Clinical Stage IA Adenocarcinoma Research Articles

CT-based radiomic consensus clustering association with tumor biological behavior in clinical stage IA adenocarcinoma: a retrospective study.

Research has demonstrated that radiomics models are capable of forecasting the characteristics of lung cancer. Nevertheless, due to radiomics' poor interpretability, its applicability in clinical settings remains restricted. This investigation sought to verify the correlation between radiomics features (RFs) and the biological behavior of clinical stage IA adenocarcinomas. A retrospective analysis was conducted on patients diagnosed with clinical stage IA lung adenocarcinoma who underwent resection between May 2005 and December 2018. Detailed radiomics examination of the primary tumor was carried out utilizing preoperative computed tomography (CT) images. Subsequently, patients were grouped based on their RFs using consensus clustering, enabling comparison of tumor biological characteristics among the clusters. Survival disparities among the clusters were evaluated through Kaplan-Meier and Cox analyses. A consensus cluster analysis was performed on 669 patients [median age, 58 years; interquartile range (IQR), 50-64 years, 257 males, 412 females], and three distinct clusters were identified. Cluster 2 was associated with radiological solid adenocarcinoma [119 of 324 (36.7%), P<0.001], larger tumors with median tumor size of 2.1 cm with IQR of 1.7 to 2.5 cm (P<0.001), central tumor [91 of 324 (28.1%), P=0.002], pleural invasion [87 of 324 (26.9%), P<0.001], occult lymph node metastasis (ONM) [106 of 324 (32.7%), P<0.001], and a higher frequency of metastasis or recurrence [62 of 324 (19.1%), P<0.001]. The frequency of histological grade 3 was the highest in Cluster 3 [8 of 34 (23.5%), P<0.001]. Cluster 1 was associated with pure ground glass nodules (pGGNs) [184 of 310 (59.4%), P<0.001], smaller tumors with median tumor size of 1.1 cm with IQR of 0.8 to 1.4 cm (P<0.001), no pleural invasion [276 of 310 (89.0%), P<0.001], histological grade 1 [114 of 248 (46.0%), P<0.001], ONM negative [292 of 310 (94.2%), P<0.001], and a lower rate of metastasis or recurrence [298 of 310 (96.1%), P<0.001]. Differences in tumor biological behavior were detected among consensus clusters based on the RFs of clinical stage IA adenocarcinoma.

Distinct Prognostic Impact of PET Findings Based on Radiological Appearance in Clinical Stage IA Lung Adenocarcinoma

IntroductionAlthough solid appearance on computed tomography and positive findings on positron emission tomography (PET) have been both associated with poor outcome in lung adenocarcinoma, the extent to which these findings overlap is unknown. This study aimed to determine the differences in prognostic significance of PET findings in part-solid nodules (PSNs) and solid nodules. Materials and MethodsWe retrospectively investigated 417 patients with clinical stage IA adenocarcinoma who underwent curative resection between 2010 and 2017. We compared disease-free survival (DFS), cumulative incidence of disease recurrence (CIR) and clinicopathological characters between PET-positive and negative groups among PSNs and solid nodules, respectively. We used 2.5 as a cut-off value of maximum standardized uptake value (SUV max). ResultsIn PSNs (n = 235), PET-positive group (n = 59) showed more aggressive features in several clinicopathological variables, poorer DFS (P < .001) and higher CIR (P < .001) than PET-negative group (n = 176). In contrast, in solid nodules (n = 182), DFS (P = .521) and CIR (P = .311) were not significantly different between PET-positive (n = 128) and negative groups (n = 54). SUV max was proved to be the independent prognostic factor of DFS by multivariate analysis (HR, 1.155; 95% CI, 1.036-1.287) only in PSNs. ConclusionThese findings showed distinct impact on prognosis of PET findings between PSNs and solid nodules. PET-positive finding was more important prognostic factor in PSNs than in solid nodules among clinical stage IA lung adenocarcinoma.

Prognostic Stratification According to Size and Dominance of Radiologic Solid Component in Clinical Stage IA Lung Adenocarcinoma

