Part-solid Nodules Research Articles

The Impact of Extended Delayed Surgery for Indolent Lung Cancer or Part-Solid Ground Glass Nodules

BackgroundDuring the COVID-19 pandemic, patients with lung cancer may experience treatment delays. The objective of this study was to evaluate the impact of extended treatment delays on survival among patients with stage I typical bronchopulmonary carcinoid (BC), lepidic predominant adenocarcinoma (LPA) or invasive adenocarcinoma with a lepidic component (ADL). MethodsUsing National Cancer Database data (2004-2015), multivariable Cox regression analysis with penalized smoothing splines was performed to examine the association between treatment delay and all-cause mortality for stage I BC, LPA, and ADL. Propensity score–matched analyses compared the overall survival of patients who received “early” vs “delayed” surgery (ie, 0-30 vs 90-120 days after diagnosis) across the different histologic subtypes. ResultsDuring the study period, patients with stage I BC (n = 4947), LPA (n = 5340), and ADL (n = 6816) underwent surgery. Cox regression analysis of these cohorts showed a gradual steady increase in the hazard ratio the longer treatment is delayed. However, in propensity score–matched analyses that created cohorts of patients who underwent early and delayed surgery that were well-balanced in patient characteristics, no significant differences in 5-year survival were found between early and delayed surgery for stage I BC (87% [95% CI:77%-93%] vs 89% [95% CI: 80%-94%]), stage I LPA (73% [95% CI: 64%-80%] vs 77% [95% CI: 68%-83%]), and stage I ADL (71% [95% CI: 64%-76%] vs 69% [95% CI: 60%-76%]). ConclusionsDuring the COVID-19 pandemic, for early-stage indolent lung tumors and part-solid ground glass lung nodules, a delay of surgery by 3-4 months after diagnosis can be considered.

Progress in diagnosis and treatment of lung adenocarcinomas imaging manifesting as radiological part-solid nodule

The incidence and mortality of lung cancer ranked the first in China. China had 787, 000 new cases of lung cancer in 2015, and a majority of these patients with advanced lung cancer. With the development and popularization of high-resolution computed tomography, more and more early-stage lung adenocarcinomas are found in screening. The imaging finding of early-stage lung adenocarcinomas often manifests as part solid nodule (PSN) containing ground glass opacity (GGO). Although the imaging manifestation of the nodules can't accurately predict the pathologic type of nodules, the parts of solid nodule and GGO still have some pathologic indications, and the prognostic evaluation effect of the maximum diameter of PSN is superior to that of the whole nodule. With the development of the molecular radiography and molecular pathology, the relationship of imaging manifestation of the PSN and metastasis were focused on. Some PSNs with special nature are more active and rapidly progressed than the pure GGOs. While compared to the pure solid nodules, the aggressiveness of PSNs are insufficient, with lower metastatic rates of lymph node and better prognoses. Currently, international acknowledge recommends to take active intervention measure for PSNs which are highly suspected to be malignant. We focus on the diagnosis and treatment of PSNs, systemically depict their staging, follow-up, surgical treatment, gene detection and immunotherapy.

Value of PET/CT Combined with CT Three-dimensional Reconstruction in Distinguishing Different Pathological Subtypes of Early Lung Adenocarcinoma

