Purpose: This study investigated the recurrence patterns and timing in patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) according to the residual tumor (R) descriptor proposed by the International Association for the Study of Lung Cancer (IASLC). Materials and Methods: From 2004 to 2021, patients with pN2 NSCLC who underwent anatomical resection were analyzed according to the IASLC R criteria using medical records from a single center. Survival analysis was performed using Cox proportional hazards models. Recurrence patterns between complete (R0) and uncertain resections (R[un]) were compared. Results: In total, 1,373 patients were enrolled in this study: 576 (42.0%) in R0, 286 (20.8%) in R(un), and 511 (37.2%) in R1/R2 according to the IASLC R criteria. The most common reason for R(un) classification was positivity for the highest lymph node (88.8%). In multivariable analysis, the hazard ratios for recurrence in R(un) and R1/R2 compared to R0 were 1.18 (95% confidence interval [CI], 0.96–1.46) and 1.58 (1.31–1.90), respectively. The hazard rate curves displayed similar patterns among groups, peaking at approximately 12 months after surgery. There was a significant difference in distant recurrence patterns between R0 and R(un). Further analysis after stratification with the IASLC N2 descriptor showed significant differences in distant recurrence patterns between R0 and R(un) in patients pN2a1 and pN2a2 disease, but not in those with pN2b disease. Conclusion The IASLC R criteria has prognostic relevance in patients with pN2 NSCLC. R(un) is a highly heterogeneous group, and the involvement of the highest mediastinal lymph node can affect distant recurrence patterns.

Purpose: The International Association for the Study of Lung Cancer suggests further subdivision of pathologic N (pN) category in non–small-cell lung cancer (NSCLC) by incorporating the location and number of involved lymph node (LN) stations. We reclassified patients with the station-based N2b disease into single-zone and multi-zone N2b groups and compared survival outcomes between the groups. Materials and Methods: This retrospective study included patients with pN2 NSCLC who underwent lobectomy from 2006 to 2019. The N2 disease was subdivided into four categories: single-station N2 without N1 (N2a1), single-station N2 with N1 (N2a2), multiple-station N2 with single zone involvement (single-zone N2b), and multiple-station N2 with multiple zone involvement (multi-zone N2b). LN zones included in the subdivision of N2 disease were upper mediastinal, lower mediastinal, aortopulmonary, and subcarinal. Results: Among 996 eligible patients, 211 (21.2%), 394 (39.6%), and 391 (39.3%) were confirmed to have pN2a1, pN2a2, and pN2b disease, respectively. In multivariable analysis after adjustment for sex, age, pT category, and adjuvant chemotherapy, overall survival was significantly better with single-zone N2b disease (n=125, 12.6%) than with multi-zone N2b disease (n=266, 26.7%) (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49 to 0.90; p=0.009) and was comparable to that of N2a2 disease (HR, 1.12; 95% CI, 0.83 to 1.49; p=0.46). Conclusion Prognosis of single-zone LN metastasis was better than that of multiple-zone LN metastasis in patients with N2b NSCLC. Along with the station-based N descriptors, zone-based descriptors might ensure optimal staging, enabling the most appropriate decision-making on adjuvant therapy for patients with pN2 NSCLC.

Purpose: This study investigated the recurrence patterns and timing in patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) according to the residual tumor (R) descriptor proposed by the International Association for the Study of Lung Cancer (IASLC). Materials and Methods: From 2004 to 2021, patients with pN2 NSCLC who underwent anatomical resection were analyzed according to the IASLC R criteria using medical records from a single center. Survival analysis was performed using Cox proportional hazards models. Recurrence patterns between complete (R0) and uncertain resections (R[un]) were compared. Results: In total, 1,373 patients were enrolled in this study: 576 (42.0%) in R0, 286 (20.8%) in R(un), and 511 (37.2%) in R1/R2 according to the IASLC R criteria. The most common reason for R(un) classification was positivity for the highest lymph node (88.8%). In multivariable analysis, the hazard ratios for recurrence in R(un) and R1/R2 compared to R0 were 1.18 (95% confidence interval [CI], 0.96–1.46) and 1.58 (1.31–1.90), respectively. The hazard rate curves displayed similar patterns among groups, peaking at approximately 12 months after surgery. There was a significant difference in distant recurrence patterns between R0 and R(un). Further analysis after stratification with the IASLC N2 descriptor showed significant differences in distant recurrence patterns between R0 and R(un) in patients pN2a1 and pN2a2 disease, but not in those with pN2b disease. Conclusion The IASLC R criteria has prognostic relevance in patients with pN2 NSCLC. R(un) is a highly heterogeneous group, and the involvement of the highest mediastinal lymph node can affect distant recurrence patterns.

