The eighth edition of nodal classification for non-small cell lung cancer (NSCLC) is defined only by the anatomical location of metastatic lymph nodes.
We sought to evaluate the prognostic ...significance and discriminatory capability of the number of involved nodal stations (nS) in a large Chinese cohort.
A total of 4,011 patients with NSCLC undergoing surgical resection between 2009 and 2013 were identified. The optimal cutoff values for nS classification were determined with X-tile software. Kaplan-Meier and multivariate Cox analysis were used to examine the prognostic performance of nS classification in comparison with location-based N classification. A decision curve analysis was performed to evaluate the standardized net benefit of nS classification in predicting prognosis.
All the patients were classified into four prognostically different subgroups according to the number of involved nodal stations: (1) nS0 (none positive), (2) nS1 (one involved station), (3) nS2 (two involved stations), and (4) nS ≥ 3 (three or more involved stations). The prognoses among all the neighboring categories of nS classification were statistically significantly different in terms of disease-free survival and overall survival. The multivariate Cox analysis demonstrated that nS was an independent prognostic factor of disease-free survival and overall survival. Patients with N1 or N2 stage disease could be divided into three prognostically different subgroups according to nS classification. However, the prognosis was similar between the N1 and N2 subgroups when patients were staged in the same nS category. The decision curve analysis showed that nS classification tended to have a higher predictive capability than location-based N classification.
The nS classification could be used to provide a more accurate prognosis for patients with resected NSCLC. The nS is worth taking into consideration when defining nodal category in the forthcoming ninth edition of the staging system.
Invasive adenocarcinoma intraoperatively misdiagnosed as adenocarcinoma in situ or minimally invasive adenocarcinoma is more likely to undergo potentially insufficient resection. The purpose of our ...study was to evaluate the diagnostic accuracy of frozen section. We retrospectively reviewed 1,111 lung adenocarcinomas from January to March 2016 to evaluate the diagnostic performance of frozen section. A derivation cohort consisting of 436 cases of adenocarcinoma in situ or minimally invasive adenocarcinoma diagnosed by frozen section in the same period were analyzed to find predictive factors for invasive adenocarcinoma as the final diagnosis. Validation cohorts (first: April to June 2016, second: January to March 2015) were included to confirm the results. The overall concordance rate between frozen section and final diagnosis was 92%. Most frozen section errors were underestimation. The sensitivity of frozen section diagnosis for minimally invasive adenocarcinoma (74%) was significantly lower than others. Intraoperatively measured tumor size was the only independent factor for invasive adenocarcinoma as the final diagnosis (<1 cm: 2%, reference; 1-1.4 cm: 15%, odds ratio, 5.678; > 1.5 cm: 18%, odds ratio, 5.878; P = 0.001) in the derivation cohort, and was confirmed by validation cohorts. Fifty-nine misdiagnosed invasive adenocarcinomas in the three cohorts consisted of 54 lepidic predominant type, 1 papillary and 4 acinar predominant type. There were no positive N1, N2 node, pleural, lymphatic and vascular invasion cases found. Thirty-seven (37/59, 63%) cases of misdiagnosis were attributed to sampling error, which was the main reason. Our study suggests that adenocarcinoma in situ or minimally invasive adenocarcinoma ≥1 cm by frozen section were more likely to be invasive adenocarcinoma because of sampling error. Frozen section diagnosis of adenocarcinoma in situ or minimally invasive adenocarcinoma should be considered cautiously for tumors ≥1 cm to avoid potentially insufficient resection.
We aimed to assess the predictive value of different T descriptors, including the whole tumour size (Dwhole) and solid component size (Dsolid), in patients with clinical Stage IA adenocarcinoma who ...underwent sublobar resection.
According to computed tomography images in the lung window, T descriptors, Dwhole and Dsolid, were applied. To evaluate the predictive value of these 2 different descriptors in predicting tumour recurrence and pathological malignant behaviours, Cox hazard regression and a receiver-operating characteristic curve analysis, respectively, were used.
In total, 247 patients were included. Of these patients, 109 and 138 had ground glass and solid nodules, respectively. When the T descriptor was changed from Dwhole to Dsolid, 37 tumours (15%) were downgraded to T1a status from T1b/T1c status. Multivariable Cox analysis showed that Dsolid was an independent risk factor of worse recurrence-free survival hazard ratio (HR) 2.36, 95% confidence interval (CI) 1.24-4.47; P = 0.009, while Dwhole was not (HR 1.51, 95% CI 0.79-2.89; P = 0.215). In the receiver-operating characteristic analysis, the areas under the curves for Dwhole and Dsolid used to identify pathological malignant behaviours were 0.598 and 0.739, respectively.
