Computed tomography characteristics of cN0 primary non-small cell lung cancer predict occult lymph node metastasis.

RATIONALE: Occult lymph node metastasis (OLNM) is frequently found in patients with resectable non-small cell lung cancer (NSCLC), despite using diagnostic methods recommended by guidelines. OBJECTIVES: To evaluate the risk of OLNM in NSCLC patients using the radiologic characteristics of the primary tumor on computed tomography (CT). METHODS: We retrospectively reviewed clinicopathologic features of 2042 clinical T1-4N0 NSCLC patients undergoing curative intent pulmonary resection. Unique radiological features (i.e., air-bronchogram throughout the whole tumor, heterogeneous ground-glass opacity (GGO), mainly cystic appearance, endobronchial location), percentage of solid portion, and shape of tumor margin were analyzed via a stepwise approach. We used multivariable logistic regression to assess the relationship between OLNM and tumor characteristics. RESULTS: Compared with the other unique features, endobronchial tumors were associated with the highest risk of OLNM (OR = 3.9, 95% confidence interval (CI) = 2.29-6.62), and heterogeneous GGO and mainly cystic tumors were associated with a low risk of OLNM. For tumors without unique features, the percentage of the solid portion was measured, and solid tumors were associated with OLNM (OR = 2.49, 95% CI = 1.86-3.35). Among part-solid tumors with solid proportion > 50%, spiculated margin, and peri-tumoral GGO were associated with OLNM. CONCLUSIONS: The risk of OLNM could be assessed using radiologic characteristics on CT. This could allow us to adequately select optimal candidates for invasive nodal staging procedures (INSPs) and complete systematic lymph node dissection. CLINICAL RELEVANCE STATEMENT: These data may be helpful for clinicians to select appropriate candidates for INSPs and complete surgical systematic lymph node dissection in NSCLC patients. KEY POINTS: Lymph node metastasis status plays a key role in both prognostication and treatment planning. Solid tumors, particularly endobronchial tumors, were associated with occult lymph node metastasis (OLNM). The risk of OLNM can be assessed using radiologic characteristics acquired from CT images.

Preoperative DLco and FEV1 are correlated with postoperative pulmonary complications in patients after esophagectomy.

Limited information is available regarding the association between preoperative lung function and postoperative pulmonary complications (PPCs) in patients with esophageal cancer who undergo esophagectomy. This is a retrospective cohort study. Patients were classified into low and high lung function groups by the cutoff of the lowest fifth quintile of forced expiratory volume in 1 s (FEV1) %predicted (%pred) and diffusing capacity of the carbon monoxide (DLco) %pred. The PPCs compromised of atelectasis requiring bronchoscopic intervention, pneumonia, and acute lung injury/acute respiratory distress syndrome. Modified multivariable-adjusted Poisson regression model using robust error variances and inverse probability treatment weighting (IPTW) were used to assess the relative risk (RR) for the PPCs. A joint effect model considered FEV1%pred and DLco %pred together for the estimation of RR for the PPCs. Of 810 patients with esophageal cancer who underwent esophagectomy, 159 (19.6%) developed PPCs. The adjusted RR for PPCs in the low FEV1 group relative to high FEV1 group was 1.48 (95% confidence interval [CI] = 1.09-2.00) and 1.98 (95% CI = 1.46-2.68) in the low DLco group relative to the high DLco group. A joint effect model showed adjusted RR of PPCs was highest in patients with low DLco and low FEV1 followed by low DLco and high FEV1, high DLco and low FEV1, and high DLco and high FEV1 (Reference). Results were consistent with the IPTW. Reduced preoperative lung function (FEV1 and DLco) is associated with post-esophagectomy PPCs. The risk was further strengthened when both values decreased together.

A novel A2a adenosine receptor inhibitor effectively mitigates hepatic fibrosis in a metabolic dysfunction-associated steatohepatitis mouse model.

