Surgical Resection Of Lung Adenocarcinoma Research Articles

AI-driven Characterization of Solid Pulmonary Nodules on CT Imaging for Enhanced Malignancy Prediction in Small-sized Lung Adenocarcinoma

ObjectivesDistinguishing 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 methodsOur 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. ResultsSolid 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. ConclusionIn 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.

A new model using deep learning to predict recurrence after surgical resection of lung adenocarcinoma

This study aimed to develop a deep learning (DL) model for predicting the recurrence risk of lung adenocarcinoma (LUAD) based on its histopathological features. Clinicopathological data and whole slide images from 164 LUAD cases were collected and used to train DL models with an ImageNet pre-trained efficientnet-b2 architecture, densenet201, and resnet152. The models were trained to classify each image patch into high-risk or low-risk groups, and the case-level result was determined by multiple instance learning with final FC layer’s features from a model from all patches. Analysis of the clinicopathological and genetic characteristics of the model-based risk group was performed. For predicting recurrence, the model had an area under the curve score of 0.763 with 0.750, 0.633 and 0.680 of sensitivity, specificity, and accuracy in the test set, respectively. High-risk cases for recurrence predicted by the model (HR group) were significantly associated with shorter recurrence-free survival and a higher stage (both, p < 0.001). The HR group was associated with specific histopathological features such as poorly differentiated components, complex glandular pattern components, tumor spread through air spaces, and a higher grade. In the HR group, pleural invasion, necrosis, and lymphatic invasion were more frequent, and the size of the invasion was larger (all, p < 0.001). Several genetic mutations, including TP53 (p = 0.007) mutations, were more frequently found in the HR group. The results of stages I-II were similar to those of the general cohort. DL-based model can predict the recurrence risk of LUAD and identify the presence of the TP53 gene mutation by analyzing histopathologic features.

Potential of the cell-free blood-based biomarker uroplakin 2 RNA to detect recurrence after surgical resection of lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, and ~30% of patients with LUAD develop cancer recurrence after surgery. The present study aimed to identify and validate biomarkers that may be used to monitor recurrence following LUAD surgery. Data from patients with LUAD were downloaded from The Cancer Genome Atlas database and postoperative recurrence samples were selected. Subsequently, weighted gene co-expression network analysis (WGCNA) was subsequently performed to identify key co-expression gene modules. Additionally, enrichment analysis of the key gene modules was performed using the Database for Annotation, Visualization and Integrated Discovery. Furthermore, survival analysis was performed on the most notable biomarker, uroplakin 2 (UPK2), which was downloaded from the Oncomine database, and its effect on prognosis was assessed. WGCNA identified 39 gene modules, of which one was most associated with recurrence. Among them, UPK2, kelch domain containing 3, galanin receptor 2 and tyrosinase-related protein 1 served a central role in the co-expression network and were significantly associated with the survival of patients. A total of 132 blood samples were collected from patients with LUAD with free UPK2 in the plasma. The expression levels of UPK2 relative to GADPH were 0.1623 and 0.2763 in non-relapsed and relapsed patients, respectively. Receiver operating characteristic curve analysis was used to detect free UPK2 mRNA in the blood in order to monitor postoperative recurrence, resulting in an area under the curve of 0.767 and a 95% CI of 0.675–0.858. Patients with high free UPK2 mRNA expression had unfavorable survival outcomes compared with those with low UPK2 expression. Therefore, free UPK2 mRNA expression in the plasma may have the potential to act as an indicator of postoperative recurrence in patients with early stage LUAD.

Time-varying effect of sex on prognosis of lung adenocarcinoma surgical patients in China.

