ABSTRACT
To compare the pathological results and long-term survival results of early surgery and surgery after at least one year follow-up for ground-glass component predominant lung adenocarcinoma patients. From January 1, 2013 to August 31, 2017, a total of 279 patients with ground-glass nodules (GGNs) undergoing surgical resection and pathologically proved to be pulmonary adenocarcinoma were included in this study. All patients were divided into early surgery group (ES Group) (210 cases) and surgery after follow-up group (FS Group) (69 cases). Patients in FS group experienced at least one year surveillance. Clinical and imaging features were analyzed by using univariate analysis. After analysis, there was no statistical difference in pathological results and long-term prognosis between the two groups. In the follow-up group, grown GGNs have proved to have more aggressive pathological results. The one-year follow-up may be a feasible management method for patients with ground-glass component predominant GGN.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Male , Female , Middle Aged , Prognosis , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Lung Neoplasms/diagnostic imaging , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/mortality , Adenocarcinoma of Lung/diagnostic imaging , Aged , Follow-Up Studies , Retrospective Studies , Adult , Solitary Pulmonary Nodule/surgery , Solitary Pulmonary Nodule/pathology , Solitary Pulmonary Nodule/diagnostic imaging , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Adenocarcinoma/mortalityABSTRACT
INTRODUCTION: Previous studies demonstrated that wedge resection is sufficient for ground glass-dominant lung adenocarcinoma (LUAD) with tumour diameter ≤2 cm, however, the optimal surgical type for ground glass-dominant LUAD with tumour diameter of 2-3 cm remains unclear. The purpose of this trial is to investigate the safety and efficacy of segmentectomy for ground glass-dominant invasive LUAD with tumour size of 2-3 cm. METHODS AND ANALYSIS: We initiated a phase III trial to investigate whether segmentectomy is suitable for ground glass-dominant invasive LUAD with tumour size of 2-3 cm. This trial plans to enrol 307 patients from multiple institutions including four general hospitals and two specialty cancer hospitals over a period of 5 years. The primary endpoint is 5 year disease-free survival. Secondary endpoints are lung function, 5 year overall survival, the site of tumour recurrence and metastasis, segmentectomy completion rate, radical segmentectomy (R0 resection) completion rate and surgery-related complications. ETHICS AND DISSEMINATION: This trial has been approved by the Ethics Committee of Fudan University Shanghai Cancer Centre (reference 2212267-18) and by the institutional review boards of each participating centre. Written informed consent is required from all participants. The study results will be published in a peer-reviewed international journal. TRIAL REGISTRATION NUMBER: NCT05717803.
Subject(s)
Lung Neoplasms , Pneumonectomy , Humans , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Pneumonectomy/methods , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/pathology , Female , Male , Clinical Trials, Phase III as Topic , Disease-Free Survival , Multicenter Studies as Topic , Middle Aged , Adult , Neoplasm Recurrence, Local , China , Aged , Tumor BurdenABSTRACT
Gamma knife radiosurgery (GKRS) is recommended as the first-line treatment for brain metastases of lung adenocarcinoma (LUAD) in many guidelines, but its specific mechanism is unclear. We aimed to study the changes in the proteome of brain metastases of LUAD in response to the hyperacute phase of GKRS and further explore the mechanism of differentially expressed proteins (DEPs). Cancer tissues were collected from a clinical trial for neoadjuvant stereotactic radiosurgery before surgical resection of large brain metastases (ChiCTR2000038995). Five brain metastasis tissues of LUAD were collected within 24 h after GKRS. Five brain metastasis tissues without radiotherapy were collected as control samples. Proteomics analysis showed that 163 proteins were upregulated and 25 proteins were downregulated. GO and KEGG enrichment analyses showed that the DEPs were closely related to ribosomes. Fifty-three of 70 ribosomal proteins were significantly overexpressed, while none of them were underexpressed. The risk score constructed from 7 upregulated ribosomal proteins (RPL4, RPS19, RPS16, RPLP0, RPS2, RPS26 and RPS25) was an independent risk factor for the survival time of LUAD patients. Overexpression of ribosomal proteins may represent a desperate response to lethal radiotherapy. We propose that targeted inhibition of these ribosomal proteins may enhance the efficacy of GKRS.
