Expansion of tumor-infiltrating lymphocytes in non-small cell lung cancer: Clinical potential and efficacy in EGFR mutation subsets.

Our study aimed to expand tumor-infiltrating lymphocytes (TILs) from primary non-small cell lung cancers (NSCLCs) and evaluate their reactivity against tumor cells. We expanded TILs from 103 primary NSCLCs using histopathological analysis, flow cytometry, IFN-γ release assays, cell-mediated cytotoxicity assays, and in vivo efficacy tests. TIL expansion was observed in all cases, regardless of EGFR mutation status. There was also an increase in the median CD4+/CD8+ ratio during expansion. In post-rapid expansion protocol (REP) TILs, 13 out of 16 cases, including all three cases with EGFR mutations, exhibited a two-fold or greater increase in IFN-γ secretion. The cytotoxicity assay revealed enhanced tumor cell death in three of the seven cases, two of which had EGFR mutations. In vivo functional testing in a patient-derived xenograft model showed a reduction in tumor volume. The anti-tumor activity of post-REP TILs underscores their potential as a therapeutic option for advanced NSCLC, irrespective of mutation status.

Surgical Outcomes in Non-Small Cell Lung Cancer with Distant Metastasis: The Prognostic Significance of Delayed Metastasis Diagnosis.

BACKGROUND: The diagnosis of distant metastasis on preoperative examinations for non-small cell lung cancer (NSCLC) can be challenging, leading to surgery for some patients with uncertain metastasis. This study evaluated the prognostic impact of delayed diagnosis of metastasis on patients who underwent upfront surgery. METHODS: The study enrolled patients who underwent lobectomy or pneumonectomy for NSCLC between June 2010 and December 2017 and evaluated the presence of distant metastasis before surgery. Overall survival (OS) for patients with stage IV cancer was compared with that for patients without metastasis, and the prognostic factors were analyzed. RESULTS: Of 3046 patients (mean age, 63 years; 1770 men), 100 (3.3 %) had distant metastasis, diagnosed preoperatively in 1.4 % (42/3046) and postoperatively in 1.9 % (58/3046) of the patients. The two most common metastasis sites diagnosed after surgery were contralateral lung (22/58, 37.9 %) and ipsilateral pleura (16/58, 27.6 %). The OS (median, 42.7 months) for the patients with stage IV cancer diagnosed postoperatively was comparable with that for the patients with stage IIIB cancer (P = 0.865), whereas the OS (median OS, 91.7 months) for the patients with stage IV cancer diagnosed preoperatively was better than for the patients with stage IIIB cancer (P = 0.001). Among the patients with distant metastasis, squamous cell type (hazard ratio [HR], 3.15; P = 0.002) and systemic treatment for metastasis (HR, 2.42; P = 0.002) were independent predictors of worse OS. CONCLUSIONS: Among NSCLC patients undergoing upfront surgery, the OS for the patients with stage IV cancer diagnosed postoperatively was comparable with that for the patients with stage IIIB cancer. For patients with stage IV disease, squamous cell type and systemic treatment for metastasis were prognostic factors for poorer OS.

Prognostic Implications of Synchronous Subsolid Nodules in Patients with Resected Subsolid Lung Adenocarcinoma.

Background For multiple subsolid nodules (SSNs) observed at lung CT, current management focuses on removal of the dominant (≥6 mm) nodule and monitoring of remaining SSNs. Whether the presence of these synchronous SSNs is related to postoperative patient outcomes has not been well established. Purpose To evaluate the prognostic value of single versus multiple synchronous SSNs at preoperative CT in patients with resected subsolid lung adenocarcinoma nodules. Materials and Methods This retrospective study included patients who underwent lobectomy or sublobar resection for lung adenocarcinoma manifesting as an SSN and clinical stage IA from January 2010 to December 2017. The radiologic features of the resected SSN (dominant nodule) and synchronous SSNs were assessed on preoperative CT scans. The effects of synchronous SSNs on time to secondary intervention, time to recurrence (TTR), and overall survival (OS) were evaluated using Cox regression analysis. Results Of the 684 included patients (mean age, 60.9 years ± 9.5 [SD]; 389 female), 515 (75.3%) had a single SSN and 169 (24.7%) had multiple SSNs on preoperative CT scans. During follow-up (median, 71.8 months), 38 secondary interventions were performed, primarily due to growth of synchronous SSNs (21 of 38) or metachronous nodules (14 of 38). As the number of synchronous SSNs greater than or equal to 6 mm in size increased, the time to secondary intervention decreased (P < .001). No association was observed between synchronous SSNs and TTR (P = .53) or OS (P = .65), but these measures were associated with features of the resected nodule, specifically solid portion size for TTR (P = .01) and histologic subtype for TTR and OS (P < .001 for both). Conclusion In patients with subsolid lung adenocarcinoma, the presence of synchronous SSNs on preoperative CT scans was not associated with TTR or OS, but the presence of synchronous SSNs greater than or equal to 6 mm in size was associated with an increased likelihood of secondary intervention. © RSNA, 2023 Supplemental material is available for this article.