BackgroundLittle is known about the prognostic advantage of sex for pulmonary adenocarcinoma among Chinese patients. In this study, we aimed to investigate the true sex differences in prognosis by adjusting for confounders and to explore whether the differences were time‐varying.MethodsWe identified 4438 lung adenocarcinoma patients who underwent surgery at a regional Cancer Center of China from 2008 to 2016, retrospectively. Sex, age group, smoking history, year of diagnosis and pathological stage were collected. Time‐dependent Cox regression models with inverse probability of treatment weighting (IPTW) based on propensity score were used to assess the effect of sex and account for confounders. Landmark analyses were conducted to assess survival before, and after, five years.ResultsOf these patients, 1761 (39.7%) were men and 2677 (60.3%) were women. Median follow‐up time was 52.6 months. After IPTW adjustment, women were found to have significantly better survival than men varying with time in both crude and IPTW models (hazard ratio [HR] [t] = 0.453*1.015t, where t is the length of time from treatment and its unit is month, p < 0.001). Women had significantly better survival than men within 0–5 years after surgery (HR = 0.763, 95% CI: 0.649–0.897, p = 0.001), whereas there was no difference after five years (HR = 1.135, 95% CI: 0.803–1.605, p = 0.472). In subgroup analysis, women in the 61–71+ age group, in the more than 20 year packs group, pathological stage 0–IB group, and 2013–2016 diagnosis period group revealed the same prognostic pattern.ConclusionsCompared with men, women had better survival after surgical resection of lung adenocarcinoma, especially those who were older and nonsmokers or heavy‐smokers and were pathological stage 0–IB in early years, while the advantage for women diminished with time.

Prognostic impact of extranodal extension in patients with pN1-N2 lung adenocarcinoma.

Lymph node involvement is one of the important prognostic factors of patients with lung adenocarcinoma. In the tumor, node, and metastasis classification, lymph node involvement is categorized only according to the anatomical station and not the involvement pattern. The aim of this study was to investigate which morphological pattern of lymph node involvement affects the prognosis of patients with surgically resected lung adenocarcinoma. We retrospectively reviewed 168 consecutive patients who underwent surgical resection for primary lung adenocarcinoma with lymph node involvement. The morphological patterns of lymph node involvement (tumor area, number of metastatic lymph nodes, presence of necrosis, and extranodal extension) were histologically examined. The relationships between the patterns of lymph node involvement, clinicopathological features, and survival of patients were analyzed. Eighty patients had N1 disease, and 88 patients had N2 disease. Univariate analysis revealed that invasive size, history of adjuvant chemotherapy, and presence of extranodal extension were significant prognostic factors in N1 patients, and vascular invasion, pleural invasion, presence of epidermal growth factor receptor mutation, history of adjuvant chemotherapy, and presence of extranodal extension were significant prognostic factors in N2 patients. In a bivariate analysis including other clinicopathological factors and patterns of lymph node involvement, the presence of extranodal extension was significantly associated with poor 3-year overall and recurrence-free survival of both N1 and N2 patients. In patients who underwent surgical resection for lung adenocarcinoma with lymph node involvement, the extranodal extension was the most important prognostic factor among morphological lymph node involvement patterns.

Consolidation volume and integration of computed tomography values on three-dimensional computed tomography may predict pathological invasiveness in early lung adenocarcinoma.

To investigate the relationship between three-dimensional computed tomography (3D-CT) findings and pathological invasiveness in lung adenocarcinoma. We retrospectively evaluated 95 patients who underwent surgical resection of lung adenocarcinoma of ≤ 20mm. The diameters, volumes, and CT values of tumor consolidation were analyzed. We defined the modified CT value by setting air as 0 and water as 1000 and assumed a correlation with pathological invasiveness. Pre-invasive lesions and minimally invasive adenocarcinomas were classified as non-invasive adenocarcinoma. We compared the clinico-radiological features with pathological invasiveness. Receiver operator characteristic (ROC) curves and recurrence-free survival curves were constructed. Twenty-six non-invasive adenocarcinomas and 69 invasive adenocarcinomas were evaluated. The multivariate analysis revealed that the consolidation volume and the integration of modified CT values were the most important predictors of pathological invasion. The area under the ROC curve and the cut-off values of the consolidation volume were 0.868 and 75mm3, respectively. The area under the ROC curve and the cut-off values of the integration of modified CT values were 0.871 and 80,000, respectively. There was no recurrence in cases with values below the cut-off across all parameters. The consolidation volume and integration of modified CT values were shown to be highly predictive of pathological invasiveness.