Subject(s)
Adenocarcinoma of Lung , Brain Neoplasms , Lung Neoplasms , Proteomics , Radiosurgery , Ribosomal Proteins , Humans , Ribosomal Proteins/metabolism , Radiosurgery/methods , Brain Neoplasms/secondary , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/radiotherapy , Male , Female , Proteomics/methods , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/mortality , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/radiotherapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/radiotherapy , Middle Aged , Aged , Gene Expression Regulation, Neoplastic , Proteome/metabolismABSTRACT
Patient-derived xenografts (PDXs) are increasingly utilized in preclinical drug efficacy studies due to their ability to retain the molecular, histological, and drug response characteristics of patient tumors. This study aimed to investigate the factors influencing the successful engraftment of PDXs. Lung adenocarcinoma PDXs were established using freshly resected tumor tissues obtained through surgery. Radiological data of pulmonary nodules from this PDX cohort were analyzed, categorizing them into solid tumors and tumors with ground-glass opacity (GGO) based on preoperative CT images. Gene mutation status was obtained from next generation sequencing data and MassARRAY panel. A total of 254 resected primary lung adenocarcinomas were utilized for PDX establishment, with successful initial engraftment in 58 cases (22.8 %); stable engraftment defined as at least three serial passages was observed in 43 cases (16.9 %). The stable engraftment rates of PDXs from solid tumors and tumors with GGO were 22.1 % (42 of 190 cases) and 1.6 % (1 of 64 cases), respectively (P < 0.001). Adenocarcinomas with advanced stage, poor differentiation, solid histologic subtype, and KRAS or TP53 gene mutations were associated with stable PDX engraftment. Avoiding tumors with GGO features could enhance the cost-effectiveness of establishing PDX models from early-stage resected lung adenocarcinomas.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Mutation , Humans , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/genetics , Male , Female , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Lung Neoplasms/genetics , Animals , Aged , Middle Aged , Mice , Heterografts , Neoplasm Staging , High-Throughput Nucleotide Sequencing , Adult , Xenograft Model Antitumor Assays , Aged, 80 and over , Proto-Oncogene Proteins p21(ras)/geneticsABSTRACT
BACKGROUND: ROS1 fusion is a relatively low prevalence (0.6-2.0%) but targetable driver in lung adenocarcinoma (LUAD). Robust and low-cost tests, such as immunohistochemistry (IHC), are desirable to screen for patients potentially harboring this fusion. The aim was to investigate the prevalence of ROS1 fusions in a clinically annotated European stage I-III LUAD cohort using IHC screening with the in vitro diagnostics (IVD)-marked clone SP384, followed by confirmatory molecular analysis in pre-defined subsets. METHODS: Resected LUADs constructed in tissue microarrays, were immunostained for ROS1 expression using SP384 clone in a ready-to-use kit and Ventana immunostainers. After external quality control, analysis was performed by trained pathologists. Staining intensity of at least 2+ (any percentage of tumor cells) was considered IHC positive (ROS1 IHC + ). Subsequently, ROS1 IHC + cases were 1:1:1 matched with IHC0 and IHC1 + cases and subjected to orthogonal ROS1 FISH and RNA-based testing. RESULTS: The prevalence of positive ROS1 expression (ROS1 IHC + ), defined as IHC 2+/3+, was 4 % (35 of 866 LUADs). Twenty-eight ROS1 IHC + cases were analyzed by FISH/RNA-based testing, with only two harboring a confirmed ROS1 gene fusion, corresponding to a lower limit for the prevalence of ROS1 gene fusion of 0.23 %. They represent a 7 % probability of identifying a fusion among ROS1 IHC + cases. Both confirmed cases were among the only four with sufficient material and H-score ≥ 200, leading to a 50 % probability of identifying a ROS1 gene fusion in cases with an H-score considered strongly positive. All matched ROS1 IHC- (IHC0 and IHC1 + ) cases were also found negative by FISH/RNA-based testing, leading to a 100 % probability of lack of ROS1 fusion for ROS1 IHC- cases. CONCLUSIONS: The prevalence of ROS1 fusion in an LUAD stage I-III European cohort was relatively low. ROS1 IHC using SP384 clone is useful for exclusion of ROS1 gene fusion negative cases.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Neoplasm Staging , Protein-Tyrosine Kinases , Proto-Oncogene Proteins , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/surgery , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/metabolism , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Male , Female , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , Middle Aged , Aged , Immunohistochemistry , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Europe , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Adult , In Situ Hybridization, FluorescenceABSTRACT
OBJECTIVES: Ground-glass nodules-featured lung cancer have been identified in some teenagers in recent years. This study aims to investigate the characteristics and surgical outcomes of these patients and explore proper management strategy. METHODS: Patients aged ≤20 with incidentally diagnosed lung cancer were retrospectively reviewed from February 2016 to March 2023. Based on lymph node evaluation status, these patients were divided into non-lymph node evaluation and lymph node evaluation groups. The clinical and pathological characteristics were analysed. RESULTS: A total of 139 teenage patients were included, with an obviously increased cases observed from 2019, corresponding to the COVID-19 pandemic. The median age of the 139 patients was 18 years (range 12-20). Eighty-five patients had pure ground-glass nodules, while others had mixed ground-glass nodules. The mean diameter of nodules was 8.87 ± 2.20 mm. Most of the patients underwent wedge resection (64%) or segmentectomy (31.7%). Fifty-two patients underwent lymph node sampling or dissection. None of these patients had lymph node metastasis. The majority of lesions were adenocarcinoma in situ (63 cases) and minimally invasive adenocarcinoma (72 cases), while four lesions were invasive adenocarcinoma. The median follow-up time was 2.46 years, and none of these patients experienced recurrence or death during follow-up. The lymph node evaluation group had longer hospital stays (P < 0.001), longer surgery time (P < 0.001), and greater blood loss (P = 0.047) than the non-lymph node evaluation group. CONCLUSIONS: The COVID-19 pandemic significantly increased the number of teenage patients incidentally diagnosed with lung cancer, presenting as ground-glass nodules on CT scans. These patients have favourable surgical outcomes. We propose a management strategy for teenage patients, and suggest that sub-lobar resection without lymph node dissection may be an acceptable surgical procedure for these patients.