IntroductionAlthough several studies have investigated the prognostic significance of the radiographic appearance of stage IA lung adenocarcinoma, the prognostic impact of solid component size or consolidation-to-tumor ratio (CTR) of part-solid nodules (PSNs) still remains controversial. This study aimed to clarify the combined prognostic impact of the mentioned radiographic features of PSNs and compare it with that of pure solid nodules in the current TNM classification. MethodsWe retrospectively investigated 1014 patients with clinical stage IA (TNM eighth edition) adenocarcinoma who underwent curative resection. Overall survival (OS) and pathologic characteristics of pure solid nodules, solid-dominant PSNs (CTR > 0.5), and ground-glass opacity (GGO)-dominant PSNs (CTR ≤ 0.5) were compared according to T category. ResultsPatients with pure solid nodules (297 cases) had significantly shorter OS compared with those with PSNs (717 cases) (p < 0.001) but a marginal difference compared with those with solid-dominant PSNs (286 cases) (p = 0.051). No significant difference in OS was found according to T category in those with GGO-dominant PSNs (431 cases). Patients with cT1b and T1c solid-dominant PSNs had significantly worse prognosis compared with those with other PSNs and had comparable prognosis with those with cT1b pure solid nodules (p = 0.892). Higher frequency of nodal and lymphovascular involvement and pathologic upstaging was observed with T category progression in solid-dominant PSNs. ConclusionsAn hierarchy of prognosis and pathologic malignant characteristics was observed according to T category in patients with solid-dominant PSNs but not in those with GGO-dominant PSNs, suggesting the importance of classifying PSNs on the basis of solid component size and CTR for accurate prognostic comparison with pure solid nodules.

Correlation between maximum standardized uptake values on FDG-PET and microenvironmental factors in patients with clinical stage IA radiologic pure-solid lung adenocarcinoma

ObjectivesThe purpose of this study was to investigate whether fluorodeoxyglucose (FDG) accumulation is associated with the expression of microenvironmental factors in radiological pure-solid lung adenocarcinoma. MethodsWe selected 50 cases involving patients with clinical stage IA radiological pure-solid lung adenocarcinoma who were examined with 18 F-FDG positron emission tomography (18 F-FDG PET) prior to surgery and whose FDG–PET maximal standardized uptake values (SUVmax) were calculated. Tumor specimens were analyzed by immunohistochemistry (IHC) for phosphorylated AKT (pAKT), glucose transporter type 1 (GLUT-1), carbonic anhydrase IX (CA IX), podoplanin-positive cancer associated fibroblasts (PDPN + CAFs), and CD204-positive tumor-associated macrophages (CD204+ TAMs). We compared the clinicopathological characteristics and the immunophenotypes between two groups with high and low SUVmax. ResultsA multivariate analysis revealed that SUVmax was an independently significant prognostic factor (P = .03). The 5-year overall survival (OS) and recurrence free survival (RFS) rates of the SUV max high and low groups were 68.0% versus 100% ((P = .002; OS) 54.3% versus 90.8% (P < .001; RFS)), respectively. Vascular invasion, pleural invasion, and the prevalence of solid predominant subtype tumors were more frequent in the SUVmax high group. Additionally, the expression levels of GLUT-1 and pAKT in cancer cells were significantly higher in this group (P < .001, and P < .001 respectively). Furthermore, the numbers of the tumor-promoting stromal cells, i.e., PDPN + CAFs and CD204+ TAMs, were also significantly higher in the SUVmax high group (P = .001, and P < .001 respectively). ConclusionOur results indicated that a close association exists between the SUVmax and expressions of not only metabolism associated markers in cancer cells but also of tumor promoting markers in stromal cells among patients with clinical stage IA adenocarcinoma with radiologically pure-solid nodules.

Potential value of FDG PET-CT in predicting occult lymph node metastasis in clinical stage ⅠA lung adenocarcinoma

Objective: To investigate the predictive value of (18)F-FDG PET-CT scan for occult lymph node metastasis in patients with stage ⅠA lung adenocarcinoma. Methods: The image and pathological data of 272 patients with stage ⅠA lung adenocarcinoma from October 2006 to September 2015 were retrospectively analyzed. All patients underwent preoperative (18)F-FDG PET-CT scan followed by lobectomy and systematic lymph node dissection. The correlation between occult lymph node metastasis and the maximum standardized uptake value (SUV(max)) of primary tumor as well as other clinicopathological factors was analyzed to screen the risk factors of occult lymph node metastasis in stage ⅠA lung adenocarcinoma. Results: Occult lymph node metastasis was detected in 50 patients (18.4%), with 24 (8.8%) patients of pN1 involvement and 26 (9.6%) of pN2 involvement. Among the 272 patients enrolled, 39 had pure ground glass nodule, 59 had part-solid nodule and 174 had solid nodule. All patients with pure ground glass nodule or nodule≤1 cm were pN0. For the 233 patients with part-solid and solid nodule, no lymph node metastasis was found in T1a stage (tumor length ≤1 cm). Primary tumor SUV(max) (Z=-5.663, P<0.001), nodule type (χ(2)=21.586, P<0.001), tumor location (χ(2)= 12.790, P< 0.001), histological grade (χ(2)= 22.784, P< 0.001) and visceral pleural invasion (χ(2)=5.357, P=0.021) showed significant differences between occult lymph node metastasis group (pN+ ) and non-lymph node metastasis group (pN0). With SUV(max)=2.405 as cut-off value, the sensitivity and specificity for predicting occult lymph node metastasis were 90.0% and 61.7%, the area under curve was 0.761(95%CI=0.700~0.823), and the negative predictive value was 95.8%. Multivariate analysis revealed that SUV(max) >2.405 (P<0.001), central location (P=0.030) and higher histological grade (P=0.024) were independent predictors of occult lymph node metastasis. Conclusions: For clinical stage ⅠA adenocarcinoma, primary tumor SUV(max) > 2.405, central location and higher histological grade were independent risk factors for occult lymph node metastasis. Systematic lymph node dissection may be avoided in lung adenocarcinoma with pure ground glass density, tumor length ≤1 cm or SUV(max) ≤ 2.405, due to the very low probability of nodal involvement.