背景与目的早期肺腺癌中病理亚型以贴壁为主型的浸润性腺癌（lepidic predominant invasive adenocarcinoma, LPA）与原位腺癌（adenocarcinoma in situ, AIS）、微浸润性腺癌（microinvasive adenocarcinoma, MIA）的良好预后相似，临床上也迫切需要能够区分LPA与非LPA型浸润性腺癌（non-lepidic predominant invasive adenocarcinoma, non-LPA）的手段，本研究拟通过正电子发射型计算机断层显像（positron emission computed tomography, PET）/计算机断层扫描（computed tomography, CT）的最大标准化摄取值（maximal standard uptake value, SUVmax）和CT三维重建后参数探讨术前影像学表现为部分实性结节（part-solid nodules, PSNs）的早期肺腺癌不同病理亚型间的关系。方法回顾性分析2016年1月-2019年1月于江苏省苏北人民医院胸外科行解剖性肺切除术且影像学表现为PSNs的早期肺腺癌患者资料，所有患者胸部增强CT和PET/CT资料完整可获取，利用Mimics软件行三维重建，获取肿瘤体积、肿瘤三维平均CT值（3-dimensional mean-CT value, 3Dm-CT）、SUVmax等数据，采用SPSS 25.0进行统计分析，GraphPad Prism 8.3.0绘制受试者工作曲线（receiver operating curve, ROC），P < 0.05为差异有统计学意义。结果最终共计67例患者纳入本研究，按病理亚型不同将所有患者分为两组，AIS、MIA及浸润性腺癌（invasive adenocarcinoma, IAC）中的LPA归为低危组28例（41.8%），其余non-LPA如腺泡型（acinar pattern-predominant adeno-carcinoma, APA）、乳头型（papillary pattern-predominant adenocarcinoma, PPA）、微乳头型（micropapillary pattern-predominant adeno-carcinoma, MPA）归为高危组39例（58.2%），两组间SUVmax（t=3.153, P=0.002）、肿瘤体积（t=3.331, P=0.001)、实性/磨玻璃成分体积（t=2.74, P=0.006) /（t=3.127, P=0.002）、实性/磨玻璃成分3Dm-CT（t=3.655, P < 0.001) /（t=7.082, P < 0.001) 均具有显著统计学意义。ROC曲线提示：SUVmax[曲线下面积（area under curve, AUC）=0.727]、肿瘤体积（AUC=0.740）、磨玻璃成分体积（AUC=0.725）、实性成分3Dm-CT（AUC=0.763）、磨玻璃成分3Dm-CT（AUC=0.756）预测效能最佳。将上述AUC > 0.7的协变量纳入多因素ROC曲线分析，获得联合预测因子（AUC=0.835）具有中等以上预测价值。结论PET/CT中SUVmax和CT三维重建参数与影像学表现为PSNs的早期肺腺癌的不同病理亚型具有显著相关性，联合SUVmax、肿瘤体积、磨玻璃成分体积和实性/磨玻璃成分3Dm-CT对鉴别表现为PSNs的早期肺腺癌的病理亚型具有一定价值。

Decreasing Prevalence of Benign Etiology in Resected Lung Nodules Suspicious for Lung Cancer over the Last Decade

This study investigated treatment strategy for suspicious lung cancer with postoperatively proven benign etiology. In this retrospective study, we collected patients who underwent pulmonary resection for radiologically suspected lung cancer from 2010 to 2019 at Department of Thoracic Surgery, Fudan University Shanghai Cancer Center (FUSCC). Radiological features, preoperative follow-up time, preoperative pathology and postoperative pathology of these patients were documented. We classified resected benign lesions based on paraffin section and compared the therapy management performed on indeterminate lung nodules of 2 time periods (2010-2014 vs 2015-2019). 17,188 patients were included in this cohort and 1,381 (8.03%) cases were postoperatively proved to be benign lesions. Resected benign lesions proportion significantly decreased by years, from 14.5-6.2%. The respective resected benign lesions proportions for pure GGO nodules, part solid nodules and solid nodules were 5.3%, 3.0% and 11.7%. The resected benign lesions rate for patients with longer preoperative follow-up time was much lower (p < 0.001). Among the benign lesions, 14.2% were benign tumors, 25.7% were granulomatous, 30.2% were pneumonia, 18.0% were fibrosis and 11.9% were other types. If we consider that resections for granulomatous and pneumonia radiologically featured as solid nodules exceeding 2 cm, benign tumor and inflammatory pseudotumor are therapeutic, the nontherapeutic pulmonary resection rate is 4.26%. For patients with GGO nodules, the median preoperative follow-up time increased with the time being and the resected benign rate in period 2 (2015-2019) was significantly lower than that in period 1 (2010-2014). Wedge resection was the most common surgery strategy especially for small nodules and no matter for small or large nodules, the frequency of sublobar resection in period 2 was higher than that in period 1. The resected benign lesions rate at our department was relatively low and decreasing over the last decade. Meanwhile, our follow-up and surgical strategy improved over time. For patients with GGO nodules, 4-6months preoperative follow-up is recommended to avoid surgical intervention for benign lesions. For solid nodules with inconclusive diagnosis, limited resection should be first considered to maintain the balance between reducing the risk of cancer progressing and minimizing the resection for benign lesions.

Preoperative computed tomographic-guided percutaneous coil localization of pulmonary nodules: 184 Cases in Single-center.

The aim of this study was to evaluate the feasibility, accuracy, and safety of computed tomographic (CT)-guided coil localization before video-assisted thoracoscopic surgery. One hundred and eighty-four consecutive patients with 200 pulmonary nodules who underwent CT-guided percutaneous coil localization before thoracoscopic surgery were retrospectively analyzed in this study. Success rate for localization, complication rates, CT findings, and pathological results of the lesions, as well as the data related to surgery were all recorded and analyzed. All 184 patients with 200 lesions completed localization and resection. The success rate of the coil localization on lesion baseline was 99.0% (198/200) and 98.9% (182/184) on patient baseline. The number of wedge resection, segmental resection, and lobectomy were 179 (89.5%), 19 (9.5%), and 2 (1.0%), respectively. The malignancy rates in a lesion-based analysis were 83.5% (91.1% in ground-glass nodules, 91.4% in part-solid nodules, and 37.9% in solid nodules). No serious complications occurred in all localization procedures. Preoperative CT-guided percutaneous coil localization is a safe and effective method to facilitate high success rates for both wedge and segmental resection for peripheral pulmonary nodules.