Subject(s)
Adenocarcinoma of Lung , COVID-19 , Lung Neoplasms , Pneumonectomy , Humans , Male , Adolescent , Female , Retrospective Studies , Lung Neoplasms/surgery , Lung Neoplasms/pathology , COVID-19/epidemiology , Young Adult , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/pathology , Pneumonectomy/methods , Child , SARS-CoV-2 , Tomography, X-Ray Computed , Treatment Outcome , Lymph Node ExcisionABSTRACT
INTRODUCTION: Tumor Inflammatory microenvironment (TIME) encompasses several immune pathways modulating cancer development and escape that are not entirely uncoded. The results achieved with immunotherapy elicited the scientific debate on TIME also in non-small cell lung cancer (NSCLC). We aimed to investigate whether TIME (in terms of PD-L1 expression and/or Tumor Infiltrating Lymphocytes - TILs) played a separate role in terms of survival (OS) in resected upstaged lung adenocarcinomas (ADCs), excluding other perioperative variables as confounders. MATERIALS AND METHODS: This retrospective study included 50 patients with a clinically resectable lung ADC, undergoing surgery (lobectomy or segmentectomy) at the Thoracic Unit of Padova University Hospital between 2016 and 2022 and receiving an unexpected pathological upstaging (IIB or higher). RESULTS: Despite microscopical variables increasing from IIB to IIIB, survival was not significantly related to them. OS was better in TIME-active patients (defined as the presence of positive PD-L1 and/or TILs>10 %) than double negatives (PD-L1-/TILs-) (p = 0.01). In IIB or higher ADCs, TIME-active patients showed an improved survival compared to double negatives, merging the current TIME theories. CONCLUSION: TIME seems to be associated with survival independently from other microscopical parameter, even in case of resected upstaged adenocarcinomas.
Subject(s)
B7-H1 Antigen , Lung Neoplasms , Lymphocytes, Tumor-Infiltrating , Tumor Microenvironment , Humans , Tumor Microenvironment/immunology , Male , Female , Retrospective Studies , Aged , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Lung Neoplasms/mortality , Lung Neoplasms/immunology , Middle Aged , Lymphocytes, Tumor-Infiltrating/immunology , B7-H1 Antigen/metabolism , Neoplasm Staging , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/mortality , Survival Rate , Pneumonectomy , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Adenocarcinoma/immunologyABSTRACT
BACKGROUND: A standard surgical procedure for patients with small early-stage lung adenocarcinomas remains unknown. Hence, we aim in this study to assess the clinical utility of the consolidation-to-tumor ratio (CTR) when treating patients with small (2 cm) early stage lung cancers. METHODS: A retrospective cohort of 298 sublobar resection and 266 lobar resection recipients for early stage lung adenocarcinoma ≤ 2 cm was assembled from the First Affiliated Hospital of Chongqing Medical University between 2016 and 2019. To compare survival rates among the different groups, Kaplan-Meier curves were calculated, and the log-rank test was used. A multivariate Cox proportional hazard model was constructed utilizing variables that were significant in univariate analysis of survival. RESULTS: In the study, 564 patients were included, with 298 patients (52.8%) undergoing sublobar resection and 266 patients (47.2%) undergoing lobar resection. Regarding survival results, there was no significant difference in the 5-year overall survival (OS, P = 0.674) and 5-year recurrence-free survival (RFS, P = 0.253) between the two groups. Cox regression analyses showed that CTR ≥ 0.75(P < 0.001), age > 56 years (P = 0.007), and sublobar resection(P = 0.001) could predict worse survival. After examining survival results based on CTR categorization, we segmented the individuals into three categories: CTR<0.7, 0.7 ≤ CTR<1, and CTR = 1.The lobar resection groups had more favorable clinical outcomes than the sublobar resection groups in both the 0.7 ≤ CTR < 1(RFS: P < 0.001, OS: P = 0.001) and CTR = 1(RFS: P = 0.001, OS: P = 0.125). However, for patients with 0 ≤ CTR < 0.7, no difference in either RFS or OS was found between the lobar resection and sublobar resection groups, all of which had no positive events. Patients with a CTR between 0.7 and 1 who underwent lobar resection had similar 5-year RFS and OS rates compared to those with a CTR between 0 and 0.7 who underwent sublobar resection (100% vs. 100%). Nevertheless, a CTR of 1 following lobar resection resulted in notably reduced RFS and OS when compared to a CTR between 0.7 and 1 following lobar resection (P = 0.005 and P = 0.016, respectively). CONCLUSION: Lobar resection is associated with better long-term survival outcomes than sublobar resection for small lung adenocarcinomas ≤ 2 cm and CTR ≥ 0.7.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Pneumonectomy , Humans , Male , Female , Retrospective Studies , Lung Neoplasms/surgery , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Middle Aged , Aged , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/mortality , Pneumonectomy/methods , Survival Rate , PrognosisABSTRACT