A Genomic-Pathologic Annotated Risk Model to Predict Recurrence in Early-Stage Lung Adenocarcinoma

Recommendations for adjuvant therapy after surgical resection of lung adenocarcinoma (LUAD) are based solely on TNM classification but are agnostic to genomic and high-risk clinicopathologic factors. Creation of a prediction model that integrates tumor genomic and clinicopathologic factors may better identify patients at risk for recurrence. To identify tumor genomic factors independently associated with recurrence, even in the presence of aggressive, high-risk clinicopathologic variables, in patients with completely resected stages I to III LUAD, and to develop a computational machine-learning prediction model (PRecur) to determine whether the integration of genomic and clinicopathologic features could better predict risk of recurrence, compared with the TNM system. This prospective cohort study included 426 patients treated from January 1, 2008, to December 31, 2017, at a single large cancer center and selected in consecutive samples. Eligibility criteria included complete surgical resection of stages I to III LUAD, broad-panel next-generation sequencing data with matched clinicopathologic data, and no neoadjuvant therapy. External validation of the PRecur prediction model was performed using The Cancer Genome Atlas (TCGA). Data were analyzed from 2014 to 2018. The study end point consisted of relapse-free survival (RFS), estimated using the Kaplan-Meier approach. Associations among clinicopathologic factors, genomic alterations, and RFS were established using Cox proportional hazards regression. The PRecur prediction model integrated genomic and clinicopathologic factors using gradient-boosting survival regression for risk group generation and prediction of RFS. A concordance probability estimate (CPE) was used to assess the predictive ability of the PRecur model. Of the 426 patients included in the analysis (286 women [67%]; median age at surgery, 69 [interquartile range, 62-75] years), 318 (75%) had stage I cancer. Association analysis showed that alterations in SMARCA4 (clinicopathologic-adjusted hazard ratio [HR], 2.44; 95% CI, 1.03-5.77; P = .042) and TP53 (clinicopathologic-adjusted HR, 1.73; 95% CI, 1.09-2.73; P = .02) and the fraction of genome altered (clinicopathologic-adjusted HR, 1.03; 95% CI, 1.10-1.04; P = .005) were independently associated with RFS. The PRecur prediction model outperformed the TNM-based model (CPE, 0.73 vs 0.61; difference, 0.12 [95% CI, 0.05-0.19]; P < .001) for prediction of RFS. To validate the prediction model, PRecur was applied to the TCGA LUAD data set (n = 360), and a clear separation of risk groups was noted (log-rank statistic, 7.5; P = .02), confirming external validation. The findings suggest that integration of tumor genomics and clinicopathologic features improves risk stratification and prediction of recurrence after surgical resection of early-stage LUAD. Improved identification of patients at risk for recurrence could enrich and enhance accrual to adjuvant therapy clinical trials.

Novel imprint cytological classification is correlated with tumor spread through air spaces in lung adenocarcinoma

ObjectivesSpread through air spaces (STAS) is a risk factor for local recurrence after sublobar resection in lung cancer patients. We recently proposed the novel Nakayama-Higashiyama imprint cytological classification (N-H classification) based on small-sized lung adenocarcinoma surgical specimens, which correlated with histological patterns and nodal involvement. This study aimed to evaluate the correlation between STAS and the N-H classification and to validate the N-H classification as an intraoperative predictor of the presence of STAS. Materials and methodsWe retrospectively analyzed 164 intraoperative imprint cytologies and their paired histologic specimens from patients undergoing surgical resection for lung adenocarcinoma in our institute in 2017–2019. Using the NH classification, imprint cytological findings were classified into 5 groups (Groups I to V) based on cell cluster shape, cell and nucleus size, and the existence of necrosis. We examined the characteristics of imprint cytology and STAS in the resected tissues and analyzed the relationship between them. ResultsTumor STAS was observed in 29 (17.7 %) cases. The presence of STAS was significantly associated with the NH classification (P < 0.0001). STAS was present in 6 of 57 cases (10.5 %) in NH classification Group II, 11 of 42 cases (26.2 %) in Group III, and 12 of 28 cases (42.9 %) in Group IV/V; STAS was not observed in any case in Group I. Logistic regression analysis revealed that tumors with a ground glass opacity rate of <50 % on computed tomography (P = 0.00867) and Groups III–V of the NH classification (P = 0.00201) were significant independent predictors for STAS. ConclusionIntraoperative imprint cytology with the N-H classification for lung adenocarcinoma is well correlated with the STAS status of the tumor and might have applications as an intraoperative predictive marker of STAS. This classification may be useful for intraoperative detection of STAS and in the decision-making process for the surgical procedure.