Which T descriptor is more predictive of recurrence after sublobar resection: whole tumour size versus solid component size?

We aimed to assess the predictive value of different T descriptors, including the whole tumour size (Dwhole) and solid component size (Dsolid), in patients with clinical Stage IA adenocarcinoma who underwent sublobar resection. According to computed tomography images in the lung window, T descriptors, Dwhole and Dsolid, were applied. To evaluate the predictive value of these 2 different descriptors in predicting tumour recurrence and pathological malignant behaviours, Cox hazard regression and a receiver-operating characteristic curve analysis, respectively, were used. In total, 247 patients were included. Of these patients, 109 and 138 had ground glass and solid nodules, respectively. When the T descriptor was changed from Dwhole to Dsolid, 37 tumours (15%) were downgraded to T1a status from T1b/T1c status. Multivariable Cox analysis showed that Dsolid was an independent risk factor of worse recurrence-free survival [hazard ratio (HR) 2.36, 95% confidence interval (CI) 1.24-4.47; P = 0.009], while Dwhole was not (HR 1.51, 95% CI 0.79-2.89; P = 0.215). In the receiver-operating characteristic analysis, the areas under the curves for Dwhole and Dsolid used to identify pathological malignant behaviours were 0.598 and 0.739, respectively. The T descriptor, which is represented by Dsolid, rather than Dwhole, is a better predictor of tumour recurrence after sublobar resection in clinical Stage IA lung adenocarcinoma. Furthermore, our results provide some clues indicating that sublobar resection should be performed cautiously in patients with lung adenocarcinoma manifesting as ground glass nodule with Dsolid >2 cm.

Risk Factors of Recurrence in Patients With Clinical Stage IA Adenocarcinoma Presented as Ground-Glass Nodule

BackgroundIn this study we aimed to identify the risk factors of recurrence in patients with clinical stage IA adenocarcinoma presented as ground glass nodule (GGN) on computed tomography scans. Patients and MethodsThe study included 245 patients with clinical stage IA adenocarcinoma presented as GGN who underwent surgery during 2010 to 2013. All patients were divided into 2 subgroups on the basis of consolidation diameter to tumor diameter (C/T) ratio on lung window: (1) ground-glass opacity (GGO)-dominant subgroup (C/T ≤ 0.5; n = 179); (2) solid-dominant subgroup (C/T > 0.5; n = 66). Recurrence-free survival (RFS) was analyzed to identify independent risk factors of recurrence using the Kaplan–Meier approach and multivariable Cox models. ResultsPatients in the GGO-dominant subgroup had a better prognosis than those in the solid-dominant subgroup (5-year RFS: 98% vs. 87%; P < .001). Multivariate analysis confirmed that C/T ratio was an independent risk factor for RFS in patients with clinical stage IA adenocarcinoma presented as GGN (hazard ratio [HR], 9.47; 95% confidence interval [CI], 1.75-51.1; P = .009). In the analysis of the solid-dominant group, multivariate analysis showed that limited resection was an independent risk factor of recurrence in this subgroup (HR, 6.86; 95% CI, 1.50-31.42; P = .013). Regarding the GGO-dominant subgroup, surgical type was not a risk factor of recurrence. ConclusionPatients with clinical stage IA solid-dominant adenocarcinoma (C/T ratio > 0.5) had a higher rate of recurrence after limited resection than lobectomy. Thus, limited resection should be performed cautiously in these patients (C/T ratio > 0.5).

