Prognostic And Genomic Analysis Of Surgically Resected Synchronous Multiple Primary Lung Cancer

BackgroudThe 8th edition lung cancer staging system described a detailed classification of synchronous multiple primary lung cancer,and the changes are quite different from previous versions.In this system,multifocal ground glass/lepidic(GG/L)nodules is listed separately as a unique type of synchronous multiple primary lung cancer.However,the staging of multiple primary lung cancer is still based on the traditional TNM stage.By reviewing the previous studies and clinical data,we found that even for the same stage of multiple primary lung cancer,the recurrence free survival(RFS)and overall survival(OS)of patients would be significantly different.Therefore,we sough to develop clinical nomograms for predicting recurrence free survival and overall survival of patients with resected synchronous multiple primary lung cancer(sMPLC).Methods926 patients with sMPLC were retrospectively screened from our medical record system.Patients were divided into two groups:multifocal ground glass/lepidic(GG/L)adenocarcinoma and second primary lung cancer(SPLC).We identified and integrated significant prognostic factors for survival to build nomogram respectively.The model was subjected to bootstrap internal validation.The predictive accuracy and discriminative ability were measured by concordance index(C-index)and risk group stratification.ResultsOf 926 patients with sMPLC,there were 561 GG/L and 365 SPLC patients,respectively.There were significant differences in clinical characteristics between SPLC and GG/L patients.In GG/L group,three independent prognostic factors influencing RFS were identified,and three independent prognostic factors influencing OS were identified.In SPLC,three independent prognostic factors influencing RFS were identified,and four independent prognostic factors influencing OS were identified.According to the selected variables,four nomograms were established to predict the RFS and OS of GG/L and SPLC patients.The calibration curves for probability of 1-,3-,and 5-year RFS and OS showed optimal agreement between nomogram prediction and actual observation.The C-index of the four nomogram was higher than that of the eighth edition American Joint Committee on Cancer TNM staging system for predicting RFS and OS(GG/L:RFS,0.798 vs,P=;OS:0.732 vs,P=;SPLC:RFS,0.798 vs,P=;OS:0.732 vs,P=).The stratification into different risk groups allowed significant distinction between survival curves within respective TNM categories.ConclusionThis study,for the first time,analyzed the risk factors influencing the prognosis of sMPLC in a large cohort,and developed a novel nomogram,which can provide individual prediction of RFS and OS for patients with resected sMPLC.This practical prognosis model based on the clinicopathological of patients may help clinicians in decision making,and provide the basis for the further accurate staging of multiple primary lung cancer.BackgroundThe aim of the study was to explore the outcomes of wedge resection on patients with early-stage lung adenocarcinoma and further identify potential prognostic factors for these patients.Further to determine whether wedge resection is suitable for multiple primary lung adenocarcinoma.MethodsA retrospective cohort of 190 patients(99 solitary lung adenocarcinoma and 91 multifocal lung adenocarcinoma)undergone wedge resection from October 2014 to September 2015 was established.Cox proportional-hazards model was used to evaluate the significant clinical prognostic factors.Further,data on patients with multifocal adenocarcinoma after anatomical partial lobectomy(APL)were retrieved and propensity score matching was used to compare the outcomes of patients with multiple pulmonary nodules(MPN)after wedge resection and anatomical partial lobectomy.ResultsThe 5-year overall survival,recurrence-free survival,and lung cancer specific survival of the 190 patients after wedge resection were 95.5%,87.9%,and 97.7%,respectively.Multivariable analysis showed that MPN(hazard ratio[HR]3.07;95%confidence interval[CI],1.05-8.98)and solid-dominant lesions(HR 15.87;95%CI,0.21-4.76)were independently associated with worse recurrence-free survival(RFS).Further,propensity score matching analysis showed that MPN patients had better RFS after anatomical partial lobectomy compared with wedge resection(94%vs 80.9%,P=0.008).MPN patients were more likely to perform systematic mediastinal nodal sampling(95.6%versus 59.3%,P<0.001)after anatomical partial lobectomy compared to patients who underwent wedge