Hepatic fibrosis exacerbates mortality and complications in progressive metabolic dysfunction-associated steatohepatitis (MASH). The role of the adenosine 2A receptor (A2aAR) in hepatic fibrosis within the context of MASH remains uncertain. This study aims to elucidate the involvement of the A2aAR signaling pathway and the efficacy of a novel potent A2aAR antagonist in treating hepatic fibrosis in MASH-induced mice fed a chlorine-deficient, L-amino acid-defined, high fat diet (CDAHFD). A2aAR overexpression in LX-2 cells increased fibrosis markers, whereas the known A2aAR antagonist, ZM241385, decreased these markers. A novel A2aAR antagonist, RAD11, not only attenuated fibrosis progression but also exhibited greater inhibition of the A2aAR signaling pathway compared to ZM241385 in mice with MASH, activated primary hepatocytes, and LX-2 cells. RAD11 exhibited a dual antifibrotic mechanism by targeting both activated HSCs and hepatocytes. Its superior antifibrotic efficacy over ZM241385 in the MASH condition stems from its ability to suppress A2aAR-mediated signaling, inhibit HSC activation, reduce hepatic lipogenesis in hepatocytes, and mitigate lipid accumulation-induced oxidative stress-mediated liver damage. This study has shed light on the relationship between A2aAR signaling and hepatic fibrosis, presenting RAD11 as a potent therapeutic agent for managing MASH and hepatic fibrosis.

Importance of Lymph Node Evaluation in ≤2-cm Pure-Solid Non-Small Cell Lung Cancer.

BACKGROUND: The prevalence of lymph node (LN) metastasis in small-sized lung cancer varies depending on the tumor size and proportion of ground-glass opacity. We investigated occult LN metastasis and prognosis in patients with small-sized non-small cell lung cancer (NSCLC), mainly focusing on the pure-solid tumor. METHODS: We retrospectively reviewed patients with ≤2-cm clinical N0 NSCLC who underwent lung resection with curative intent from 2003 to 2017. Among them we analyzed patients who also underwent adequate complete systematic LN dissection. Pathologic results and disease-free survival of the radiologically mixed ground-glass nodule (mGGN) and pure-solid nodule (PSN) groups were analyzed. RESULTS: Of 1329 patients analyzed, 591 had mGGNs and PSNs. As tumor size increased, patients in the mGGN group showed no difference in LN metastasis: ≤1 cm, 2.27%; 1.0 to 1.5 cm, 2.19%; and 1.5 to 2.0 cm, 2.18% (P = .999). However the PSN group showed a significant difference in LN metastasis as the tumor size increased: ≤1 cm, 2.67%; 1.0 to 1.5 cm, 12.46%; and 1.5 to 2.0 cm, 21.31% (P < .001). In the multivariate analysis tumor size was a significant predictor of nodal metastasis in the PSN group but not in the mGGN group. In terms of 5-year disease-free survival, the mGGN group showed a better prognosis than the PSN group (94.4% vs 71.2%, P < .001). CONCLUSIONS: We need to conduct a thorough LN dissection during surgery for small-sized NSCLC, especially for pure-solid tumors ≥ 1 cm.

Factors associated with failure of cardiopulmonary function recovery after lung cancer surgery.

