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Background: Metabolic syndrome (MetS) is believed to increase the risk of esophageal cancer. However, most studies have been conducted in Western countries, focusing on esophageal adenocarcinoma (EAC). We aimed to investigate the association between MetS and risk of esophageal cancer in nationally representative large dataset in Korea, where esophageal squamous cell carcinoma (ESCC) is predominant. Methods: We analyzed the health examinations and claims data from the Korean National Health Insurance Service (NHIS). A total of 6,795,738 subjects who received an NHIS provided health examination in 2009 (index year) were included. Cox proportional hazards models were used to estimate multivariable adjusted HRs (aHR) and 95% confidence intervals (CI) for the association of MetS and its components (elevated waist circumference, blood pressure, triglycerides, fasting blood glucose, reduced high-density lipoprotein cholesterol) with the risk of esophageal cancer. Results: During a mean (± SD) follow-up of 8.2 (± 1.1) years, 6,414 cases of esophageal cancer occurred. MetS was associated with an increased risk of esophageal cancer (aHR, 1.11; 95% CI, 1.05–1.18). Among the components of MetS, elevated waist circumference (aHR, 1.24; 95% CI, 1.16–1.33), high blood pressure (aHR, 1.29; 95% CI, 1.22–1.37), and fasting blood glucose (aHR, 1.16; 95% CI, 1.11–1.22) were associated with increased risk of esophageal cancer. Conclusions: MetS was associated with an increased risk of esophageal cancer. Impact: Our findings suggest that individuals with MetS may be at increased risk for esophageal cancer, specifically ESCC. Further studies are needed to establish the relationship between MetS and esophageal cancer.

In esophageal cancer surgery, it is difficult to perform thorough dissection of lymph nodes along the recurrent laryngeal nerve (RLN-LN). However, there are limited data regarding the necessity of RLN-LN dissection in surgery for superficial esophageal squamous carcinoma (focused on T1b tumor) and its role in locoregional control and accurate nodal staging. Between 2001 and 2016, 567 patients with pT1N0 and 927 patients with cT1N0 squamous cell carcinoma were identified in a prospectively maintained, single institution esophagectomy registry. Sufficient or insufficient RLN-LN assessment group was defined by receiver operating characteristic curve analysis of the number of RLN-LN harvested. To mitigate bias, inverse probability weighting adjustment and several sensitivity analyses were performed. In the pT1N0 cohort, patients with sufficient (≥ 4) harvested RLN-LNs showed significantly superior 5-year recurrence-free survival (89.1% versus 74.8%, log-rank P < 0.001). Patients with insufficient RLN-LN dissection mainly developed locoregional failure at the upper mediastinal or cervical area (87% of total recurred cases). The survival impact of sufficient RLN-LN dissection was more prominent in subsets of upper-middle thoracic tumors or with deep submucosal invasion. In the analysis on cT1N0 cohort, sufficient RLN-LN assessment conferred a 1.5-fold increase in the discovery of positive-nodal disease (19.4% versus 27.8%, P = 0.008). Adequate RLN-LN dissection during surgery may help reduce the risk of recurrence and enhance the accuracy of nodal staging in early-stage esophageal squamous cell carcinoma. Therefore, meticulous surgical evaluation for this region should not be underrated, particularly in the high-risk subset with lymph node metastasis. Visual Abstract Graphical summary of key study findings. T wo cohorts (pT1 and cT1 ; both mainly comprised T1b ) were analyzed for separate purposes; the former controlled for pathologic stage was primarily analyzed in terms of survival and recurrence hazard, whereas the latter (controlled for clinical was used for stage migration ( and intention to treat analysis. Th e results show the significance of adequate bilateral RLN LN in the surgery for early stage ESCC (particularly those with T1b)T1b), in terms of accurate nodal staging, effective nodal clearance, and reduced regional.

Neoadjuvant chemoradiation followed by surgery (NCRT+S) has been widely applied to patients with locally advanced esophageal squamous cell carcinoma (ESCC); however, treatment trends and their survival outcomes in a real-world clinical setting are poorly understood. This study aimed to analyze real-world evidence to understand treatment patterns and outcomes for patients with ESCC. We analyzed the treatment pattern and 5-year overall survival (5yOS) by synthesizing the individuals’ general characteristics, cancer information, and treatment records extracted from the Clinical Data Warehouse from 1994 to 2018. Of a total of 2151 patients, most patients received upfront surgery and 5yOS was 36.8% (31.4–43.1%). From 2003 to 2012, the use of NCRT increased, and 5yOS was improved to 42.2% (38.8–45.7%). Notably, after 2013, the proportion of NCRT+S markedly increased up to >50% of patients: 5yOS was much improved to 56.3% (53.2–59.6%). With regard to treatment, patients with NCRT+S had the most favorable 5yOS of 58.1% (53–63.7%), although that for patients with upfront surgery was 48.6% (45.9–51.5%, p < 0.001). Moreover, patients who received adjuvant therapy after surgery had better OS than those with surgery alone (58.4% (52.7–64.7%) vs. 47.3% (44.1–50.7%), p < 0.001). This analysis of real-world data demonstrated a significantly improved survival outcome for locally advanced ESCC over time since NCRT prior to surgery had been routinely applied. We revealed that NCRT+S was the most effective treatment for locally advanced ESCC and that adjuvant chemotherapy may be an encouraging therapeutic option for patients with positive nodes after upfront surgery.

The prevalence of multiple lung cancers has been increasing recently. Molecular analysis of epidermal growth factor receptor (EGFR) mutations in individual tumors of multiple lung cancers is essential for devising an optimal therapeutic strategy. The EGFR mutation status in multiple lung cancers was evaluated to determine its therapeutic implications. In total, 208 tumors from 101 patients who underwent surgery for multiple lung cancers were analyzed. Individual tumors were subjected to histological evaluation and EGFR analysis using a real-time polymerase chain reaction. Additionally, EGFR-wildtype tumors were subjected to next-generation sequencing (NGS). EGFR mutations were detected in 113 tumors from 72 patients, predominantly in females (p < 0.001) and non-smokers (p < 0.001). Among patients with at least one EGFR-mutant tumor, approximately 72% of patients (52/72) had different EGFR mutations in individual tumors. NGS analysis of EGFR-wildtype tumors from 12 patients revealed four and eight cases with concordant and discordant molecular alterations, respectively. These findings revealed a high proportion of discordant EGFR mutations among multiple lung tumors. Hence, EGFR analysis of individual tumors of multiple lung tumors is essential for the evaluation of clonality and the development of an optimal treatment strategy.

Background The aim of this study was to investigate the impact of thoracic duct embolization (TDE) on the management of postoperative chyle leakage. Methods We retrospectively reviewed the electronic medical record database of 4171 patients who underwent curative resection for lung or esophageal cancer between January 2015 and June 2017. We classified the period before the introduction of TDE as the first period and the period after the introduction of TDE as the second period. Results A total of 105 patients who developed chyle leakage after surgery were included. In the first period, 49 patients who underwent lung surgery developed chylothorax. Of those, two patients (4.1%) underwent surgical ligation of the thoracic duct (TD). Of eight patients with chyle leakage after esophagectomy, four patients (50%) underwent TD ligation. In the second period, 30 patients developed postoperative chyle leakage after pulmonary resection. Only one (3.3%) of them required surgical ligation. Of eight patients with chyle leakage after esophagectomy, only two (11.1%) patients underwent TD ligation. Five patients (16.7%) received TDE after lung surgery and five patients (27.7%) after esophageal surgery. Also, in the second period, the hospital stay of patients who underwent lung cancer surgery was shorter than the first period (12.6 ± 4.6 days vs. 16.3 ± 9.7 days; p = 0.026). Conclusions TDE is an effective method for the management of chyle leakage and might help to avoid invasive surgery., After the introduction of thoracic duct embolization (TDE), only three of 48 patients underwent surgical ligation of thoracic duct. The length of hospital stay of patients who underwent lung cancer surgery was shorter than that before the introduction of TDE. This study demonstrated that TDE is an effective method for the management of postoperative chyle leakage and can help avoid invasive surgery in this group of patients.