Prognostic impact of the integration of volumetric quantification of the solid part of the tumor on 3DCT and FDG-PET imaging in clinical stage IA adenocarcinoma of the lung

ObjectivesThe aim of this study was to conduct comparative analyses of the biological malignant potential of clinical stage IA adenocarcinoma using positron emission tomography/computed tomography (PET/CT), high-resolution CT (HRCT), and three-dimensional CT (3DCT). The predictive performance of these parameters was evaluated in terms of clinical outcomes and pathological invasiveness (positive lymphatic permeation, blood-vessel invasion, pleural invasion, and lymph-node metastasis). Materials and methodsWe enrolled 170 patients with c-IA adenocarcinoma who underwent PET/CT, HRCT, and 3D reconstruction of lung structures using the Synapse Vincent system (Fujifilm Corporation, Tokyo, Japan) followed by complete resection. Maximum standardized uptake values (SUVmax) of F18-fluorodeoxyglucose and the size and volume of the solid part of the tumor were quantified and analyzed in relation to surgical outcomes. ResultsUnivariate analysis demonstrated that all the three parameters and whole-tumor volume were associated with unfavorable disease-free survival (DFS), while the volume of the solid part was the independent predictor on multivariate analysis (p < .001). The receiver operating characteristic curves for pathological invasiveness, determined using the variables dichotomized at each cut-off level (SUVmax 2.4; solid-part size 1.23 cm; solid-part volume 779 mm3), showed that all were significantly correlated with pathological invasiveness and prognosis, whereas the combination of SUVmax and the solid-part volume was the most powerful predictor of survival and pathological invasiveness compared to any other parameters: the 4-year DFS and proportion of pathological invasiveness in patients with SUVmax > 2.4 and solid-part volume > 779 mm3 versus those with SUVmax ≤ 2.4 or solid-part volume ≤779 mm3 were 81.2% versus 98.3% (p < .001) and 84.3% versus 15.1% (p < .001), respectively. ConclusionIn c-IA adenocarcinoma, the volume of the solid part of the tumor was the independent predictor for unfavorable DFS, and the integration of the volume of the solid part and SUVmax was highly beneficial for the prediction of survival and pathological invasiveness.

Prognostic significance of combined radiologic imaging modalities for prognosis of clinical IA adenocarcinomas.

BackgroundWe previously proposed measuring tumor size using mediastinal window setting on high-resolution computed tomography (CT) as a simple and useful modality for preoperative prognostication of small adenocarcinoma. Hence, the importance of tumor volume and positron emission tomography (PET) for preoperative prognostication of clinical stage IA (cIA) adenocarcinoma was studied.Materials and MethodsWe retrospectively evaluated total 324 patients who underwent pulmonary resection of cIA adenocarcinoma between July 2008 and August 2015. Reconstructed three-dimensional (3D) images from 1–1.5 mm-sliced CT were evaluated for whole tumor volume including ground grass opacity, consolidation volume on lung window setting, and mediastinal window volume (MWV). The values examined by PET were total lesion glycolysis (TLG), and maximum standardized uptake (SUV max) and mean. Pathologic status was evaluated according to tumor maximum size, invasive size (IS), lymphatic and vascular vessels, pleural invasion (ly/v/pl), and TNM staging.ResultsAccording to ly/v/pl invasion and lymph node positivity, no variables were superior to IS. We used Mean/MWV (SUV mean x MWV) to evaluate tumor quality and quantity in the role of surrogate TLG. Mean/MWV were superior to IS. Additionally, Mean/MV was associated with lymph node metastases. Among the various histologic subtypes, solid-predominant had the highest expression of Mean/MV. The higher Mean/MV significantly contributed to unfavorable disease-free survival in cIA adenocarcinomas, but not to overall survival.ConclusionsThe mean/MWV value determination on 3D-reconstructed CT images was a simple and useful preoperative modality for predicting invasive facet in cIA adenocarcinoma. However, higher values didn't significantly affect overall survival.

426P Combined radiologic imaging modalities for prognosis of clinical IA adenocarcinomas