The T descriptor, which is represented by Dsolid, rather than Dwhole, is a better predictor of tumour recurrence after sublobar resection in clinical Stage IA lung adenocarcinoma. Furthermore, our results provide some clues indicating that sublobar resection should be performed cautiously in patients with lung adenocarcinoma manifesting as ground glass nodule with Dsolid >2 cm.
This study aimed to investigate the relationship between lymph node micrometastasis and histologic patterns of adenocarcinoma, with a particular focus on their joint effect on prognosis. We ...retrospectively reviewed 235 patients with stage I adenocarcinoma from January 2009 to December 2009. Lymph node micrometastasis was evaluated by immunohistochemical staining for cytokeratin (AE1/AE3) and thyroid transcription factor-1. A logistic regression model was applied to confirm the predictive factors of micrometastasis. Survival analysis was performed to evaluate the effect of micrometastasis on prognosis. Lymph node micrometastasis was observed in 35 patients (15%). Patients with micrometastasis had significantly worse recurrence-free survival (P<0.001) and overall survival (P<0.001) compared with those without micrometastasis. Micropapillary component was confirmed as an independent predictor of increased frequency of micrometastasis (P<0.001). Among 62 patients with adenocarcinoma with a micropapillary component, 23 (37%) had lymph node micrometastasis. Micropapillary-positive/micrometastasis-positive patients had significantly worse survival compared with micropapillary-positive/micrometastasis-negative patients (RFS, P=0.039; OS, P=0.002) and micropapillary-negative patients (recurrence-free survival, P<0.001; overall survival, P<0.001). Moreover, the presence of micrometastasis correlated with a higher risk of locoregional recurrence (P=0.031) rather than distant recurrence (P=0.456) in micropapillary-positive patients. In summary, lymph node micrometastasis was more frequently observed in adenocarcinoma with a micropapillary component. Moreover, lymph node micrometastasis could provide helpful prognostic information in patients with resected stage I lung adenocarcinoma with a micropapillary component; thus, immunohistochemical detection of micrometastatic tumor cells in lymph nodes should be recommended.
Objectives
The performance of positron emission tomography/computed tomography (PET/CT) for the prediction of ypN2 disease in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy ...has not been reported. This multicenter study investigated the utility of PET/CT to assess ypN2 disease in these patients.
Methods
A total of 181 consecutive patients (chemoimmunotherapy = 86, chemotherapy = 95) at four institutions were enrolled in this study. Every patient received a PET/CT scan prior to surgery and complete resection with systematic nodal dissection. The diagnostic performance was evaluated through area under the curve (AUC). Kaplan–Meier method and Cox analysis were performed to identify the risk factors affecting recurrences.
Results
The sensitivity, specificity, and accuracy of PET/CT for ypN2 diseases were 0.667, 0.835, and 0.779, respectively. Therefore, the AUC was 0.751. Compared with the false positive cases, the mean value of max standardized uptake value (SUV
max
) (6.024 vs. 2.672,
p
< 0.001) of N2 nodes was significantly higher in true positive patients. Moreover, the SUV
max
of true positive (7.671 vs. 5.976,
p
= 0.365) and false (2.433 vs. 2.339,
p
= 0.990) positive cases were similar between chemoimmunotherapy and chemotherapy, respectively. Survival analysis proved that pathologic N (ypN) 2 patients could be stratified by PET/CT-N2(+ vs. -) for both chemoimmunotherapy (
p
= 0.023) and chemotherapy (
p
= 0.010).
Conclusions
PET/CT is an accurate and non-invasive test for mediastinal restaging of NSCLC patients who receive neoadjuvant chemoimmunotherapy. The ypN2 patients with PET/CT-N2( +) are identified as an independent prognostic factor compared with PET/CT-N2(-).
Clinical relevance statement
Imaging with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) plays an integral role during disease diagnosis, staging, and therapeutic response assessments in patients with NSCLC. PET/CT could be an effective non-invasive tool for predicting ypN2 diseases after neoadjuvant chemoimmunotherapy.
Key Points
•
PET/CT could serve as an effective non-invasive tool for predicting ypN2 diseases.
•
The ypN2 patients with PET/CT-N2(
+
) were a strong and independent prognostic factor.
•
The application of PET/CT for restaging should be encouraged in clinical practice.