BACKGROUND AND OBJECTIVE: This study aimed to evaluate the longitudinal changes in cardiopulmonary function (CPF) and identify predictors of cardiopulmonary recovery failure after lung cancer surgery. METHODS: Data was obtained from a prospective CATCH-LUNG cohort study, where patients were divided into two groups based on 6-min walk distance (6MWD) at baseline and 6 months after surgery. CPF recovery failure was defined as a participant whose 6MWD dropped over 50 m from baseline to 6 months after surgery. Patients with a baseline 6MWD less than 400 m were excluded. The analysis was investigated using mixed effects models, and the relative estimates for the predictors were expressed relative risk (RR) and 95% CI using a Poisson regression. RESULTS: Among 419 patients, 24.1% and 17.7% showed failure of CPF recovery at 6 months and 1 year after surgery, respectively. In the multivariable analysis, baseline step count [RR per 1000 steps lower = 1.05 (95% CI, 1.01-1.09)], baseline dyspnoea [RR per 10 points higher = 1.15(1.07-1.23)], decreased FEV1 % predicted from baseline to 2 weeks after surgery [RR per 10% lower = 1.30(1.10-1.53)] and decreased moderate-to-vigorous physical activity (MVPA) from baseline to 2 weeks [RR = 1.95(1.22, 3.11)] or persistent low MVPA at baseline and 2 weeks after surgery [RR = 1.63(1.04, 2.54)] were significant factors for loss of CPF. CONCLUSION: The inability to recover CPF at 6 months after surgery was linked to reduction of lung function and MVPA from baseline to 2 weeks as well as baseline physical activity (PA) and dyspnoea. These results imply that engagement of perioperative PA is necessary to facilitate recovery of CPF after lung cancer surgery.

Study on the standard components of digital forensics laboratory.

Recently, digital forensics has become increasingly important as it is used by investigation agencies, corporate, and private sector. To supplement the limitations of evidence capacity and be recognized in court, it is essential to establish an environment that ensures the integrity of the entire process ranging from collecting and analyzing to submitting digital evidence to court. In this study, common elements were extracted by comparing and analyzing ISO/IEC 17025, 27001 standards and Interpol and Council of Europe (CoE) guidelines to derive the necessary components for building a digital forensic laboratory. Subsequently, based on 21 digital forensic experts in the field, Delphi survey and verifications were conducted in three rounds. As a result, 40 components from seven areas were derived. The research results are based on the establishment, operation, management, and authentication of a digital forensics laboratory suitable for the domestic environment, with added credibility through collection of the opinions of 21 experts in the field of digital forensics in Korea. This study can be referred to in establishing digital forensic laboratories in national, public, and private digital forensic organizations as well as for employing as competency measurement criteria in courts to evaluate the reliability of the analysis results.

Different prognostic role of EGFR mutation according to the IASLC histological grade in patients with resected early-stage lung adenocarcinoma.

AIMS: The prognostic role of EGFR mutations remains controversial. We aimed to evaluate the prognostic role of EGFR mutation in consideration of the IASLC histological grade in patients with resected early-stage lung adenocarcinoma. METHODS AND RESULTS: A total of 3297 patients with stages I-IIA resected lung adenocarcinoma who had had EGFR mutation tests between January 2014 and December 2019 at the Samsung Medical Center, Seoul, Korea were included. Recurrence-free survival (RFS) was compared by EGFR mutation status (EGFR-M+ versus EGFR-WT) and IASLC histological grade (G1, G2 and G3). Cox proportional hazards models were used to estimate the adjusted HRs (aHRs) and 95% confidence intervals (CIs). RESULTS: Compared to the EGFR-WT group, the EGFR-M+ group had a significantly lower proportion of G3 tumour (16 versus 33%, P < 0.001). During a median follow-up of 41.4 months, 376 patients experienced recurrence. After adjusting for histological grade, the aHR for recurrence comparing the EGFR-M+ to the EGFR-WT was 1.30 (95% CI = 1.04-1.62, P = 0.022). The EGFR-M+ group had a significantly lower 5-year RFS than the EGFR-WT group among G3 patients (58.4 versus 71.5%, P < 0.001), but not among G1 and G2 patients. CONCLUSIONS: EGFR mutation status was associated with a risk of recurrence after consideration of the IASLC histological grading, especially in G3 tumours. The results of this study would be useful for developing a new staging system and identifying a subset of patients who may benefit from adjuvant targeted therapy.

Enhanced Recovery After Surgery Program and Opioid Consumption in Pulmonary Resection Surgery: A Retrospective Observational Study.