CT-Detected Subsolid Nodules: A Predictor of Lung Cancer Development at Another Location?

Simple SummaryThe risk assessment of pulmonary nodules on chest computed tomography (CT) is key to the early detection of lung cancer. Whereas a nodule’s morphological characteristics are strong predictors of malignancy for that individual nodule, it remains unclear whether the frequency and CT features of pulmonary nodules contribute to the prediction accuracy of future development of LC in another location. This was found by performing risk prediction modelling using age, sex, and CT measures from lung-cancer-free scans as predictors. We found that a greater number of part-solid and ground-glass nodules in the earliest scan was linearly associated with a higher risk of lung cancer developing in another location in the future. There were also indications that CT biomarkers of other pulmonary and heart diseases are risk factors for lung cancer. Our findings endorse the utilization of information from the entire scan to improve the accuracy of lung risk assessment.The purpose of this case–cohort study was to investigate whether the frequency and computed tomography (CT) features of pulmonary nodules posed a risk for the future development of lung cancer (LC) at a different location. Patients scanned between 2004 and 2012 at two Dutch academic hospitals were cross-linked with the Dutch Cancer Registry. All patients who were diagnosed with LC by 2014 and a random selection of LC-free patients were considered. LC patients who were determined to be LC-free at the time of the scan and all LC-free patients with an adequate scan were included. The nodule count and types (solid, part-solid, ground-glass, and perifissural) were recorded per scan. Age, sex, and other CT measures were included to control for confounding factors. The cohort included 163 LC patients and 1178 LC-free patients. Cox regression revealed that the number of ground-glass nodules and part-solid nodules present were positively correlated to future LC risk. The area under the receiver operating curve of parsimonious models with and without nodule type information were 0.827 and 0.802, respectively. The presence of subsolid nodules in a clinical setting may be a risk factor for future LC development in another pulmonary location in a dose-dependent manner. Replication of the results in screening cohorts is required for maximum utility of these findings.

Subsolid Lung Adenocarcinomas: Radiological, Clinical and Pathological Features and Outcomes

Lung adenocarcinomas manifesting as subsolid nodules usually have a favorable prognosis. This study aimed to have a comprehensive investigation of the radiological and clinicopathologic features and oncological outcomes of subsolid nodules. Between March 2010 and December 2015, 865 patients with surgically resected clinical IA subsolid lung adenocarcinoma were retrospectively reviewed. Patients were classified into the pure ground-glass nodules (GGN) (pGGN [n=358], without solid component on lung and mediastinal windows), heterogeneous GGN (hGGN [n=65], only with solid components on lung window), and real part-solid nodule (rPSN [n=442], with solid component on both lung and mediastinal windows) groups. The clinicopathological features and survival time of the three groups were compared between groups. There was a significant increase in median tumor size (P < 0.001), solid component size measured at lung window (LW-SCS) (P < 0.001), and the proportion of invasive adenocarcinoma subtypes (P < 0.001) from pGGNs to hGGNs to rPSNs. After adjustment for LW-SCS, adenocarcinomas with predominant lepidic patterns were still more common in hGGNs than in rPSNs (P=0.009). Patients with rPSNs had a significantly worse recurrence-free survival (RFS) than those with pGGNs and hGGNs (5-year: 91.9% versus 100% versus 100%, P < 0.001). Multivariate Cox analyses revealed that gender (both P < 0.05) and clinical T category (based on lung window [LW-cT] [P=0.002] or mediastinal window [MW-cT] [P < 0.001]) were independent prognostic factors of RFS in the rPSN group. HGGNs represented as an intermediate subtype between pGGNs and rPSNs. Both pGGNs and hGGNs had excellent outcomes, while rPSNs exhibited a worse prognosis than them. Clinical T category and gender had prognostic implications for rPSNs.

Should resection extent be decided by total lesion size or solid component size in ground glass opacity-containing lung adenocarcinomas?