PurposeSurvival probability changes over time in cancer survivors. This study examined conditional survival in patients undergoing curative resection for non-small cell lung cancer (NSCLC).Materials and MethodsFive-year conditional recurrence-free survival (CRFS), conditional overall survival (COS), and conditional relative survival (CRS) up to 10 years after surgery were calculated in patients who underwent NSCLC resection from 1994 to 2016. These rates were stratified according to age, sex, year of diagnosis, pathological stage, tumor histology, smoking status, comorbidity, and lung function.ResultsFive-year CRFS increased from 65.6% at baseline to 90.9% at 10 years after surgery. Early differences in 5-year CRFS according to stratified patient characteristics disappeared, except for age: older patients exhibited persistently lower 5-year CRFS. Five-year COS increased from 72.7% to 78.3% at 8 years and then decreased to 75.4% at 10 years. Five-year CRS increased from 79.0% at baseline to 86.8% at 10 years. Older age and higher pathologic stage were associated with lower 5-year COS and CRS up to 10 years after surgery. Female patients, those with adenocarcinoma histology, non-smokers, patient without comorbidities and had good lung function showed higher COS and CRS.ConclusionCRFS improved over time, but significant risk remained after 5 years. CRS slightly improved over time but did not reach 90%, suggesting significant excess mortality compared to the general population. Age and stage remained significant predictors of conditional survival several years after surgery. Our conditional survival estimates should help clinicians and patients make informed treatment and personal life decisions based on survivorship status.

Background: Early detection of lung cancer is extremely important for timely and effective therapeutic interventions to increase the survival rate of patients. Emerging evidence suggests that tumor-derived small extracellular vesicle (sEV) cargo may serve as cancer-specific biomarkers. We previously reported the identification of GRIP and coiled-coil domain-containing 2-enriched sEV (sEV-GCC2) as a promising biomarker for lung adenocarcinoma in a pilot study. In this multicenter study, we explored the diagnostic and therapeutic potential of sEV-GCC2 in early-stage lung adenocarcinoma. Methods: A total of 470 blood plasma samples (150 healthy controls and 320 patients with lung adenocarcinoma) were retrospectively obtained from five institutions. sEVs were isolated by size exclusion chromatography and sEV-GCC2 was quantified by enzyme-linked immunosorbent assay. Effect of sEV-GCC2 on lung cancer cell proliferation was investigated in vitro and in vivo. Results: sEV-GCC2 concentration was significantly higher in patients than that in controls with an area under the curve (AUC) of 0.856 (95% confidence interval [CI], 0.820-0.886). In patients at TisN0-T1miN0 stages vs controls, the AUC was 0.802 (95% CI, 0.734-0.859). The association between sEV-GCC2 and lung adenocarcinoma remained after adjustment for pathological TNM stage and tumor location in the left lower lobe. Immunohistochemical staining revealed that GCC2 expression was significantly higher in lung adenocarcinoma tissues than in the controls (p < 0.001). Furthermore, sEV-GCC2 enhanced cancer cell proliferation and accelerated tumor growth and lymph node metastasis. Conclusions: We identified sEV-GCC2 as a potential diagnostic marker for very early-stage lung cancer. sEV-GCC2 represents a promising therapeutic target for lung adenocarcinoma and may be quantified as key molecules in the progression of lung adenocarcinoma. Citation Format: Byeong Hyeon Choi, Hyonggin An, Sukki Cho, Sungsoo Lee, Hyeong Ryul Kim, Jong Ho Cho, Hyunku Shin, Ok Hwa Jeon, Yeonho Choi, Hyun Koo Kim. GCC2 on small extracellular vesicles for the early diagnosis of lung adenocarcinoma: A multicenter trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB292.

Background: Several studies have reported the predictive and prognostic value of novel transcriptional factor-based molecular subtypes in small-cell lung cancer (SCLC). We conducted an in-depth analysis using multi-omics data to elucidate the underlying characteristics that lead to differences in clinical outcomes between subtypes. Patients and Methods: Immunohistochemistry (IHC, n=252), target exome sequencing (n=422), and whole transcriptome sequencing (WTS, n=189) data generated from 427 patients with SCLC patients were comprehensively analyzed. The differences in the mutation profile, gene expression profile were analyzed according to the IHC-based molecular subtype. Clinical implication was evaluated based on treatment outcomes of individual patients. Results: IHC based molecular subtyping revealed a high incidence of ASCL1 subtype (SCLC-A, 56.3%) followed by ASCL1/NEUROD1 co-expressed (SCLC-trans, 17.9%), NEUROD1 (SCLC-N, 12.3%), POU2F3 (SCLC-P, 9.1%), triple-negative (SCLC-TN, 4.4%) subtypes showing high concordance with WTS-based subtyping. We delineated the SCLC-trans subtype resembling SCLC-A rather than SCLC-N in terms of both gene expression profiles and clinical outcomes. SCLC-TN type was defined as non-significant expression of A, N, P. Favorable overall survival (OS) was observed in SCLC-A compared to SCLC-N (adjusted HR 2.4, 95% CI 1.5-3.9, p < 0.001) and SCLC-P (adjusted HR 1.7, 95% CI 0.9-2.9, p = 0.087). SCLC-TN showed a similar OS with SCLC-A (adjusted HR 1.2, 95% CI 0.6 -2.7, p = 0598). The clinical outcome based on inflamed phenotype, clustered by effector cell gene expression profile which are only found in 5% of SCLC-N but 60% of SCLC-P, was more likely to benefit from first-line immunotherapy treatment than non-inflamed phenotype (p = 0.013). Inflammed phenotype demonstrated longer progression-free survival to the first line immunotherapy compared to the non-inflammed phenotype. (10.5 vs 4.3, p = 0.013) Conclusions: This study provides fundamental data, including the incidence and basic demographics of molecular subtypes of SCLC using both IHC and WTS from a comparably large cohort including potential differences in the distribution of subtypes based on ethnicity. Additionally, our results reveal differences in the underlying biological pathway activities and immunogenicity based on molecular subtype, possibly related to the difference in clinical outcomes, including immunotherapy response. Citation Format: Sehhoon Park, Tae Hee Hong, Soohyun Hwang, Hyun-Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Jong Ho Cho, Yong Soo Choi, Jhingook Kim, Young Mog Shim, Hong Kwan Kim, Yoon-La Choi, Se-hoon Lee, Keunchil Park. Comprehensive analysis using transcriptional factor based molecular subtypes and correlation to clinical outcomes in small-cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4546.

Purpose This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery.Materials and Methods The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded.Results The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS.Conclusion Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.

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.

Background Nuclear protein in testis (NUT) carcinoma is a rare tumor associated with NUT rearrangement that can present as poorly differentiated to undifferentiated carcinoma, with or without abrupt squamous differentiation. It is often misdiagnosed as poorly differentiated carcinoma or undifferentiated carcinoma if NUT is not suspected. In this study, we retrospectively analyzed pulmonary NUT carcinoma cases diagnosed with NUT immunohistochemical staining and discuss the differential diagnosis to provide information for this rare and aggressive entity. Methods Cases, diagnosed as “NUT carcinoma” in lung pleura and “metastatic NUT carcinoma from the lung” in lymph nodes were diagnosed between 2017 and 2019 at the Samsung Medical Center (SMC). Clinical features such as age, sex, treatment and follow‐up period, and pathological reports were obtained by reviewing patients’ electronic medical records. Results A total of 10 NUT carcinoma cases were found in the SMC pathology database. Seven patients were men and six were non‐smokers. Tumor cells showed various cellular features such as round, squamoid, and spindle. Some cases had initially been misdiagnosed as spindle cell neoplasm, round cell sarcoma, squamous cell carcinoma and small cell carcinoma. All cases showed diffuse strong nuclear expression of NUT immunohistochemical staining, and some were positive for p63 staining and negative for CD56 staining. Conclusions NUT carcinoma is often misdiagnosed because of its various morphologies. It is important to consider NUT as one of the differential diagnoses when encountering lung biopsy with undifferentiated morphology. Key points Due to various morphological features, NUT carcinoma can be misdiagnosedIt is important to consider NUT carcinoma when diagnosing a poorly differentiated or undifferentiated tumor, NUT carcinoma showed poorly differentiated to undifferentiated features with strong nuclear expression of NUT. NUT carcinoma can show various morphologies that can be misdiagnosed. It is important to consider NUT carcinoma in patients of relatively young age.