BACKGROUND: Pulmonary resection surgery causes severe postoperative pain and usually requires opioid-based analgesia, particularly in the early postoperative period. However, the administration of large amounts of opioids is associated with various adverse events. We hypothesized that patients who underwent pulmonary resection under an enhanced recovery after surgery (ERAS) program consumed fewer opioids than patients who received conventional treatment. METHODS: A total of 2147 patients underwent pulmonary resection surgery between August 2019 and December 2020. Two surgeons (25%) at our institution implemented the ERAS program for their patients. After screening, the patients were divided into the ERAS and conventional groups based on the treatment they received. The 2 groups were then compared after the stabilized inverse probability of treatment weighting. The primary end point was the total amount of opioid consumption from surgery to discharge. The secondary end points included daily average and highest pain intensity scores during exertion, opioid-related adverse events, and clinical outcomes, such as length of intensive care unit (ICU) stay, hospital stay, and postoperative complication grade defined by the Clavien-Dindo classification. Additionally, the number of patients discharged without opioids prescription was assessed. RESULTS: Finally, 2120 patients were included in the analysis. The total amount of opioid consumption (median [interquartile range]) after surgery until discharge was lower in the ERAS group (n = 260) than that in the conventional group (n = 1860; morphine milligram equivalents, 44 [16-122] mg vs 208 [146-294] mg; median difference, -143 mg; 95% CI, -154 to -132; P < .001). The number of patients discharged without opioids prescription was higher in the ERAS group (156/260 [60%] vs 329/1860 [18%]; odds ratio, 7.0; 95% CI, 5.3-9.3; P < .001). On operation day, both average pain intensity score during exertion (3.0 ± 1.7 vs 3.5 ± 1.8; mean difference, -0.5; 95% CI, -0.8 to -0.3; P < .001) and the highest pain intensity score during exertion (5.5 ± 2.1 vs 6.4 ± 1.7; mean difference, -0.8; 95% CI, -1.0 to -0.5; P < .001) were lower in the ERAS group than in the conventional group. There were no significant differences in the length of ICU stay, hospital stay, or Clavien-Dindo classification grade. CONCLUSIONS: Patients who underwent pulmonary resection under the ERAS program consumed fewer opioids than those who received conventional management while maintaining no significant differences in clinical outcomes.

Changes of lysosome by L-serine in rotenone-treated hippocampal neurons.

Oxidative stress destroys cellular organelles and damages DNA, eventually leading to degenerative brain disorders. Persistent mitochondrial damage by oxidative stress eventually causes cells to inhibit the function of lysosomes. Rotenone used in this study inhibits complex 1 of the mitochondrial electron transport chain. Due to this inhibition, the production of free radicals is promoted, and oxidative stress can occur. To test as a role of antioxidant, L-serine was treated before treatment of rotenone to HT22 hippocampal cells. Then, changes in the activity and structure of lysosomes were analyzed. As a result, the oxidative stress caused by rotenone in HT22 cells was protected by L-serine. L-serine reduced free radicals in cells, and the damaged lysosomal structure and lysosome activity were also protected.

Validation of the IASLC Residual Tumor Classification in Patients With Stage III-N2 Non-Small Cell Lung Cancer Undergoing Neoadjuvant Chemoradiotherapy Followed By Surgery.