BackgroundIndication for sublobar resections in early-stage lung adenocarcinomas has been controversial. The purpose of this study was to find appropriate selection criteria for sublobar resections in ground glass opacity (GGO)-containing early-stage lung adenocarcinomas.MethodsWe retrospectively studied 985 consecutive patients with clinical stage IA, peripheral GGO-containing lung adenocarcinomas ≤3 cm in size. According to their radiological appearance, they were divided into a pure GGO group and a part-solid nodule (PSN) group. The PSN group was further divided into a GGO-predominant subgroup and a solid-predominant subgroup. Propensity-score matching (PSM) was conducted first in PSNs with similar total lesion size and then in those with similar solid component size to eliminate potential confounders. Histological characteristics and prognosis were compared between matched patients to investigate the prognostic value of total lesion size and solid component size. Then solid component size was chosen as the selection criterion to compare the prognosis of patients receiving lobectomy or sublobar resections.ResultsComparing to PSNs, pure GGO lesions had significantly more favorable histological characteristics and prognosis, with 100% 5-year overall survival (OS), even though 33.3% of patients with pure GGO lesions >20 mm in total lesion size received sublobar resections. For 157 pairs of PSNs with similar total lesion size but different solid component size after the first PSM, the solid-predominant subgroup had significantly worse histological characteristics and prognosis than the GGO-predominant subgroup. After the second PSM, histological characteristics and prognosis were comparable between 73 pairs of PSNs with similar solid component size but different total lesion size. Multivariable analysis showed that solid component size, rather than total lesion size or consolidation-to-tumor ratio (CTR), was an independent prognostic factor. For PSNs containing solid component size ≤2 cm, relapse-free survival (RFS) was similar after sublobar resections or lobectomy (95.0% vs. 93.6%, P=0.592). The results remained similar for PSNs of total lesion size >2 cm but solid component size ≤2 cm (88.9% vs. 90.0%, P=0.893).ConclusionsSolid component size better predicts histological characteristics and prognosis than total lesion size in early-stage GGO-containing lung adenocarcinomas. Instead of total lesion size, solid component size ≤2 cm may be a more appropriate selection criterion for sublobar resections in such patients.

Fast fully automatic detection, classification and 3D reconstruction of pulmonary nodules in CT images by local image feature analysis

This study develops a computer-aided diagnosis (CAD) system for automatic detection and classification of pulmonary nodules in lung computed tomography (CT) images, which can simultaneously detect and classify ground-glass opacity (GGO), part-solid, and solid nodules. From the morphological feature and local image features of pulmonary nodules, a total of ten features were selected for artificial neural network (ANN) training and testing, to ensure the system can detect and classify pulmonary nodules. Then, the cross-sectional area of each slice of pulmonary nodule was extracted. The response evaluation criteria in solid tumor (RECIST) value was obtained using the Euclidean distance formula, and the number of pixels of the maximum cross-sectional area was counted for area computation. The nodule volume and 3D reconstruction was obtained using the marching cube algorithm and Riemann integral formula. The sensitivity of system detection and classification were 93.13% and 92.70%, respectively. The proposed system can detect GGO, part-solid, and solid nodules, and takes only 0.1 s to process a single image. This study used the clay model imitating pulmonary nodule morphology as physical samples. Each physical sample underwent three CT. The average difference between the physical volume and the volume derived from this study was 0.37%. The detection and classification results of the system enhanced the clinical detection of missing nodules. 3D reconstruction and volume information of the nodules can give their volume doubling time and growth rate when the patient undergoes CT for the second time, thus enhancing the effect of diagnosis and treatment.

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.

Narrative review of optimal prognostic radiological tools using computed tomography for T1N0-staged non-small cell lung cancer.

Various radiological tools can predict the prognosis of non-small cell lung cancer (NSCLC). In this study, we evaluated the prognostic effect of different radiological tools such as whole tumor size (WTS), consolidation size (CS), consolidation tumor ratio (CTR), tumor disappearance ratio (TDR), mediastinal diameter (MD), and ground glass opacity (GGO) using high-resolution computed tomography (HRCT). We reviewed recent retrospective studies on the predictive effect of these radiological tools on disease-free survival (DFS) and overall survival (OS) in patients with T1N0-staged NSCLC. We searched PubMed and the British Library databases for the English literature published from January 2010 to December 2020 and generated a total of 32 publications (NSCLC, n=16; adenocarcinoma, n=16). The TNM classification version 7 was used in 18 studies, and version 8 in 14 studies. The evaluated radiological parameters were WTS, CS including T category, CTR, TDR, MD, presence of GGO, GGO ratio, and pure GGO. This review suggested that CS, MD, and the presence of GGO are optimal prognostic radiological tools for cT1N0-Staged NSCLC. CTR or TDR for part solid nodules (PSNs) is not a well-accepted prognostic factor. Further investigations are required to differentiate between benign scars and malignant components on HRCT and evaluate the prognosis of PSNs (1< CS ≤2 cm) with large WTS in the future.

Artificial intelligence-based vessel suppression for detection of sub-solid nodules in lung cancer screening computed tomography.

