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Objective: To investigate the influence of simple preoperative exercise tests as prognostic factors for early-stage lung cancer., Methods: This single-institution retrospective study included consecutive patients who underwent pulmonary resection for stage 0 to I lung cancer between April 2017 and December 2019. Before surgery, 7 metabolic equivalents of task in the double Master 2-step test were loaded into the exercise echocardiogram. The relationship between prognosis and exercise stress test results in terms of availability, symptoms, and saturation of percutaneous oxygen was investigated., Results: This study included 862 patients with pathological stage 0 to I lung cancer. Among the 862 patients, 673 patients (78.1%) who were able to complete 7 metabolic equivalents of task exercise for 3 minutes without assistance were classified into the complete group. The 5-year survival of the complete group was significantly better than that of the incomplete group. Multivariable analysis revealed that age (hazard ratio, 1.06; P = .008), male sex (hazard ratio, 2.23; P = .011), carcinoembryonic antigen level >5 ng/mL (hazard ratio, 2.33; P = .011), and inability to complete 7 metabolic equivalents of task exercise (hazard ratio, 3.90; P < .001) were the prognostic factors. Patients in the older group who had the ability to complete exercise had a better prognosis than those in the younger group without the ability (P = .003)., Conclusions: Preoperative exercise ability is a prognostic factor for early-stage lung cancer. Patients who can tolerate an exercise load of 7 metabolic equivalents of task, even if they are aged 70 years or older, have a better prognosis than patients younger than age 70 years without exercise tolerance., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: We evaluated the clinicopathological and oncological characteristics of epidermal growth factor receptor-mutated clinical stage IA radiological pure-solid lung adenocarcinoma and compared them with those of a ground-glass opacity component., Methods: Between 2008 and 2020, data from 1014 surgically resected clinical stage 0-IA epidermal growth factor receptor-mutated lung adenocarcinomas were evaluated. Oncological outcomes were assessed using multivariable analysis. Overall survival was estimated using Kaplan-Meier analysis and the log-rank test. The cumulative incidence of recurrence was estimated using the Gray's test., Results: Of these, 233 (23%) were radiologically pure-solid tumors, which demonstrated a higher proportion of nodal metastasis, micropapillary component, spread through alveolar space, and Ex19 subtype compared with those of tumors with ground-glass opacity (P < .001). Multivariable analysis revealed that the presence of ground-glass opacity was an independently significant factor for overall survival (P = .037) and cumulative incidence of recurrence (P < .001). In cases where the oncological outcomes were stratified by the presence of ground-glass opacity component, the 5-year overall survival was excellent at more than 90% in tumors with ground-glass opacity despite clinical-T categories (P = .2044); however, tumor size significantly affected survival only in pure-solid tumors (T1a, 100%; T1b, 77.7%; T1c, 68.5%; P = .0056). Furthermore, the cumulative incidence of recurrence was low in tumors with ground-glass opacity despite the clinical-T categories, whereas tumor size significantly affected the cumulative incidence of recurrence only in pure-solid tumors (5-year cumulative incidence of recurrence: T1a-b, 18.9%; T1c, 41.3%; P < .001)., Conclusions: Oncologic behavior and prognosis of radiologically pure-solid tumors were significantly poorer than those of tumors with ground-glass opacity among patients with epidermal growth factor receptor-mutated early-stage lung adenocarcinoma. These findings imply distinct tumorigenesis based on the presence of ground-glass opacity, even in tumors with epidermal growth factor receptor mutations., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the surgical outcomes of salvage extended surgery after definitive medical treatment with an immune-checkpoint inhibitor (ICI) for locally advanced or unresectable non-small-cell lung cancer (NSCLC)., Methods: The subjects of this single-center retrospective analysis were 14 patients who underwent salvage surgery after ICI treatment between May, 2017 and April, 2023 at our institute. We reviewed the comprehensive surgical outcomes, including operative procedures, intraoperative findings, and postoperative morbidities. Overall survival (OS) was calculated using a Kaplan-Meier estimation., Results: The initial clinical stage before medical treatment (c-stage) was stage III in eight patients, stage IV in five patients, and one patient had postoperative lung cancer recurrence. The indications for surgery were as follows: local control for relapse or residual tumor in ten patients and discontinuation of systemic therapy because of treatment-related complications in four patients. The surgical modes were segmentectomy (n = 1), lobectomy (n = 4), bilobectomy (n = 3), pneumonectomy (n = 6), and bronchoplasty (n = 7). Grade 3 or higher postoperative morbidities were observed in six patients, including only one case of 90-day mortality., Conclusions: Our series demonstrated that the surgical outcome of salvage extended surgery after ICI therapy may be positive with careful selection of the procedure and indication., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