Recurrence Patterns and Patient Outcomes in Resected Lung Adenocarcinoma Differ according to Ground-Glass Opacity at CT.

Background Although lung adenocarcinoma with ground-glass opacity (GGO) is known to have distinct characteristics, limited data exist on whether the recurrence pattern and outcomes in patients with resected lung adenocarcinoma differ according to GGO presence at CT. Purpose To examine recurrence patterns and associations with outcomes in patients with resected lung adenocarcinoma according to GGO at CT. Materials and Methods Patients who underwent CT followed by lobectomy or pneumonectomy for lung adenocarcinoma between July 2010 and December 2017 were retrospectively included. Patients were divided into two groups based on the presence of GGO: GGO adenocarcinoma and solid adenocarcinoma. Recurrence patterns at follow-up CT examinations were investigated and compared between the two groups. The effects of patient grouping on time to recurrence, postrecurrence survival (PRS), and overall survival (OS) were evaluated using Cox regression. Results Of 1019 patients (mean age, 62 years ± 9 [SD]; 520 women), 487 had GGO adenocarcinoma and 532 had solid adenocarcinoma. Recurrences occurred more frequently in patients with solid adenocarcinoma (36.1% [192 of 532 patients]) than in those with GGO adenocarcinoma (16.2% [79 of 487 patients]). Distant metastasis was the most common mode of recurrence in the group with solid adenocarcinoma and all clinical stages. In clinical stage I GGO adenocarcinoma, all regional recurrences appeared as ipsilateral lung metastasis (39.2% [20 of 51]) without regional lymph node metastasis. Brain metastasis was more frequent in patients with clinical stage I solid adenocarcinoma (16.5% [16 of 97 patients]). The presence of GGO was associated with time to recurrence and OS (adjusted hazard ratio [HR], 0.6 [P < .001] for both). Recurrence pattern was an independent risk factor for PRS (adjusted HR, 2.1 for distant metastasis [P < .001] and 3.9 for brain metastasis [P < .001], with local-regional recurrence as the reference). Conclusion Recurrence patterns, time to recurrence, and overall survival differed between patients with and without ground-glass opacity at CT, and recurrence patterns were associated with postrecurrence survival. © RSNA, 2023 Supplemental material is available for this article.

Clinical impact of pre-existing acute exacerbation in patients with interstitial lung disease who underwent lung transplantation.

BACKGROUND: Acute exacerbation of interstitial lung disease (AE-ILD) significantly impacts prognosis, leading to high mortality rates. Although lung transplantation is a life-saving treatment for selected patients with ILD, its outcomes in those presenting with AE-ILD have yielded conflicting results compared with those with stable ILD. This study aims to investigate the impact of pre-existing AE on the prognosis of ILD patients who underwent lung transplantation. METHOD: We conducted a single-center retrospective study by reviewing the medical records of 108 patients who underwent lung transplantation for predisposing ILD at Asan Medical Center, Seoul, South Korea, between 2008 and 2022. The primary objective was to compare the survival of patients with AE-ILD at the time of transplantation with those without AE-ILD. RESULTS: Among the 108 patients, 52 (48.1%) experienced AE-ILD at the time of lung transplantation, and 81 (75.0%) required pre-transplant mechanical ventilation. Although the type of ILD (IPF vs. non-IPF ILD) did not affect clinical outcomes after transplantation, AE-ILD was associated with worse survival outcomes. The survival probabilities at 90 days, 1 year, and 3 years post-transplant for patients with AE-ILD were 86.5%, 73.1%, and 60.1%, respectively, while those for patients without AE-ILD were higher, at 92.9%, 83.9%, and 79.6% (p = 0.032). In the multivariable analysis, pre-existing AE was an independent prognostic factor for mortality in ILD patients who underwent lung transplantation. CONCLUSIONS: Although lung transplantation remains an effective treatment option for ILD patients with pre-existing AE, careful consideration is needed, especially in patients requiring pre-transplant mechanical respiratory support.

Automated CT quantification of interstitial lung abnormality and interstitial lung disease according to the Fleischner Society in patients with resectable lung cancer: prognostic significance.

