Aritoshi Hattori

The size of consolidation on thin-section computed tomography is a better predictor of survival than the maximum tumour dimension in resectable lung cancer

OBJECTIVES Ground-glass opacity (GGO) is a preoperative prognostic factor in resectable lung cancer. However, the impact of GGO on the T factor in the TNM staging system remains unclear and the maximum tumour dimension is also an uncertain measurement for assessing the prognosis of early lung cancer with a mixture of consolidation and GGO. Thus, we sought to determine which the better prognostic factor was, the size of the consolidation on computed tomography scan or the conventional maximum tumour dimension. METHODS Between January 2004 and January 2011, 398 consecutive clinical stage IA lung cancer patients underwent surgical resection at our hospital. Univariate and multivariate analyses were performed by the logistic regression procedure to determine the relationship between pathological lymph node metastasis-positive status and clinical or radiological findings such as the maximum dimensions of consolidation and the tumour, the presence of air bronchogram, pleural indentation and the preoperative serum carcinoembryonic antigen (CEA) level. RESULTS Of the 398 patients, 59 (14.8%) had pathological lymph node metastasis. Univariate analysis revealed four significant predictors of pathological nodal involvement: the presence of air bronchogram, the size of consolidation, the maximum tumour dimension and the preoperative CEA level (P < 0.01, respectively). In a multivariate analysis, the size of consolidation and the presence of air a bronchogram were significant predictors of nodal metastasis (P < 0.01, respectively). CONCLUSIONS The maximum dimension of the consolidation was an independent unfavourable prognostic factor, regardless of the maximum tumour dimension. This could lead to the more accurate prediction of pathological lymph node metastasis with both GGO and consolidation.

Tumour standardized uptake value on positron emission tomography is a novel predictor of adenocarcinoma in situ for c-Stage IA lung cancer patients with a part-solid nodule on thin-section computed tomography scan†

OBJECTIVES Adenocarcinoma in situ (AIS), which is considered to be pathologically non-invasive in the new International Association for the Study of Lung Cancer/the American Thoracic Society/the European Respiratory Society classification, might be present in patients who show a part-solid nodule on thin-section computed tomography (CT) scan. METHODS Between 2008 and 2011, 556 clinical Stage IA (c-Stage IA) lung cancer patients underwent pulmonary resection. For all the patients, the findings obtained by preoperative thin-section CT were reviewed and categorized as pure ground-glass nodule (GGN), part-solid nodule or pure-solid nodule based on the findings on thin-section CT, i.e. based on the consolidation/tumour ratio (CTR). A part-solid nodule was defined as a tumour with 0 < CTR < 1.0, which indicated focal nodular opacity that contained both solid and GGN components. All the 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 in clinical Stage IA lung cancer patients with a part-solid nodule radiologically, using multivariate analyses. RESULTS One-hundred and twelve c-Stage IA lung cancer patients showed a part-solid appearance on thin-section CT. Among them, AIS was found in 10 (32%) of the tumours with 0 < CTR ≤ 0.5, in contrast to 3 (5%) with 0.5 < CTR < 1.0. According to multivariate analyses, SUVmax and CTR significantly predicted AIS in patients with a part-solid nodule (P = 0.04, 0.02). The mean SUVmax of the patients with AIS was 0.57 (0-1.6). Moreover, in the subgroup of part-solid nodule with a SUVmax of ≤1.0 and a CTR of ≤0.40, which were calculated as cut-off values for AIS based on the results for a receiver operating characteristic curve, 6 (40%) patients with these criteria showed a pathological non-invasive nature, even patients with a part-solid nodule. CONCLUSIONS Among c-Stage IA adenocarcinoma with a part-solid nodule on thin-section CT scan, an extremely low level of SUVmax could reflect a pure GGN equivalent radiologically and AIS pathologically. The preoperative tumour SUVmax on PET could yield important information for predicting non-invasiveness in patients with a part-solid nodule.

What is the appropriate operative strategy for radiologically solid tumours in subcentimetre lung cancer patients

