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.

CT-guided percutaneous transthoracic needle biopsy for anterior mediastinal lymphoma: the role of PET/CT.

BACKGROUND: Computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) is not recommended as the diagnostic modality of choice for anterior mediastinal lymphoma, despite its advantages of minimal invasiveness and easy accessibility. PURPOSE: To identify the modifiable risk factors for non-diagnostic results from CT-guided PTNB for anterior mediastinal lymphoma. MATERIAL AND METHODS: This retrospective study identified CT-guided PTNB for anterior mediastinal lesions diagnosed as lymphoma between May 2007 and December 2021. The diagnostic sensitivity and complications were investigated. The appropriateness of PTNB targeting was evaluated using positron emission tomography (PET)/CT and images from intra-procedural CT-guided PTNB. Targeting was considered inappropriate when the supposed trajectory of the cutting needle was within a region of abnormally low metabolism. The risk factors for non-diagnostic results were determined using logistic regression analysis. RESULTS: A total of 67 PTNBs in 60 patients were included. The diagnostic sensitivity for lymphoma was 76.1% (51/67), with an immediate complication rate of 4.5% (3/67). According to the PET/CT images, PTNB targeting was inappropriate in 10/14 (71.4%) of the non-diagnostic PTNBs but appropriate in all diagnostic PTNBs (P <0.001). Inappropriate targeting was the only significant risk factor for non-diagnostic results (odds ratio = 203.69; 95% confidence interval = 8.17-999.99; P = 0.001). The number of specimen acquisitions was not associated with non-diagnostic results (P = 0.40). CONCLUSIONS: Only inappropriate targeting of the non-viable portion according to PET/CT was an independent risk factor for non-diagnostic results. Acquiring PET/CT scans before biopsy and targeting the viable portion on PET/CT may help improve the diagnostic sensitivity of PTNB.

Sublobar resection in non-small cell lung cancer: patient selection criteria and risk factors for recurrence.

OBJECTIVE: To validate selection criteria for sublobar resection in patients with lung cancer with respect to recurrence, and to investigate predictors for recurrence in patients for whom the criteria are not suitable. METHODS: Patients who underwent sublobar resection for lung cancer between July 2010 and December 2018 were retrospectively included. The criteria for curative sublobar resection were consolidation-to-tumor ratio ≤0.50 and size ≤3.0 cm in tumors with a ground-glass opacity (GGO) component (GGO group), and size of ≤2.0 cm and volume doubling time ≥400 days in solid tumors (solid group). Cox regression was used to identify predictors for time-to-recurrence (TTR) in tumors outside of these criteria (non-curative group). RESULTS: Out of 530 patients, 353 were classified into the GGO group and 177 into the solid group. In the GGO group, the 2-year recurrence rates in curative and non-curative groups were 2.1 and 7.7%, respectively (p = 0.054). In the solid group, the 2-year recurrence rates in curative and non-curative groups were 0.0 and 28.6%, respectively (p = 0.03). Predictors of 2-year TTR after non-curative sublobar resection were pathological nodal metastasis (hazard ratio [HR], 6.63; p = 0.02) and lymphovascular invasion (LVI; HR, 3.28; p = 0.03) in the GGO group, and LVI (HR, 4.37; p < 0.001) and fibrosis (HR, 3.18; p = 0.006) in the solid group. CONCLUSION: The current patient selection criteria for sublobar resection are satisfactory. LVI was a predictor for recurrence after non-curative resection. ADVANCES IN KNOWLEDGE: This result supports selection criteria of patients for sublobar resection. LVI may help predict recurrence after non-curative sublobar resection.

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.

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.

Interstitial Lung Abnormalities at CT in the Korean National Lung Cancer Screening Program: Prevalence and Deep Learning-based Texture Analysis.