OBJECTIVE: To assess the prognostic significance of automatically quantified interstitial lung abnormality (ILA) according to the definition by the Fleischner Society in patients with resectable non-small-cell lung cancer (NSCLC). METHODS: Patients who underwent lobectomy or pneumonectomy for NSCLC between January 2015 and December 2019 were retrospectively included. Preoperative CT scans were analyzed using the commercially available deep-learning-based automated quantification software for ILA. According to quantified results and the definition by the Fleischner Society and multidisciplinary discussion, patients were divided into normal, ILA, and interstitial lung disease (ILD) groups. RESULTS: Of the 1524 patients, 87 (5.7%) and 20 (1.3%) patients had ILA and ILD, respectively. Both ILA (HR, 1.81; 95% CI: 1.25-2.61; p = .002) and ILD (HR, 5.26; 95% CI: 2.99-9.24; p < .001) groups had poor recurrence-free survival (RFS). Overall survival (OS) decreased (HR 2.13 [95% CI: 1.27-3.58; p = .004] for the ILA group and 7.20 [95% CI: 3.80-13.62, p < .001] for the ILD group) as the disease severity increased. Both quantified fibrotic and non-fibrotic ILA components were associated with poor RFS (HR, 1.57; 95% CI: 1.12-2.21; p = .009; and HR, 1.11; 95% CI: 1.01-1.23; p = .03) and OS (HR, 1.59; 95% CI: 1.06-2.37; p = .02; and HR, 1.17; 95% CI: 1.03-1.33; and p = .01) in normal and ILA groups. CONCLUSIONS: The automated CT quantification of ILA based on the definition by the Fleischner Society predicts outcomes of patients with resectable lung cancer based on the disease category and quantified fibrotic and non-fibrotic ILA components. CLINICAL RELEVANCE STATEMENT: Quantitative CT assessment of ILA provides prognostic information for lung cancer patients after surgery, which can help in considering active surveillance for recurrence, especially in those with a larger extent of quantified ILA. KEY POINTS: • Of the 1524 patients with resectable lung cancer, 1417 (93.0%) patients were categorized as normal, 87 (5.7%) as interstitial lung abnormality (ILA), and 20 (1.3%) as interstitial lung disease (ILD). • Both ILA and ILD groups were associated with poor recurrence-free survival (hazard ratio [HR], 1.81, p = .002; HR, 5.26, p < .001, respectively) and overall survival (HR, 2.13; p = .004; HR, 7.20; p < .001). • Both quantified fibrotic and non-fibrotic ILA components were associated with recurrence-free survival and overall survival in normal and ILA groups.

Comparison of Long-Term Outcomes Between Minimally Invasive Pulmonary Resection With and Without Video-Assisted Mediastinoscopic Lymphadenectomy for Left-Sided Lung Cancer.

BACKGROUND: This study aimed to assess the long-term outcomes of video-assisted mediastinoscopic lymphadenectomy (VAMLA) combined with video-assisted thoracic surgery (VATS) for left-sided lung cancer pulmonary resection. PATIENTS AND METHODS: We retrospectively reviewed 1194 consecutive patients who underwent VATS anatomical resection for left-sided lung cancer between January 2007 and December 2016. Using propensity score-based inverse probability of treatment weighting (IPTW), perioperative outcomes and long-term survival outcomes were compared. RESULTS: Among 1194 patients, 295 (24.7%) underwent additional VAMLA (VATS + VAMLA group) and 899 patients (75.3%) underwent VATS only (VATS group). The proportion of patients with advanced N stage were higher in the VATS + VAMLA group (24.7%) than in the VATS group (18.3%). After IPTW adjustment, all baseline profiles between the two groups became similar. The long-term overall survival (OS) and recurrence-free survival (RFS) rates were similar between the VATS + VAMLA group and the VATS group (5-year OS, 77.8% versus 79.3%, p = 0.957; 5-year RFS, 69.6% versus 70.1%, p = 0.498). However, among patients with borderline pulmonary function (FEV1 ≤ 60% or DLCO ≤ 60%), the VATS + VAMLA group (n = 23) had a better prognosis than the VATS group (n = 36) (5-year OS, 67.4% versus 46.7%, respectively; p = 0.047; 5-year RFS, 74.6% versus 53.5%, respectively; p = 0.027). CONCLUSIONS: VAMLA might be a good complement to VATS for left-sided lung cancer, wherein optimal mediastinal lymph node dissection is not feasible under one-lung ventilation, such as when patients have borderline pulmonary function.

Differences in the prognostic implication of ground-glass opacity on CT according to pathological nodal status in lung cancers treated with lobectomy or pneumonectomy.

