OBJECTIVE:Although recent trials on intentional segmentectomy have made mediastinal lymph node dissection (MLND) mandatory, the necessity of MLND in segmentectomy remains uncertain. We conducted a retrospective study to evaluate the necessity of MLND in segmentectomy for patients with peripheral stage IA (≤2 cm) non-small cell lung cancer. METHODS:Of the 5222 surgical cases for non-small cell lung cancer from 3 institutions between 2010 and 2021, 1457 patients met the JCOG0802 trial eligibility criteria. Initially, we analyzed 574 patients who underwent lobectomy with MLND to identify preoperative risk factors for cN0-pN2 occurrence (cohort 1). Subsequently, we evaluated the relationship between these factors and the cumulative postoperative recurrence in 390 patients who underwent segmentectomy (cohort 2). RESULTS:In cohort 1, risk factors for cN0-pN2 occurrence were consolidation-to-tumor ratio = 1.0 and maximum standardized uptake value ≥2.0. When classifying patients into 3 groups (group A, without any factors, group B, with either factor, and group C, with both factors), the occurrence of cN0-pN2 was significantly greater in group C than in the other groups (0.9%, 3.4%, and 8.4%, respectively, P = .005). When classifying patients in cohort 2 using the classification identified in cohort 1 (117, 131, and 142 were categorized into group A, group B, and group C, respectively), the 5-year cumulative incidence of recurrence rate was significantly greater in group C than in others (2.0%, 2.0%, and 15.9%, respectively, P < .001). CONCLUSIONS:MLND is unlikely to be beneficial in intentional segmentectomy for patients with tumors showing consolidation-to-tumor ratio <1.0 and maximum standardized uptake value <2.0.

The recent Cancer and Leukemia Group B 140503 multicenter randomized trial compared sublobar resection (wedge resection vs. segmentectomy) for treatment of peripheral cN0 non-small cell lung cancer (NSCLC) measuring ≤2 cm, with consolidation tumor (CT) ratio >0.25 and reported comparable intergroup findings with regard to postoperative disease-free survival (DFS) and overall survival (OS). However, the differences, if any, in prognosis between wedge resection and segmentectomy performed for NSCLC remain unknown.

The current N classification for lung cancer has a high heterogeneity owing to the characteristics of involved lymph nodes. The International Association for the Study of Lung Cancer has proposed further subdivisions of the N classification in the upcoming TNM staging system. In the present study, we aimed to verify whether current N1 and N2 staging could stratify prognosis based on the zone and the number of involved nodal stations using a multicenter database in Japan.

KRAS mutation is one of the major somatic variants in lung adenocarcinoma. KRAS inhibitor for G12C variant has been clinically available and clinical trials evaluating the combination of KRAS G12C inhibitor and another target inhibitor are on-going. A nucleotide change from guanine to thymine occurs in KRAS G12C (c.34G>T), and this change is also known as smoking-inducing somatic variant. G12C can occur in squamous cell carcinoma but its frequency or the therapeutic effectiveness of KRAS G12C inhibitor is unknown in squamous cell carcinoma.

Based on the results of the JCOG0802 and CALGB 140503 trials, segmentectomy has becomes one of the standard procedures for stage IA non-small-cell lung cancer (NSCLC) with tumor size ≤2 cm. However, it is still unclear whether mediastinal lymph node dissection is necessary in segmentectomy for these cases because the JCOG 0802 trial required mediastinal lymph node dissection for their participants.

The effect of adjuvant chemotherapy for tumors with epidermal growth factor receptor (EGFR) mutation has not been fully elucidated. The aim of this study was to evaluate the role and effect of adjuvant chemotherapy based on EGFR mutation status in patients with stage II/III lung adenocarcinoma.

The major risk factor in diffuse pleural mesothelioma (PM) is occupational and/or geographical asbestos exposure. Surgery is a treatment option in only a limited number of cases. Prognosis is very poor with current therapies and new treatment options are needed. Immune checkpoint inhibitors (ICIs) may be a treatment option in PM, as in other malignant tumors. However, it is necessary to use predictive biomarkers to determine which patients will benefit from treatment. PD-L1 immunohistochemistry is widely used to predict therapy response to ICIs in many tumors.

Recurrence risk of resected lung adenocarcinoma is represented by pathological stage (pStage), histological subtype, and potentially by EGFR mutation status. However, the relationship among these factors and their combined impact on prognosis are unclear. Using a multicenter database, we retrospectively investigated the recurrence risk of pN0–1M0 non-variant lung adenocarcinoma based on pStage, histological subtype, and EGFR mutation status.