Background Interstitial lung abnormalities (ILAs) are associated with worse clinical outcomes, but ILA with lung cancer screening CT has not been quantitatively assessed. Purpose To determine the prevalence of ILA at CT examinations from the Korean National Lung Cancer Screening Program and define an optimal lung area threshold for ILA detection with CT with use of deep learning-based texture analysis. Materials and Methods This retrospective study included participants who underwent chest CT between April 2017 and December 2020 at two medical centers participating in the Korean National Lung Cancer Screening Program. CT findings were classified by three radiologists into three groups: no ILA, equivocal ILA, and ILA (fibrotic and nonfibrotic). Progression was evaluated between baseline and last follow-up CT scan. The extent of ILA was assessed visually and quantitatively with use of deep learning-based texture analysis. The Youden index was used to determine an optimal cutoff value for detecting ILA with use of texture analysis. Demographics and ILA subcategories were compared between participants with progressive and nonprogressive ILA. Results A total of 3118 participants were included in this study, and ILAs were observed with the CT scans of 120 individuals (4%). The median extent of ILA calculated by the quantitative system was 5.8% for the ILA group, 0.7% for the equivocal ILA group, and 0.1% for the no ILA group (P < .001). A 1.8% area threshold in a lung zone for quantitative detection of ILA showed 100% sensitivity and 99% specificity. Progression was observed in 48% of visually assessed fibrotic ILAs (15 of 31), and quantitative extent of ILA increased by 3.1% in subjects with progression. Conclusion ILAs were detected in 4% of the Korean lung cancer screening population. Deep learning-based texture analysis showed high sensitivity and specificity for detecting ILA with use of a 1.8% lung area cutoff value. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Egashira and Nishino in this issue.

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.

Air embolism in CT-guided transthoracic needle biopsy: emphasis on pulmonary vein injury.

OBJECTIVE: To assess whether pulmonary vein injury is detectable on CT and associated with air embolism after percutaneous transthoracic needle biopsy (PTNB) in a tertiary referral hospital. METHODS: Between January 2012 and November 2021, 11,691 consecutive CT-guided PTNBs in 10,685 patients were retrospectively evaluated. Air embolism was identified by reviewing radiologic reports. Pulmonary vein injury was defined as the presence of the pulmonary vein in the needle pathway or shooting range of the cutting needle with the presence of parenchymal hemorrhage. The association between pulmonary vein injury and air embolism was assessed using logistic regression analysis in matched patients with and without air embolism with a ratio of 1:4. RESULTS: A total of 27 cases of air embolism (median age, 67 years; range, 48-80 years; 24 men) were found with an incidence of 0.23% (27/11,691). Pulmonary vein injury during the procedures was identifiable on CT in 24 of 27 patients (88.9%), whereas it was 1.9% (2/108) for matched patients without air embolism The veins beyond the target lesion (70.8% [17/24]) were injured more frequently than the veins in the needle pathway before the target lesion (29.2% [7/24]). In univariable and multivariable analyses, pulmonary vein injury was associated with air embolism (odds ratio, 485.19; 95% confidence interval, 68.67-3428.19, p <.001). CONCLUSION: Pulmonary vein injury was detected on CT and was associated with air embolism. Avoiding pulmonary vein injury with careful planning of the needle pathway on CT may reduce air embolism risk. KEY POINTS: • Pulmonary vein injury during CT-guided biopsy was identifiable on CT in most of the patients (88.9% [24/27]). • The veins beyond the target lesion (70.8% [17/24]) were injured more frequently than the veins in the needle pathway before the target lesion (29.2% [7/24]). • Avoiding the distinguishable pulmonary vein along the pathway or shooting range of the needle on CT may reduce the air embolism risk.

Characteristics and outcomes of anterior mediastinal cystic lesions diagnosed on chest MRI: implications for management of cystic lesions.

BACKGROUND: Chest MRI is a useful diagnostic modality for the evaluation of anterior mediastinal lesions but the outcomes of anterior mediastinal cystic lesions diagnosed on chest MRI are unclear. METHODS: In this multicenter retrospective study, patients who underwent contrast-enhanced chest MRI in two tertiary centers to assess anterior mediastinal cystic lesions were included after excluding overt solid tumors and thymic hyperplasia. Anterior mediastinal cystic lesions were classified into two categories: probable (simple) cyst or indeterminate lesion (complex cyst). Size and imaging features of lesions during follow-up were evaluated and clinical outcomes were assessed. RESULTS: A total of 204 patients (mean age, 59 ± 11 years; M:F = 111:93) were studied; 186 (91.2%) were classified as probable cysts and 18 (8.8%) as indeterminate lesions on MRI. Among patients with probable cysts and more than 2 years of follow-up, lesion size was unchanged in 39.6% (36/91), decreased in 16.5% (15/91), and fluctuated in 8.8% (8/91). All patients who underwent surgery were confirmed cysts. None developed mural nodules or irregular wall thickening, suspicious for malignancy during follow-up. In patients with indeterminate lesions, 16.7% (3/18) had pathologically confirmed thymoma and 44.4% (8/18) had proven cysts. Follow-up numbers and intervals after MRI in patients with probable cysts were variable among physicians and institutions in clinical practice (p < 0.05) but more than half were followed for up to 2 years in two centers. CONCLUSION: Diagnosing anterior mediastinal cysts using MRI is reliable. MRI-based management of anterior mediastinal lesions may reduce the number of unnecessary follow-ups and surgeries.