OBJECTIVE: To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma. METHODS: We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January, 2013 to December, 2021. The 5-year disease-free survival (DFS) and overall survival (OS) rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs group, n=111), chemotherapy (CT group, n=108) and clinical observation (CO group, n=434). RESULTS: In TKIs, CT, and CO groups, the 5-year DFS rates were 92.8%, 80.7%, and 81.7%, respectively, significantly higher in TKIs group than in CO group (P < 0.01). The 3-year OS rates of the 3 groups were 96.8%, 97.1%, and 91.7%, respectively. Subgroup analysis showed that in TKIs, CT, and CO groups, the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%, 84.0%, and 81.4%, respectively, significantly higher in TKIs group than in CO group (P < 0.05); the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%, 71.4%, and 83.5%, respectively. Multivariate COX regression analysis showed that age (P < 0.05; HR=0.631, 95% CI: 0.401-0.993), solid nodules (P < 0.01; HR=7.620, 95% CI: 3.037-19.121), micropapillary or solid component (P < 0.05; HR= 1.776, 95% CI: 1.010-3.122), lymphovascular invasion (P < 0.05; HR=2.981, 95% CI: 1.198-7.419), and adjuvant therapy (P < 0.01) were independent predictors of DFS. The most common adverse effects included rashes, paronychia, and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy, and TKIs were associated with a higher incidence of grade 3 or above adverse effects (44.4% vs 9.0%). CONCLUSION: Adjuvant therapy with TKIs helps improve DFS in patients with stage IB (T3-4cmN0M0) lung adenocarcinoma but not in patients with T2ViscPlN0M0. Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Neoplasm Staging , Humans , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/surgery , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/drug therapy , Female , Male , Chemotherapy, Adjuvant , Middle Aged , Protein Kinase Inhibitors/therapeutic use , Disease-Free Survival , Survival Rate , Postoperative Period , ErbB Receptors/antagonists & inhibitors , AgedABSTRACT
BACKGROUND: Accurate prediction of visceral pleural invasion (VPI) in lung adenocarcinoma before operation can provide guidance and help for surgical operation and postoperative treatment. We investigate the value of intratumoral and peritumoral radiomics nomograms for preoperatively predicting the status of VPI in patients diagnosed with clinical stage IA lung adenocarcinoma. METHODS: A total of 404 patients from our hospital were randomly assigned to a training set (n = 283) and an internal validation set (n = 121) using a 7:3 ratio, while 81 patients from two other hospitals constituted the external validation set. We extracted 1218 CT-based radiomics features from the gross tumor volume (GTV) as well as the gross peritumoral tumor volume (GPTV5, 10, 15), respectively, and constructed radiomic models. Additionally, we developed a nomogram based on relevant CT features and the radscore derived from the optimal radiomics model. RESULTS: The GPTV10 radiomics model exhibited superior predictive performance compared to GTV, GPTV5, and GPTV15, with area under the curve (AUC) values of 0.855, 0.842, and 0.842 in the three respective sets. In the clinical model, the solid component size, pleural indentation, solid attachment, and vascular convergence sign were identified as independent risk factors among the CT features. The predictive performance of the nomogram, which incorporated relevant CT features and the GPTV10-radscore, outperformed both the radiomics model and clinical model alone, with AUC values of 0.894, 0.828, and 0.876 in the three respective sets. CONCLUSIONS: The nomogram, integrating radiomics features and CT morphological features, exhibits good performance in predicting VPI status in lung adenocarcinoma.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Neoplasm Invasiveness , Neoplasm Staging , Nomograms , Tomography, X-Ray Computed , Humans , Male , Female , Lung Neoplasms/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Middle Aged , Tomography, X-Ray Computed/methods , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/diagnostic imaging , Adenocarcinoma of Lung/pathology , Neoplasm Staging/methods , Aged , Retrospective Studies , Pleura/diagnostic imaging , Pleura/pathology , Pleural Neoplasms/diagnostic imaging , Pleural Neoplasms/surgery , Pleural Neoplasms/pathology , RadiomicsABSTRACT