Background The number of patients with operable lung cancer with a history of percutaneous coronary intervention (PCI) has increased. However, cardiovascular outcomes and mortality, according to the time from PCI to surgery, and the follow‐up time after surgery are largely unknown. Here, we aimed to compare the cardiovascular outcomes and mortality of these patients with a history of PCI to those of patients without a history of PCI. Methods Using the Korean National Health Insurance Service Database, we selected 30 750 patients who underwent surgery for lung cancer between 2006 and 2014. Study outcome variables were all‐cause mortality, revascularization, intensive care unit (ICU) readmission, and stroke incidence. Patients were followed‐up until 2016. Results Of the 30 750 patients, 513 (1.7%) underwent PCI before surgery. The PCI group did not show an increased risk of death, ICU readmission, or stroke within one year of surgery, despite an increased risk of revascularization. However, one year after surgery, they showed a higher risk of death and revascularization than the non‐PCI group. The risk of revascularization was highest when the interval between PCI and surgery was 3 years. Conclusions Patients who underwent PCI before surgery for lung cancer were at a higher risk of death than those in the non‐PCI group at one year after surgery. In addition, they showed higher short‐ and long‐term risks of revascularization than patients in the non‐PCI group. Careful long‐term management of cardiovascular risk is necessary for this population., The PCI group had higher short‐ and long‐term risks of revascularization. Careful long‐term management of cardiovascular risk is required for the PCI group.

Background Treatment of human lung squamous cell carcinoma (LUSC) using current targeted therapies is limited because of their diverse somatic mutations without any specific dominant driver mutations. These mutational diversities preventing the use of common targeted therapies or the combination of available therapeutic modalities would require a preclinical animal model of this tumor to acquire improved clinical responses. Patient-derived xenograft (PDX) models have been recognized as a potentially useful preclinical model for personalized precision medicine. However, whether the use of LUSC PDX models would be appropriate enough for clinical application is still controversial. Methods In the process of developing PDX models from Korean patients with LUSC, the authors investigated the factors influencing the successful initial engraftment of tumors in NOD scid gamma mice and the retainability of the pathological and genomic characteristics of the parental patient tumors in PDX tumors. Conclusions The authors have developed 62 LUSC PDX models that retained the pathological and genomic features of parental patient tumors, which could be used in preclinical and co-clinical studies. Trial registration Tumor samples were obtained from 139 patients with LUSC between November 2014 and January 2019. All the patients provided signed informed consents. This study was approved by the institutional review board (IRB) of Samsung Medical Center (2018-03-110)

Objectives Primary pulmonary salivary gland-type tumors (PSGT) are rare among all types of lung cancer. The purpose of this study was not only to evaluate the clinical outcomes and prognostic factors after treatment, but also to assess the role for bronchoscopic intervention in PSGT. Methods We analyzed the medical data of 181 PSGT patients who were treated between 1995 and 2018. Patients were divided into three groups according to the initial treatment, as follows: surgical resection with/without adjuvant therapy including bronchoscopic intervention (surgery group, n = 116); bronchoscopic intervention without surgical resection (bronchoscopic intervention group, n = 51); and other treatments group (n = 14). A multivariable Cox proportional hazard regression analysis was used to identify the independent prognostic factors associated with overall survival (OS) and progression free survival (PFS) after the first treatment. In addition, subgroup analysis was performed according to the clinical stage. Results Among the 181 patients, 104 (57.5%) patients were diagnosed with adenoid cystic carcinoma (ACC), 71 (39.2%) with mucoepidermoid carcinoma, and 6 (3.3%) with epithelial-myoepithelial carcinoma. In the surgery group, 21 patients underwent bronchoscopic intervention as a bridge therapy before surgery because of respiratory distress. Poor OS was associated with older age, the existence of other malignancy, higher clinical stages, larger tumor size, and non-surgical treatments. Lower PFS was associated with ACC, larger tumor size, and non-surgical treatments. The surgery group had the best OS and PFS among all treatment groups. However, there was no significant difference in the OS between the surgery and bronchoscopic intervention groups (p = 0.66) in patients at high clinical stages. Conclusions Surgical resection was the best initial treatment choice. However, bronchoscopic intervention may be useful as the initial treatment in patients at high clinical stage and as a bridge therapy prior to surgery.

Background Reproductive factors and hormone use in postmenopausal women have been hypothesised to affect the risk of developing lung cancer, but the epidemiological evidence is inconsistent. Methods Using the Korean National Health Insurance System database, we identified 4,775,398 postmenopausal women older than 40 years who had undergone both cardiovascular health- and cancer screening between 1 January 2009 and 31 December 2014. Information about reproductive factors was obtained from a self-administered questionnaire. The risk of lung cancer was estimated using Cox proportional hazard regression models. Results During a median follow-up of 4.4 years, 16,556 women (15,223 non-smokers) were diagnosed with lung cancer. The risk of lung cancer was not significantly influenced by early menarche age (adjusted hazard ratio [aHR] 1.03 for menarche ≥18 vs. ≤14; 95% confidence interval [CI], 0.98–1.09) or late age at menopause (aHR 1.02 for menopause ≥55 vs. Conclusions No statistically significant association was found between reproductive factors and the risk of lung cancer in postmenopausal Korean women.

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).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.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).In MPSOL(+) patients, complete LN assessment affects the OS and RFS rather than the extent of lung resection. In patients with solid tumor or tumor2 cm, a complete LN assessment would be required, even if sublobar resection is unavoidable.

Introduction The International Association for the Study of Lung Cancer recently proposed a new N descriptor by combining the location of metastatic lymph nodes (LNs), nN (single-station versus multiple-station), and absence versus presence of skip metastasis as pN1a, pN1b, pN2a1, pN2a2 and pN2b. This study aimed to evaluate the discriminatory ability and prognostic performance of the proposed N descriptor in a large independent NSCLC cohort. Methods We analyzed 1228 patients who underwent major pulmonary resection for pathological N1 or N2 NSCLC between 2004 and 2014. Survival analysis using the Cox proportional hazard model was performed to assess the prognostic significance of the N descriptor. Results From 2004 to 2014, a total of 7437 patients were operated on for NSCLC. Patients pathologically confirmed as having N1 (n = 732) or N2 (n = 496) disease after surgery were included. The median total number of dissected LNs was 24 (range 10–83), and the median number of involved LNs was 2 (range 1–40). The 5-year overall survival rates were 62.6%, 57.0%, 64.7%, 48.4%, and 42.8% for stages N1a, N1b, N2a1, N2a2, and N2b, respectively. Analysis of overall and recurrence-free survival revealed that N2a1 is not sufficiently distinguished from N1a and N1b. In terms of overall survival, N1b is not sufficiently distinguished from N2a2. Conclusion On the basis of the N descriptor proposed by the International Association for the Study of Lung Cancer, some of the prognostic implications of the five groups overlapped. It would be better to classify similar prognostic groups into three or four groups to divide the group. A large-scale prospective study is needed to validate these N descriptors.