OBJECTIVE: The aim of this study was to validate the International Association for the Study of Lung Cancer (IASLC) residual tumor classification in patients with stage III-N2 non-small cell lung cancer (NSCLC) undergoing neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by surgery. BACKGROUND: As adequate nodal assessment is crucial for determining prognosis in patients with clinical N2 NSCLC undergoing nCCRT followed by surgery, the new classification may have better prognostic implications. METHODS: Using a registry for thoracic cancer surgery at a tertiary hospital in Seoul, Korea, between 2003 and 2019, we analyzed 910 patients with stage III-N2 NSCLC who underwent nCCRT followed by surgery. We classified resections using IASLC criteria: complete (R0), uncertain (R[un]), and incomplete resection (R1/R2). Recurrence and mortality were compared using adjusted subdistribution hazard model and Cox-proportional hazards model, respectively. RESULTS: Of the 96.3% (n = 876) patients who were R0 by Union for International Cancer Control (UICC) criteria, 34.5% (n = 3O2) remained R0 by IASLC criteria and 37.6% (n = 329) and 28% (n = 245) migrated to R(un) and R1, respectively. Most of the migration from UICC-R0 to lASLC-R(un) and IASLC-R1/R2 occurred due to inadequate nodal assessment (85.5%) and extracapsular nodal extension (77.6%), respectively. Compared to R0, the adjusted hazard ratios in R(un) and R1/R2 were 1.20 (95% confidence interval, 0.94-1.52), 1.50 (1.17-1.52) ( P fortrend = .001) for recurrence and 1.18 (0.93-1.51) and 1.51 (1.17-1.96) for death ( P for trend = .002). CONCLUSIONS: The IASLC R classification has prognostic relevance in patients with stage III-N2 NSCLC undergoing nCCRT followed by surgery. The IASLC classification will improve the thoroughness of intraoperative nodal assessment and the completeness of resection.

Learning Polymorphic Neural ODEs With Time-Evolving Mixture.

Neural ordinary differential equations (NODE) present a new way of considering a deep residual network as a continuous structure by layer depth. However, it fails to overcome its representational limits, where it cannot learn all possible homeomorphisms of input data space, and therefore quickly saturates in terms of performance even as the number of layers increases. Here, we show that simply stacking Neural ODE blocks could easily improve performance by alleviating this issue. Furthermore, we suggest a more effective way of training neural ODE by using a time-evolving mixture weight on multiple ODE functions that also evolves with a separate neural ODE. We provide empirical results that are suggestive of improved performance over stacked as well as vanilla neural ODEs where we also confirm our approach can be orthogonally combined with recent advances in neural ODEs.

Psychometric Validation of the Korean Version of the Cancer Survivors' Unmet Needs (CaSUN) Scale among Korean Non-Small Cell Lung Cancer Survivors.

PURPOSE: The purpose of the study was to validate the Korean version of Cancer Survivors' Unmet Needs (CaSUN) scale among non-small cell lung cancer survivors. MATERIALS AND METHODS: Participants were recruited from outpatient clinics at the Samsung Medical Center in Seoul, South Korea, from January to October 2020. Participants completed a survey questionnaire that included the CaSUN. Exploratory and confirmatory factor analysis and Pearson's correlations were used to evaluate the reliability and validity of the Korean version of the CaSUN (CaSUN-K). We also tested known-group validity using an independent t test or ANOVA. RESULTS: In total, 949 provided informed consent and all of which completed the questionnaire. Among the 949 patients, 529 (55.7%) were male; the mean age and median time since the end of active treatment (standard deviation) was 63.4±8.8 years and the median was 18 months. Although the factor loadings were different from those for the original scale, the Cronbach's alpha coefficients of the six domains in the CaSUN-K ranged from 0.68 to 0.95, indicating satisfactory internal consistency. In the CFA, the goodness-of-fit indices for the CaSUN-K were high. Moderate correlations demonstrated the convergent validity of CaSUN-K with the relevant questionnaire. More than 60% of the participants reported information-related unmet needs, and the CaSUN-K discriminated between the needs reported by the different subgroups that we analyzed. CONCLUSION: The CaSUN-K is a reliable and valid measure for assessing the unmet needs in a cancer population, thus this tool help population to receive timely, targeted, and relevant care.

Longitudinal changes in pulmonary function and patient-reported outcomes after lung cancer surgery.