Background We previously proposed measuring tumor size using mediastinal window setting on high-resolution computed tomography (CT) as a simple and useful modality for preoperative prognostication of small adenocarcinoma. Here, the importance of tumor volume and positron emission tomography (PET) for preoperative prognostication of clinical stage IA (cIA) adenocarcinoma for anatomical pulmonary resection was studied. Methods We retrospectively evaluated total 326 patients who underwent pulmonary resection of cIA adenocarcinoma between July 2008 and August 2015. Reconstructed three-dimensional (3D) images from 1-1.5 mm-slice multi-detectorrow CT were evaluated for tumor total volume (TTV), consolidation volume (CV) on lung window setting, and mediastinal volume (MV) on MWS. The values examined by PET were total lesionglycolysis, maximum standardized uptake (SUVmax), and mean SUV. Patient age, gender, preoperative CEA levels, and clinical staging were examined. Pathologic statuswasevaluatedaccordingto tumorsize (PS), invasivesize(IS), lymphaticand vascular vessels, pleural invasion, and TNM staging. Results Pathologic lymph node positivity, and IS were equivalent or superior to 3D imaging factors, preoperative patient variables, and PS, respectively. We used mean/MV to evaluate tumor quality and quantity, because only MV and CV were equivalent to IS. AUCs for mean/MV were 0.80,0.82, and 0.81 and were >IS. Mean/MV was associated with lymph node metastasis, tumor invasiveness, histologic grade, and two-dimensional mediastinal diameter on MDCT. Among the various histologic subtypes, solid- predominant tumors had the highest mean/MV; the number of genomictriple-negative adenocarcinoma was significantly higher than adenocarcinoma harboring an exclusive gene of EGFR, KRAS, or ALK. Moreover, highermean/MV significantly contributed to unfavorable disease-free survival in cIA adenocarcinomas. Conclusions The mean/MV value determination on 3D-reconstructed CT images was a simple and useful preoperative modality for predicting invasiveness, lymph node metastasis, and stage migration in cIA adenocarcinomas; higher values correlated with poorer prognosis and reflected tumor aggressiveness and extent ofinvasion. Legal entity responsible for the study N/A Funding N/A Disclosure All authors have declared no conflicts ofinterest.

Prognostic value of the new IASLC/ATS/ERS classification of clinical stage IA lung adenocarcinoma.

We analyzed and validated the prognostic utility of the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) for clinical stage IA lung adenocarcinoma (ADC) classification of adenocarcinoma (ADC). We retrospectively reviewed 347 patients with clinical stage IA nonmucinous ADC, who had undergone complete resection. The histological subtype was classified according to the predominant subtype, as proposed by the new IASLC/ATS/ERS ADC classification. The histopathological subtypes, defined according to the new IASLC/ATS/ERS ADC classification, were ADC in situ (AIS) in 56 patients (16.1%), minimally invasive ADC (MIA) in 15 (4.3%), lepidic-predominant ADC in 109 (31.4%), papillary-predominant ADC in 70 (20.2%), acinar-predominant ADC in 61 (17.6%), solid-predominant ADC in 30 (8.6%), and micropapillary-predominant ADC in 6 (1.7%). The 5-year disease-free survival (DFS) rate was 100% for both AIS and MIA. All cases of recurrence involved invasive ADC. The 5-year DFS for lepidic-predominant ADC was 99.0%; acinar-predominant ADC, 82.4%; papillary-predominant ADC, 80.8%; solid-predominant ADC, 73.6%; and micropapillary-predominant ADC, 33.3%. The predominant subtype of ADC was significantly correlated with DFS (P<0.0001). Multivariate analysis indicated that the pathological stage was an independent predictor of DFS (P=0.031). Other independent predictors of increased risk of recurrence were the presence of vascular or lymphatic invasion (HR=4.96, P=0.001), and a pathological stage more advanced than IB (HR=2.87, P=0.010). The coincidence between the clinical stage and pathological stage was 79.8%. The stage migration was found in 53.3% of solid-predominat ADC and in 83.3% of micropapillary-predominant ADC. The new IASLC/ATS/ERS ADC classification has prognostic value in predicting the recurrence and survival of patients with clinical stage IA ADC. The frequency of stage migration was found in more than half of solid and micropapillary predominant ADCs.

A critical analysis of segmentectomy versus lobectomy for non-small-cell lung cancer