463P - Prediction of invasiveness in lung adenocarcinoma using machine learning algorithm based on 3D-CT imaging

BackgroundT factor depends on consolidation diameter in lung adenocarcinoma. Adenocarcinoma with short consolidation diameter could be indicated for sublobar resection. However, measurement of consolidation diameter under lung window in 2D-CT could be problematic, as the outline is not clear. We evaluated the relationship between consolidation lesion under mediastinal window in 3D-CT and pathological invasiveness, and aimed to predict invasiveness using machine learning algorithm. MethodsNinety-five patients who underwent surgical resection of lung adenocarcinoma that is less than 20 mm in diameter and has consolidation were analyzed retrospectively, in our Hospital from 2010 to 2016. The total tumor diameter and the volume and diameter of consolidation were analyzed using thin-slice CT and 3D-CT. Preoperative FDG-PET and serum CEA were also measured. Preinvasive lesion and minimally invasive adenocarcinoma were classified as pathologically non-invasive group, and invasive adenocarcinoma was classified as pathologically invasive group. The statistical differences were assessed by the Mann-Whitney U test or chi-square test. We used two machine learning algorithm. Three logistic regression (LR) models were trained based on sex, total tumor diameter, SUVmax, CEA, and (1) consolidation diameter (LR-Cd), (2) consolidation volume (LR-Cv), (3) consolidation diameter and volume (LD-Cd+Cv). Similarly, three random forest (RF) models were trained (RF-Cd, RF-Cv, RF-Cd+Cv). Patients were split into a training set (n = 76) and test set (n = 19). Model performance was measured area under the curve (AUC), and compared using receiver-operating characteristics curve analysis on the test set. ResultsTwenty-six non-invasive adenocarcinomas and 69 invasive adenocarcinomas were evaluated. The consolidation diameter and volume, and SUVmax of invasive group were significantly greater than those of non-invasive group (p < 0.001). On the test set, AUC of LR-Cd, RF-Cd, LR-Cv, RF-Cv, LR-Cd+Cv and RF-Cd+Cv were 0.687, 0.703,0.628, 0.744, 0.628 and 0.744 respectively. ConclusionsThe pathological invasiveness could be predicted by using machine learning algorithm. Especially, higher AUCs were obtained in RF-Cv and RF-Cd+Cv model. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

P2.17-37 Prognostic Implication of Surgical Treatment for the Dominant Lung Adenocarcinoma Associated with Part-Solid Nodules

The aim was to analyze the prognostic implication of surgical resection for lung adenocarcinoma appearing as part-solid nodules (PSNs) on computed tomography scans. From 2004 to 2017, the cases of a total of 651 patients (male:female = 259:392, median age, 65years) with surgically resected lung adenocarcinomas manifesting as PSNs were retrospectively reviewed. We compared patient characteristics with t tests for continuous variables and χ2 tests for categorical variables. The prognostic implication of the multiplicity of the surgical extent and other clinical variables in relation to overall-survival (OS) and disease-free survival (DFS) was analyzed by using Cox regression. Median maximum diameter and solid component diameter of PSNs were 2.0cm and 1.1cm. (range 0.8-7, 0.5-3.4) PSNs were resected by wedge resection, segmentectomy, or lobectomy in 94 (14.4%), 92 (14.2%), and 465 (71.4%) cases, respectively. Pathologic diagnosis was adenocarcinoma in situ, minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA) in 4 (0.6%), 70 (10.8%), and 577 (88.6%) cases, respectively. The median follow-up duration was 35.4 months. There was no significant difference of OS and DFS among the surgical extent and type of lymph node dissection (Figure 1). Multivariate Cox regression analysis demonstrated that multiple pulmonary nodules [hazard ratio (HR) = 8.3; 95% confidence interval (CI): 3.5-19.8 1.173; p <0.001] and wedge resection (HR = 3.8; 95% CI: 1.19-11.9; p = 0.02) were independent risk factors for the tumor recurrence. Among the resected lung adenocarcinoma associated with PSNs, multiple PSN and wedge resection is a significant prognostic factor in the lung cancer recurrence.