BACKGROUND: With further understanding and research into non-small cell lung cancer with tumours ≤2 cm in maximum diameter, segmental lung resection is able to achieve the same long-term prognosis as lobectomy. However, there are few studies on the prognostic effect of wedge resection on small volume invasive lung adenocarcinoma with an invasion depth of 0.5 to 1.0 cm. Therefore, this study focuses on the clinical efficacy and prognosis of wedge resection in patients with small-volume invasive lung adenocarcinoma. METHODS: A retrospective analysis of the medical records of 208 patients who underwent surgery in the Department of Thoracic Surgery of the Affiliated Provincial Hospital of Anhui Medical University from February 2016 to December 2017 was made, and the postoperative pathological results confirmed small volume invasive lung adenocarcinoma. According to their surgical methods, they were divided into lobectomy group (n=115), segmentectomy group (n=48) and wedge resection group (n=45). Kaplan-Meier survival curve estimation and Cox proportional risk regression model were used to explore the influence of different surgical methods on the prognosis of patients with small volume invasive lung adenocarcinoma. RESULTS: The wedge resection group had better perioperative outcomes compared with the segmentectomy group and lobectomy group, with statistically significant differences in intraoperative bleeding (P=0.036), postoperative drainage (P<0.001), operative time (P=0.018), postoperative time with tubes (P=0.001), and postoperative complication rate (P=0.006). There were no significant differences when comparing the three groups in terms of survival rate (lobectomy group vs segmentectomy group, P=0.303; lobectomy group vs wedge resection group, P=0.742; and segmentectomy group vs wedge resection group, P=0.278) and recurrence-free survival rate (lobectomy group vs segmentectomy group, P=0.495; lobectomy group vs wedge resection group, P=0.362; segmentectomy group vs wedge resection group, P=0.775). Univariate and multivariate survival analyses showed that consolidation tumor ratio (CTR) was the prognostic factor of overall survival and revurrence-free survival for patients with small-volume invasive lung adenocarcinoma (P<0.05). CONCLUSIONS: Wedge resection in patients with small volume invasive lung adenocarcinoma can achieve long-term outcomes similar to segmentectomy and lobectomy. When the CTR≤0.5, wedge resection is preferred in such patients.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Pneumonectomy , Humans , Male , Female , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/pathology , Middle Aged , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Retrospective Studies , Aged , Pneumonectomy/methods , Treatment Outcome , Neoplasm Invasiveness , Adult , PrognosisABSTRACT
OBJECTIVE: This study developed and validated a nomogram utilizing clinical and multi-slice spiral computed tomography (MSCT) features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma. Additionally, we assessed the predictive accuracy of Ki-67 expression levels, as determined by our model, in estimating the prognosis of stage IA lung adenocarcinoma. MATERIALS AND METHODS: We retrospectively analyzed data from 395 patients with pathologically confirmed stage IA lung adenocarcinoma. A total of 322 patients were divided into training and internal validation groups at a 6:4 ratio, whereas the remaining 73 patients composed the external validation group. According to the pathological results, the patients were classified into high and low Ki-67 labeling index (LI) groups. Clinical and CT features were subjected to statistical analysis. The training group was used to construct a predictive model through logistic regression and to formulate a nomogram. The nomogram's predictive ability and goodness-of-fit were assessed. Internal and external validations were performed, and clinical utility was evaluated. Finally, the recurrence-free survival (RFS) rates were compared. RESULTS: In the training group, sex, age, tumor density type, tumor-lung interface, lobulation, spiculation, pleural indentation, and maximum nodule diameter differed significantly between patients with high and low Ki-67 LI. Multivariate logistic regression analysis revealed that sex, tumor density, and maximum nodule diameter were significantly associated with high Ki-67 expression in stage IA lung adenocarcinoma. The calibration curves closely resembled the standard curves, indicating the excellent discrimination and accuracy of the model. Decision curve analysis revealed favorable clinical utility. Patients with a nomogram-predicted high Ki-67 LI exhibited worse RFS. CONCLUSION: The nomogram utilizing clinical and CT features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma demonstrated excellent performance, clinical utility, and prognostic significance, suggesting that this nomogram is a noninvasive personalized approach for the preoperative prediction of Ki-67 expression.