BACKGROUND: Surgery is the mainstay of treatment for non-small cell lung cancer, but the decline in pulmonary function after surgery is noticeable and requires attention. This study aimed to evaluate longitudinal changes in pulmonary function and integrated patient-reported outcomes (PROs) after lung cancer surgery. METHODS: Data were obtained from a prospective cohort study, the Coordinate Approach to Cancer Patients' Health for Lung Cancer. Changes in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) at 2 weeks, 6 months, and 1 year after surgery, and the corresponding modified Medical Research Council (mMRC) dyspnea scale and chronic obstructive lung disease assessment test (CAT) scores were evaluated. Mixed effects model was used to investigate changes in pulmonary function and PROs. RESULTS: Among 620 patients, 477 (76.9%) underwent lobectomy, whereas 120 (19.4%) and 23 (3.7%) were treated with wedge resection/segmentectomy and bilobectomy/pneumonectomy, respectively. Both FVC and FEV1 markedly decreased 2 weeks after surgery and improved thereafter; however, they did not recover to baseline values. The corresponding mMRC dyspnea scale and CAT scores worsened immediately after surgery. The dyspnea scale of the mMRC was still higher, while CAT scores returned to baseline one year after surgery, although breathlessness and lack of energy persisted. Compared to the changes from baseline of FVC and FEV1 in patients who underwent lobectomy, patients who underwent bilobectomy/pneumonectomy showed a greater decrease in FVC and FEV1, while wedge resection/segmentectomy patients had smaller decreases in FVC and FEV1 at 2 weeks, 6 months, and 1 year after surgery. Bilobectomy/pneumonectomy patients had the highest mMRC dyspnea grade among the three groups, but the difference was not statistically significant one year after surgery. CONCLUSIONS: After lung cancer surgery, pulmonary function and PROs noticeably decreased in the immediate post-operative period and improved thereafter, except for dyspnea and lack of energy. Proper information on the timeline of changes in lung function and symptoms following lung cancer surgery could guide patient care approaches after surgery. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03705546; URL: www. CLINICALTRIALS: gov.

Role of intraoperative feeding jejunostomy in esophageal cancer surgery.

BACKGROUND: Feeding jejunostomy was routinely placed during esophagectomy to ensure postoperative enteral feeding. Improved anastomosis technique and early oral feeding strategy after esophagectomy has led to question the need for the routine placement of feeding jejunostomy. The aim of this study is to evaluate role of feeding jejunostomy during Ivor Lewis operation. METHODS: We retrospectively reviewed 414 patients who underwent the Ivor Lewis operations from January 2015 to December 2018. RESULTS: 61 patients (14.7%) received jejunostomy insertion. The most common indication for jejunostomy was neoadjuvant concurrent chemoradiation therapy (CCRT). 48 patients (79%) had jejunostomy removed within 60 days after the surgery and the longest duration of jejunostomy inserted state was 121 days. About two-third of the patients with jejunostomy had never prescribed with an enteral feeding product. Among 353 patients without intraoperative feeding jejunostomy, 11(3.1%) received delayed jejunostomy insertion. Graft-related problems (6 patients), cancer progression (3 patients), acute lung injury (1 patient), and swallowing difficulty (1 patient) were reasons for delayed feeding jejunostomy insertion. Complication rate was relatively high as 24 patients (33.3%) out of 72 patients with jejunostomy insertion had complications and 7 patients (9.7%) visited ER more than twice with jejunostomy-related complications. CONCLUSION: Only 3.6% patients who underwent the Ivor Lewis operation during 4-year span had anastomosis leakage. Although one-third of the patients with jejunostomy were benefited with alternative method of feeding after discharge, high complication rate regarding jejunostomy should be also considered. We believe feeding jejunostomy should not be applied routinely with prophylactic measures and should be reserved to very carefully selected patients with multiple high-risk factors.

Clinical, Pathologic, and Molecular Prognostic Factors in Patients with Early-Stage EGFR-Mutant NSCLC.