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) helps early lung cancer detection, commonly presenting as small pulmonary nodules. Artificial intelligence (AI)-based vessel suppression (AI-VS) and automatic detection (AI-AD) algorithm can improve detection of subsolid nodules (SSNs) on LDCT. We assessed the impact of AI-VS and AI-AD in detection and classification of SSNs [ground-glass nodules (GGNs) and part-solid nodules (PSNs)], on LDCT performed for LCS. Following regulatory approval, 123 LDCT examinations with sub-solid pulmonary nodules (average diameter ≥6 mm) were processed to generate three image series for each examination-unprocessed, AI-VS, and AI-AD series with annotated lung nodules. Two thoracic radiologists in consensus formed the standard of reference (SOR) for this study. Two other thoracic radiologists (R1 and R2; 5 and 10 years of experience in thoracic CT image interpretation) independently assessed the unprocessed images alone, then together with AI-VS series, and finally with AI-AD for detecting all ≥6 mm GGN and PSN. We performed receiver operator characteristics (ROC) and Cohen's Kappa analyses for statistical analyses. On unprocessed images, R1 and R2 detected 232/310 nodules (R1: 114 GGN, 118 PSN) and 255/310 nodules (R2: 122 GGN, 133 PSN), respectively (P>0.05). On AI-VS images, they detected 249/310 nodules (119 GGN, 130 PSN) and 277/310 nodules (128 GGN, 149 PSN), respectively (P≥0.12). When compared to the SOR, accuracy (AUC) for detection of PSN on the AI-VS images (AUC 0.80-0.81) was greater than on the unprocessed images (AUC 0.70-0.76). AI-VS images enabled detection of solid components in five nodules deemed as GGN on the unprocessed images. Accuracy of AI-AD was lower than both the radiologists (AUC 0.60-0.72). AI-VS improved the detection and classification of SSN into GGN and PSN on LDCT of the chest for the two radiologist (R1 and R2) readers.

Is flexible bronchoscopy necessary in the preoperative workup of patients with peripheral cT1N0 subsolid lung cancer? -a prospective multi-center cohort study.

BackgroundNecessity of flexible bronchoscopy (FB) examination as a routine preoperative work-up for peripheral clinical T1N0 subsolid lung cancer was unknown.MethodsThis was a prospective, multi-center clinical trial (NCT03591445). Patients with peripheral GGO nodules (GGNs) who were candidates for surgical resection were enrolled. FB examination was performed preoperatively. Surgical plan could be changed if any aberrant histologic and anatomic findings were detected by FB examination. Primary endpoint was the rate that surgical plan was changed by positive FB findings. Secondary endpoints were rate of positive FB findings and rate of procedural complications.ResultsSix hundred and fifteen patients with peripheral subsolid nodules detected by thoracic CT were enrolled. There were 187 (30.4%) male and 428 (69.6%) female patients, mean age was 54.85±10.41 y (range, 26–78). 262 (42.6%) patients had pure GGNs and 353 (57.4%) patients had part-solid nodules. Mean size of nodules was 13.87±6.37 mm (range, 5–30). FB examinations confirmed one (0.16%) adenocarcinoma, seven (1.14%) bronchial variations, one (0.16%) segmental bronchostenosis, one (0.16%) segmental bronchial occlusion and one (0.16%) bronchial inflammation. No complications of FB examinations occurred. 568 (92.35%) thoracoscopic and 47 (7.65%) open surgeries were performed. No established surgical plan was changed by positive FB findings. Final pathologies revealed 26 (4.2%) adenocarcinoma in situ (AIS), 240 (39%) minimal invasive adenocarcinomas (MIAs), 343 (55.8%) invasive adenocarcinomas (IADs), one (0.2%) adenosquamous cell carcinoma, one (0.2%) squamous cell carcinoma, two (0.3%) atypical adenoid hyperplasia and two (0.3%) inflammations.ConclusionsFB examination was unnecessary in the preoperative assessment of peripheral clinical T1N0 subsolid lung cancer.

Interobserver variability in Lung CT Screening Reporting and Data System categorisation in subsolid nodule-enriched lung cancer screening CTs.