Subject(s)
Adenocarcinoma of Lung , Ki-67 Antigen , Lung Neoplasms , Neoplasm Staging , Nomograms , Humans , Ki-67 Antigen/metabolism , Male , Female , Middle Aged , Retrospective Studies , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Adenocarcinoma of Lung/diagnostic imaging , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , Prognosis , Aged , Tomography, Spiral Computed/methods , AdultABSTRACT
PURPOSE: Driver mutations inform lung adenocarcinoma (LUAD) targeted therapy. Association of histopathological attributes and molecular profiles facilitates clinically viable testing platforms. We assessed correlations between LUAD clinicopathological features, mutational landscapes, and two grading systems among Chinese cases. METHODS: 79 Chinese LUAD patients undergoing resection were subjected to targeted sequencing. 68 were invasive nonmucinous adenocarcinoma (INMA), graded via: predominant histologic pattern-based grading system (P-GS) or novel IASLC grading system (I-GS). Driver mutation distributions were appraised and correlated with clinical and pathological data. RESULTS: Compared to INMA, non-INMA exhibited smaller, well-differentiated tumors with higher mucin content. INMA grade correlated with size, lymph invasion (P-GS), and driver/EGFR mutations. Mutational spectra varied markedly between grades, with EGFR p.L858R and exon 19 deletion mutations predominating in lower grades; while high-grade P-GS tumors often harbored EGFR copy number variants and complex alterations alongside wild-type cases. I-GS upgrade of P-GS grade 2 to grade 3 was underpinned by ≥20â¯% high-grade regions bearing p.L858R or ALK fusions. Both systems defined tumors of distinctive phenotypic attributes and molecular genotypes. CONCLUSIONS: INMA represent larger, mucin-poor, molecularly heterogeneous LUAD with divergent grade-specific mutation profiles. Stronger predictor of clinicopathological attributes and driver mutations, P-GS stratification offers greater accuracy for molecular testing. A small panel encompassing EGFR and ALK captures the majority of P-GS grade 1/2 mutations whereas expanded panels are optimal for grade 3.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Mutation , Neoplasm Grading , Humans , Male , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/surgery , Female , Middle Aged , Aged , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/surgery , Adult , Aged, 80 and over , Asian People/genetics , China , ErbB Receptors/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , East Asian PeopleABSTRACT
OBJECTIVES: Distinguishing solid nodules from nodules with ground-glass lesions in lung cancer is a critical diagnostic challenge, especially for tumors ≤2 cm. Human assessment of these nodules is associated with high inter-observer variability, which is why an objective and reliable diagnostic tool is necessary. This study focuses on artificial intelligence (AI) to automatically analyze such tumors and to develop prospective AI systems that can independently differentiate highly malignant nodules. MATERIALS AND METHODS: Our retrospective study analyzed 246 patients who were diagnosed with negative clinical lymph node metastases (cN0) using positron emission tomography-computed tomography (PET/CT) imaging and underwent surgical resection for lung adenocarcinoma. AI detected tumor sizes ≤2 cm in these patients. By utilizing AI to classify these nodules as solid (AI_solid) or non-solid (non-AI_solid) based on confidence scores, we aim to correlate AI determinations with pathological findings, thereby advancing the precision of preoperative assessments. RESULTS: Solid nodules identified by AI with a confidence score ≥0.87 showed significantly higher solid component volumes and proportions in patients with AI_solid than in those with non-AI_solid, with no differences in overall diameter or total volume of the tumors. Among patients with AI_solid, 16% demonstrated lymph node metastasis, and a significant 94% harbored invasive adenocarcinoma. Additionally, 44% were upstaging postoperatively. These AI_solid nodules represented high-grade malignancies. CONCLUSION: In small-sized lung cancer diagnosed as cN0, AI automatically identifies tumors as solid nodules ≤2 cm and evaluates their malignancy preoperatively. The AI classification can inform lymph node assessment necessity in sublobar resections, reflecting metastatic potential.
Subject(s)
Adenocarcinoma of Lung , Artificial Intelligence , Lung Neoplasms , Positron Emission Tomography Computed Tomography , Humans , Male , Retrospective Studies , Female , Lung Neoplasms/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/diagnostic imaging , Adenocarcinoma of Lung/surgery , Aged , Middle Aged , Positron Emission Tomography Computed Tomography/methods , Tomography, X-Ray Computed/methods , Multiple Pulmonary Nodules/diagnostic imaging , Multiple Pulmonary Nodules/pathology , Multiple Pulmonary Nodules/surgery , Adult , Aged, 80 and over , Lymphatic Metastasis/diagnostic imagingABSTRACT
OBJECTIVES: Lung cancer is characterized by its high incidence and case fatality rate. Factors related to population composition and cancer prevention programme policy have an effect on the incidence and diagnosis of lung cancer. This study aims to provide scientific support for early diagnosis and treatment of lung cancer by investigating the clinic information, pathological, and imaging characteristics of surgical patients with lung cancer. METHODS: The data of 2 058 patients, who underwent surgery for lung cancer in the Department of Thoracic Surgery of Xiangya Hospital of Central South University from 2016 to 2019, were retrospectively collected to analyze changes in clinic information, pathological, and imaging characteristics. RESULTS: From 2016 to 2019, the number of patients per year was 280, 376, 524, and 878, respectively. Adenocarcinoma (68.1%) was the most common pathological type of surgical patients with lung cancer. From 2016 to 2019, the proportion of adenocarcinoma was increased from 55.5% to 74.1%. The proportion lung cancer patients in stage IA was increased from 38.9% to 62.3%, and the proportion of patients who underwent sublobar resection was increased from 1.8% to 8.6%. The proportion of lymph node sampling was increased in 2019. Compared with the rate in 2016, the detection rate of nodules with diameter≤1 cm detected by CT before surgery in 2019 was significantly improved (2.0% vs 18.2%), and the detection rate of nodules with diameter>3 cm was decreased (34.7% vs 18.3%). From 2016 to 2019, the proportion of lesions with pure ground-glass density and partial solid density detected by CT was increased from 2.0% and 16.6% to 20.0% and 37.3%, respectively. The proportion of solid density was decreased from 81.4% to 42.7%. CONCLUSIONS: The number of lung cancer surgery patients is rapidly increasing year by year, the proportion of CT-detected purely ground-glass density and partially solid density lesions are increasing, the proportion of patients with adenocarcinoma is rising, the proportion of early-stage lung cancer is increasing, smaller lung cancers are detected in earlier clinical stage leading to a more minimally invasive approach to the surgical methods.