OBJECTIVE:The aim of this study was to evaluate the role and effect of adjuvant chemotherapy based on epidermal growth factor receptor mutation status in patients with stage I lung adenocarcinoma.METHODS:Between 2010 and 2016, of 1901 patients with pathologic stage I (8th edition) non-small cell lung cancer, we identified 475 with high-risk (pT1c/T2a or positive for lymphovascular invasion) stage I lung adenocarcinoma who underwent lobectomy. We estimated propensity scores to adjust for confounding variables, including age, sex, Brinkman index, pulmonary functions, comorbidities, surgical approach, invasive component tumor size, visceral pleural, lymphatic, and vascular invasion, adenocarcinoma subtype, epidermal growth factor receptor mutation status, postoperative complications, and institution associated with the administration of adjuvant chemotherapy. The primary end point was recurrence-free survival.RESULTS:Of 292 patients without/unknown epidermal growth factor receptor mutation, 105 (36.0%) received adjuvant chemotherapy and 187 (64.0%) did not. In 69 pairs of patients who were propensity score matched, the 5-year recurrence-free survival was significantly better in those who underwent adjuvant chemotherapy (88.4%) than in those who did not (63.6%; P = .001). Of 183 patients with epidermal growth factor receptor mutation, 78 (42.6%) received adjuvant chemotherapy and 105 (57.4%) did not. In 49 pairs of propensity score-matched patients, there was no significant difference in the 5-year recurrence-free survival between those who underwent adjuvant chemotherapy (74.3%) and those who did not (80.5%; P = .573).CONCLUSIONS:The effect of adjuvant chemotherapy for high-risk stage I lung adenocarcinoma varied by epidermal growth factor receptor mutation status. Epidermal growth factor receptor mutation status may help to identify patients with high-risk stage I lung adenocarcinoma who may benefit from adjuvant chemotherapy.

Circulating small RNAs have been reported as biomarkers for cancer diagnosis, including lung cancer. The purpose of this study is to identify the small RNA for the early detection of lung adenocarcinoma. In this study, we used next generation sequencing (NGS) in order to screen and validate expressions of the small RNAs between persons with and without adenocarcinoma and built the RNA-based biomarker panel. We used next generation sequencing in all phases (screening set, validation set, and the panel evaluation set) and researched micro RNAs(miR) and transfer RNA fragments(tRF) as small RNAs. We analyzed the RNAs from serum of 21 patients with adenocarcinoma and 20 healthy control for screening and assessed small RNAs from 22 patients with adenocarcinoma and 20 healthy control for validation. Regarding significantly upregulated and downregulated small RNAs, we built RNA-based biomarker panel and evaluated the panel with a different dataset (33 patients with adenocarcinoma and 27 healthy control). Based on screening and validation set, four miR and one tRF were upregulated. Tow miR and nine tRF were downregulated. An area under the curve value of each small RNA was 0.65 to 0.85. Among them, nine small RNA were adopted to the biomarker panel by using multiple regression analysis. In the cohort of screening and validation set, the panel showed a sensitivity of 93.0% and specificity of 88.0%, with an area under the curve value of 0.983, which was much larger than that of a single RNA. The panel was evaluated with a different dataset and showed a sensitivity of 90% and specificity of 74.1% when the threshold was 1.8. In conclusion, we built the small RNA-based biomarker panel which included nine small RNA and our results showed the diagnostic efficacy of the panel. Further investigation is required to understand the cause for the expression change of each small RNA.

Background In early stage non-small cell lung cancer (NSCLC), the anatomical resection with lymph node dissection is a standard procedure as a curative intent while wedge resection is considered as a passive treatment. However, optimal treatment strategy for elderly ( > = 80 y.o.) patients remains controversial. We attempted to disclose the role of wedge resection without lymph node dissection as a treatment option in octogenarians or older. Methods Among 671 patients with clinical stage IA NSCLC with whole tumor size is 2 cm or less and consolidation to tumor ratio is more than 0.5 underwent R0 resection in three institutions between 2010 and 2015, 55 octogenarians or older were investigated about clinicopathological findings and prognosis based on surgical procedures and lymph node dissection status. Results The median follow-up time was 35 months. The 3-year overall survival (OS) rate for octogenarians or older was 83.8% (95% confidential interval (CI): 69.7-91.7%). No significant differences for OS were detected among three surgical procedures (3-year OS rate: wedge resection: 88.5% (95%CI: 68.4-96.1%), segmentectomy: 83.3% (95%CI: 27.3-97.5%) , and lobectomy: 78.9% (95%CI: 53.0-91.6%), P = 0.72) or lymph node dissection status (3-year OS rate: ND0: 88.9% (95%CI: 69.4-96.3%) and ND1 or 2: 77.0% (95%CI: 50.8-90.4%), P = 0.95). The multivariable Cox regression analysis revealed that male gender (Hazard ratio (HR): 4.7 (1.1-20.2), P = 0.039) and larger solid tumor size (HR: 5.8 (1.1-29.9), P = 0.035) were independent poor prognostic factors whereas surgical procedure (wedge resection vs. segmentectomy or lobectomy) (HR: 0.50 (0.15-1.7), P = 0.27) was not. In another model, lymph node dissection status (ND0 vs. ND1 or 2) (HR: 0.51 (0.15-1.8), P = 0.28) was not found to be a prognostic factor. Conclusions In octogenarians or older with early stage NSCLC, wedge resection without lymph node dissection might be an alternative option to lobectomy or segmentectomy with lymph node dissection. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