OBJECTIVES: To clarify the prognostic significance of a ground-glass opacity (GGO) component according to T category and pathological nodal status in patients with resectable non-small cell lung cancer (NSCLC). METHODS: Patients who underwent lobectomy or pneumonectomy for NSCLC between July 2010 and December 2017 were retrospectively included. Patients were divided into GGO and solid groups based on the presence of a GGO component on CT. The effects on survival of interactions between GGO and (a) pathological nodal status (pN) and (b) cT category were evaluated using Cox regression. RESULTS: Out of 1545 patients, 548 were classified into the GGO group (pN0: 457, pN1/2: 91) and 997 into the solid group (pN0: 660, pN1/2: 337). There were interactions between the presence of GGO and pathological nodal status on 5-year disease-free survival (DFS; p = .006) and 5-year overall survival (OS; p = .02). In multivariate analysis, better survival of patients in the GGO group than in the solid group was observed only in pN0 category (adjusted hazard ratio [HR], 0.63 for 5-year DFS; p = .002 and 0.47 for 5-year OS; p = .002), but not in pN1/2 category. Moreover, in those with pN0 category, the favorable prognostic value of GGO was limited to those with cT1 category for 5-year DFS (adjusted HR, 0.48; p < .001) and those with cT1/2 category for 5-year OS (adjusted HR, 0.37; p = .002). CONCLUSIONS: GGO was a favorable predictor of survival only in patients with pN0 category, showing an advantage in DFS for those with cT1 category and OS for those with cT1/2 category. KEY POINTS: • The presence of ground-glass opacity was associated with a favorable prognosis, only in pathological node-negative patients (5-year disease-free survival, p = .002; 5-year overall survival, p = .002). • Within pathological node-negative patients, the effect of ground-glass opacity on 5-year disease-free survival was valid in patients with cT1 category (adjusted hazard ratio, 0.48; 95% confidence interval, 0.32-0.72; p < .001), but not in patients with cT2 or above category. • Within pathological node-negative patients, the effect of ground-glass opacity on 5-year overall survival was valid in patients with cT1/2 category (adjusted hazard ratio, 0.37; 95% confidence interval, 0.20-0.68; p = .002), but not in patients with cT3/4 category.

Diagnostic and prognostic values of 2-[18F]FDG PET/CT in resectable thymic epithelial tumour.

OBJECTIVES: We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[18F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs). METHODS: One hundred and fourteen patients with TETs who underwent pretreatment 2-[18F]FDG PET/CT between 2012 and 2018 were retrospectively evaluated. TETs were classified into three histologic subtypes: low-risk thymoma (LRT, WHO classification A/AB/B1), high-risk thymoma (HRT, B2/B3), and thymic carcinoma (TC). Area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic performance of PET/CT variables (maximum standardised uptake value [SUVmax], metabolic tumour volume [MTV], total lesion glycolysis [TLG], maximum diameter). Cox proportional hazards models were built using PET/CT and clinical variables. RESULTS: The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 - 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 - 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor (p < 0.001), whereas MTV and TLG were not. SUVmax was a significant predictor for overall survival in conjunction with clinical stage and resection margin. CONCLUSION: SUVmax showed excellent diagnostic performance for prediction of TC and significant prognostic value in terms of recurrence and survival. KEY POINTS: • Maximum standardised uptake value (SUVmax) shows excellent performance in the differentiation of thymic carcinoma from low- and high-risk thymoma. • SUVmax is an independent prognostic factor for freedom-from-recurrence in the multivariable Cox proportional hazard model and a significant predictor for overall survival. • 2-[18F]FDG PET/CT can provide a useful diagnostic and prognostic imaging biomarker in conjunction with histologic classification and stage and help choose appropriate management for thymic epithelial tumours.

Volume Doubling Times of Pulmonary Metastases in Patients With Bone and Soft-Tissue Sarcomas: Associations With Subsequent New Metastases and Survival After Metastasectomy.

BACKGROUND. Pulmonary metastases of bone and soft-tissue sarcoma are common and have a high recurrence rate after metastasectomy. Factors associated with postmetastasectomy recurrence are not well studied. OBJECTIVE. The purpose of this study was to investigate the association of the volume doubling time (VDT) of pulmonary metastases with the subsequent development of new pulmonary nodules and survival after metastasectomy in patients with bone or soft-tissue sarcoma. METHODS. This retrospective study included patients with bone or soft-tissue sarcoma who, between January 2010 and December 2020, underwent first complete metastasectomy of pulmonary nodules visualized on two sequential preoperative CT scans. Semiautomatic volumetric segmentation of the pulmonary metastases was performed on the two CT scans, and VDTs were calculated. VDT was compared between patients with and without subsequent new metastases after metastasectomy. Cox proportional hazards regression analyses were performed to determine risk factors for recurrence-free survival (RFS) after metastasectomy and for postmetastasectomy overall survival (OS). RESULTS. Forty patients (21 women, 19 men; mean age, 51.1 ± 14.3 [SD] years) were included. Of these patients, 23 (57.5%) developed new metastatic nodules after metastasectomy, and 10 (25.0%) died during follow-up. Median VDT was shorter in patients with, versus those without, new metastases after metastasectomy (56 vs 140 days, p = .002). Only four of 23 patients with new metastases had VDT of 140 days or more. In multivariable analysis, older age (hazard ratio [HR], 1.06; p = .004), female sex (HR, 2.80; p = .03), and VDT less than 140 days (HR, 4.22; p = .01) were independent predictors of worse RFS. Also in multivariable analysis, only older age (HR, 1.17; p = .005) and VDT less than 50 days (HR, 8.60; p = .02) were independent predictors of worse OS. OS was significantly worse in patients with VDT less than 140 days (10 deaths among 27 patients) than in patients with VDT of 140 days or more (no deaths in 13 patients) (p = .01). CONCLUSION. In patients with bone and soft-tissue sarcoma, shorter VDT of pulmonary metastases is independently associated with subsequent new metastases after metastasectomy and worse OS. CLINICAL IMPACT. VDT of pulmonary nodules may be considered in patient selection for pulmonary metastasectomy and in postoperative patient management.