Prognostic Impact of Programmed Death-Ligand 2 Expression in Primary Lung Adenocarcinoma Patients.

Programmed death-ligand 1 (PD-L1) expression on lung cancer cells is a prognostic marker and a predictive biomarker for response to immunotherapy. However, previous clinical trials have suggested that other programmed cell death 1 ligands, including programmed death-ligand 2 (PD-L2), might have clinical impacts. This study aimed to analyze the prognostic significance of PD-L2 expression in lung adenocarcinoma patients. The study included 433 patients who underwent surgical resection for lung adenocarcinoma between 2003 and 2012 at Kyushu University Hospital. Both PD-L1 and PD-L2 expression were evaluated by immunohistochemistry. The cutoff value for PD-L2 positivity was set at 1% according to a time-dependent receiver operating characteristic curve for 5-year survival. Of the 433 patients, 306 (70.7%) were positive for PD-L2. No significant association between PD-L1 and PD-L2 expression was observed (P = 0.094). The multivariate analysis showed that the independent predictors of PD-L2 positivity were never-smoker status (P = 0.002), poor differentiation grade (P = 0.008), and advanced stage (P = 0.048). The PD-L2-positive patients had significantly shorter disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016). Both PD-L1 and PD-L2 positivity were independent predictors of OS (P < 0.001 and P = 0.027, respectively). In the subgroup analysis of the PD-L1-negative patients, PD-L2 positivity was significantly associated with shorter DFS (P = 0.018). The study demonstrated that the clinical characteristics of patients with PD-L1 expression may differ from those of patients with PD-L2 expression, and that both might contribute to poor prognoses. The potential role of PD-L2 expression as a predictive biomarker for response to immunotherapy should be investigated in future studies.

Pulmonary &amp;lt;i&amp;gt;Mycobacterium avium &amp;lt;/i&amp;gt; Complex Disease Requiring Differentiation from Recurrence of Lung Cancer during the Follow-Up Period for Lung Cancer

Case 1 was a 49-year-old woman who visited with a dry cough. She had an underlying disease of lung adenocarcinoma and received cancer immunotherapy because of an ALK-positive response and several cancer chemotherapies. The clinical effect was a complete response. Chest CT was performed because of continuous dry cough, and a new tumor shadow was recognized in the lingula portion of the left upper lobe. We performed CT-guided lung biopsy and could aspirate pus-fluid. The culture test for acid-fast bacilli was positive and the causative microorganism was identified as Mycobacterium avium by the DDH method. The final diagnosis was pulmonary abscess due to M. avium. Treatment using combined chemotherapy including CAM was performed and a good clinical response was obtained. Case 2 was a 67-year-old man who had a past history of surgical resection of lung adenocarcinoma eight and two years ago and received several cancer chemotherapies and radiation therapy. Because a new nodular shadow appeared in the right middle lobe one year ago and showed strong positivity on PET/CT, surgical resection was performed with the suspected recurrence of lung cancer. Subsequently, the histological diagnosis was epithelioid granuloma and a culture test of acid-fast bacilli was positive, with the identification of Mycobacterium intracellulare by the DDH method. Combined chemotherapy was not performed because the lesion was completely resected. Afterwards, a new nodular shadow appeared in the left lower lobe again and bronchoscopy was performed. Because M. intracellulare was isolated from the local specimen, we diagnosed the patient with recurrence of pulmonary MAC disease and combined chemotherapy including CAM was performed for one year. Finally, the nodular lesion disappeared. It is difficult to differentiate pulmonary MAC disease from lung cancer. Therefore, careful follow-up of patients with lung cancer while keeping in mind the possible complication of pulmonary MAC disease is necessary.