To assess interobserver agreement in Lung CT Screening Reporting and Data System (Lung-RADS) categorisation in subsolid nodule-enriched low-dose screening CTs. A retrospective review of low-dose screening CT reports from 2013 to 2017 using keyword searches for subsolid nodules identified 54 baseline CT scans. With an additional 108 negative screening CT scans, a total of 162 CT scans were categorised according to the Lung-RADS by two fellowship-trained thoracic radiologists in consensus. We randomly selected 20, 20, 10, and 10 scans from categories 1/2, 3, 4A, and 4B CT scans, respectively, to ensure balanced category representation. Five radiologists classified the 60 CT scans into Lung-RADS categories. The frequencies of concordance and minor and major discordance were calculated, with major discordance defined as at least 6 months of management discrepancy. We used Cohen's κ statistics to analyse reader agreement. An average of 60.3% (181 of 300) of all cases and 45.0% (90 of 200) of positive screens were correctly categorised. The minor and major discordance rates were 12.3% and 27.3% overall and 18.5% and 36.5% in positive screens, respectively. The concordance rate was significantly higher among experienced thoracic radiologists. Overall, the interobserver agreement was moderate (mean κ, 0.45; 95% confidence interval: 0.40-0.51). The proportion of part-solid risk-dominant nodules was significantly higher in cases with low rates of accurate categorisation. This retrospective study observed variable accuracy and moderate interobserver agreement in radiologist categorisation of subsolid nodules in screening CTs. This inconsistency may affect management recommendations for lung cancer screening. • Diagnostic performance for Lung-RADS categorisation is variable among radiologists with fair to moderate interobserver agreement in subsolid nodule-enriched CT scans. • Experienced thoracic radiologists showed more accurate and consistent Lung-RADS categorisation than radiology residents. • The relative abundance of part-solid nodules was a potential factor related to increased disagreement in Lung-RADS categorisation.

Clinical Significance of Lung-RADS Category 3 Lesions in the National Lung Screening Trial

IntroductionTo determine the clinical significance of category 3 (CAT3) abnormalities and the necessity of a 6-month follow-up computed tomography (CT). We also explored features associated with increased lung cancer risk. MethodsFrom the National Lung Screening Trial database, we identified participants with CAT3 lesions at prevalence screen. Rates of lung cancer and lung cancer-specific deaths (LSDs) were compared between those who underwent first follow-up CT before 6 months (early diagnostic group) and those who underwent annual screening (annual diagnostic group). We estimated the change in LSD if the 6-month CT was eliminated. Regression analysis was performed to identify features associated with participants with CAT3 who developed lung cancer. ResultsA total of 1763 CAT3s were identified (6.6% of all participants who had low-dose CT), with 108 lung cancers (6.1%) and 41 LSDs (2.3%) in a 7-year period. Rates of lung cancer (7.5% versus 3.1%) and LSD (4.0% versus 1.0%) were higher in the early diagnostic group than in the annual diagnostic group. We estimated an increase in LSD of 0.6% of all participants with CAT3 (24.4% of all LSDs) if the 6-month CT was not performed. Multivariate regression analysis found that increased age, emphysema, and a part-solid nodule greater than 5 mm were associated with participants with CAT3 who developed lung cancer. ConclusionsCAT3 lesions are uncommon, and eliminating the 6-month CT would potentially increase LSD by 0.6% of all patients with CAT3. Age, emphysema, and part-solid nodule greater than 5 mm may be useful in risk prediction models to determine which participants with CAT3 are more likely to develop lung cancer and suggest which patients may need more intense follow-up.

LNDb challenge on automatic lung cancer patient management.

Lung cancer is the deadliest type of cancer worldwide and late detection is the major factor for the low survival rate of patients. Low dose computed tomography has been suggested as a potential screening tool but manual screening is costly and time-consuming. This has fuelled the development of automatic methods for the detection, segmentation and characterisation of pulmonary nodules. In spite of promising results, the application of automatic methods to clinical routine is not straightforward and only a limited number of studies have addressed the problem in a holistic way. With the goal of advancing the state of the art, the Lung Nodule Database (LNDb) Challenge on automatic lung cancer patient management was organized. The LNDb Challenge addressed lung nodule detection, segmentation and characterization as well as prediction of patient follow-up according to the 2017 Fleischner society pulmonary nodule guidelines. 294 CT scans were thus collected retrospectively at the Centro Hospitalar e Universitrio de So Joo in Porto, Portugal and each CT was annotated by at least one radiologist. Annotations comprised nodule centroids, segmentations and subjective characterization. 58 CTs and the corresponding annotations were withheld as a separate test set. A total of 947 users registered for the challenge and 11 successful submissions for at least one of the sub-challenges were received. For patient follow-up prediction, a maximum quadratic weighted Cohen's kappa of 0.580 was obtained. In terms of nodule detection, a sensitivity below 0.4 (and 0.7) at 1 false positive per scan was obtained for nodules identified by at least one (and two) radiologist(s). For nodule segmentation, a maximum Jaccard score of 0.567 was obtained, surpassing the interobserver variability. In terms of nodule texture characterization, a maximum quadratic weighted Cohen's kappa of 0.733 was obtained, with part solid nodules being particularly challenging to classify correctly. Detailed analysis of the proposed methods and the differences in performance allow to identify the major challenges remaining and future directions - data collection, augmentation/generation and evaluation of under-represented classes, the incorporation of scan-level information for better decision-making and the development of tools and challenges with clinical-oriented goals. The LNDb Challenge and associated data remain publicly available so that future methods can be tested and benchmarked, promoting the development of new algorithms in lung cancer medical image analysis and patient follow-up recommendation.