Objectives With advances in lung cancer treatments, the number of lung cancer survivors has increased. As cardiovascular diseases (CVD) are some of the major causes of non-cancer deaths, CVD management is an integral part of cancer survivorship care. However, there is sparsity of data on cardiovascular risk in lung cancer survivors who underwent lung cancer surgery. We aimed to compare the incidence of CVD between lung cancer survivors and the general non-cancer population. Materials and methods Using the Korean National Health Insurance Service Database, we selected 20,458 patients who underwent surgery for lung cancer between 2007 and 2013. Study outcome variables were coronary heart disease (CHD), myocardial infarction (MI), ischemic stroke (IS), and death. Patients were followed until 2016. Results A total of 20,458 lung cancer patients undergoing lung cancer surgery were compared to 27,321 non-cancer control subjects. Lung cancer survivors showed a greater risk for all cardiovascular (CV) events (adjusted hazard ratio [aHR] = 1.27, 95% confidence interval [CI]: 1.19–1.36), CHD (aHR = 1.26, 95% CI: 1.16–1.36), and IS (aHR = 1.22, 95% CI: 1.07–1.39). Chemotherapy and radiotherapy were associated with an increased risk of CV events, CHD, and MI. Lung cancer survivors who were CV event-free for one year, and up to three years, were still at a higher risk for all CV events compared to the non-cancer control population. Conclusions Lung cancer survivors showed an increased risk of CHD and IS compared with the general non-cancer population. Therefore, paying careful attention to cardiovascular risk in lung cancer survivors is suggested, especially for those who receive chemotherapy and/or radiotherapy, in order to ensure both early and long-term survivorship.

To report the trends in incidence and survival associated with thymic epithelial tumors (TETs) in Korea.Data from 1999 to 2017 were obtained from the Korean Central Cancer Registry. Age-standardized incidence rates and average annual percentage changes (AAPCs) were calculated. Net survival (NS) was estimated by the Pohar-Perme method.Among 5812 patients diagnosed with having TETs, 58.9%, 38.1%, and 3.0% were diagnosed with having thymoma, thymic carcinoma, and thymic neuroendocrine tumor (NET), respectively. Age-standardized incidence rates were 0.50, 0.30, 0.18, and 0.02 per 100,000 for all TETs and the respective subtypes. There was an increase in incidence of all TETs (AAPC = 6.1%) and subtypes: thymoma (AAPC = 5.6%), thymic carcinoma (AAPC = 7.0%), and thymic NET (AAPC = 3.4%). Proportions of patients with thymoma, thymic carcinoma, and thymic NET were 58.9%, 38.1%, and 3.0%, respectively. For thymoma, the relative proportion of distant stage decreased (19.4% in 2005 to 8.8% in 2017) and low-grade WHO subtype (A, AB, B1) increased faster than high-grade WHO type (B2, B3) (AAPC = 19.8% versus 9.6%). For thymoma, the 5-year NS was 82.3%. This increased from 64.3% in 1999 to 2002 to 90.6% in 2013 to 2017. For thymic carcinoma, the 5-year NS was 46.2% and only slightly increased from 39.4% in 1999 to 2002 to 47.9% in 2013 to 2017.This study indicates a high incidence of TET and its continuous increase in Korea. The proportion of thymic carcinoma was relatively higher than in the United States or Europe. Survival for thymoma improved during the study period, whereas this was not evident for thymic carcinoma or thymic NET.

Background Recurrent laryngeal nerve paralysis (RLNP) is a common complication after esophagectomy which can cause severe pulmonary complications. However, bilateral RLNP has been rarely reported in esophagectomy patients. The objective of our study is to investigate the clinical significance of patients who had bilateral RLNP following esophagectomy. Methods We retrospectively reviewed patients who underwent esophagectomy at a single center from 1994 to 2018. Among these, patients with bilateral vocal cord paralysis were included in this study. Results A total of 3217 patients were reviewed and 400 (12.4%) patients had RLNP, including 56 patients with bilateral RLNP identified by laryngoscopic examination. During the postoperative managements, 10 of the 56 patients (17.9%) required tracheostomy. Among them, two died of acute respiratory distress syndrome and the other eight patients were discharged after removing the tracheostomy tube. The median lengths of hospital and intensive care unit stay were 19.5 (range 8–157) and 2 (range 1–46) days, respectively. Forty‐six patients (83.6%) were discharged with oral feeding after swallowing therapy including tongue holding maneuver and head tilt exercise. The other five patients (8.9%) were discharged with alternative enteral feeding via jejunostomy, but they were able to achieve oral diet 2–3 months after surgery. Conclusion Bilateral RLNP following esophagectomy was rare, but it required great attention to prevent severe respiratory complications. However, only a few patients required tracheostomy and the majority achieved oral ingestion after intensive rehabilitation. Feeding education and respiratory rehabilitation are critical during the management of patients with bilateral RLNP., In 3217 patients who underwent esophagectomy, 400 (12.4%) patients had recurrent laryngeal nerve palsy (RLNP), including 56 (1.7%) patients with bilateral RLNP. Only 10 patients required tracheostomy and the majority achieved oral ingestion after rehabilitation. Feeding education and respiratory rehabilitation are critical during the management of patients with bilateral RLNP.

BACKGROUND: This study evaluated the lymph node ratio (LNR) defined as the ratio of the number of metastatic lymph nodes to the number of dissected lymph nodes as a prognostic factor for survival in patients with pT1–2N1M0 non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 413 patients with pathologic T1–2N1M0 NSCLC after complete surgical resection and mediastinal LN dissection between January 2004 and December 2012. The cut-off value for LNR was determined using χ(2) tests, which were calculated using Cox proportional hazards regression model. Based on this model, the optimal cut-off value for LNR was 0.1. RESULTS: The study included 337 males and 76 females with a mean age of 62 years (range, 34–83 years). Patients with a high LNR (≥0.1) were more likely to be female and have more adenocarcinomas compared with patients with a low LNR (

Although the video-assisted thoracic surgery (VATS) approach has been accepted as a safe and effective alternative to lobectomy, its advantage remains unclear in advanced-stage lung cancer. This study is aimed to evaluate the feasibility and long-term outcomes of VATS in lung cancer with clinical N1 (cN1) disease.We retrospectively reviewed the records of 1149 consecutive patients who underwent lobectomy for cN1 disease from 2006 to 2016. Perioperative outcomes and long-term survival rates were compared using a propensity score-based inverse probability of treatment weighting (IPTW) technique.We performed VATS and open thoracotomy for 500 and 649 patients, respectively. All preoperative characteristics became similar between the two groups after IPTW adjustment. Compared to thoracotomy, VATS was associated with shorter hospitalization (7.7 days vs. 9.2 days, p0.001), earlier adjuvant chemotherapy (41.7 days vs. 46.6 days, p = 0.028), similar complete resection rates (95.2 % vs. 94.0 %, p = 0.583), and equivalent dissected lymph nodes (27.5 vs. 27.8, p = 0.704). On IPTW-adjusted analysis, overall survival (OS) (59.4 % vs. 60.3 %, p = 0.588) and recurrence-free survival (RFS) (59.2 % vs. 56.9 %, p = 0.651) at 5 years were also similar between the two groups. Multivariable Cox analysis revealed that VATS was not a significant prognostic factor for cN1 disease (p = 0.764 for OS and p = 0.879 for RFS).VATS lobectomy is feasible for patients with cN1 disease, providing comparable perioperative outcomes, oncologic efficacy, and long-term outcomes as open thoracotomy.