The Association Between Imaging Features of TSCT and the Expression of PD-L1 in Patients With Surgical Resection of Lung Adenocarcinoma

ObjectivesProgrammed death-ligand 1 (PD-L1) expression might serve as a predictive biomarker for immune checkpoint inhibitors in lung cancer. However, the relationship between PD-L1 expression and imaging features of lung cancer has not been fully understood. Patients and MethodsA total of 350 patients with pathologically confirmed adenocarcinoma who received surgical treatment and had preoperative thin section computed tomography (CT) examination were included. Quantitative CT features including the mean CT value and tumor mass were measured on multiplanar reconstructed images. PD–L1-positive tumor was defined as the tumor proportion score > 5%. ResultsSeventy-four of 350 (21.1%) specimens were detected as PD–L1-positive tumors. PD-L1 expression was adversely associated with epidermal growth factor receptor mutation status (P < .001) and was significantly associated with invasive adenocarcinomas rather than preinvasive lesions and minimally invasive adenocarcinomas (P < .001). Multivariate analysis identified absence of surrounding ground glass opacity (P = .022), shape (P = .008), pleural indentation (P = .007), tumor mean CT value (P = .004), and the ratio of consolidation mass to tumor mass (P = .003) as being significantly associated with the expression of PD-L1. To improve the diagnostic accuracy, a joint model that combined 5 imaging traits was conducted. The area under the curve of the joint model was 0.783, with a sensitivity of 81.1% and specificity of 64.1%, respectively. ConclusionPD-L1 expression was associated with pathologic invasiveness of adenocarcinomas and CT features, which suggested the possibility of predicting PD-L1 expression status via imaging features.

18F-fluorodeoxyglucose positron emission tomography is correlated with the pathological necrosis and decreased microvessel density in lung adenocarcinomas.

We explored the relationship between preoperative 18F-FDG-PET parameters, tumor necrosis, and microvessel density (MVD) in patients with pulmonary adenocarcinomas. A total of 164 patients, who underwent surgical resection for lung adenocarcinoma, were reviewed retrospectively. The maximum standardized uptake value (SUVmax), peak SUV corrected for lean body mass (SULpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) values were measured by preoperative 18F-FDG-PET. The extent of tumor necrosis was examined and CD31 expression was evaluated to count the MVD. The SUVmax, SULpeak, MTV, and TLG levels were significantly lower in patients exhibiting no necrosis compared to those with necrosis. When we divided the patients into two groups based on high vs. low PET parameter values, elevated SUVmax, SULpeak, MTV, and TLG values were significantly more associated with partial or diffuse necrosis than were lower values (p < 0.001). A negative correlation was evident between the MVD and SUVmax, MVD and SULpeak, MVD and MTV, and MVD and TLG. Tumor necrosis was correlated with a shorter overall survival (OS) (p = 0.007) and recur-free survival (RFS) (p < 0.001). However, multivariate analysis revealed that necrosis was not of prognostic significance. The SUVmax, MTV and TLG were associated with inferior OS or RFS rates in univariate analysis, however, not in multivariate analysis. High-level FDG accumulation is correlated with tumor necrosis in lung adenocarcinoma.

P3.16-03 Uncommon EGFR Mutations as a Worse Prognostic Factor for Surgically Resected Lung Adenocarcinoma