Prognosis for Pneumonic-Type Invasive Mucinous Adenocarcinoma in a Single Lobe on CT: Is It Reasonable to Designate It as Clinical T3?

OBJECTIVE: To compare pneumonic-type invasive mucinous adenocarcinoma (pIMA) confined to a single lobe with clinical T2, T3, and T4 stage lung cancer without pathological node metastasis regarding survival after curative surgery and to identify prognostic factors for pIMA. MATERIALS AND METHODS: From January 2010 to December 2017, 41 patients (15 male; mean age ± standard deviation, 66.0 ± 9.9 years) who had pIMA confined to a single lobe on computed tomography (CT) and underwent curative surgery were identified in two tertiary hospitals. Three hundred and thirteen patients (222 male; 66.3 ± 9.4 years) who had non-small cell lung cancer (NSCLC) without pathological node metastasis and underwent curative surgery in one participating institution formed a reference group. Relapse-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox proportional hazard regression analysis was performed to identify factors associated with the survival of patients with pIMA. RESULTS: The 5-year RFS and OS rates in patients with pIMA were 33.1% and 56.0%, respectively, compared with 74.3% and 91%, 64.3% and 71.8%, and 46.9% and 49.5% for patients with clinical stage T2, T3, and T4 NSCLC in the reference group, respectively. The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 NSCLC and significantly worse than that of patients with clinical stage T3 NSCLC (p = 0.012). The differences in OS between patients with pIMA and those with clinical stage T3 or T4 NSCLC were not significant (p = 0.11 and p = 0.37, respectively). In patients with pIMA, the presence of separate nodules was a significant factor associated with poor RFS and OS {unadjusted hazard ratio (HR), 4.66 (95% confidence interval [CI], 1.95-11.11), p < 0.001 for RFS; adjusted HR, 4.53 (95% CI, 1.59-12.89), p = 0.005 for OS}. CONCLUSION: The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 lung cancer. Separate nodules on CT were associated with poor RFS and OS in patients with pIMA.

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.

Application of computer-aided diagnosis for Lung-RADS categorization in CT screening for lung cancer: effect on inter-reader agreement.

OBJECTIVES: To evaluate the effects of computer-aided diagnosis (CAD) on inter-reader agreement in Lung Imaging Reporting and Data System (Lung-RADS) categorization. METHODS: Two hundred baseline CT scans covering all Lung-RADS categories were randomly selected from the National Lung Cancer Screening Trial. Five radiologists independently reviewed the CT scans and assigned Lung-RADS categories without CAD and with CAD. The CAD system presented up to five of the most risk-dominant nodules with measurements and predicted Lung-RADS category. Inter-reader agreement was analyzed using multirater Fleiss κ statistics. RESULTS: The five readers reported 139-151 negative screening results without CAD and 126-142 with CAD. With CAD, readers tended to upstage (average, 12.3%) rather than downstage Lung-RADS category (average, 4.4%). Inter-reader agreement of five readers for Lung-RADS categorization was moderate (Fleiss kappa, 0.60 [95% confidence interval, 0.57, 0.63]) without CAD, and slightly improved to substantial (Fleiss kappa, 0.65 [95% CI, 0.63, 0.68]) with CAD. The major cause for disagreement was assignment of different risk-dominant nodules in the reading sessions without and with CAD (54.2% [201/371] vs. 63.6% [232/365]). The proportion of disagreement in nodule size measurement was reduced from 5.1% (102/2000) to 3.1% (62/2000) with the use of CAD (p < 0.001). In 31 cancer-positive cases, substantial management discrepancies (category 1/2 vs. 4A/B) between reader pairs decreased with application of CAD (pooled sensitivity, 85.2% vs. 91.6%; p = 0.004). CONCLUSIONS: Application of CAD demonstrated a minor improvement in inter-reader agreement of Lung-RADS category, while showing the potential to reduce measurement variability and substantial management change in cancer-positive cases. KEY POINTS: • Inter-reader agreement of five readers for Lung-RADS categorization was minimally improved by application of CAD, with a Fleiss kappa value of 0.60 to 0.65. • The major cause for disagreement was assignment of different risk-dominant nodules in the reading sessions without and with CAD (54.2% vs. 63.6%). • In 31 cancer-positive cases, substantial management discrepancies between reader pairs, referring to a difference in follow-up interval of at least 9 months (category 1/2 vs. 4A/B), were reduced in half by application of CAD (32/310 to 16/310) (pooled sensitivity, 85.2% vs. 91.6%; p = 0.004).