Bao et al. [1] should be commended for completing a thorough and timely meta-analysis to compare the survival outcomes of segmentectomy versus lobectomy for Stage I non-small-cell lung cancer (NSCLC). This analysis represents the first of its kind to distinguish segmentectomies from wedge resections, an important distinction from both an oncological and technical perspective that has been overlooked in previous meta-analyses that compared ‘sublobar resections’ with lobectomy procedures [2, 3]. We concur with the authors that the current literature lacks robust high-level evidence on this topic and a meta-analysis of observational studies may provide insightful guidance for clinicians. Results of this study found that patients who underwent segmentectomy for Stage I, IA and IA (2–3 cm) NSCLC were associated with inferior combined overall survival (OS) and cancer-specifi cs urvival (CSS) outcomes compared with those who underwent lobectomy. However, patients with Stage IA (≤2 cm) NSCLC had no statistically significant difference in survival compared with lobectomy. It is imperative to analyse these results in detail to avoid misleading conclusions. In two of the four analysed subgroups, Stage IA and Stage IA (2–3 cm), OS outcomes were significantly worse after segmentectomy, but CSS was not significant. The combined OS/CSS were significant in both subgroups, and the authors concluded that patients who underwent segmentectomy in these cohorts resulted in inferior outcomes. However, it must be emphasized that patient baseline characteristics between these two treatment groups differed significantly, and patients were often selected for segmentectomies due to significant comorbidities and limited pulmonary reserve prohibiting them from lobectomy procedures [4, 5]. In such cases, differences in OS may be misleading compared with CSS, as patients died due to causes unrelated to NSCLC and the oncological efficacy of their surgical procedures. Hence, worse OS outcomes in the segmentectomy group may be a reflection of their patient characteristics rather than their operative outcome. Similarly, a combined statistic of OS and CSS may overestimate the adverse survival outcomes of segmentectomy procedures. To address the issue of differing patient baseline characteristics, Tsutani et al. [6] recently published a propensity-score analysis involving 481 patients with clinical Stage IA adenocarcinoma who were subsequently matched into 81 pairs according to clinicopathological factors. Results of this study demonstrated no differences in regard to OS and recurrence-free survival at 3 years. In our opinion, it is no longer controversial to perform sublobar resections for patients with NSCLC who are deemed ineligible for lobectomy procedures due to comorbidities or limited pulmonary function. The area of interest lies with the cohort of patients who can tolerate either a segmentectomy or a lobectomy procedure. For this growing patient population who are diagnosed with early stage NSCLC through more aggressive screening programmes, oncological efficacy needs to be balanced with pulmonary preservation and potentially reduced perioperative complications associated with segmentectomy. Future analyses should aim to differentiate data from studies that included ‘compromised’ patients who underwent sublobar resections as a result of their inability to undergo lobectomy, or ‘intentional’ patients who could have tolerated either procedure.

Segmentectomy versus lobectomy for clinical stage IA lung adenocarcinoma.

Despite the increasing prevalence of the early discovery of small-sized non-small cell lung cancers (NSCLCs), particularly adenocarcinoma, sublobar resection has not yet gained acceptance for patients who can tolerate lobectomy. We compared the outcomes of segmentectomy (n=155) and lobectomy (n=479) in 634 consecutive patients with clinical stage IA lung adenocarcinoma and in propensity score-matched pairs. Those who had undergone wedge resection were excluded. The 30-day postoperative mortality rate in this population was zero. Patients with large or right-sided tumors, high maximum standardized uptake value (SUVmax), pathologically invasive tumors (with lymphatic, vascular, or pleural invasion), and lymph node metastasis underwent lobectomy significantly more often. Three-year recurrence-free survival (RFS) was significantly higher after segmentectomy compared to lobectomy (92.7% vs. 86.9%, P=0.0394), whereas three-year overall survival (OS) did not significantly differ (95.7% vs. 94.1%, P=0.162). Multivariate analyses of RFS and OS revealed age and SUVmax as significant independent prognostic factors, whereas gender, tumor size and procedure (segmentectomy vs. lobectomy) were not. In 100 propensity score-matched pairs with variables adjusted for age, gender, tumor size, SUVmax, tumor location, the three-year RFS (90.2% vs. 91.5%) and OS (94.8% vs. 93.3%) after segmentectomy and lobectomy respectively were comparable. Segmentectomy with reference to SUVmax should be considered as an alternative for clinical stage IA adenocarcinoma, even for low-risk patients.

Prognostic Role of Positron Emission Tomography and High-Resolution Computed Tomography in Clinical Stage IA Lung Adenocarcinoma

This multicenter study aimed to validate the ability of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) plus high-resolution computed tomography (HR-CT) to predict the malignant behavior and prognosis of early adenocarcinomas of the lung. We calculated maximum standardized uptake values (maxSUV) from PET/CT images and ground-glass opacity (GGO) ratios on HR-CT images before complete surgical intervention in 610 patients with clinical stage IA lung adenocarcinoma. Pathologic invasiveness and survival were compared with clinical factors and radiographic findings including the maxSUV, which was revised to correct for interinstitutional discrepancies that confer limitations upon multicenter PET studies. Analyses of receiver-operating characteristic curves revealed optimal maxSUV and GGO ratio cutoffs to predict recurrence of 2.9 and 25%, respectively. Both the maxSUV and GGO ratio reflected tumor invasiveness, nodal metastasis, recurrence, and patient survivals, and were significant prognostic factors for recurrence-free and cancer-specific survivals on multivariate Cox analysis (all,p< 0.001). The combination of maxSUV and GGO ratio is a better predictor of malignant tumor grade than either alone. The combination of maxSUV and GGO ratio as well as each alone are important predictors of prognosis in patients with clinical stage IA adenocarcinoma of the lung and should be considered before selecting therapeutic strategies.