PS01.02 National Lung Cancer Screening Program in Taiwan: The TALENT Study

Lung cancer in never-smoker is a global rising threat especially in East Asia. Our recent proteogenomics study has revealed the demographically distinct signatures of oncogenesis and progression of this dreadful disease and provide new insights into the precision management of early lung cancer. Currently, early detection is the most effective way to improve lung cancer survival. Low-dose computed tomography (LDCT) has been proven effective for lung cancer screening. However, most of the lung cancer screenings focused on heavy smoker which may not be suitable for East Asian population. In Taiwan, lung cancer is the leading cause of cancer mortality and 53% were never-smoker. We therefore conducted a nationwide lung cancer LDCT screening focused on never-smoker (TALENT: Taiwan Lung Cancer Screening for Never Smoker Trial) aiming to develop an effective strategy for screening of lung cancer in never-smoker and establish a risk prediction model to identify high-risk population that may benefit from LDCT screening. Here we report on behalf of the TALENT study group the first round (T0) results. This is a prospective, multicenter study sponsored by The Ministry of Health and Welfare, Taiwan. The inclusion criteria were age between 55-75 years, never-smoker and having one of the following risks: family history of lung cancer within third-degree, passive smoking exposure, TB/COPD, cooking index ≥ 110, and not using ventilator during cooking. The LDCT was conducted according to the guideline suggested by ACR. A solid or part-solid (PS) nodule larger than 6 mm or pure ground glass nodule (GGN) larger than 5 mm in diameter was designated as positive on LDCT. The PBMC DNA was obtained for SNP typing analysis. Institutional Review Board approved the study and informed consent was obtained from each participating subject. From Feb. 2015 to July 2019, a total of 12,011 subjects (Table 1) were enrolled. Among them, 6,012 (50.1%) had lung cancer family history, 5,999 (49.9%) did not. In 12,011 scans, 2,094 (17.4%) were considered positive, there were 392 subjects (3.3%) underwent lung biopsies or surgeries at T0, lung cancer (2.6%) were diagnosed in 311 subjects, 254 (2.1%) were invasive lung cancer. All but one was adenocarcinoma and 96.5% were stage 0 or I, 81 had benign lung disease or malignancy other than primary lung cancer. The prevalence of lung cancer was 3.2% and 2.0% in subjects with and without lung cancer family history, respectively. The prevalence of invasive lung cancer was 2.6% and 1.6%, respectively. For subjects with lung cancer family history, the prevalence of lung cancer was 3.3%, 1.6% and 1.7% in those with 1st degree, 2nd degree and 3rd degree families had lung cancer, respectively. The TALENT study confirmed the effectiveness of LDCT screening in a pre-defined, never-smoker high-risk population. The T0 lung cancer detection rate was 2.6%, which was even higher than NLST study (1.1%) and NELSON study (0.9%). Most importantly, 96.5% patients were stage 0 or 1, that were potentially curable by surgery. Our study also revealed the high risk of family history, especially those subjects with 1st degree families had lung cancer.

Solid Components in the Mediastinal Window of Computed Tomography Define a Distinct Subtype of Subsolid Nodules in Clinical Stage I Lung Cancers

BackgroundWe aimed to validate the clinicopathologic characteristics and prognostic value of the presence of solid components in the mediastinal window of computed tomography scan in clinical stage I pulmonary subsolid nodules (SSNs). MethodsWe retrospectively evaluated patients with pulmonary SSNs resected between 2011 and 2016. We classified SSNs into heterogeneous ground-glass nodules (HGGNs) (solid component detected only in lung window) and part-solid nodules (PSNs) (solid component detected both in lung/mediastinal windows). ResultsA total of 487 patients (216 PSNs) were included. PSNs were associated with higher frequencies of micropapillary or solid pathologic patterns (18.1% vs. 3.3%; P < .001), epidermal growth factor receptor gene mutation (39.4% vs. 32.8%), and other types of gene mutations (2.3% vs. 1.1%; P = .043). Logistic regression analysis revealed that male sex (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.20-5.57; P = .016) and higher consolidation tumor ratio (CTR) (OR, 110.04; 95% CI, 8.56-1414.39; P < .001) remained independent for invasive adenocarcinomas with poor differentiation. Receiver operating characteristic analyses revealed that solid component size in the mediastinal window (area under the curve [AUC], 0.731; 95% CI, 0.653-0.808; P < .0001) showed a better predictive ability to poor differentiation compared with solid component size in the lung window and CTR. The 5-year recurrence-free survival (RFS) rate of PSNs was worse than that of HGGNs (94.6% vs. 99.1%; P = .019). Multivariate Cox regression revealed that positive lymph node status (hazard ratio, 22.99; 95% CI, 4.52-116.86; P < .001) indicated worse RFS for PSNs. ConclusionSSNs with solid components in mediastinal window demonstrated clinicopathologic and prognostic features different from those without in clinical stage I lung cancer. Solid components in mediastinal window was a strong predictor of poor differentiation.