The characteristics and prognosis of patients with lung adenocarcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations have not been clarified. Here, we examined whether the presence of uncommon EGFR mutations is a prognostic factor for patients treated surgically. In this multi-institutional retrospective cohort study, clinicopathological data were collected from 1,463 patients who underwent complete surgical resection for lung adenocarcinoma between 2005 and 2012 at five institutions and were examined for EGFR mutation status. Differences in postoperative overall survival (OS) and recurrence-free survival (RFS) according to EGFR mutation status were evaluated. Of 1,031 eligible patients, 500 (48.5%), 497 (48.2%), and 34 (3.3%) had wild-type EGFR (WT), common EGFR mutations (CMs), and uncommon EGFR mutations (UCMs), respectively. In the UCM group, 19 patients had a single mutation, including exon 18 G719X (n = 7), exon 20 T790M (n = 6), or exon 21 L861Q (n = 5), and 15 patients had compound mutations. The clinicopathological characteristics were not significantly different between the CM and UCM groups. The 5-year OS rates in the WT, CM, and UCM groups were 76.3%, 88.6%, and 68.4%, respectively. OS was significantly shorter in the UCM than CM group (p = 0.011), although no significant difference was observed between the UCM and WT groups (p = 0.83). The 5-year RFS rates in the WT, CM, and UCM groups were 63.7%, 75.4%, and 58.1%, respectively. RFS was significantly shorter in the UCM than CM group (p = 0.006), although no significant difference was observed between the UCM and WT groups (p = 0.41). The use of EGFR–tyrosine kinase inhibitors after recurrence did not affect the prognosis with respect to EGFR mutation type. Among those with single mutations in the UCM group, patients harboring T790M were younger, more likely to be males and smokers, and more likely to have a larger tumor size, lymph node metastasis, pleural invasion, and lymphovascular invasion, compared with those harboring G719X or L861Q. T790M was also associated with shorter OS and RFS; the 3-year OS rates were 50.0%, 83.3%, and 100% and the 3-year RFS rates were 16.7%, 71.4%, and 80.0% for patients harboring T790M, G719X, and L861Q, respectively. Among patients with surgically resected lung adenocarcinoma, OS and RFS were significantly shorter in those with UCMs compared with CMs, implying that UCMs may be a worse prognostic factor.

Lung Adenocarcinoma: CT Features Associated with Spread through Air Spaces.

Purpose To identify the features at CT that are predictive of spread through air spaces (STAS) in surgically resected lung adenocarcinomas. Materials and Methods For this retrospective study, presence of STAS was evaluated in 948 consecutive patients who underwent surgical resection for lung adenocarcinoma from April 2015 to December 2016. Patients who were positive for STAS and negative for STAS were matched at a ratio of 1:2 by using patient variables (age, sex, and smoking status). CT features (ie, percentage of solid component, maximum diameter of solid component, lesion density, location, margin, shape, pseudocavity, calcification, central low attenuation, ill-defined peripheral opacity, air bronchogram, satellite lesions, and pleural retraction) were analyzed by using multivariable logistic regression and receiver operating characteristic curves. Results The final study population consisted of 276 patients (mean age, 59 years; age range, 32-78 years) including 129 men (mean age, 60 years; age range, 36-78 years) and 147 women (mean age, 59 years; age range, 32-78 years). Ninety-two patients were positive for STAS and 184 patients were negative for STAS. STAS was more common in solid tumors (71 of 92; 77%) than in part-solid (21 of 92; 23%) or ground-glass lesions (0 of 92; 0%) (P < .001). STAS was also associated with central low attenuation, ill-defined opacity, air bronchogram, and percentage of solid component (all P < .001). Percentage of solid component was an independent predictor of STAS (odds ratio, 1.06; 95% confidence interval: 1.03, 1.08) and a cut-off value of 90% showed a discriminatory power with a sensitivity of 89.2% and a specificity of 60.3%. Conclusion Percentage of solid component was independently associated with spread through air spaces in lung adenocarcinomas. © RSNA, 2018 Online supplemental material is available for this article.

Epidermal Growth Factor Receptor Mutation as a Risk Factor for Recurrence in Lung Adenocarcinoma

The presence of epidermal growth factor receptor (EGFR) mutations is an established prognostic factor for patients with advanced lung adenocarcinoma. Here, we examined whether EGFR mutation status is a prognostic factor for patients who had undergone surgery. Clinicopathologic data from 1,463 patients who underwent complete surgical resection for lung adenocarcinoma between 2005 and 2012 were collected. Differences in postoperative recurrence-free survival and overall survival according to EGFR mutation status were evaluated. Of 835 eligible patients, the numbers of patients with wild-type EGFR (WT), exon 19 deletion (Ex19), and exon 21 L858R (Ex21) were 426, 175, and 234, respectively. Patients with Ex19 had a significantly higher incidence of extrathoracic recurrence than patients with Ex21 (p= 0.004). The 5-year recurrence-free survival rates for patients with WT, Ex19, and Ex21 were 63.0%, 67.5%, and 78.2%, respectively. The Ex21 group had a significantly longer recurrence-free survival than the WT group (p < 0.001) and the Ex19 group (p= 0.016). The 5-year overall survival for patients with WT, Ex19, and Ex21 were 76.9%, 86.5%, and 87.5%, respectively. Patients with Ex19 and Ex21 had a significantly longer overall survival than patients with WT (Ex19, p= 0.009; Ex21, p < 0.001). Multivariate analysis for recurrence-free survival showed that Ex19 was significantly associated with a worse prognosis than Ex21 (p= 0.019). Patients with Ex19 had significantly shorter recurrence-free survival and had extrathoracic recurrence more frequently than patients with Ex21 among patients with resected lung adenocarcinoma, implying that Ex19 could be a worse prognostic factor.