The aim of this study was to investigate the associations of aspirin, metformin, and statins with lung cancer risk and mortality using population-based nationwide cohort data.This study included a total of 732,199 participants who underwent a national health check-up from 2002 to 2003. Lung cancer incidence and mortality were identified using a registered lung cancer diagnosis code (International Classification of Diseases, 10th revision, code C34) and the Korean National Death Registry. The study participants were followed up from January 1, 2004 to December 31, 2013. Medication exposure was defined by the cumulative duration of use and cumulative defined daily dose per 2-year interval. To avoid immortal-time bias, drug exposure was inserted as a time-dependent variable in Cox analysis, which evaluated the associations of these medications with lung cancer.Metformin use had a protective association with lung cancer incidence (p's for trend 0.008) and mortality (p's for trend0.001) in a dose-response fashion, and these associations were prominent among participants with a metformin cumulative defined daily dose of 547.5 and above compared with patients without diabetes. Lung cancer mortality was dose-dependently reduced with the use of aspirin (p's for trends 0.046) and statin (p's for trends0.001). The combined use of aspirin, statins, and metformin exhibited more prominent protective associations with lung cancer risk and mortality.The use of aspirin, metformin, and statins had independent protective associations with lung cancer mortality, and metformin had an inverse association with lung cancer risk. Further studies are necessary to develop clinically applicable anticancer strategies using these drugs for the reduction of lung cancer and related mortality.

Background The aim of this study was to analyze the surgical outcomes of locally advanced lung cancer invading the great vessels or heart, according to the extension of cancer invasion. Methods From 1995 to 2015, 59 patients who were surgically treated and pathologically diagnosed with T4N0-1 non-small cell lung cancer with invasion to the great vessels or heart were enrolled. Surgical outcomes were compared between patient groups with and without intrapericardial invasion. Results The median age was 64 years (interquartile range [IQR] 57-68) and 56 patients (95%) were male. In-hospital mortality was 9% and median overall survival was 30 months (IQR 12-83). One and five-year overall survival rates were 75% and 44%, respectively. The median overall survival in patients with lung cancer invasion to the intrapericardial space (n = 45) was 27 months (IQR 10-63), while it was 42 months (IQR 18-104) in patients without intrapericardial invasion (n = 14). Median disease-free survival was significantly poorer in patients with intrapericardial invasion (12 months; IQR 6-55), especially in patients with heart invasion (n = 11, 7 months, IQR 5-27), than in patients without intrapericardial invasion (30 months, IQR 13-103). Conclusion Patients with lung cancer invading the intrapericardial space showed worse surgical outcomes in both overall and disease-free survival. Therefore, surgical management should be carefully considered in patients with intrapericardial invasion.

Objectives Understanding the timing and pattern of cancer recurrence is essential to explain the causes of treatment failure. We investigated the recurrence pattern and rate over time in patients with completely resected N1-stage II lung adenocarcinoma. Materials and methods We retrospectively reviewed the medical records of 333 patients who underwent complete surgical resection for N1-stage II lung adenocarcinoma. Results The median recurrence-free survival (RFS) was 38.8 months and the 5-year RFS rate was 39.6%. Left-sided tumors, large tumor size, and lymph node (LN) ratio higher than 0.15 were significantly correlated with a worse RFS, whereas female sex, direct LN involvement, and adjuvant chemotherapy were significantly correlated with a better RFS. Among the 182 patients who experienced recurrences, 46 (25.3%) had only loco-regional recurrences and 136 (74.7%) had distant metastases. The organs most commonly involved in initial recurrence were the lungs (n = 89, 48.9%), followed by bone (n = 41, 22.5%) and the brain (n = 38, 20.9%). The recurrence hazard curve for the entire study population demonstrated a similarly shaped and sized initial and second peak at 15 and 23 months, and a third smaller peak during the fourth year. The recurrence hazard curve of patients who received adjuvant chemotherapy exhibited a more delayed and smaller first peak than those who did not receive adjuvant chemotherapy. The patients treated with adjuvant chemotherapy had a lower rate of distant metastasis (p = 0.037); adjuvant chemotherapy had no effect on brain metastasis (p = 0.640). Conclusion In the present cohort, the hazard curves suggested that bone and brain recurrences exhibited an earlier first peak, while lung recurrences presented later. Adjuvant chemotherapy not only reduced the recurrence hazard but also delayed the recurrence and altered the pattern of recurrence. However, these results need to be confirmed in a prospective study.

Purpose Data are limited on programmed death ligand 1 (PD-L1) expression in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Materials and methods We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free survival (RFS) and overall survival in 319 patients with EGFR-mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS). Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis. Results All patients had ≥1 EGFR mutation-54% in exon 19 and 39% in exon 21. Overall, 51% of patients had PD-L1-positive tumors. The prevalence of PD-L1 positivity was higher among patients with stages II-IV versus stage I disease (64% vs. 44%) and among patients with other EGFR mutations (75%) than with L858R mutation (39%) or exon 19 deletion (52%). PD-L1 positivity was associated with shorter RFS, with an adjusted hazard ratio of 1.52 (95% confidence interval [CI], 0.81 to 2.84; median, 18 months) for the PD-L1 TPS ≥ 50% group, 1.51 (95% CI, 1.02 to 2.21; median, 31 months) for the PD-L1 TPS 1%-49% group, and 1.51 (95% CI, 1.05 to 2.18) for the combined PD-L1-positive groups (TPS ≥ 1%) compared with the PD-L1-negative group (median, 35 months). Conclusion PD-L1 expression is associated with disease stage and type of EGFR mutation. PD-L1 positivity might be associated with worse RFS among patients with surgically treated EGFR-mutant NSCLC.

The prognostic significance of tumor size in thymic epithelial tumors (TETs) has not been fully evaluated. We aimed to clarify the prognostic value of tumor size in limited-stage and advanced-stage TETs.Clinical records of patients with completely resected TETs were retrospectively collected from 4 tertiary centers between January 2000 and February 2013. Information on the Masaoka-Koga stage was available for 1215 patients (M-K group), and 433 patients were classified according to the eighth edition of the Tumor-Node-Metastasis staging system (TNM group). Limited-stage and advanced-stage TETs were defined according to whether they were confined within the surrounding fatty tissues without invasion. The optimal cutoff value was selected using a maximally selected log-rank statistic.The median tumor size was 6.0 ± 2.8 cm in the M-K group and 6.5 ± 3.0 cm in the TNM group. In the multivariable analysis, tumor size had a significant effect on both overall survival (P = .003) and recurrence-free survival (P .001) for limited-stage tumors (M-K stage I or II or TNM stage I), but not for advanced-stage tumors (M-K stage III or IV or TNM stage II-IV; P = .349 for overall survival and P = .439 for recurrence-free survival). The optimal cutoff value for tumor size was5.5 cm for both overall survival and recurrence-free survival in limited-stage TETs.Tumor size is an independent prognostic factor in patients with completely resected limited-stage TETs and a cutoff value5.5 cm might help clinicians enact proper treatment strategies and surveillance.

Background The aim of this study was to identify risk factors associated with mortality in patients re-admitted to an intensive care unit (ICU) after initial recovery from major lung resection. Methods We retrospectively reviewed the case records of all patients who underwent major lung resection between February 2011 and May 2013. A total of 1916 patients underwent major resection surgery for various lung diseases, 63 (3.3%) of which required ICU admission after initial recovery. We analyzed preoperative and perioperative data, including ICU factors and outcomes. Results The patient group included 57 men (90.5%) with a mean age of 65.3 years. Pathologic diagnosis was malignancy in 92.1% of patients, while 7.9% had benign disease. Open thoracotomy was performed in 84.1%, whereas minimally invasive approaches were performed in 15.9%. In-hospital mortality occurred in 16 (25.4%) patients. Patients were classified as either survivors (n = 47, 74.6%) or non-survivors (n = 16, 25.4%). The most common reason for ICU readmission was pulmonary complication (n = 50, 79.4%). Thirty-one patients (49.2%) required mechanical ventilation, seven (11.1%) required extracorporeal membrane oxygenation, and three (4.8%) required renal support. Multivariate analysis showed that acute respiratory distress syndrome (ARDS) and delirium were independent risk factors for in-hospital mortality. In addition, delirium frequently occurred in patients with ARDS. Conclusion ARDS and delirium were independent risk factors for in-hospital mortality in patients who were readmitted to the ICU after major lung resection. Future studies are needed to determine if the prevention of delirium and ARDS can improve postoperative outcomes for patients with lung cancer.