•FS (frozen section) had high diagnostic accuracy for IASLC grading system.•The interobserver agreement for IASLC grading system on FS were satisfactory.•Presence of complex glands were associated ...with discrepancy between FS and final pathology diagnosis.•The IASLC grading system diagnosed by FS could well stratify prognosis for patients with stage I invasive lung ADC.
The International Association for the Study of Lung Cancer (IASLC) newly proposed grading system for lung adenocarcinomas (ADC) has been shown to be of prognostic significance. Hence, intraoperative consultation for the grading system was important regarding the surgical decision-making. Here, we evaluated the accuracy and interobserver agreement for IASLC grading system on frozen section (FS), and further investigated the prognostic performance.
FS and final pathology (FP) slides were reviewed by three pathologists for tumor grading in 373 stage I lung ADC following surgical resection from January to June 2013 (retrospective cohort). A prospective multicenter cohort (January to June 2021, n = 212) were included to confirm the results.
The overall concordance rates between FS and FP were 79.1% (κ = 0.650) and 89.6% (κ = 0.729) with substantial agreement in retrospective and prospective cohorts, respectively. Presence of complex gland was the only independent predictor of discrepancy between FS and FP (presence versus. absence: odds ratio, 2.193; P = 0.015). The interobserver agreement for IASLC grading system on FS among three pathologists were satisfactory (κ = 0.672 for retrospective cohort; κ = 0.752 for prospective cohort). Moreover, the IASLC grading system by FS diagnosis could well predict recurrence-free survival and overall survival for patients with stage I invasive lung ADC.
Our results suggest that FS had high diagnostic accuracy and satisfactory interobserver agreement for IASLC grading system. Future prospective studies are merited to validate the feasibility of using FS to match patients into appropriate surgical type.
Objectives
To develop and validate a nomogram to estimate the pretest probability of malignancy in Chinese patients with solid solitary pulmonary nodule (SPN).
Materials and Methods
A primary cohort ...of 1798 patients with pathologically confirmed solid SPNs after surgery was retrospectively studied at five institutions from January 2014 to December 2015. A nomogram based on independent prediction factors of malignant solid SPN was developed. Predictive performance also was evaluated using the calibration curve and the area under the receiver operating characteristic curve (AUC).
Results
The mean age of the cohort was 58.9 ± 10.7 years. In univariate and multivariate analysis, age; history of cancer; the log base 10 transformations of serum carcinoembryonic antigen value; nodule diameter; the presence of spiculation, pleural indentation, and calcification remained the predictive factors of malignancy. A nomogram was developed, and the AUC value (0.85; 95%CI, 0.83‐0.88) was significantly higher than other three models. The calibration cure showed optimal agreement between the malignant probability as predicted by nomogram and the actual probability.
Conclusions
We developed and validated a nomogram that can estimate the pretest probability of malignant solid SPNs, which can assist clinical physicians to select and interpret the results of subsequent diagnostic tests.
In lung adenocarcinoma (LUAD), the appearance of morphologically diverse tumor regions, termed histological patterns, is closely associated with disease progression and lymph node metastasis. ...However, the molecular characteristics of the histological patterns in LUAD and the underlying molecular evolutionary mechanisms between the histological patterns in primary tumors and lymph node metastases are poorly understood. Here, we re‐analyzed the large TCGA‐LUAD dataset and depicted a comprehensive profiling of the genome and transcriptome across the histological patterns in LUAD. Tumor phylogenetic trajectory analysis suggested that the complex glands is more apt to metastasize to the lymph node. Further deconvolution of the tumor microenvironment demonstrated that the complex glands had a higher infiltration of cancer‐associated fibroblasts (CAFs). Single‐cell transcriptome profiling of complex glands pattern identified a novel CAF subtype co‐expressing fibroblast activation protein‐alpha (FAP) and stimulator of interferon genes (STING). Moreover, our data demonstrated that FAP is an important downstream effector of STING in CAFs. In summary, our results provide the basis for the development of innovative therapeutic guidelines and intervention strategies for LUAD patients.
Combining TCGA‐LUAD and our own validation data, we systematically revealed the heterogeneity of genomic alterations profiles and tumor microenvironment across the histological patterns in lung adenocarcinoma. We found the most aggressive complex glands were enriched cancer‐associated fibroblasts exhibiting a higher possibility of lymph node metastasis.
PDF
![Clinical utility of [18F]FD...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1432-1084_0938-7994/small "Clinical utility of [18F]FDG PET/CT in the assessment of mediastinal lymph node disease after neoadjuvant chemoimmunotherapy for non-small cell lung cancer")