PURPOSE: In early-stage, EGFR mutation-positive (EGFR-M+) non-small cell lung cancer (NSCLC), surgery remains the primary treatment, without personalized adjuvant treatments. We aimed to identify risk factors for recurrence-free survival (RFS) to suggest personalized adjuvant strategies in resected early-stage EGFR-M+ NSCLC. EXPERIMENTAL DESIGN: From January 2008 to August 2020, a total of 2,340 patients with pathologic stage (pStage) IB-IIIA, non-squamous NSCLC underwent curative surgery. To identify clinicopathologic risk factors, 1,181 patients with pStage IB-IIIA, common EGFR-M+ NSCLC who underwent surgical resection were analyzed. To identify molecular risk factors, comprehensive genomic analysis was conducted in 56 patients with matched case-controls (pStage II and IIIA and type of EGFR mutation). RESULTS: Median follow-up duration was 38.8 months (0.5-156.2). Among 1,181 patients, pStage IB, II, and IIIA comprised 577 (48.9%), 331 (28.0%), and 273 (23.1%) subjects, respectively. Median RFS was 73.5 months [95% confidence interval (CI), 62.1-84.9], 48.7 months (95% CI, 41.2-56.3), and 22.7 months (95% CI, 19.4-26.0) for pStage IB, II, and IIIA, respectively (P < 0.001). In multivariate analysis of clinicopathologic risk factors, pStage, micropapillary subtype, vascular invasion, and pleural invasion, and pathologic classification by cell of origin (type II pneumocyte-like tumor cell vs. bronchial surface epithelial cell-like tumor cell) were associated with RFS. As molecular risk factors, the non-terminal respiratory unit (non-TRU) of the RNA subtype (HR, 3.49; 95% CI, 1.72-7.09; P < 0.01) and TP53 mutation (HR, 2.50; 95% CI, 1.24-5.04; P = 0.01) were associated with poor RFS independent of pStage II or IIIA. Among the patients with recurrence, progression-free survival of EGFR-tyrosine kinase inhibitor (TKI) in those with the Apolipoprotein B mRNA Editing Catalytic Polypeptide-like (APOBEC) mutation signature was inferior compared with that of patients without this signature (8.6 vs. 28.8 months; HR, 4.16; 95% CI, 1.28-13.46; P = 0.02). CONCLUSIONS: The low-risk group with TRU subtype and TP53 wild-type without clinicopathologic risk factors might not need adjuvant EGFR-TKIs. In the high-risk group, with non-TRU subtype and/or TP 53 mutation, or clinicopathologic risk factors, a novel adjuvant strategy of EGFR-TKI with others, e.g., chemotherapy or antiangiogenic agents needs to be investigated. Given the poor outcome to EGFR-TKIs after recurrence in patients with the APOBEC mutation signature, an alternative adjuvant strategy might be needed.

Reappraising the clinical usability of consolidation-to-tumor ratio on CT in clinical stage IA lung cancer.

OBJECTIVES: Ground-glass opacity (GGO) on computed tomography is associated with prognosis in early-stage non-small cell lung cancer (NSCLC) patients. However, the stratification of the prognostic value of GGO is controversial. We aimed to evaluate clinicopathologic characteristics of early-stage NSCLC based on the consolidation-to-tumor ratio (CTR), conduct multi-pronged analysis, and stratify prognosis accordingly. METHODS: We retrospectively investigated 944 patients with clinical stage IA NSCLC, who underwent curative-intent lung resection between August 2018 and January 2020. The CTR was measured and used to categorize patients into six groups (1, 0%; 2, 0-25%; 3, 25-50%; 4, 50-75%; 5, 75-100%; and 6, 100%). RESULTS: Pathologic nodal upstaging was found in 1.8% (group 4), 9.0% (group 5), and 17.4% (group 6), respectively. The proportion of patients with a high grade of tumor-infiltrating lymphocytes tended to decrease as the CTR increased. In a subtype analysis of patients with adenocarcinoma, all of the patients with predominant micro-papillary patterns were in the CTR > 50% groups, and most of the patients with predominant solid patterns were in group 6 (47/50, 94%). The multivariate analysis demonstrated that CTR 75-100% (hazard ratio [HR], 3.85; 95% confidence interval [CI], 1.58-9.36) and CTR 100% (HR, 5.58; 95% CI, 2.45-12.72) were independent prognostic factors for DFS, regardless of tumor size. CONCLUSION: We demonstrated that the CTR could provide various noninvasive clinicopathological information. A CTR of more than 75% is the factor associated with a poor prognosis and should be considered when making therapeutic plans for patients with early-stage NSCLC.