Background Oesophageal cancer with airway invasion presents a challenge for therapy and often has serious complications. We analysed the clinical outcomes of radiation therapy (RT) in patients with clinical T4b oesophageal cancer with airway invasion. Methods We retrospectively reviewed the medical records of 73 patients with oesophageal cancer who had clinical T4 disease and who received RT between January 1994 and June 2017. Among them, 47 patients with clinical T4b disease with airway invasion were included in this study; 31 had gross invasion on bronchoscopy and 16 had extrinsic compression with mucosal change. We investigated the survival outcomes, clinical courses, and toxicities. Results The median survival (MS) time was 9 months. The 1- and 2-year overall survival (OS) rates were 41.4 and 27.4%, respectively. The MS times for patients treated with curative or palliative aims were 15 and 4 months, respectively (p = 0.001). Seven patients (14.9%) had fistulae at diagnosis; after RT, three had no change in size, three closed, and one had increased. Newly developed oesophageal fistulae after treatment were observed in 13 patients (27.7%). The median time to a newly developed fistula was 3 months (range, 1–15). Among them, a fistula was closed in only one patient. Death from aspiration pneumonia occurred in one patient who had a fistula at diagnosis and in nine patients who newly developed fistulae after treatment. Severe oesophageal bleeding causing death occurred in two patients. Patients with gross invasion on bronchoscopy had a higher risk of developing a fistula than did patients with mucosal change (37.5% vs. 25.0%, respectively). Conclusions Even for clinical T4b disease with airway invasion, RT with a curative aim showed acceptable survival outcomes in patients with good performance status and no distant metastasis at initial diagnosis. However, the risk of fistula development associated with fatal events remains high. Further study is warranted to decrease the risks of treatment and improve clinical outcomes. Trial registration Retrospectively registered.

Background In lung cancer survivors, cardiovascular diseases (CVDs) are the leading cause of noncancer deaths. Nonetheless, there is lack of information on management of dyslipidemia, a major risk factor for future CVD events, in lung cancer survivors. This study aimed to assess dyslipidemia management and prevalence of statin eligibility in lung cancer survivors. Methods From the Korean National Health Insurance Service database, we selected 7349 lung cancer survivors who received surgery for lung cancer from 2007 to 2014. We used descriptive statistics for analyses of dyslipidemia management status on the basis of the National Cholesterol Education Program Adult Treatment Panel III guidelines. We also identified those who met the criteria for treatment on the basis of CVD risk according to the 2018 American College of Cardiology and American Heart Association (ACC/AHA) guidelines. Results The overall awareness and treatment rates for lung cancer survivors with dyslipidemia were 31.8% and 29.7%, respectively. The overall control rate for those receiving treatment was 88.7%, but was lowest in the highest risk group (78.1%). Furthermore, undertreatment of dyslipidemia was more prominent in young, male lung cancer survivors and those diagnosed with lung cancer within 3 years. Among those not receiving treatment for dyslipidemia, 61.7% were indicated for statin according to the ACC/AHA guidelines. Conclusion Over half of lung cancer survivors were not receiving treatment, although they were eligible for statin under current guidelines. To reduce noncancer mortality, statin use and adequate management of CVD risk factors should be encouraged in lung cancer survivors.

The objective of this study was to evaluate the treatment outcomes and prognostic factors of neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgical resection for non-small cell lung cancer (NSCLC) with N2 disease.A retrospective review of patients with N2 disease who underwent neoadjuvant CCRT followed by surgery at our institution was performed and multivariate Cox regression analysis was used to determine the factors associated with survival outcomes.From 1997 to 2013, 574 patients underwent curative-intent surgery after neoadjuvant CCRT for NSCLC with N2 disease. The mean age was 59 years (444 men, 77%). The extent of surgery included lobectomy in 418 patients (73%), pneumonectomy in 73 (13%), and sleeve resection in 25 (4.3%). Complete resection was obtained in 543 patients (95%). Postoperative complications and in-hospital mortality occurred in 199 patients (35%) and 21 (3.7%), respectively. Pathologic complete response was achieved in 72 patients (13%) and 304 (53%) experienced mediastinal clearance. With a mean follow-up of 36 months, median overall survival (OS) and recurrence-free survival (RFS) were 56 months and 18 months, respectively. The 5-year OS rates were 61% in ypN0, 49% in ypN1, and 35% in ypN2 (p=0.001). The 5-year RFS rates were 45% in ypN0, 23% in ypN1, and 17% in ypN2 (p0.001). Older age, advanced pT stage, persistent N2, large cell carcinoma, and pneumonectomy were independent prognostic factors associated with worse OS and poorer RFS.Neoadjuvant CCRT followed by surgery could be performed with acceptable early postoperative outcomes, satisfactory local control, and encouraging long-term survival. Care should be taken in selecting patients when necessitating pneumonectomy after neoadjuvant CCRT. Further efforts to improve outcomes in patients with persistent N2 disease are required.

Background Patients with malignant pleural effusion have a limited life expectancy. An increase in pleural and oncological treatment options and more accurate prognostic evaluation may help individualize treatment strategies. The aim of this study was to identify the prognostic indicators of overall survival (OS) after video‐assisted thoracic surgery (VATS) talc pleurodesis for malignant pleural effusion. Methods We examined the medical records of all consecutive patients with malignant pleural effusion who underwent VATS talc pleurodesis from 2006 to 2008 at the Samsung Medical Center. Univariate and multivariate analyses were used to identify predictors of OS after VATS talc pleurodesis. Results During the study period, 91 patients underwent VATS talc pleurodesis to treat malignant pleural effusion. Early (within 30 days) and late (within 90 days) postoperative mortality rates were 9.9% (9 patients), and 25.3% (23), respectively. Median survival time after VATS talc pleurodesis was 10.5 months. The postoperative respiratory complication rate was 11% (10 patients), and included pneumonia (9) and acute respiratory distress syndrome (4). Multivariate analysis revealed that preoperative chemotherapy (P = 0.012), preoperative radiotherapy (P = 0.003), and Eastern Cooperative Oncology Group (ECOG) performance score 3 or 4 (P = 0.013) were independent risk factors of OS after VATS talc pleurodesis. Conclusions We identified previous chemotherapy or radiotherapy and poor performance status (ECOG 3 or 4) as significant predictors of OS after VATS talc pleurodesis. These prognostic factors can help surgeons select candidates for VATS pleurodesis for malignant pleural effusion.

Introduction Potential disparities in the diagnosis, treatment, and survival of patients with lung cancer with and without disabilities have rarely been investigated. Methods We conducted a retrospective cohort study with a data set linking the Korean National Health Service database, disability registration data, and Korean Central Cancer Registry data. A total of 13,591 people with disabilities in whom lung cancer had been diagnosed and 43,809 age- and sex-matched control subjects in whom lung cancer had been diagnosed were included. Results Unknown stage was more common in people with severe disabilities (13.1% versus 10.3%), especially those with a communication (14.2%) or mental/cognitive disability (15.7%). People with disabilities were less likely to undergo a surgical procedure (adjusted OR [aOR] = 0.82, 95% confidence interval [CI]: 0.77–0.86), chemotherapy (aOR = 0.80, 95% CI: 0.77–0.84), or radiotherapy (aOR = 0.92, 95% CI: 0.88–0.96). This higher likelihood was more evident for people with severe communication impairment (aORs of 0.46 for surgery and 0.64 for chemotherapy) and severe brain/mental impairment (aORs 0.39 for surgery, 0.47 for chemotherapy, and 0.49 for radiotherapy). Patients with disabilities had a slightly higher overall mortality than did people with no disability (adjusted hazard ratio = 1.08, 95% CI: 1.06–1.11), especially in the group with a severe disability (a hazard ratio = 1.20, 95% CI: 1.16–1.24). Conclusions Patients with lung cancer and disabilities, especially severe ones, underwent less staging work-up and treatment even though their treatment outcomes were only slightly worse than those of people without a disability. Although some degree of disparity might be attributed to reasonable clinical judgement, unequal clinical care for people with communication and brain/mental disabilities suggests unjustifiable disability-related barriers that need to be addressed.