OBJECTIVES Solid lung cancers, even subcentimetre lesions, are considered to be invasive pathologically. However, the clinicopathological features and appropriate operative strategies in patients with these small lesions are still controversial, especially for those with a radiologically solid appearance. METHODS Between 2004 and 2011, 135 patients underwent pulmonary resection for subcentimetre lung cancer with clinical-N0 (c-N0) status. The findings of preoperative thin-section computed tomography (CT) were reviewed, and subcentimetre lung cancer was divided into three groups: pure ground-glass nodule, part-solid and pure-solid lesions. RESULTS Among the 135 subcentimetre lung cancer patients with c-N0 status, 71 showed a solid appearance on thin-section CT scan. Furthermore, pathological nodal examinations were performed in 49 patients, and nodal involvement was found pathologically in 6 (12.2%) patients. All of them had pure-solid tumours (P = 0.0010). Among the patients with solid subcentimetre lung cancers, the maximum standardized uptake value (SUVmax) was the only significant predictor of nodal involvement by a multivariate analysis (P = 0.0205). With regard to the surgical outcomes, the overall 5-year survival and disease-free survival rates were 100 and 97.8% for part-solid lesions, and 87.3 and 74.8% for pure-solid lesions, respectively. Moreover, there was a significant difference in disease-free survival between a high SUVmax group (60.0%) and a low SUVmax group (94.9%) (P = 0.0013). CONCLUSIONS There might be a possibility of lymph node metastasis despite subcentimetre lung cancer, especially for radiological pure-solid nodules that show a high SUVmax. If limited surgery is indicated for solid subcentimetre lung cancer, a thorough intraoperative evaluation of lymph nodes is needed to prevent loco-regional failure.

Lung cancer with scattered consolidation: detection of new independent radiological category of peripheral lung cancer on thin-section computed tomography

OBJECTIVES Ground glass opacity (GGO) on thin-section computed tomography (CT) has been reported to be a favourable prognostic marker in lung cancer, and the size or area of GGO is commonly used for preoperative evaluation. However, it can sometimes be difficult to evaluate the status of GGO. METHODS A retrospective study was conducted on 572 consecutive patients with resected lung cancer of clinical stage IA between 2004 and 2011. All patients underwent preoperative CT and their radiological findings were reviewed. The areas of consolidation and GGO were evaluated for all lung cancers. Lung cancers were divided into three categories on the basis of the status of GGO: GGO, part solid and pure solid. Lung cancers in which it was difficult to measure GGO were selected and their clinicopathological features were investigated. RESULTS Seventy-one (12.4%) patients had lung cancer in whom it was difficult to measure GGO. In all these cases, consolidation and GGO were not easily measured because of their scattered distribution. In this cohort, nodal metastases were not observed at all. The frequency of other pathological factors, such as lymphatic and/or vascular invasion, was significantly lower (P < 0.0001). CONCLUSIONS This new category of lung cancer with scattered consolidation on thin-section CT scan tended to be pathologically less invasive. When lung cancer has GGO and is difficult to measure because of a scattered distribution, its prognosis could be favourable regardless of the area of GGO. This new category could be useful for the preoperative evaluation of lung cancer.

Oncological Characteristics of Radiological Invasive Adenocarcinoma with Additional Ground-Glass Nodules on Initial Thin-Section Computed Tomography: Comparison with Solitary Invasive Adenocarcinoma.

Introduction: We aimed to evaluate the oncological outcomes of radiological invasive adenocarcinoma with additional ground‐glass nodules (AGGNs) on initial thin‐section computed tomography (CT). Methods: We examined 473 patients with surgically resected clinical stage IA lung adenocarcinoma showing a radiological invasive appearance on thin‐section CT. Radiological invasiveness was defined as a solid tumor with a consolidation tumor ratio of at least 0.5 but no greater than 1.0 on thin‐section CT. Results: Ninety patients (19%) had dominant invasive adenocarcinoma (DA) with AGGNs, whereas 383 (81%) had solitary invasive adenocarcinoma (SA). DA showed a significantly lower maximum standardized uptake value of 18F‐fluorodeoxyglucose on positron emission tomography (p = 0.0086), higher frequency of radiological part solid tumor (p = 0.0232) and histological lepidic predominant tumor (p = 0.0015), and lesser presence of nodal involvement (p = 0.0350) and lymphovascular invasion (p = 0.0001) than with SA. Surgically resected AGGNs were shown to be pathologically atypical adenomatous hyperplasia in 17% of patients, adenocarcinoma in situ in 53%, and minimally invasive adenocarcinoma in 21%. Furthermore, the 5‐year overall survival of DA with AGGNs was better than that of SA, and the difference was significant (92.2% versus 79.9%, p = 0.0323). On the basis of a multivariate analysis, tumor size, maximum standardized uptake value, and consolidation status of DA/SA were significant prognostic factors of survival for all patients (p = 0.0039, 0.0236, and 0.0385, respectively), whereas the presence of AGGNs was not associated with poor overall survival (p = 0.4809). Conclusion: DA accompanied by AGGNs showed an oncologically less invasive nature compared with SA. Presence of AGGNs is not related to poor prognosis, and is neither indicative of an advanced stage nor a contraindication to surgical resection in patients with clinical stage IA radiological invasive adenocarcinoma.