Predicting Postoperative Complications and Long-Term Survival After Lung Cancer Surgery Using Eurolung Risk Score.

BACKGROUND: This study aimed to assess the clinical relevance of the parsimonious Eurolung risk scoring system for predicting postoperative morbidity, mortality, and long-term survival in Korean patients with surgically resected non-small cell lung cancer. METHODS: This retrospective analysis used the data of patients who underwent anatomical resection for non-small cell lung cancer between 2004 and 2018 at a single institution. The parsimonious aggregate Eurolung score was calculated for each patient. The Cox regression model was used to determine the ability of the Eurolung scoring system for predicting long-term outcomes. RESULTS: Of the 7,278 patients in the study, cardiopulmonary complications and mortality occurred in 687 (9.4%) and 53 (0.7%) patients, respectively. The rate of cardiopulmonary complications and mortality gradually increased with the increase in the Eurolung risk scores (all P < 0.001). When risk scores were grouped into four categories, the Eurolung scoring system showed a stepwise deterioration of overall survival with the increase in risk scores, and this association was statistically significant (P < 0.001). Multivariate Cox analysis showed that the Eurolung scoring system, classified into four categories, was a significant prognostic factor of overall survival even after adjusting for covariates such as tumor histology and pathological stage (P < 0.001). CONCLUSION: Stratification based on the parsimonious Eurolung scoring system showed good discriminatory ability for predicting postoperative morbidity, mortality, and long-term survival in South Korean patients with surgically resected non-small cell lung cancer. This might help clinicians to provide a detailed prognosis and decide the appropriate treatment option for high-risk patients with non-small cell lung cancer.

Performance of radiomics models for survival prediction in non-small-cell lung cancer: influence of CT slice thickness.

OBJECTIVES: To investigate whether CT slice thickness influences the performance of radiomics prognostic models in non-small-cell lung cancer (NSCLC) patients. METHODS: CT images including 1-, 3-, and 5-mm slice thicknesses acquired from 311 patients who underwent surgical resection for NSCLC between May 2014 and December 2015 were evaluated. Tumor segmentation was performed on CT of each slice thickness and total 94 radiomics features (shape, tumor intensity, and texture) were extracted. The study population was temporally split into development (n = 185) and validation sets (n = 126) for prediction of disease-free survival (DFS). Three radiomics models were built from three different slice thickness datasets (Rad-1, Rad-3, and Rad-5), respectively. Model performance was assessed and compared in three slice thickness datasets and mixed slice thickness dataset using C-indices. RESULTS: In corresponding slice thickness datasets, the C-indices of Rad-1, Rad-3, and Rad-5 for prediction of DFS were 0.68, 0.70, and 0.68 in the development set, and 0.73, 0.73, and 0.76 in the validation set (p = 0.40-0.89 and 0.27-0.90, respectively). Performance of the models was not significantly changed when they were applied to different slice thicknesses data in the validation set (C-index, 0.73-0.76, 0.72-0.73, 0.75-0.76; p = 0.07-0.92). In the mixed slice thickness dataset, performances of the models were similar to or slightly lower than their performances in the corresponding slice thickness datasets (C-index, 0.72-0.75 vs. 0.73-0.76) in the validation set. CONCLUSIONS: The performance of radiomics models for predicting DFS in NSCLC patients was not significantly affected by CT slice thickness. KEY POINTS: • Three radiomics models based on 1-, 3-, and 5-mm CT datasets showed C-indices for predicting disease-free survival of 0.68-0.70 in the development set and 0.73-0.76 in the validation set, without statistical differences (p = 0.27-0.90). • Application of the radiomics models to different slice thickness datasets showed no significant differences in performance between the values in the prediction of disease-free survival (p = 0.07-0.99). • Three radiomics models based on 1-, 3-, and 5-mm CT datasets performed well in mixed slice thickness datasets, showing similar or slightly lower performances.