Surgical Resection of Lung Adenocarcinoma ≤20 mm in Diameter

Purpose: There are clinical trials to prove feasibility of limited lung resection for N0 small lung cancers in Japan and North America. However, a treatment strategy for these tumours has not yet been clarified. In our department limited resection for clinical stage IA lung cancer was performed when the diameter of the tumour was <15 mm and a consolidation Tumor Ratio iCTR jwas <0.5 on preoperative high-resolution computed tomography. We reviewed our experience of lung adenocarcinoma ≤20 mm diameter resection.

Matched-pair analysis of a multi-institutional cohort reveals that epidermal growth factor receptor mutation is not a risk factor for postoperative recurrence of lung adenocarcinoma

ObjectiveIt is unclear whether epidermal growth factor receptor (EGFR) mutation status is a risk factor for postoperative recurrence of surgically resected lung adenocarcinoma (ADC). Therefore, we conducted a multi-institutional study employing matched-pair analysis to compare recurrence-free survival (RFS) and overall survival (OS) of patients with lung ADC according to EGFR mutation status. MethodsWe collected the records of 909 patients who underwent surgical resection for lung ADC between 2005 and 2012 at five participating institutions and were also examined their EGFR mutation status. For each patient with an EGFR mutation, we selected one with the wild-type EGFR sequence and matched them according to institution, age, gender, smoking history, pathological stage (pStage), and adjuvant treatment. We compared RFS and OS of the matched cohort. ResultsThe patients were allocated into groups (n=181 each) with mutated or wild-type EGFR sequences. Both cohorts had identical characteristics as follows: institution, median age (68 years), men (85, 47%), ever smokers (77, 43%), and pStage (IA, 108, 60%; IB, 48, 27%; II, 14, 8%; III, 11, 6%). The 3- and 5-year RFS rates of patients with mutated or wild-type EGFR sequence were 79%, 68% and 77%, 68%, respectively (p=0.557). The respective OS rates were 92%, 81%, and 89%, 79% (p=0.574). ConclusionMatched-pair and multi-institutional analysis reveals that an EGFR mutation was not a significant risk factor for recurrence of patients with surgically resected lung adenocarcinoma.

Epidermal growth factor receptor mutation status is strongly associated with smoking status in patients undergoing surgical resection for lung adenocarcinoma.

The purpose of this analysis was to examine the relationship between epidermal growth factor receptor (EGFR) mutation status and clinicopathological factors in a cohort of patients who underwent surgical resections for lung adenocarcinoma. From the patients who underwent surgical resections for primary lung cancers between 2005 and 2012, 371 consecutive adenocarcinoma patients were enrolled in this study, and their tumours were analysed for EGFR mutations. We examined the clinicopathological factors of all enrolled patients, including age, sex, pathological stage and smoking status and tested for associations with EGFR mutation status. Among the 371 enrolled patients, 195 (52%) patients had EGFR mutations. There were significantly more women, never smokers and tumours of lower grade histology in the EGFR mutation group than in the wild-type group (P < 0.001 each). However, other factors, such as pathological stage and World Health Organization classification, were not significantly associated with mutation status. Multivariable analysis showed that age, smoking history and histological grade were independently associated with EGFR mutations (P = 0.026, P < 0.001 and P < 0.001, respectively), but sex was not. Regarding smoking status, especially, frequency of EGFR mutation decreased, as smoking index increased. On the other hand, sex and smoking cessation (whether the patients were former or current smokers) were not significantly associated with EGFR mutation status. In our cohort of patients who underwent surgical resection for lung adenocarcinoma, EGFR mutation status was strongly associated with smoking status, especially smoking index.