The ground glass opacity (GGO) ratio is associated with the prognosis of small (<30 mm) non-small cell lung cancer (NSCLC). However, the clinical features, especially the GGO ratio, and prognosis of NSCLC exceeding 30 mm are not well known. Therefore, this study aimed to determine the characteristics of patients with NSCLC exceeding 30 mm and analyze the clinical significance of the GGO ratio on prognosis. Totally, 271 patients with NSCLC tumors exceeding 30 mm on preoperative computed tomography scans and who underwent complete resection at our institution between January 2007 and December 2017 were included. The patients were divided into three groups based on the GGO ratio: pure solid tumors, GGO ratio 0–40%, and GGO ratio ≥40%. The cut-off value of 40% was determined based on the recurrence rate for each GGO ratio group. Clinical feature and prognosis of each group were analyzed. Of the included patients, 147 (54%) had pure solid nodule, 67 (25%) had nodules with a GGO ratio 0–40%, and 57 (21%) had nodules with a GGO ratio ≥40%. Among the patients with a GGO ratio ≥40%, 10 underwent limited resection (segmentectomy in 9 patients and wedge resection in 1); no patients experienced recurrence. Among the 147 patients with pure solid nodules, 47 (32%) experienced recurrence. Among the 67 and 57 patients with GGO ratio 0–40% and GGO ratio ≥40%, 16 (24%) and 2 (4%), respectively, experienced recurrence. The 3-year recurrence-free survival (RFS) rate was significantly shorter in patients with pure solid nodules (60.5%) than in patients with GGO ratio 0–40% (74.0%; p=0.010) and GGO ratio ≥40% ( 93.6%; p<0.001). Moreover, RFS was significantly shorter in patients with GGO ratio 0–40% than in patients with GGO ratio ≥40% (p=0.009). Similar results were observed for overall survival (OS). The 3-year OS rate was significantly shorter in patients with pure solid nodules (79.1%) than in patients with GGO ratio 0–40% (88.2%; p=0.046) and GGO ratio ≥40% (95.6%; p<0.001). Moreover, OS was shorter in patients with GGO ratio 0–40% than in patients with GGO ratio ≥40% with marginal significance (p=0.052). A pure solid nodule was a major component among NSCLC tumors exceeding 30 mm. Among such patients, as the GGO ratio decreased, the recurrence rate increased. A GGO ratio of 40% is the appropriate cut-off value, and patients with GGO ratio ≥40% have better prognosis compared to patients with GGO ratio <40% or pure solid nodules. The prognosis of patients with GGO ratio ≥40% who undergo limited resection may be similar to that of patients undergoing lobectomy, the standard operation procedure.

Lung cancer complicated with idiopathic interstitial pneumonia (IIPs) is known to lead to worse prognosis. Recently, it has been reported that the pathological characteristics differ between the lung cancer arising the honeycomb lesion of interstitial pneumonia (H-IIP group) and arising in other lesions (NH-IIP group). In this study, we aimed to assess the clinicopathologic outcome of resected lung cancer in each group. From a single center database of 1065 consecutive patients with clinical stage IA non-small cell lung cancer who had undergone preoperative high-resolution computed tomography and F-18-fluorodeoxyglucose positron emission tomography/ computed tomography, 112 patients with a radiologically determined IIP (H-IIPs; n=33, NH-IIP; n=79) were included in this study. Examination of clinicopathological outcomes were performed comparing each group. Median solid tumor size of each group were similar (18.4mm vs 18.6mm p=0.928), but median ground gloss opacity rate is significantly higher in NH-IIP group (6.7% vs 21.4% p=0.042). In the histopathological types, H-IIP group had significantly high rate of squamous cell carcinoma (45.5% vs 27.9%) and NH-IIP group had adenocarcinoma (27.3% vs 57.0%). As in previous reports, the proportion of EGFR mutation in adenocarcinomas tended to be high in NH-IIPs and also the high proportion of lepidic predominant. The disease-free survival (DFS) and overall survival (OS) were worse in patients of H-IIP group compared to NH-IIP group (DFS p=0.028, OS p=0.035). In a multivariate analysis, the H-IIP group and lower diffusing capacity for carbon of preoperative pulmonary functional test were significant worse predictors of OS and RFS (P <0.001, respectively). Lung cancer arising the honeycomb lesion of IIP had a great unfavorable impact on the prognosis of NSCLC, because of the worse pathological features.