Sublobar Resection in Stage IA Non-Small Cell Lung Cancer: Role of Preoperative CT Features in Predicting Pathologic Lymphovascular Invasion and Postoperative Recurrence.

BACKGROUND. Prognostic factors on preoperative CT in stage IA non-small cell lung cancer (NSCLC) may help select patients for sublobar resection or lobectomy. OBJECTIVE. The purpose of this study was to identify CT features predictive of pathologic lymphovascular invasion (LVI) in stage IA NSCLC and to evaluate the features' prognostic value in patients who undergo sublobar resection. METHODS. This retrospective study included 904 patients (mean age, 62.0 years; 453 men, 451 women) who underwent lobectomy (n = 574) or sublobar resection (n = 330) for stage IA NSCLC. Two thoracic radiologists independently evaluated findings on pre-operative chest CT and then resolved discrepancies. Recurrences were identified from medical record review. Multivariable logistic regression was used to identify independent predictors of pathologic LVI. Multivariable Cox proportional hazards models were used to identify prognostic features. Interreader agreement was assessed. RESULTS. Pathologic LVI was present in 10.2% (92/904) of patients. It was present only in solid-dominant part-solid nodules (PSNs) and solid nodules and only in nodules with a solid portion diameter over 10 mm. Among solid-dominant PSNs and solid nodules with a solid portion diameter over 10 mm, independent (p < .05) predictors of pathologic LVI were peritumoral interstitial thickening (odds ratio [OR], 13.22) and pleural contact (defined as pleural contact measuring over one-quarter of the circumference of the nodule's solid portion) (OR, 2.45). Also among such nodules, peritumoral interstitial thickening achieved 80.4% sensitivity, 76.7% specificity, and 77.4% accuracy; pleural contact achieved 35.9% sensitivity, 82.5% specificity, and 74.3% accuracy; and presence of either feature achieved 90.2% sensitivity, 64.3% specificity, and 68.9% accuracy for predicting pathologic LVI. In patients undergoing sublobar resection, after adjusting for T category and operative type, recurrence-free survival (RFS) was independently (p < .05) predicted by solid-dominant PSN or solid nodule with a solid portion diameter over 10 mm also showing peritumoral interstitial thickening (hazard ratio [HR], 5.37) or also showing either peritumoral interstitial thickening or pleural contact (HR, 6.05). The interreader agreement kappa values were 0.67 for peritumoral interstitial thickening and 0.77 for pleural contact. CONCLUSION. Pathologic LVI occurred only in solid-dominant PSNs and solid nodules with solid portion over 10 mm. Among such nodules, peritumoral interstitial thickening and pleural contact independently predicted pathologic LVI and RFS. CLINICAL IMPACT. CT features may help select patients with stage IA NSCLC for sublobar resection rather than more extensive surgery.

Surgical outcomes of pulmonary metastasectomy in hepatocellular carcinoma patients according to approach method: thoracoscopic versus open approach.

BACKGROUND: The role of surgical intervention as a treatment for pulmonary metastasis (PM) from hepatocellular carcinoma (HCC) has not been established. In this study, we investigated the clinical outcomes of pulmonary metastasectomy. Using propensity score matching (PSM) analysis, we compared the results according to the surgical approach: video-assisted thoracic surgery (VATS) versus the open method. METHODS: A total of 134 patients (115 men) underwent pulmonary metastasectomy for isolated PM of HCC between January 1998 and December 2010 at Seoul Asan Medical Center. Of these, 84 underwent VATS (VATS group) and 50 underwent thoracotomy or sternotomy (open group). PSM analysis between the groups was used to match them based on the baseline characteristics of the patients. RESULTS: During the median follow-up period of 33.4 months (range, 1.8-112.0), 113 patients (84.3%) experienced recurrence, and 100 patients (74.6%) died of disease progression. There were no overall survival rate, disease-free survival rate, and pulmonary-specific disease-free survival rate differences between the VATS and the open groups (p = 0.521, 0.702, and 0.668, respectively). Multivariate analysis revealed local recurrence of HCC, history of liver cirrhosis, and preoperative alpha-fetoprotein level as independent prognostic factors for overall survival (hazard ratio, 1.729/2.495/2.632, 95% confidence interval 1.142-2.619/1.571-3.963/1.554-4.456; p = 0.010/< 0.001/< 0.001, respectively). CONCLUSIONS: Metastasectomy can be considered a potential alternative for selected patients. VATS metastasectomy had outcomes comparable to those of open metastasectomy.