Prognostic impact of a ground glass opacity component in the clinical T classification of non–small cell lung cancer

Objective: To determine whether solid component size and the presence of a ground glass opacity (GGO) component are independently associated with survival outcomes in patients with early‐stage non–small cell lung cancer (NSCLC) using the eighth edition Lung Cancer Stage Classification. Methods: We retrospectively evaluated 1029 surgically resected early‐stage NSCLCs. T categories were assigned based on solid component size using the eighth classification. All tumors were classified into 1 of 2 groups: the GGO group or the solid group. We evaluated the prognostic impact of several clinicopathological variables in clinical T classification using a Cox proportional hazard model. Results: On multivariable analysis, the presence of a GGO component (hazard ratio [HR], 0.314; 95% confidence interval [CI], 0.181–0.529: P < .001) and solid component size (HR, 1.021; 95% CI, 1.006–1.036; P = .006) were identified as independently significant prognostic factors of overall survival. However, after accounting for the presence of a GGO component, neither maximum tumor size nor solid component size added to the prediction of long‐term survival. Moreover, tumor size significantly affected survival outcome only in the solid group (HR, 1.020; 95% CI, 1.006–1.034; P = .004). Survival was excellent at ≥90% despite the revised T categories, provided that the tumor had a ground glass appearance. Meanwhile, tumor size significantly affected survival only in the solid group (P < .001). Conclusions: The presence of a GGO component is a significant prognostic factor in early‐stage NSCLC. External validation is required to assess whether it should be adopted as a novel factor in clinical T staging.

Indications for sublobar resection of clinical stage IA radiologic pure-solid lung adenocarcinoma

Objectives: The aim of this study was to identify clinical factors associated with lepidic growth in resected clinical stage IA radiologic pure‐solid lung adenocarcinoma for identifying a possible sublobar resection candidate in the population. Methods: Clinicopathologic data were reviewed for 200 surgically resected clinical stage IA pure‐solid lung adenocarcinomas. Radiologic pure‐solid tumor was defined as a tumor without a ground‐glass opacity component, that is, a consolidation tumor ratio equal to 1.0. Lepidic predominant adenocarcinoma included adenocarcinomas in situ, minimally invasive adenocarcinomas, and lepidic predominant invasive adenocarcinomas. Results: A total of 57 patients (29%) had lepidic predominant adenocarcinoma. The 5‐year overall survival of clinical stage IA pure‐solid adenocarcinoma was 83.4% and that of lepidic predominant adenocarcinoma and nonlepidic predominant adenocarcinoma was 98.1% versus 76.6% (P = .0012). A multivariate analysis revealed that maximum standardized uptake value was an independently significant variable of lepidic predominant adenocarcinoma (P < .0001) and a significant prognostic factor (P = .034). The predictive criterion of lepidic predominant adenocarcinoma was maximum standardized uptake value 3.3 or less based on a receiver operating characteristic curve, and 77 patients (39%) who met this criterion showed less pathologic invasiveness regarding lymphatic (P = .0012) and vascular (P < .0001) invasions, nodal metastasis (P = .0007), and better overall survival than those who did not (maximum standardized uptake value ≤3.3 vs >3.3 rates being 91.7% vs 78.6%, P = .0031). Moreover, the 3‐year locoregional recurrence‐free survival of the sublobar resection arm was significantly worse than that of the lobectomy arm when the tumor showed maximum standardized uptake value greater than 3.3 (62.7% vs 82.9%, P = .0281). Conclusions: Higher maximum standardized uptake value may be useful for identifying patients with clinical stage IA radiologic pure‐solid lung adenocarcinoma in whom sublobar resection should not be considered, even if technically feasible.

Prognostic Impact of the Findings on Thin-Section Computed Tomography in Patients with Subcentimeter Non–Small Cell Lung Cancer

Introduction: Subcentimeter NSCLC is not always an early‐stage disease despite its small tumor size. We investigated the prognostic impact of such cancers on the basis of the findings of thin‐section computed tomography (CT). Methods: We evaluated the clinicopathological features and prognosis of 328 surgically resected clinical‐N0 NSCLCs 1.0 cm or less in size. Consolidation‐to‐tumor ratio (CTR) was evaluated for all, and tumors were classified into three groups, namely, pure ground glass opacity (GGO) (CTR = 0 [n = 139]), part solid (0 < CTR < 1.0 [n = 123]), and pure solid (CTR = 1.0 [n = 66]). Results: Pathological nodal involvement was observed in seven patients, with all cases found exclusively in pure solid subcentimeter NSCLC (10.9%). Furthermore, a multivariate analysis revealed that the presence of GGO was an independently significant clinical factor in overall survival (OS) and recurrence‐free survival (RFS) (OS: p = 0.0340; RFS: p = 0.0018). Histological examination revealed that 134 of the 139 cases of pure GGO (97%), 99 of the 123 cases of part solid tumor (81%), and 16 of the 66 cases of pure solid tumor (25%) were lepidic predominant lung adenocarcinoma. Evaluation of the oncological outcomes on the basis of CTR revealed that 5‐year OS and RFS rates were significantly better in patients with nonsolid tumors (OS and RFS = 100%) or part solid tumors (OS = 97.5% and RFS=94.9%), whereas the OS and RFS rates of patients with pure solid subcentimeter NSCLC were 87.6% and 79.3%, respectively (OS: p = 0.0015; RFS: p < 0.0001). Conclusions: The findings of thin‐section CT are extremely important when considering the prognosis of subcentimeter NSCLC. Radiologically determined solid subcentimeter NSCLCs should be treated as invasive tumors regardless of their small size.