resection.ConclusionsWedge resection is a practical option for appropriately selected early-stage lung adenocarcinoma where tumor size is less than 2cm and has a consolidation-to-tumor ratio?0.5.However,for MPNs,wedge resection may be not reliable and alternative procedures such as anatomical partial lobectomy should be used.BackgroundThe detection rate of multiple pulmonary nodules in computed tomography(CT)screening has increased significantly in recent years.In cases with multiple nodules within the same lung lobe or segment,it is often difficult for thoracic surgeons and pathologists to accurately locate all lesions in the surgically resected specimens.Therefore,the objective of our study was to use three-dimensional(3D)reconstruction in conjunction with 3D printing as an auxiliary method for localizing multiple small nodules in specimens after surgery and to evaluate its effectiveness.MethodsA single-center prospective cohort study was conducted between September 2019 and September 2020 at the National Cancer Center(Beijing,China).In total,43 surgical candidates with multiple nodules were recruited to undergo lobectomy or segmentectomy and 40 patients were ultimately enrolled in this study.With the assistance of 3D reconstruction/printing models,the obtained specimens were marked and then identified by a pathologist.The primary outcome was the success rate of nodule localization in the resected specimens,and the secondary outcome was the agreement rate between the pathological results of the samples and CT images.ResultsIn the 40 patients enrolled,126 nodules were detected by preoperative imaging,of which 124 nodules(positive rate:98.4%)were successfully located in the resected specimens using 3D reconstruction/printing.For the 124 nodules,the agreement rate of the pathological results of samples and CT images with the assistance of 3D reconstruction/printing models was 100.0%.ConclusionsThe results show that 3D reconstruction/printing models allow for the rapid and accurate localization of nodules in resected specimens.Also,the pathological results of lesions show good agreement with the results of preoperative CT imaging,which is of great significance for further study into the clinicopathological characteristics and radiomics of multiple pulmonary nodules.BackgroudLarge-scale sequencing studies have revealed the complex genomic landscape of NSCLC.Many of these lesions are atypical adenomatous hyperplasia(AAH),adenocarcinoma in situ(AIS),minimally invasive adenocarcinoma(MIA),and sometimes invasive adenocarcinoma(IAC).These lesions were surgically resected with excellent outcomes.However,little attention has been paid to the genomic evolution of these lesions from preinvasive to invasive lung adenocarcinoma in multiple primary lung cancer.In order to explore the pathogenesis of lung adenocarcinoma,we systematically explored the genomic characteristics of these lesions.At the same time,we explored the tumor immune microenvironment of early-stage multiple primary lung adenocarcinoma based on single cell sequencing analysis.MethodsWe performed whole exon sequencing analysis of 23 tumor samples and corresponding paracarcinomatic tissue samples from 4 patients.Among them,there were 7 cases with AAH,5 cases with AIS,2cases with MIA and 9 cases with IAC.Subsequently,we performed single-cell sequencing analysis on 17 tumor samples from another 6 patients.All the 17 samples were invasive lung adenocarcinoma.ResultsDifferent lesions of the same patient showed different genomic mutation characteristics,suggesting that these patients were multiple primary lung adenocarcinoma.NEFH(20.7%),NOTCH1(20.7%)and EGFR(17.2%)were the three most common mutated oncogenes.Tumor mutation burden of IAC was significantly higher than that of preinvasive lesions.Single cell sequencing showed that the relative abundance of B cells in multiple primary lung adenocarcinomas were higher than that in normal lung tissues.Compared with normal lung tissue,the relative abundance of monocyte macrophages increased,but T cells showed no significant difference.At the same time,the microenvironment of different nodules in the same patient is different.suggesting that different lesions genesis and development independently in different tumor microenvironment.ConclusionIn this study,SCS analysis of sMPLC was performed,and the tumor microenvironment of different lesions were displayed.At the same time,we analyzed the tumor evolution of early-stage multiple primary lung cancer,and revealed classes of genome alterations that increase in frequency during the progression to malignancy.