Reclassifying the International Association for the Study of Lung Cancer Residual Tumor Classification According to the Extent of Nodal Dissection for NSCLC: One Size Does Not Fit All.

INTRODUCTION: The extent of nodal assessment may require risk-based adjustments in NSCLC. We reclassified the International Association for the Study of Lung Cancer Residual tumor classification according to the extent of nodal dissection and evaluated its long-term prognosis by tumor stage and histologic subtype. METHODS: We reclassified 5117 patients who underwent resection for clinical stages I to III NSCLC and had complete or uncertain resection by International Association for the Study of Lung Cancer classification into the following 3 groups according to compliance with three components (N1, N2, and subcarinal node) of systematic nodal dissection criteria: fully compliant group (FCG), partially compliant group (PCG), and noncompliant group (NCG). Recurrence-free survival (RFS) and overall survival (OS) were compared. RESULTS: Of the 5117 patients, 2806 (55%), 1959 (38%), and 359 (7%) were FCG, PCG, and NCG, respectively. PCG and NCG were more likely to be of lower clinical stage and adenocarcinoma with lepidic component than FCG. The 5-year RFS and OS were significantly better in NCG than in FCG or PCG (RFS, 86% versus 70% or 74%, p < 0.001; OS, 90% versus 80% or 83%, p < 0.001). In particular, NCG had better RFS and OS than FCG or PCG in clinical stage I and in lepidic-type adenocarcinoma. CONCLUSIONS: In early stage NSCLC with low-risk histologic subtype, a less rigorous nodal assessment was not associated with a worse prognosis. Although surgeons should continue to aim for complete resection and thorough nodal assessment, a uniform approach to the extent and invasiveness of nodal assessment may need to be reconsidered.

Prognostic impact of micropapillary and solid histological subtype on patients undergoing curative resection for stage I lung adenocarcinoma according to the extent of pulmonary resection and lymph node assessment.

BACKGROUND: We aimed to evaluate the impact of micropapillary and/or solid (MPSOL) components on survival and recurrence of patients with resected stage I lung adenocarcinoma (LUAD) according to the extent of surgery and completeness of lymph node assessment (LNA). METHODS: We retrospectively reviewed 1886 consecutive patients who underwent surgical resection for pathologic stage I LUAD between 2009 and 2014. The patients were classified by the presence (≥1%) of MPSOL into the MPSOL(+) (n = 489) and MPSOL(-) (n = 1397) group.We analyzed the outcomes according to the extent of surgery (sublobar resection [SR] vs. lobectomy) and the LNA (complete vs. incomplete). Complete LNA was defined as systematic LN dissection according to European Society of Thoracic Surgeons guideline. RESULTS: In the MPSOL(+) patients, there was no significant difference in adjusted overall survival (OS), recurrence-free survival (RFS), and recurrence pattern between the lobectomy and SR group. Of note, patients with complete LNA had higher adjusted OS and RFS than those with incomplete LNA (aOS, 86.3% vs. 78%, p = 0.002; aRFS, 70% vs 63.1%, p = 0.06). In the MPSOL(-) patients, adjusted RFS of the SR group was better than the lobectomy group (95% vs. 90.5%, p = 0.021), although there was no difference in survival regarding to the LNA. Complete LNA was a favorable prognostic factor for RFS in the MPSOL(+) patients (HR = 0.463, 95% CI: 0.227-0.944, p = 0.034). CONCLUSIONS: In MPSOL(+) patients, complete LN assessment affects the OS and RFS rather than the extent of lung resection. In patients with solid tumor or tumor>2 cm, a complete LN assessment would be required, even if sublobar resection is unavoidable.