Identification of predictors for brain metastasis in newly diagnosed non-small cell lung cancer: a single-center cohort study.

OBJECTIVES: To identify clinical and staging chest CT characteristics predictive of brain metastasis in patients with newly diagnosed NSCLC dichotomized according to resectability. METHODS: Patients newly diagnosed with NSCLC of clinical stages II-IV between November 2017 and October 2018 were enrolled and classified into resectable (stage II+IIIA) and unresectable stages (stage IIIB/C+IV) according to chest CT. Associations of clinicopathological characteristics and CT findings with brain metastasis were analyzed using logistic regression. Predictive models were evaluated using receiver operating characteristics curve analysis. A subgroup analysis for unresectable-stage patients with known epidermal growth factor receptor gene (EGFR) mutation status was performed. RESULTS: This study included 911 NSCLC patients (mean age, 65 ± 11 years; 620 men), 194 of whom were diagnosed with brain metastasis. For resectable stages, independent predictors for brain metastasis were N2-stage (13 of 25 patients), absence of air-bronchogram/bubble lucency (23 of 25 patients), and presence of spiculation (15 of 25 patients), with a model combining the two imaging features showing an AUC of 0.723. In unresectable stages, independent predictors of brain metastasis were younger age, female sex, extrathoracic metastasis, and adenocarcinoma, with models combining these showing AUCs of 0.675-0.766. In the subgroup with known EGFR-mutation status, extrathoracic metastasis and positive EGFR mutation were independent predictors of brain metastasis, with the model showing AUCs of 0.641-0.732. CONCLUSION: CT-derived imaging features, clinical stages, lung cancer subtype, and EGFR mutation were associated with brain metastasis in patients with newly diagnosed NSCLC. The predictors were completely different between resectable and unresectable stages. KEY POINTS: • In resectable stages of NSCLC, two imaging features (absence of air-bronchogram/bubble lucency and presence of spiculation) and N2 stage were independent predictors of brain metastasis. • In unresectable stages of NSCLC, younger age, female sex, extrathoracic metastasis, and adenocarcinoma were associated with brain metastasis. • In the subgroup of NSCLC with known EGFR-mutation status, extrathoracic metastasis and positive EGFR mutation were independent predictors of brain metastasis.

Learning Curve for CT-Guided Percutaneous Transthoracic Needle Biopsy: Retrospective Evaluation Among 17 Thoracic Imaging Fellows at a Tertiary Referral Hospital.