F-054TUMOUR STANDARDIZED UPTAKE VALUE ON POSITRON EMISSION TOMOGRAPHY IS A NOVEL PREDICTOR OF ADENOCARCINOMA IN SITU FOR C-STAGE IA LUNG CANCER PATIENTS WITH PART-SOLID NODULE ON THIN-SECTION COMPUTED TOMOGRAPHY SCAN

Adenocarcinoma in situ (AIS), which was defined as having a pathologically non-invasive nature by the new IASLC/ATS/ERS classification, might be included in patients that showed part-solid nodule on thin-section CT. Between 2008 and 2011, 556 c-stage IA lung cancer patients underwent pulmonary resection. The findings obtained by preoperative thin-section CT were reviewed for all patients and categorized as pure ground-glass nodule (GGN), part-solid, or pure-solid based on the findings on thin-section CT, i.e. consolidation/tumour ratio (CTR). Part-solid nodule was defined as a tumour with 0 < CTR < 1.0, which indicated focal nodular opacity containing both solid and GGN components. All patients were evaluated by positron emission tomography (PET) and the maximum standardized uptake value (SUVmax) was recorded. Several clinicopathological features were investigated to identify predictors of AIS using multivariate analyses. 112 c-stage IA lung cancer patients showed a part-solid appearance on thin-section CT. Among them, AIS was found in 10 (23.8%) of 42 patients with 0 < CTR ≤ 0.5 in contrast to 3 (4.3%) of 70 patients with 0.5 < CTR < 1.0. According to multivariate analyses, SUVmax and CTR were significant predictors of AIS in patients with part-solid nodule (P = 0.0421, 0.0221). Mean SUVmax of the patients with AIS was 0.57 (0-1.6). Moreover, in the subgroup of part-solid nodule with SUVmax ≤ 1.0 and CTR ≤ 0.40, which were shown as cutoff values of predicting AIS based on the result of receiver operating characteristics curve, 6 (40%) of 15 patients with these criteria showed pathologic non-invasive nature even in the patients with part-solid nodule. Among clinical stage IA adenocarcinoma with part-solid nodule on thin-section CT scan, extremely low level of SUVmax could correspond to a radiologically pure GGO and pathologically AIS. Preoperative tumour SUVmax on PET could yield important information for predicting the non-invasiveness in patients with part-solid nodule. All authors have declared no conflicts of interest.

Limited resection and two-staged lobectomy for non-small cell lung cancer with ground-glass opacity

BackgroundLung tumors showing ground-glass opacities on high-resolution computed tomography indicate the presence of inflammation, atypical adenomatous hyperplasia, or localized bronchioloalveolar carcinoma. We adopted a two-staged video-assisted thoracoscopic lobectomy strategy involving completion lobectomy for localized bronchioloalveolar carcinoma with an invasive component according to postoperative pathological examination by permanent section after partial resection.MethodsForty-one patients with undiagnosed small peripheral ground-glass opacity lesions underwent partial resection from 2001 to 2007 in Hokkaido University Hospital. Localized bronchioloalveolar carcinoma was classified according to the Noguchi classification for adenocarcinoma. Malignant lesions other than Noguchi types A and B were considered for completion lobectomy and systemic mediastinal lymphadenectomy. Perioperative data of completion video-assisted thoracoscopic lobectomies were compared with data of 67 upfront video-assisted thoracoscopic lobectomies for clinical stage IA adenocarcinoma performed during the same period.ResultsPostoperative pathological examination revealed 35 malignant and 6 non-malignant diseases. Histologically, all of the malignant diseases were adenocarcinomas of Noguchi type A (n = 7), B (n = 9), C (n = 18), and F (n = 1). Eleven of 19 patients (58%) with Noguchi type C or F underwent two-staged video-assisted thoracoscopic lobectomy. Three patients refused a second surgery. There was no cancer recurrence. The two-staged lobectomy group had a significantly longer operative time and more blood loss than the upfront lobectomy group. There was no surgical mortality or cancer recurrence.ConclusionsTwo-staged lobectomy for undiagnosed small peripheral ground-glass opacity lesions showed satisfactory oncological results. However, low compliance for and invasiveness of the second surgery are concerns associated with this strategy.

Solid tumors versus mixed tumors with a ground-glass opacity component in patients with clinical stage IA lung adenocarcinoma: Prognostic comparison using high-resolution computed tomography findings