The presence of air bronchogram is a novel predictor of negative nodal involvement in radiologically pure-solid lung cancer.

OBJECTIVES Phase III trials regarding the feasibility of segmentectomy for lung cancer ≤ 2 cm in size are now underway in Japan and the USA. However, despite their small size, lung cancers that show a pure-solid appearance on thin-section computed tomography (CT) are considered to be invasive with a high frequency of nodal involvement. METHODS Between 2008 and 2011, 556 clinical Stage IA lung cancer patients underwent pulmonary resection. For all patients, the findings obtained by preoperative thin-section CT were reviewed and the maximum standardized uptake value (SUVmax) on positron emission tomography was recorded. Several clinicopathological features were investigated to identify predictors of nodal metastasis using multivariate analyses. RESULTS One hundred and eighty-four clinical Stage IA lung cancer patients showed a pure-solid appearance on thin-section CT. Among them, air bronchogram was found radiologically in 58 (32%) patients. Nodal involvement was observed in 10 (17%) patients with air bronchogram, compared with 43 (34%) without air bronchogram, in clinical Stage IA pure-solid lung cancer. A multivariate analysis revealed that air bronchogram, clinical T1a and SUVmax were significant predictors of postoperative nodal involvement (P < 0.01, <0.01, and 0.03, respectively). Furthermore, nodal metastasis was never seen in patients with clinical T1a pure-solid lung cancers who had both air bronchogram and low SUVmax. CONCLUSIONS The presence of air bronchogram was a novel predictor of negative nodal involvement in clinical Stage IA pure-solid lung cancer. Segmentectomy with thorough lymph node dissection is a feasible option for these patients despite a pure-solid appearance.

Locoregional recurrence after segmentectomy for clinical-T1aN0M0 radiologically solid non-small-cell lung carcinoma†

Objectives We aimed to identify the clinicopathological features of loco-regional recurrence after segmentectomy for clinical-T1aN0M0 radiologically invasive non-small-cell lung carcinoma (NSCLC). Methods Between 2008 and 2014, 353 patients underwent pulmonary lobectomy or segmentectomy with nodal dissection for clinical-T1aN0M0 radiologically invasive NSCLC showing 0.5 ≤ consolidation tumour ratio (CTR)≤1.0 on thin-section computed tomography (CT). Radiological invasive NSCLC was divided into two groups, i.e. part-solid (0.5 ≤ CTR < 1.0) and pure-solid (CTR = 1.0). Significant prognostic factors for oncological outcomes were evaluated by multivariate analysis. Results Lobectomy was performed in 270 (76.5%) patients and segmentectomy in 83 (23.5%). Locoregional recurrence-free survival (LRFS) of clinical-T1a radiologically invasive NSCLC on the whole showed no significant differences between the lobectomy and segmentectomy arms (3-year LRFS, 93.0 vs 90.1%, P  = 0.2725). In contrast, the multivariate analysis revealed that radiologically pure-solid appearance and tumour size were significant predictors of loco-regional recurrence ( P  = 0.0106, 0.0408). Among 212 clinical-T1a radiologically pure-solid NSCLCs, frequency of loco-regional recurrence was high in the segmentectomy arm (20.7%) compared with that of lobectomy arm (8.2%). Furthermore, segmentectomy and larger tumour size were independent significant clinical factors of loco-regional recurrence based on the multivariate analysis ( P  = 0.0292, 0.0402). The 3-year LRFS of the segmentectomy arm was significantly worse than that of the lobectomy arm in the c-T1a disease (82.2 vs 90.6%, P  = 0.0488) provided the tumour showed a pure-solid appearance. Conclusions Even in cases of small-sized lung carcinoma, segmentectomy should be applied with great caution especially for a radiological pure-solid NSCLC on thin-section CT due to their high incidence of loco-regional recurrence.