BACKGROUND. CT-guided percutaneous transthoracic needle biopsy (PTNB) is widely used for evaluation of indeterminate pulmonary lesions, although guidelines are lacking regarding the experience needed to gain sufficient skill. OBJECTIVE. The purpose of our study was to investigate the learning curve among a large number of operators in a tertiary referral hospital and to determine the number of procedures required to obtain acceptable performance. METHODS. This retrospective study included CT-guided PTNBs with coaxial technique performed by 17 thoracic imaging fellows from March 2, 2011, to August 8, 2017, who were novices in the procedure. A maximum number of 200 consecutive procedures per operator were included. The cumulative summation method was used to assess learning curves for diagnostic accuracy, false-negative rate, pneumothorax rate, and hemoptysis rate. Operators were assessed individually and in a pooled analysis. Pneumothorax risk was also assessed in a model adjusting for risk factors. Acceptable failure rates were defined as 0.1 for diagnostic accuracy and false-negative rate, 0.45 for pneumothorax rate, and 0.05 for hemoptysis rate. RESULTS. The study included 3261 procedures in 3134 patients (1876 men, 1258 women; mean age, 67.7 ± 12.1 [SD] years). Overall diagnostic accuracy was 94.2% (2960/3141). All 17 operators achieved acceptable diagnostic accuracy (37 procedures required in the pooled analysis; median, 33 procedures required [range, 19-67 procedures required]). Overall false-negative rate was 7.6% (179/2370). All 17 operators achieved acceptable false-negative rate (52 procedures required in the pooled analysis; median, 33 procedures required [range, 19-95 procedures required]). Pneumothorax occurred in 32.6% of the procedures (1063/3261 procedures), and hemoptysis occurred in 2.7% of the procedures (89/3261 procedures). All 17 operators achieved acceptable pneumothorax rate (20 procedures required in the pooled analysis; median, 19 procedures required [range, 7-63 procedures required]). In the risk-adjusted model, 15 operators achieved acceptable pneumothorax rate (54 procedures required in the pooled analysis; median, 36 procedures required [range, 10-192 procedures required]). Sixteen operators achieved acceptable hemoptysis rate (67 procedures required in the pooled analysis; median, 55 procedures required [range, 41-152 procedures required]). CONCLUSION. For CT-guided PTNB, at least 37 and 52 procedures are required to achieve acceptable diagnostic accuracy and false-negative rate, respectively. Not all operators achieved acceptable complication rates. CLINICAL IMPACT. The findings may help set standards for training, supervision, and ongoing assessment of operator proficiency for this procedure.

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.

Prognostic performance in lung cancer according to tumor size: Comparison of axial, multiplanar, and 3-dimensional CT measurement to pathological size.

PURPOSE: This study aimed to compare the prognostic performance of clinical T staging based on axial, multiplanar, and 3-dimensional measurement on CT with that of pathological T staging in patients with non-small cell lung cancer. METHOD: Patients with surgically resected lung cancer without pathological node metastasis between June 2010 and December 2017 were retrospectively included. Clinical T stages were determined based on the maximal tumor size on axial, multiplanar (axial, coronal, and sagittal) images and 3-dimensional tumor mask. The prognostic performances of clinical and pathological T staging for disease-free survival (DFS) were compared using the concordance indices (C-indices). RESULTS: A total of 544 patients (64.7 ± 9.7 years, 352 men) were included; 160 patients (29.4%) experienced events including 29 (5.3%) who expired. The median DFS was 44.1 months. The mean tumor size on axial, multiplanar images, 3-dimensional tumor mask, and pathology was 30.8 ± 17.3, 33.9 ± 19.4, 39.2 ± 21.4, and 33.4 ± 18.0 mm, respectively. Clinical staging based on multiplanar measurement showed a higher agreement (67.5% [367/544]) with pathological staging than axial (60.5% [329/544]) and 3-dimensional measurement (50.9% [277/544]) based staging did (p = .0005 and <.0001, respectively). The adjusted C-indices of axial, multiplanar, 3-dimensional, and pathological tumor stages were 0.66 (95% confidence interval [CI]: 0.66-0.67), 0.66 (95% CI: 0.66-0.66), 0.67 (95% CI: 0.67-0.67), and 0.67 (95% CI: 0.66-0.67), respectively (p > .05). CONCLUSIONS: The prognostic performances of tumor staging according to size measurement methods were not significantly different. Multiplanar measurement may be preferable for clinical staging considering its highest agreement with pathological staging.

CT radiomics-based prediction of anaplastic lymphoma kinase and epidermal growth factor receptor mutations in lung adenocarcinoma.

PURPOSE: To develop and validate a CT-based radiomic model to simultaneously diagnose anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) mutation status of lung adenocarcinoma and to assess whether peritumoural radiomic features add value in the prediction of mutation status. METHODS: 503 patients with pathologically proven lung adenocarcinoma containing information on the mutation status were retrospectively included. Intratumoural and peritumoural radiomic features of the primary lesion were extracted from CT. We proposed two-level stepwise binary radiomics-based classification models to diagnose ALK (step1) and EGFR mutation status (step2). The performance of proposed models and added value of peritumoural radiomic features were evaluated by using the areas under receiver operating characteristic curves (AUC) and Obuchowski index in the development and validation sets. RESULTS: Regarding the prediction of ALK rearrangement, the diagnostic performance of the intratumoural radiomic model showed the AUC of 0.77 and 0.68 for the development and validation sets, respectively. As for EGFR mutation, the diagnostic performance of the intratumoural radiomic model showed the AUCs of 0.64 and 0.62 for the development and validation sets, respectively. The radiomics added value to the model based on clinical features (development set [radiomics + clinical model vs. clinical model]: Obuchowski index, 0.76 vs. 0.66, p < 0.001; validation set: 0.69 vs. 0.61, p = 0.075). Adding peritumoural features resulted in no improvement in terms of model performance. CONCLUSION: The CT radiomics-based model allowed the simultaneous prediction of the presence of ALK and EGFR mutations while adding value to the clinical features.