Computer-aided Detection of Subsolid Nodules at Chest CT: Improved Performance with Deep Learning-based CT Section Thickness Reduction.

Background Studies on the optimal CT section thickness for detecting subsolid nodules (SSNs) with computer-aided detection (CAD) are lacking. Purpose To assess the effect of CT section thickness on CAD performance in the detection of SSNs and to investigate whether deep learning-based super-resolution algorithms for reducing CT section thickness can improve performance. Materials and Methods CT images obtained with 1-, 3-, and 5-mm-thick sections were obtained in patients who underwent surgery between March 2018 and December 2018. Patients with resected synchronous SSNs and those without SSNs (negative controls) were retrospectively evaluated. The SSNs, which ranged from 6 to 30 mm, were labeled ground-truth lesions. A deep learning-based CAD system was applied to SSN detection on CT images of each section thickness and those converted from 3- and 5-mm section thickness into 1-mm section thickness by using the super-resolution algorithm. The CAD performance on each section thickness was evaluated and compared by using the jackknife alternative free response receiver operating characteristic figure of merit. Results A total of 308 patients (mean age ± standard deviation, 62 years ± 10; 183 women) with 424 SSNs (310 part-solid and 114 nonsolid nodules) and 182 patients without SSNs (mean age, 65 years ± 10; 97 men) were evaluated. The figures of merit differed across the three section thicknesses (0.92, 0.90, and 0.89 for 1, 3, and 5 mm, respectively; P = .04) and between 1- and 5-mm sections (P = .04). The figures of merit varied for nonsolid nodules (0.78, 0.72, and 0.66 for 1, 3, and 5 mm, respectively; P < .001) but not for part-solid nodules (range, 0.93-0.94; P = .76). The super-resolution algorithm improved CAD sensitivity on 3- and 5-mm-thick sections (P = .02 for 3 mm, P < .001 for 5 mm). Conclusion Computer-aided detection (CAD) of subsolid nodules performed better at 1-mm section thickness CT than at 3- and 5-mm section thickness CT, particularly with nonsolid nodules. Application of a super-resolution algorithm improved the sensitivity of CAD at 3- and 5-mm section thickness CT. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Goo in this issue.

Use of relative CT values to evaluate the invasiveness of pulmonary subsolid nodules in patients with emphysema.

Lung cancer is a major cause of death, and adenocarcinoma is the most common histologic subtype. Precise diagnosis and treatment of invasive adenocarcinoma (IAC) can substantially improve the survival of patients. However, early-stage adenocarcinomas frequently appear as subsolid nodules (SSN) on computed tomography (CT), and the optimal cut-off CT value for differentiating the invasiveness of SSNs in emphysematous patients is unclear. High-resolution CT targeted scans of 187 pulmonary SSNs in 175 patients with emphysema as confirmed by surgery and histology were retrospectively reviewed. The mean CT value, the relative CT (rCT) values of 1 (nodule CT value - lung CT value), and 2 (nodule CT value/lung CT value), and the size of the SSNs were measured and calculated. The differentiating performance of the CT values between pre-invasive and invasive tumors was evaluated using a receiver operating characteristic (ROC) curve. Significant differences were found in the rCT values of 1 and 2 among pure ground-glass nodules (GGNs) with different levels of invasiveness, in the rCT values of 1 and 2 for the ground-glass component (GGC) and the mean CT value of the solid component (SC) of part-solid nodules (PSNs) between minimally invasive adenocarcinoma (MIA) and IAC (all P<<0.05). The size was significantly different among pure GGNs with different invasiveness (P<0.05). The cut-off rCT values of 1, 2 and nodule size for differentiating between pre-invasive and invasive pure GGNs were 293.82 [sensitivity 58.0%, specificity 94.7%; area under the curve (AUC) 0.783], 0.68 (sensitivity 89.5%, specificity 58.0%, AUC 0.742) and 1.10 cm (sensitivity 74.0%, specificity 79.0%, AUC 0.796), respectively. The AUCs of combining rCT values 1 and 2 with the size of nodule were 0.795 (sensitivity 62.5%, specificity 89.5%) and 0.845 (sensitivity 71.6%, specificity 89.5%) respectively. There were no significant differences in the mean CT values between pure GGNs with different levels of invasiveness and between the GGC of PSNs of MIA and IAC. In patients with emphysema, the rCT values are more useful than the mean CT values for differentiating between SSNs with different invasiveness and can be valuable for patient management.