We evaluated the prognostic role of the presence of a very small ground glass opacity (GGO) component in stage IA solid-predominant non-small cell lung cancer (NSCLC). We evaluated surgically resected 1471 patients diagnosed with stage IA solid-predominant NSCLC. They were classified into 3 groups; that is, GGO group (0.5

Background: It is evident that the frequency of nodal metastasis in part-solid lung adenocarcinoma is significantly low. For those cases, the prognostic impact of the lymph node dissection (LND) is highly controversial., Methods: We reviewed 462 clinical stage I radiologic part-solid lung adenocarcinoma patients who underwent lobectomy or segmentectomy with lymphadenectomy. Consolidation tumor ratio was evaluated for all patients. Extent of LND was classified into systematic/lobe-specific mediastinal LND (m-LND) and hilar LND only (h-LND). Prognostic significance of LND was assessed by a multivariable analysis using propensity score matching. Survival was calculated by the Kaplan-Meier method using the log rank test., Results: The m-LND was performed in 314 patients (68%), and h-LND in 148 (32%). Overall survival (OS) was not significantly different between m-LND and h-LND (5-year OS, 94.2% versus 92.8%, p = 0.585), as shown in 92 matched pairs (5-year OS, 94.0% versus 93.2%, p = 0.845). Cox proportional hazards model revealed maximum standardized uptake value as an independently significant oncologic prognosticator (p = 0.003), but extent of LND was not (p = 0.997). Nodal involvement was found in 16 patients, and was exclusive in solid-dominant lesions (ie, 0.5 less than consolidation tumor ratio of 1.0 or less; 4.9%). Multivariable analysis revealed carcinoembryonic antigen and maximum standardized uptake value as significant predictors of nodal metastasis among solid-dominant lesions (0.001, 0.002). For 329 solid-dominant lesions (71%), however, survival was similar between m-LND and h-LND (5-year OS, 93.2% versus 87.1%, p = 0.097), and was proven in 58 matched pairs (5-year OS, 82.9% versus 82.9%, p = 0.822)., Conclusions: Extent of LND was not associated with survival outcome of part-solid lung adenocarcinoma. Furthermore, it had no influence on the prognosis even for solid-dominant lesions by propensity score analysis, which could be selectively omitted based on both preoperative variables including carcinoembryonic antigen or maximum standardized uptake value., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: We evaluated the clinical significance of the presence of a ground glass opacity (GGO) component in clinical stage IA radiologic invasive non-small cell lung cancer (NSCLC)., Methods: We reviewed 497 surgically resected clinical stage IA radiologic invasive NSCLCs, which were then classified into two groups based on consolidation tumor ratio (CTR), that is part-solid (0.5 ≤ CTR < 1.0, n = 177) and pure-solid (CTR = 1.0, n = 320). The part-solid tumors were subdivided into GGO-predominant (0.5 ≤ CTR < 0.75, n = 115) and solid-predominant (0.75 ≤ CTR < 1.0, n = 62) groups. Impact of tumor size was assessed based on CTR using Cox proportional hazards model., Results: Among the radiologic invasive NSCLCs, multivariate analyses revealed that the presence of the carcinoembryonic antigen and a radiologic pure-solid appearance were independent significant prognostic variables (p = 0.019 and 0.034). The 5-year overall survival (OS) revealed significant differences between pure-solid and part-solid tumors (82.7% versus 95.3%, p < 0.0001) and differed significantly among radiologic pure-solid NSCLCs in terms of maximum tumor size (≤20 mm: 86.1%, 21 to 30 mm: 78.1%, p = 0.0274). However, oncologic characteristics between GGO-predominant and solid-predominant types are clinicopathologically similar. The 5-year OS was equivalent in the GGO-predominant and solid-predominant arms (5-year OS: 95.3% versus 96.8%, p = 0.703). Furthermore, it was identical despite the maximum tumor size (≤20 mm: 96.6%, 21 to 30 mm: 94.9%, p = 0.4810) or the solid component size (≤20 mm: 96.0%, 21 to 30 mm: 93.8%, p = 0.6119)., Conclusions: Presence of a GGO component might have a notable impact on a favorable prognosis even in clinical stage IA radiologic invasive NSCLCs. Therefore, a clear distinction between part-solid and pure-solid findings on thin-section computed tomography is extremely important when evaluating the oncologic outcomes of radiologically solid NSCLCs., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to investigate the prognostic impact of tumor size based on the consolidation status by thin-section computed tomography., Methods: We evaluated 1,181 surgically resected clinical N0 M0 non-small cell lung carcinomas. Consolidation