Usefulness of 3D-surgical guides in breast conserving surgery after neoadjuvant treatment.

We used 3D printed-breast surgical guides (3DP-BSG) to designate the original tumor area from the pre-treatment magnetic resonance imaging (MRI) during breast-conserving surgery (BCS) in breast cancer patients who received neoadjuvant systemic therapy (NST). Targeting the original tumor area in such patients using conventional localization techniques is difficult. For precise BCS, a method that marks the tumor area found on MRI directly to the breast is needed. In this prospective study, patients were enrolled for BCS after receiving NST. Partial resection was performed using a prone/supine MRI-based 3DP-BSG. Frozen biopsies were analyzed to confirm clear tumor margins. The tumor characteristics, pathologic results, resection margins, and the distance between the tumor and margin were analyzed. Thirty-nine patients were enrolled with 3DP-BSG for BCS. The median nearest distance between the tumor and the resection margin was 3.9 cm (range 1.2-7.8 cm). Frozen sections showed positive margins in 4/39 (10.3%) patients. Three had invasive cancers, and one had carcinoma in situ; all underwent additional resection. Final pathology revealed clear margins. After 3-year surveillance, 3/39 patients had recurrent breast cancer. With 3DP-BSG for BCS in breast cancer patients receiving NST, the original tumor area can be identified and marked directly on the breast, which is useful for surgery. Trial Registration: Clinical Research Information Service (CRIS) Identifier Number: KCT0002272. First registration number and date: No. 1 (27/04/2016).

Use of a Commercially Available Deep Learning Algorithm to Measure the Solid Portions of Lung Cancer Manifesting as Subsolid Lesions at CT: Comparisons with Radiologists and Invasive Component Size at Pathologic Examination.

Background The solid portion size of lung cancer lesions manifesting as subsolid lesions is key in their management, but the automatic measurement of such lesions by means of a deep learning (DL) algorithm needs evaluation. Purpose To evaluate the performance of a commercially available DL algorithm for automatic measurement of the solid portion of surgically proven lung adenocarcinomas manifesting as subsolid lesions. Materials and Methods Surgically proven lung adenocarcinomas manifesting as subsolid lesions on CT images between January 2018 and December 2018 were retrospectively included. Five radiologists independently measured the maximal axial diameter of the solid portion of lesions. The DL algorithm automatically segmented and measured the maximal axial diameter of the solid portion. Reader measurements, software measurements, and invasive component size at pathologic examination were compared by using intraclass correlation coefficient (ICC) and Bland-Altman plots. Results A total of 448 patients (mean age, 63 years ± 10 [standard deviation]; 264 women) with 448 lesions were evaluated (invasive component size, 3-65 mm). The measurement agreements between each radiologist and the DL algorithm were very good (ICC range, 0.82-0.89). When a radiologist was replaced with the DL algorithm, the ICCs ranged from 0.87 to 0.90, with an ICC of 0.90 among five radiologists. The mean difference between the DL algorithm and each radiologist ranged from -3.7 to 1.5 mm. The widest 95% limit of agreement between the DL algorithm and each radiologist (-15.7 to 8.3 mm) was wider than pairwise comparisons of radiologists (-7.7 to 13.0 mm). The agreement between the DL algorithm and invasive component size at pathologic evaluation was good, with an ICC of 0.67. Measurements by the DL algorithm (mean difference, -6.0 mm) and radiologists (mean difference, -7.5 to -2.3 mm) both underestimated invasive component size. Conclusion Automatic measurements of solid portions of lung cancer manifesting as subsolid lesions by the deep learning algorithm were comparable with manual measurements and showed good agreement with invasive component size at pathologic evaluation. © RSNA, 2021 Online supplemental material is available for this article.