This study aimed to compare malignant behavior and prognosis between solid tumors and mixed tumors with a ground-glass opacity component on high-resolution computed tomography. We examined 436 of 502 consecutive patients with clinical stage IA adenocarcinoma who had undergone preoperative high-resolution computed tomography and F-18-fluorodeoxyglucose positron emission tomography/computed tomography; 66 patients with tumors with pure ground-glass opacity components were excluded. Tumor type (solid, n=137; mixed, n=299) and surgical results were analyzed for all patients and their matched pairs. In all patients, solid tumors showed a significantly greater association (P<.001) with lymphatic, vascular, and pleural invasion and lymph node metastasis compared with mixed tumors. The disease-free survival was also worse in patients with solid tumors (P=.0006). Analysis of 97 pairs matched for solid component size confirmed that solid tumors were significantly associated with lymphatic, vascular, and pleural invasion (P=.008, P=.029, P=.003, respectively) and poor prognosis. When maximum standardized uptake value and solid component size were matched (n=79), the differences in pathologic prognostic parameters and disease-free survivals between patients with solid and mixed tumors disappeared. Solid tumors exhibit more malignant behavior and have a poorer prognosis compared with mixed tumors, even when the solid component size is the same in both tumor types. However, differences in malignant behavior can be identified using maximum standardized uptake values determined by F-18-fluorodeoxyglucose positron emission tomography/computed tomography.

Use of High-Resolution Computed Tomography and Positron Emission Tomography/Computed Tomography in the Management of Stage IA Adenocarcinoma

Preoperative determination of malignant behavior is critical in choosing suitable therapeutic strategies such as sublobar resection for patients with small lung cancers. The aim of present review was to evaluate high-resolution computed tomography and fluorodeoxyglucose-positron emission tomography/computed tomography as tools for management of clinical stage IA adenocarcinoma.

Influence of Cigarette Smoking on Survival and Tumor Invasiveness in Clinical Stage IA Lung Adenocarcinoma

The objective of this study was to investigate the association between cigarette smoking, cancer survival, and pathological features of clinical stage IA lung adenocarcinoma. Between August 1992 and December 2007, 1,070 consecutive patients with clinical stage IA lung adenocarcinoma underwent complete resection with systematic lymph node dissection. Univariate analysis by log-rank tests was performed to determine unfavorable prognostic factors, and the Cox proportional hazards regression model was used to identify the potential independent predictors. The overall 5-year survival rate of patients with greater than 20 pack-years (PY>20) was 71%, significantly lower than patients with 20 or less pack-years (PY≤20; 86%; p<0.001). Postoperative pathological prognostic factors, including moderate or poor histologic differentiation, lymphatic permeation, intratumoral vascular invasion, visceral pleural invasion, and lymph node metastasis, were detected more often in patients with greater than 20 PY. Sixty-five percent of the patients in this study had pathological stage IA tumors, and their overall 5-year survival rates with 20 or less PY and greater than 20 PY were 97% and 86%, respectively (p<0.001). In patients with clinical stage IA adenocarcinoma, a history of heavy smoking was associated with poor outcomes and was a statistically significant predictor of histologic tumor invasion.

Multicenter analysis of high-resolution computed tomography and positron emission tomography/computed tomography findings to choose therapeutic strategies for clinical stage IA lung adenocarcinoma

The detection rates of small lung cancers, especially adenocarcinoma, have recently increased. An understanding of malignant aggressiveness is critical for the selection of suitable therapeutic strategies, such as sublobar resection. The objective of this study was to examine the malignant biological behavior of clinical stage IA adenocarcinoma and to select therapeutic strategies using high-resolution computed tomography, fluorodeoxyglucose-positron emission tomography/computed tomography, and a pathologic analysis in the setting of a multicenter study. We performed high-resolution computed tomography and fluorodeoxyglucose-positron emission tomography/computed tomography in 502 patients with clinical T1N0M0 adenocarcinoma before they underwent surgery with curative intent. We evaluated the relationships between clinicopathologic characteristics and maximum standardized uptake values on fluorodeoxyglucose-positron emission tomography/computed tomography, ground-glass opacity ratio, and tumor disappearance rate on high-resolution computed tomography and component of bronchioloalveolar carcinoma on surgical specimens, as well as between these and surgical findings. We used a phantom study to correct the serious limitation of any multi-institution study using positron emission tomography/computed tomography, namely, a discrepancy in maximum standardized uptake values among institutions. Analyses of receiver operating characteristic curves identified an optimal cutoff value to predict high-grade malignancy of 2.5 for revised maximum standardized uptake values, 20% for ground-glass opacity ratio, 30% for tumor disappearance rate, and 30% for bronchioloalveolar carcinoma ratio. Maximum standardized uptake values and bronchioloalveolar carcinoma ratio, tumor disappearance rate, and ground-glass opacity ratio mirrored the pathologic aggressiveness of tumor malignancy, nodal metastasis, recurrence, and prognosis, including disease-free and overall survival. Maximum standardized uptake value is a significant preoperative predictor for surgical outcomes. High-resolution computed tomography and fluorodeoxyglucose-positron emission tomography/computed tomography findings are important to determine the appropriateness of sublobar resection for treating clinical stage IA adenocarcinoma of the lung.