Surgical resection is a standard treatment for thymic malignancies. However, prognostic significance of nodal metastases and lymph node dissection remains unclear. The aim of this study is to determine prognostic significance of nodal metastases and the role of lymph node dissection (LND) in thymic malignancies.Between 2000 and 2013, 1597 patients who underwent thymectomy due to thymic malignancy were included. Predictive factors for nodal metastasis and prognostic significance of LND were evaluated. Patients were divided into two groups: (1) LND+ group, with intentional LND (446 patients, 27.9%); and (2) LND- group, without intentional LND (1151 patients, 72.1%). Propensity score matching was performed between the two groups.Lymph node metastasis was identified in 20 (6.7%) of 298 patients with thymoma and 47 (31.7%) of 148 patients with thymic carcinoma. In multivariable analysis, thymic carcinoma (hazard ratio: 19.2, p0.001) and tumor size (hazard ratio: 1.09, p = 0.02) were significant predictive factors for lymph node metastasis. The 10-year freedom from recurrence rate of pN1 and pN2 was significantly worse than that of pN0 (p0.001). LND did not increase operative mortality or complication. There was no significant difference in 10-year freedom from recurrence rate between LND+ and LND- groups (82.4% versus 80.9%, p = 0.46 in thymoma; 45.7% versus 44.0%, p = 0.42 in thymic carcinoma).Lymph node metastasis was a significant prognostic factor in thymic malignancies. Although LND did not improve long-term outcomes in thymic malignancies, LND played a role in accurate staging, and improved prediction of prognosis.

Introduction We investigated the timing and patterns of recurrence after the treatment of stage IIIA (N2) non-small cell lung cancer via neoadjuvant concurrent chemoradiotherapy followed by surgery. Materials and methods An institutional database was reviewed retrospectively between 1997 and 2013 (N = 570). Eligible patients had pathologically proven N2 disease, and they completed the planned trimodality therapy with curative intent. The hazard rate function and competing risk analysis were used to evaluate the recurrence dynamics. Results Among the included patients, 76% had single station N2 involvement and 95% had complete resection. The 5-year overall and recurrence-free survival rates were 47% and 29%, respectively. Of the 290 patients who experienced recurrence, 25 (8.4%) experienced loco-regional recurrence, whereas 238 (80.4%) had distant metastases. The hazard rate function for overall recurrence revealed a peak at approximately 8 months after surgery and a marked decline after 2 years. The peak recurrence frequency of distant metastasis differed at each site, with isolated brain metastases exhibiting the earliest peak (6 months) and a narrow recurrence interval (15 months). A histological comparison revealed a higher recurrence hazard rate for adenocarcinoma than for squamous cell carcinoma but similar pattern of recurrences. Patients with complete responses had a lower cumulative incidence rate of recurrence but a slightly earlier peak of recurrence. Nodal responses to induction therapy demonstrated that patents with ypN0 had the lowest recurrence risk, whereas patients with ypN1 and ypN2 had similar hazard rates and cumulative incidence rates of recurrence. Conclusions The dynamics of recurrence after trimodality therapy is organ-specific and varies according to pathologic factors. Our finding provides information on selection patients with risk of recurrence and timing of surveillance study.

BACKGROUND: Programmed death ligand 1 (PD-L1) expression may predict response to anti-programmed death 1 (anti-PD-1) or anti-PD-L1 treatment. There is limited information on changes in PD-L1 expression over time in patients with non-small cell lung cancer (NSCLC).PATIENTS AND METHODS: Eligible patients with NSCLC who received surgery or underwent biopsy at Samsung Medical Center, Seoul, Republic of Korea, and Aarhus University Hospital, Aarhus, Denmark, between February 2004 and April 2012 were included. PD-L1 expression in paired tumor tissue samples from the same patients at different dates and lesions was measured using a laboratory-developed prototype immunohistochemistry assay (22C3 antibody). PD-L1 positivity was defined as tumor cell membrane positivity in ≥ 1% of tumor cells (proportion score). Concordance of PD-L1 expression was analyzed by treating proportion score as categoric or continuous variables.RESULTS: Ninety-one patients were included in the analysis. The median interval between the 2 tumor collection dates was 20 months, with 91% of paired samples collected > 3 months apart. The concordance rate for PD-L1 classification between paired samples was 67% (95% confidence interval, 57%-77%). When treating the immunohistochemistry proportional score as a continuous variable, a significant correlation of PD-L1 expression was observed between the paired samples (Pearson correlation coefficient, 0.61; P < .001).CONCLUSION: There are good correlations of PD-L1 expression from paired NSCLC samples. For patients whose PD-L1 status is negative, it may be valuable to obtain additional tissue samples for retesting PD-L1 expression when anti-PD-1 immunotherapy is considered.

Molecular profiling of actionable mutations in refractory cancer patients has the potential to enable "precision medicine," wherein individualized therapies are guided based on genomic profiling. The molecular-screening program was intended to route participants to different candidate drugs in trials based on clinical-sequencing reports. In this screening program, we used a custom target-enrichment panel consisting of cancer-related genes to interrogate single-nucleotide variants, insertions and deletions, copy number variants, and a subset of gene fusions. From August 2014 through April 2015, 654 patients consented to participate in the program at Samsung Medical Center. Of these patients, 588 passed the quality control process for the 381-gene cancer-panel test, and 418 patients were included in the final analysis as being eligible for any anticancer treatment (127 gastric cancer, 122 colorectal cancer, 62 pancreatic/biliary tract cancer, 67 sarcoma/other cancer, and 40 genitourinary cancer patients). Of the 418 patients, 55 (12%) harbored a biomarker that guided them to a biomarker-selected clinical trial, and 184 (44%) patients harbored at least one genomic alteration that was potentially targetable. This study demonstrated that the panel-based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker-selected clinical trials. Given the expanding list of biomarker-selected trials, the guidance percentage to matched trials is anticipated to increase. Implications for practice This study demonstrated that the panel-based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker-selected clinical trials. Given the expanding list of biomarker-selected trials, the guidance percentage to matched trials is anticipated to increase.