Subject(s)
Adenocarcinoma , Lung Neoplasms , Humans , Lung Neoplasms/surgery , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Retrospective Studies , Adenocarcinoma/surgery , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Female , Male , Tomography, X-Ray Computed , Neoplasm Staging , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/diagnostic imaging , Adenocarcinoma of Lung/pathology , Middle Aged , AgedABSTRACT
BACKGROUND: Cystic lung cancer, a special type of lung cancer, has been paid more and more attention. The most common pathological type of cystic lung cancer is adenocarcinoma. The invasiveness of cystic lung adenocarcinoma is vital for the selection of clinical treatment and prognosis. The aim of this study is to analyze the multiple clinical features of cystic lung adenocarcinoma, explore the independent risk factors of its invasiveness, and establish a risk prediction model. METHODS: A total of 129 cases of cystic lung adenocarcinoma admitted to the Department of Thoracic Surgery of the First Affiliated Hospital of Nanjing Medical University from January 2021 to July 2022 were retrospectively analyzed and divided into pre-invasive group [atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA)] and invasive group [invasive adenocarcinoma (IAC)] according to pathological findings. There were 47 cases in the pre-invasive group, including 19 males and 28 females, with an average age of (51.23±14.96) years. There were 82 cases in the invasive group, including 60 males and 22 females, with an average age of (61.27±11.74) years. Multiple clinical features of the two groups were collected, including baseline data, imaging data and tumor markers. Univariate analysis, LASSO regression and multivariate Logistic regression analysis were used to screen out the independent risk factors of the invasiveness of cystic lung adenocarcinoma, and the risk prediction model was established. RESULTS: In univariate analysis, age, gender, smoking history, history of emphysema, neuron-specific enolase (NSE), number of cystic airspaces, lesion diameter, cystic cavity diameter, nodule diameter, solid components diameter, cyst wall nodule, smoothness of cyst wall, shape of cystic airspace, lobulation, short burr sign, pleural retraction, vascular penetration and bronchial penetration were statistically different between the pre-invasive group and invasive groups (P<0.05). The above variables were processed by LASSO regression dimensionality reduction and screened as follows: age, gender, smoking history, NSE, number of cystic airspaces, lesion diameter, cystic cavity diameter, cyst wall nodule, smoothness of cyst wall and lobulation. Then the above variables were included in multivariate Logistic regression analysis. Cyst wall nodule (P=0.035) and lobulation (P=0.001) were found to be independent risk factors for the invasiveness of cystic lung adenocarcinoma (P<0.05). The prediction model was established as follows: P=e^x/(1+e^x), x=-7.927+1.476* cyst wall nodule+2.407* lobulation, and area under the curve (AUC) was 0.950. CONCLUSIONS: Cyst wall nodule and lobulation are independent risk factors for the invasiveness of cystic lung adenocarcinoma, which have certain guiding significance for the prediction of the invasiveness of cystic lung adenocarcinoma.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Male , Female , Middle Aged , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , Lung Neoplasms/pathology , Retrospective Studies , Aged , Adult , Risk Factors , Neoplasm InvasivenessABSTRACT
Surgical resection of pulmonary adenocarcinoma is considered to be curative but progression-free survival (PFS) has remained highly variable. Antitumor immune response may be important, however, the prognostic significance of tumor-infiltrating natural killer (NK) and regulatory T (Treg) lymphocytes is uncertain. Resected pulmonary adenocarcinoma tissues (n = 115) were studied by immunohistochemical detection of NKp46 and FoxP3 positivity to identify NK and Treg cells, respectively. Association of cell densities with clinicopathological features and progression-free survival (PFS) as well as overall survival (OS) were analyzed with a follow-up time of 60 months. Both types of immune cells were accumulated predominantly in tumor stroma. NK cell density showed association with female gender, non-smoking and KRAS wild-type status. According to Kaplan-Meier analysis, PFS and OS proved to be longer in patients with high NK or Treg cell densities (p = 0.0293 and p = 0.0375 for PFS, p = 0.0310 and p = 0.0448 for OS, respectively). Evaluating the prognostic effect of the combination of NK and Treg cell density values revealed that PFS and OS were significantly longer in NKhigh/Treghigh cases compared to the other groups combined (p = 0.0223 and p = 0.0325, respectively). Multivariate Cox regression analysis indicated that high NK cell density was independent predictor of longer PFS while high NK and high Treg cell densities both proved significant predictors of longer OS. The NKhigh/Treghigh combination also proved to be an independent prognostic factor for both PFS and OS. In conclusion, NK and Treg cells can be components of the innate and adaptive immune response at action against progression of pulmonary adenocarcinoma.