Natural Progression of Ground-glass Nodules after Curative Resection for Non-small Cell Lung Cancer.

BACKGROUND: This retrospective study investigated the natural course of synchronous ground-glass nodules (GGNs) that remained after curative resection for non-small-cell lung cancer (NSCLC). METHODS: Prospectively collected retrospective data were reviewed concerning 2,276 patients who underwent curative resection for NSCLC between 2008 and 2017. High-resolution computed tomography or thin-section computed tomography data of 82 patients were included in the study. Growth in size was considered the most valuable outcome, and patients were grouped according to GGN size change. Patient demographic data (e.g., age, sex, and smoking history), perioperative data (e.g., GGN characteristics, histopathology and pathological stage of the resected tumours), and other medical history were evaluated in a risk factor analysis concerning GGN size change. RESULTS: The median duration of follow-up was 36.0 months (interquartile range, 23.0-59.3 months). GGN size decreased in 6 patients (7.3%), was stationary in 43 patients (52.4%), and increased in 33 patients (40.2%). In univariate analysis, male sex, the GGN size on initial CT, part-solid GGN and smoking history (≥ 10 pack-years) were significant risk factors. Among them, multivariate analysis revealed that lager GGN size, part-solid GGN and smoking history were independent risk factors. CONCLUSION: During follow-up, 40.2% of GGNs increased in size, emphasising that patients with larger GGNs, part-solid GGN or with a smoking history should be observed.

Experience of International Air Transportation and Subsequent Lung Transplant in a Patient with COVID-19-associated Acute Respiratory Distress Syndrome: a Case Report.

We report an inspiring case of a 55-year-old Korean female diagnosed with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) in Mexico. The patient was assessed for lung transplant as a salvage therapy for treatment-refractory ARDS following no signs of clinical improvement for > 7 weeks, despite best treatment. The patient was transported from Mexico to Korea by air ambulance under venovenous extracorporeal membrane oxygenation (ECMO) support. She was successfully bridged to lung transplant on day 88, 49 days after the initiation of ECMO support. ECMO was successfully weaned at the end of operation, and no bleeding or primary graft dysfunction was observed within the first 72 hours. The patient was liberated from mechanical ventilation on postoperative day 9 and transferred to the general ward 5 days later. Despite the high doses of immunosuppressants, there was no evidence of viral reactivation after transplant. At 3 months post-transplantation, she was discharged to home without complication. Our experience suggests that successful lung transplant for COVID-19-associated ARDS is feasible even in a patient with prolonged pre-transplant ECMO support. Lung transplant may be considered a salvage therapy for COVID-19-associated ARDS that does not respond to conventional treatments.

Volume Doubling Times of Lung Adenocarcinomas: Correlation with Predominant Histologic Subtypes and Prognosis.

Background The volume doubling time (VDT) is a key parameter in the differentiation of aggressive tumors from slow-growing tumors. How different histologic subtypes of primary lung adenocarcinomas vary in their VDT and the prognostic value of this measurement is unknown. Purpose To investigate differences in VDT between the predominant histologic subtypes of primary lung adenocarcinomas and to assess the correlation between VDT and prognosis. Materials and Methods This retrospective study included patients who underwent at least two serial CT examinations before undergoing operation between July 2010 and December 2018. Three-dimensional tumor segmentation was performed on two CT images and VDTs were calculated. VDTs were compared between predominant histologic subtypes and lesion types by using Kruskal-Wallis tests. Disease-free survival (DFS) was obtained in patients undergoing surgical procedures before July 2017. Univariable and multivariable Cox proportional hazards regression analyses were performed to determine predictors of DFS. Results Among 268 patients (mean age, 64 years ± 8 [standard deviation]; 143 men), there were 30 lepidic, 87 acinar, 109 papillary, and 42 solid or micropapillary predominant subtypes. The median VDT was 529 days (interquartile range, 278-872 days) for lung adenocarcinomas. VDTs differed across subtypes (P < .001) and were shortest in solid or micropapillary subtypes (229 days; interquartile range, 77-530 days). Solid lesions (VDT, 248 days) had shorter VDTs than subsolid lesions (part-solid lesions, 665 days; nonsolid lesions, 648 days) (P < .001). In the 148 patients (mean age, 64 years ± 8; 89 men) included in the survival analysis, 35 patients had disease recurrence and 17 patients died. VDT (<400 days) was an independent risk factor for poor DFS (hazard ratio, 2.6; P = .01) and higher TNM stage. Adding VDT to TNM stage improved model performance (C-index, 0.69 for TNM stage vs 0.77 for combined VDT class and TNM stage; P = .002). Conclusion Volume doubling times varied significantly according to the predominant histologic subtypes of lung adenocarcinoma and had additional prognostic value for disease-free survival. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Ko in this issue.

