clinicopathologic and surgical treatment trends of lung cancer in China during the past decade. METHODS: Data from 7184 patients with primary lung cancer who were treated between 2005 and 2014 in 8 provinces of China were retrospectively collected. Their clinicopathologic features and surgical treatment information were recorded. Simple linear regression models and the Cochrane-Armitage trend test were used to assess temporal trends. RESULTS: The proportion of female patients (from 57.4% to 59.6%; P < .001) and nonsmoking patients (from 37.1% to 48.9%; P < .001) and of patients with a family history of malignant tumors (from 7.0% to 11.5%; P < .001) increased significantly. The percentage of adenocarcinomas increased significantly (from 36.4% to 53.5%; P < .001), with a decrease in squamous cell carcinomas (from 45.4% to 34.4%; P < .001). After 2008, the application of minimally invasive surgery significantly increased in China (from 2.4% in 2008 to 34.4% in 2014; P < .001), with a decline in the rate of conversion to open operation (from 14.3% in 2008 to 4.8% in 2014; P = .146) and an increase in the proportion of systematic mediastinal lymph node dissection (from 50.0% in 2008 to 84.1% in 2014; P = .001). CONCLUSIONS: This study investigated recent 10-year trends in the clinicopathologic features and surgical treatment of lung cancer in China and found significant important changes. These findings provide valuable information and evidence for the future control of the disease in China.status: publishe

Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization

Abstract Multimodal epigenetic characterization of cell-free DNA (cfDNA) could improve the performance of blood-based early cancer detection. However, integrative profiling of cfDNA methylome and fragmentome has been technologically challenging. Here, we adapt an enzyme-mediated methylation sequencing method for comprehensive analysis of genome-wide cfDNA methylation, fragmentation, and copy number alteration (CNA) characteristics for enhanced cancer detection. We apply this method to plasma samples of 497 healthy controls and 780 patients of seven cancer types and develop an ensemble classifier by incorporating methylation, fragmentation, and CNA features. In the test cohort, our approach achieves an area under the curve value of 0.966 for overall cancer detection. Detection sensitivity for early-stage patients achieves 73% at 99% specificity. Finally, we demonstrate the feasibility to accurately localize the origin of cancer signals with combined methylation and fragmentation profiling of tissue-specific accessible chromatin regions. Overall, this proof-of-concept study provides a technical platform to utilize multimodal cfDNA features for improved cancer detection