Background Circulating tumor DNA (ctDNA) analysis has been successfully applied to therapy selection and treatment monitoring in advanced cancer patients. However, it is not yet established whether ctDNA can be used clinically for early cancer detection or recurrence prediction in early stage lung cancer patients. Methods We analyzed pre-operative plasma samples from 55 early stage NSCLC patients (stages I-IIIA) using next-generation sequencing assay incorporating somatic and epigenomic analysis, and a bioinformatic classifier to filter non-tumor derived variants. Table: 111P . Cell type Stage Somatic mutation Epigenetic pattern Total number Recurrence+, n (%) Site of recurrence Adenocarcinoma stage 1 ctDNA- methylation- 9 1 (11) Lung n = 17 methylation+ 6 2 (33.3) Stump, bone ctDNA+ 2 1 (50) lung stage 2 ctDNA- methylation- 0 0 (0) n = 2 methylation+ 0 0(0) ctDNA+ 1 1 (100) multiple stage 3 ctDNA- methylation- 0 0 (0) n = 4 methylation+ 2 0 (0) ctDNA+ 2 2 (100) brain, multiple Sqaumous cell carcinoma stage1 ctDNA- methylation- 0 0 (0) n = 7 methylation+ 3 0 (0) ctDNA+ 4 1 (25) multiple stage2 ctDNA- methylation- 0 0 (0) n = 9 methylation+ 0 0 (0) ctDNA+ 9 2 (22.2) multiple, lung stage3 ctDNA- methylation- 0 0 (0) n = 4 methylation+ 1 0 (0) ctDNA+ 3 1 (33.3) Mediastinal LNs Results Somatic mutation analysis alone detected ctDNA in 42% (23/55) of patients, whereas combined mutational and epigenomic analysis detected ctDNA in 67% (37/55). ctDNA detection rate varied by pathological subtypes; using combined approach, ctDNA was detected in all squamous cell carcinoma patients, while only 55% (12/22) in adenocarcinoma (ADC) (p=0.006). Within the ADC subgroup, ctDNA detection rates using the combined approach were dependent on disease stage: 47% (8/17) in stage I, 100% (2/2) in stage II, and 100% (2/2) in stage IIIA. Importantly, within 2 years of follow-up, pre-operative ctDNA status was correlated with tumor recurrence after resection; among 17 stage I ADC patients, three of eight (38%) ctDNA-positive cases showed recurrence, while only one of nine (11%) ctDNA-negative cased did (p=0.29). Interestingly, patients with somatic mutation in their ctDNA have shown higher recurrence rate. Conclusion Utilizing a plasma-only sequencing assay incorporating somatic genomic and epigenomic analysis, ctDNA detection rate in early stage lung cancer (stage I-III) can far outperform the detection rate of somatic sequence variant detection alone. And, the presence of pre-operative ctDNA in patients with early stage lung adenocarcinoma may identify those who are more likely to have disease recurrence. Legal entity responsible for the study: Guradant Health, Inc. Funding Guardant Health, Redwood City, CA, USA. Disclosure I. Kim: Full / Part-time employment, Officer / Board of Directors: Guardant Health. M. Shultz: Officer / Board of Directors: Guardant Health. A. Jaimovich: Officer / Board of Directors: Guardant Health. J. Odegaard: Officer / Board of Directors: Guardant health, Inc. S. Olsen: Officer / Board of Directors: Guardant Health, Inc. A. Talasaz: Officer / Board of Directors: Guardant health. J. Kim: Research grant / Funding (self): Guardant health, Inc. All other authors have declared no conflicts of interest.

8520 Background: The standard treatment option for stage IIIA-N2 subgroup is still under discussion with controversies. We hypothesize that immune checkpoint inhibitor consolidation therapy could have an additional role in prolongation of the disease-free survival (DFS) for stage IIIA-N2 NSCLC treated with tri-modalities therapy. Methods: This is a phase 2 study evaluating the clinical efficacy of pembrolizumab treatment after CCRT with curative resection in stage IIIA-N2 NSCLC pts. Pathologically confirmed pts were treated with five cycles of CCRT, weekly paclitaxel (50mg/m2) and cisplatin (25mg/m2) combined with radiotherapy (total of 44Gy over 22 fractions) followed by curative resection. Adjuvant Pembrolizumab (200mg fixed dose) is applied every three weeks up to 2 years or until disease recurrence. The primary objective is disease-free survival of more than 20 months. The first patient was recruited in October 2017, and the data for this abstract was locked at 20th of January, 2019. Results: Total of 40 pts were screened, and 37 pts received treatment. Median age was 64 years (range 39-74), and twenty-three pts were male (62.2%). As a curative surgery, pts received lobectomy (n=34), bi-lobectomy (n=2), or pneumonectomy (n=1). Adenocarcinoma was predominant (n=27, 73.0%). After the neoadjuvant CCRT, down-staging were observed in nine pts (24.3%). The median follow-up duration was 10.6 months (range 3.1-17.2), and pts received a median of 11 cycles (range 1-22) of adjuvant pembrolizumab. DFS is not reached. Fourteen patients discontinued treatment due to disease progression (n=9), adverse events (n=4) and withdraw consent (n=1). There was a case of grade 4 pneumonitis and a case of grade 3 autoimmune hepatitis which lead to discontinuation of the treatment. Otherwise, grade 1-2 hypothyroidism (n=6), pneumonitis (n=5), skin rash (n=3) were observed. Patients with sever immune-related adverse event showed a significantly high percentage of Ki-67 + cells among CD8 T-cells in peripheral blood. Conclusions: This study is the first study to demonstrate the feasibility of adjuvant pembrolizumab monotherapy in stage IIIA-N2 patients. Updated and detail clinical and exploratory biomarker outcome will be presented at the annual meeting. Clinical trial information: NCT03053856.

e14557 Background: Circulating tumor DNA (ctDNA) analysis has been successfully applied to therapy selection and treatment monitoring in advanced cancer patients. However, it is not yet established whether ctDNA can be used clinically for early cancer detection or predicting tumor recurrence in early stage lung cancer patients. Methods: We analyzed pre-operative plasma samples from 55 early stage NSCLC patients (stages I-IIIA) using next-generation sequencing to detect somatic mutations and differential epigenomics patterns, including methylation signatures. Results: Using somatic mutation analysis alone, ctDNA was detected in 42% (23/55) of patients, whereas combined mutational and epigenomic analysis detected ctDNA in 71%. ctDNA detection rate also varied markedly between lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC);using combined analysis of somatic mutations and epigenomic patterns, ctDNA was detected in all SCC patients, while only 55% of ADC (12/22) were ctDNA-positive (p= 0.006). Within the ADC subgroup, ctDNA detection rates using the combined approach were dependent on disease stage: 47% (8/17) in stage I, 100% (2/2) in stage II, and 100% (2/2) in stage IIIA. Importantly, pre-operative ctDNA status was correlated with tumor recurrence post-resection; three of eight (38%) ctDNA-positive stage I ADC patients recurred within 2 years of resection, while only one of nine (11%) ctDNA-negative stage I ADC patients recurred (p= 0.29). Conclusions: Taken together, we show that the combination of somatic mutation detection and epigenomic analysis outperforms each individual biomarker in the detection of ctDNA in early stage lung cancer. Importantly, we also demonstrate that pre-operative ctDNA detection may identify a high-risk population of early stage lung cancer patients that may benefit from (neo)adjuvant therapy.

Objectives For early-stage thymoma, complete thymectomy has classically been regarded as the standard treatment protocol. However, several studies have shown that limited thymectomy may be an alternative treatment option for thymoma. This study compared perioperative outcomes, survival, and recurrence rates between patients undergoing limited thymectomy and complete thymectomy. Materials and methods Between January 2000 and December 2013, a total of 762 patients underwent thymectomy for stage I or II thymomas at four institutions participating in the Korean Association for Research on the Thymus. Patients were divided into two groups: limited thymectomy group (n = 295) and complete thymectomy group (n = 467). Comparative clinicopathological, surgical, and oncological features were reviewed retrospectively. Results The median follow-up time was 49 months (range: 0.2–189 months). A propensity score-matching analysis, based on seven variables (age, sex, surgical approach, tumor size, WHO histological type, Masaoka-Koga stage, and adjuvant radiotherapy), was performed using 141 patients selected from each group. The 5- and 10-year freedom-from-recurrence rates in the limited thymectomy group were 96.3% and 89.7%, respectively, and those in the complete thymectomy group were 97.0% and 85.0%, respectively. No significant differences in these rates were observed between groups (p = 0.86). A multivariate Cox regression analysis showed that overall survival and freedom-from-recurrence rates did not significantly differ by surgery extent (p = 0.27, 0.66, respectively). Perioperative outcomes were better in the limited thymectomy group. Conclusion Limited thymectomy was not inferior to complete thymectomy with respect to recurrence, and had better perioperative outcomes. Limited thymectomy may be a viable treatment option for early-stage thymoma.