Outcome prediction in resectable lung adenocarcinoma patients: value of CT radiomics.

OBJECTIVES: Lung adenocarcinoma shows broad spectrum of prognosis and histologic heterogeneity. This study was to investigate the prognostic value of CT radiomics in resectable lung adenocarcinoma patients and assess its incremental value over clinical-pathologic risk factors. METHODS: This retrospective analysis evaluated 1058 patients who underwent curative surgery for lung adenocarcinoma (training cohort: N = 754; temporal validation cohort: N = 304). Radiomics features were extracted from preoperative contrast-enhanced CT. Radiomics signature to predict disease-free survival (DFS) and overall survival (OS) was generated. Association between the radiomics signature and prognosis were evaluated using univariable and multivariable Cox proportional hazards regression analyses. Incremental value of the radiomics signature beyond clinical-pathologic risk factors was assessed using concordance index (C-index). RESULTS: The radiomics signatures were independently associated with DFS (hazard ratio [HR], 1.920; p < 0.001) and OS (HR, 2.079; p < 0.001). The radiomics signature showed performance comparable to stage in estimation of DFS (C-index, 0.724 vs 0.685) and OS (0.735 vs 0.703). The radiomics added prognostic value to clinical-pathologic models (stage and histologic subtype) in predicting DFS (C-index, 0.764 vs 0.713; p < 0.001), which was also shown in the validation cohort (0.782 vs 0.734; p = 0.016). In terms of OS, including radiomics led to significant improvement in prognostic performance of the clinical-pathologic model (stage and age) in the training cohort (0.784 vs 0.737; p < 0.001), but the improvement was not significant in the validation cohort (0.805 vs 0.734; p = 0.149). CONCLUSIONS: CT radiomics was effective in predicting prognosis in lung adenocarcinoma patients, providing additional prognostic information beyond clinical-pathologic risk factors. KEY POINTS: • CT radiomics signature was an independent prognostic factor predicting disease-free and overall survival along with clinical risk factors of lung adenocarcinoma (stage, histologic subtype, and age). • CT radiomics added prognostic value to clinical-pathologic models (stage and subtype) in predicting disease-free survival (C-index for integrated model and clinical-pathologic model, 0.764 vs 0.713; p < 0.001), which was also proven in the validation cohort (0.782 vs 0.734; p = 0.016). • Integrated model incorporating radiomics signature can successfully stratify patients into high-risk, intermediate-, or low-risk groups in patients with resectable lung adenocarcinoma.

Recent Trends in Demographics, Surgery, and Prognosis of Patients with Surgically Resected Lung Cancer in a Single Institution from Korea.

BACKGROUND: Over the past few decades, demographics information has changed significantly in patients with surgically resected lung cancer. Herein, we evaluated the recent trends in demographics, surgery, and prognosis of lung cancer surgery in Korea. METHODS: Patients with surgically resected primary lung cancer from 2002 to 2016 were retrospectively analyzed. Multivariable Cox regression analysis was conducted to identify prognostic factors for overall survival. The annual percent change (APC) and statistical significance were calculated using the Joinpoint software. RESULTS: A total of 7,495 patients were enrolled. Over the study period, the number of lung cancer surgeries continued to increase (P < 0.05). The proportion of women to total subjects has also increased (P < 0.05). The proportion of elderly patients (≥ 70 years) as well as those with tumors measuring 1-2 cm and 2-3 cm significantly increased in both genders (all P < 0.05). The proportion of patients with adenocarcinoma, video-assisted thoracic surgery, sublobar resection, and pathological stage I significantly increased (P < 0.05). The 5-year overall survival rate of lung cancer surgery increased from 61.1% in 2002-2006 to 72.1% in 2012-2016 (P < 0.001). The operative period was a significant prognostic factor in multivariable Cox analysis (P < 0.001). CONCLUSION: The mean age of patients with lung cancer surgery increased gradually, whereas tumor size reduced. Prognosis of lung cancer surgery improved with recent increases in the frequency of adenocarcinoma, video-assisted thoracic surgery, sublobar resection, and pathological stage I. The operation period itself was also an independent prognostic factor for overall survival.

The First Living-Donor Lobar Lung Transplantation in Korea: a Case Report.

Lung transplantation is the only treatment for end-stage lung disease, but the problem of donor shortage is unresolved issue. Herein, we report the first case of living-donor lobar lung transplantation (LDLLT) in Korea. A 19-year-old woman patient with idiopathic pulmonary artery hypertension received her father's right lower lobe and her mother's left lower lobe after pneumonectomy of both lungs in 2017. The patient has recovered well and is enjoying normal social activity. We think that LDLLT could be an alternative approach to deceased donor lung transplantation to overcome the shortage of lung donors.