Subject(s)
Adenocarcinoma of Lung , Killer Cells, Natural , Lung Neoplasms , Lymphocytes, Tumor-Infiltrating , T-Lymphocytes, Regulatory , Humans , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Male , Female , Killer Cells, Natural/immunology , Lung Neoplasms/mortality , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Aged , Middle Aged , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/mortality , Adenocarcinoma of Lung/surgery , Prognosis , Adult , Aged, 80 and over , Adenocarcinoma/immunology , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Progression-Free Survival , Kaplan-Meier EstimateABSTRACT
BACKGROUND: We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors. METHODS: Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance. RESULTS: A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative. CONCLUSIONS: Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Neoplasm Staging , Propensity Score , Humans , Female , Male , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Lung Neoplasms/therapy , Lung Neoplasms/mortality , Middle Aged , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/therapy , Adenocarcinoma of Lung/mortality , Chemotherapy, Adjuvant , Risk Factors , Aged , Retrospective Studies , Treatment Outcome , Pneumonectomy/methods , Disease-Free Survival , Prognosis , Kaplan-Meier EstimateABSTRACT
PURPOSE: In this study, we aimed to investigate the prognosis of invasive lung adenocarcinoma that manifests as pure ground glass nodules (pGGNs) and confirm the effectiveness of sublobectomy and lymph node sampling in patients with pGGN-featured invasive adenocarcinoma (IAC). MATERIALS AND METHODS: We retrospectively enrolled 139 patients with pGGN-featured IAC, who underwent complete resection in two medical institutions between January 2011 and May 2022. Stratification analysis was conducted to ensure balanced baseline characteristics among the patients. The 5-year overall survival (OS) and disease-free survival (DFS) rates were compared between the groups using Kaplan-Meier survival curves and log-rank test. RESULTS: The 5-year OS and DFS rates for patients with IAC presenting as pGGNs after surgery were 96.5% and 100%, respectively. No lymph node metastasis or recurrence was observed in any of the enrolled patients. There was no statistically significant difference in the 5-year OS between patients who underwent lobectomy or sublobectomy, along with lymph node resection or sampling. CONCLUSION: IAC presented as pGGNs exhibited low-grade malignancy and had a relatively good prognosis. Therefore, these patients may be treated with sublobectomy and lymph node sampling.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Lymph Nodes , Lymphatic Metastasis , Pneumonectomy , Humans , Male , Female , Retrospective Studies , Middle Aged , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Lung Neoplasms/mortality , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/mortality , Aged , Prognosis , Pneumonectomy/methods , Lymph Nodes/pathology , Lymph Nodes/surgery , Neoplasm Invasiveness , Lymph Node Excision/methods , Survival Rate/trends , Disease-Free Survival , AdultABSTRACT
BACKGROUND: Sublobar resection for ground-glass opacity became a recommend surgery choice supported by the JCOG0804/JCOG0802/JCOG1211 results. Sublobar resection includes segmentectomy and wedge resection, wedge resection is suitable for non-invasive lesions, but in clinical practice, when pathologists are uncertain about the intraoperative frozen diagnosis of invasive lesions, difficulty in choosing the appropriate operation occurs. The purpose of this study was to analyze how to select invasive lesions with clinic-pathological characters. METHODS: A retrospective study was conducted on 134 cases of pulmonary nodules diagnosed with minimally invasive adenocarcinoma by intraoperative freezing examination. The patients were divided into two groups according to intraoperative frozen results: the minimally invasive adenocarcinoma group and the at least minimally invasive adenocarcinoma group. A variety of clinical features were collected. Chi-square tests and multiple regression logistic analysis were used to screen out independent risk factors related to pathological upstage, and then ROC curves were established. In addition, an independent validation set included 1164 cases was collected. RESULTS: Independent risk factors related to pathological upstage were CT value, maximum tumor diameter, and frozen result of AL-MIA. The AUC of diagnostic mode was 71.1% [95%CI: 60.8-81.3%]. The independent validation included 1164 patients, 417 (35.8%) patients had paraffin-based pathology of invasive adenocarcinoma. The AUC of diagnostic mode was 75.7% [95%CI: 72.9-78.4%]. CONCLUSIONS: The intraoperative frozen diagnosis was AL-MIA, maximum tumor diameter larger than 15 mm and CT value is more than - 450Hu, highly suggesting that the lung GGO was invasive adenocarcinoma which represent a higher risk to recurrence. For these patients, sublobectomy would be insufficient, lobectomy or complementary treatment is encouraged.