tumor ratio (CTR) was evaluated for all, and tumors were classified into three groups, namely pure ground-glass opacity (CTR = 0; n = 168), part-solid (0 < CTR < 1.0; n = 448), and solid (CTR = 1.0; n = 565). The impact of tumor size was assessed based on CTR using Cox proportional hazards model., Results: Tumor size significantly differentiated the 5-year overall survival (≤20 mm; n = 638: 93.4%; 21-30 mm; n = 284: 84.2%; 31-50 mm; n = 193: 69.3%; ≥51 mm; n = 66: 43.5%; p < 0.0001). When we evaluated the impact of tumor size based on CTR, the 5-year overall survival differed significantly in patients with radiologic solid lung cancer (≤20 mm: 83.0%; 21-30 mm: 75.4%; 31-50 mm: 56.2%; ≥51 mm: 45.3%; p < 0.0001). In contrast, it did not affect the 5-year overall survival in patients with radiologic pure ground-glass opacity (100% regardless of the tumor sizes) and part-solid lung cancer (≤20 mm: 97.7%; 21-30 mm: 94.6%; 31-50 mm: 93.4%; p = 0.1028; 0 < CTR ≤ 0.5: 98.4%; 0.5 < CTR < 1.0: 95.0%; p = 0.1247). Furthermore, maximum tumor size (p = 0.6370), solid component size (p = 0.2340), and CTR (p = 0.1395) were not associated with poor overall survival in radiologic part-solid lung cancer., Conclusions: The impact of maximum tumor size should be applied only to radiologic solid lung cancer without the ground-glass opacity component on thin-section computed tomography. On the other hand, we recommend that pure ground-glass opacity and part-solid lung cancers be described, respectively, as clinical-Tis and clinical-T1a, which are independent of maximum tumor size and solid component size on thin-section computed tomography., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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.

Background: The purpose of this study was to evaluate the new lymph node map proposed by the International Association for the Study of Lung Cancer (IASLC) from the point of prognosis, and to identify the significant prognostic factors in each pathological N stage., Methods: We reviewed 647 consecutive patients with surgically resected non-small cell lung cancers. Survival was analyzed according to N stage and three prognostic subgroups: N1a (single N1 zone), N1b (multiple N1 zones) or N2a (single N2 zone), and N2b (multiple N2 zones). The following prognostic factors were evaluated for each N stage: location of involved zones, number of involved lymph nodes, stations and zones, and the presence of skip metastases., Results: (1) The survival curves showed a stepwise deterioration as the N stage increased. (2) No significant difference was observed in survival between the different locations of involved zones in each N stage. (3) In N2 patients, the presence of skip metastases was a significant prognostic factor in multivariate analysis., Conclusions: The proposed IASLC map is valid for prognostic stratification. The prognostic impact of the presence of skip metastases on N2 disease should therefore be taken into consideration when carrying out the forthcoming revision of the TNM staging system., (Georg Thieme Verlag KG Stuttgart, New York.)

Background: The evidence of clinical value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) in lymph node (LN) staging in non-small cell lung cancer (NSCLC) has been shown in numerous papers. However, few studies have assessed its limitations. The aim of the present study is to clarify clinico-pathologic factors responsible for false PET results., Methods: From July 2000 through December 2001, 71 NSCLC patients underwent both FDG PET and surgical intervention at the National Cancer Center Hospital East, Chiba. Clinical records, computed tomographic (CT) scan findings, PET findings, and histologic findings were retrospectively reviewed., Results: Sensitivity, specificity, accuracy in nodal staging for CT were 29, 83, and 65% and for PET were 39, 79, and 66%, respectively. There were 10 (14%) false-positive PET scans and 14 (20%) false-negative PET scans. The causative factors for false-positive PET scan were: (1) inflammatory conditions in seven patients; (2) PET mis-localization of an interlobar LN as a mediastinal LN in one patient; (3) inability to distinguish the endobronchial polypoid growth of a primary tumor from a lobar LN in one patient; (4) unknown in one patient. All false-positive LNs due to inflammatory conditions showed reactive lymphoid hyperplasia histologically. The causative factors for false-negative PET scan were: (1) limitation of spatial resolution of the PET scanner in 12 patients (maximum tumor focus dimensions in false-negative LNs ranging from 1 to 7.5 mm, with an average of 3.4 mm); (2) PET mis-localization of a mediastinal LN as a hilar LN in one patient; (3) weak FDG uptake by microscopic tumor foci due to necrosis with massive bleeding in a metastatic LN in one patient., Conclusions: Inflammatory conditions were most responsible for false-positive PET scans, and spatial resolution limitation of FDG PET was the causative factor of false-negative PET scans. Recognizing these factors in advance would be clinically helpful in accurate nodal staging with FDG PET.