Purpose: The International Association for the Study of Lung Cancer suggests further subdivision of pathologic N (pN) category in non–small-cell lung cancer (NSCLC) by incorporating the location and number of involved lymph node (LN) stations. We reclassified patients with the station-based N2b disease into single-zone and multi-zone N2b groups and compared survival outcomes between the groups. Materials and Methods: This retrospective study included patients with pN2 NSCLC who underwent lobectomy from 2006 to 2019. The N2 disease was subdivided into four categories: single-station N2 without N1 (N2a1), single-station N2 with N1 (N2a2), multiple-station N2 with single zone involvement (single-zone N2b), and multiple-station N2 with multiple zone involvement (multi-zone N2b). LN zones included in the subdivision of N2 disease were upper mediastinal, lower mediastinal, aortopulmonary, and subcarinal. Results: Among 996 eligible patients, 211 (21.2%), 394 (39.6%), and 391 (39.3%) were confirmed to have pN2a1, pN2a2, and pN2b disease, respectively. In multivariable analysis after adjustment for sex, age, pT category, and adjuvant chemotherapy, overall survival was significantly better with single-zone N2b disease (n=125, 12.6%) than with multi-zone N2b disease (n=266, 26.7%) (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49 to 0.90; p=0.009) and was comparable to that of N2a2 disease (HR, 1.12; 95% CI, 0.83 to 1.49; p=0.46). Conclusion Prognosis of single-zone LN metastasis was better than that of multiple-zone LN metastasis in patients with N2b NSCLC. Along with the station-based N descriptors, zone-based descriptors might ensure optimal staging, enabling the most appropriate decision-making on adjuvant therapy for patients with pN2 NSCLC.

Purpose: This study investigated the recurrence patterns and timing in patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) according to the residual tumor (R) descriptor proposed by the International Association for the Study of Lung Cancer (IASLC). Materials and Methods: From 2004 to 2021, patients with pN2 NSCLC who underwent anatomical resection were analyzed according to the IASLC R criteria using medical records from a single center. Survival analysis was performed using Cox proportional hazards models. Recurrence patterns between complete (R0) and uncertain resections (R[un]) were compared. Results: In total, 1,373 patients were enrolled in this study: 576 (42.0%) in R0, 286 (20.8%) in R(un), and 511 (37.2%) in R1/R2 according to the IASLC R criteria. The most common reason for R(un) classification was positivity for the highest lymph node (88.8%). In multivariable analysis, the hazard ratios for recurrence in R(un) and R1/R2 compared to R0 were 1.18 (95% confidence interval [CI], 0.96–1.46) and 1.58 (1.31–1.90), respectively. The hazard rate curves displayed similar patterns among groups, peaking at approximately 12 months after surgery. There was a significant difference in distant recurrence patterns between R0 and R(un). Further analysis after stratification with the IASLC N2 descriptor showed significant differences in distant recurrence patterns between R0 and R(un) in patients pN2a1 and pN2a2 disease, but not in those with pN2b disease. Conclusion The IASLC R criteria has prognostic relevance in patients with pN2 NSCLC. R(un) is a highly heterogeneous group, and the involvement of the highest mediastinal lymph node can affect distant recurrence patterns.

Purpose: The International Association for the Study of Lung Cancer suggests further subdivision of pathologic N (pN) category in non–small-cell lung cancer (NSCLC) by incorporating the location and number of involved lymph node (LN) stations. We reclassified patients with the station-based N2b disease into single-zone and multi-zone N2b groups and compared survival outcomes between the groups. Materials and Methods: This retrospective study included patients with pN2 NSCLC who underwent lobectomy from 2006 to 2019. The N2 disease was subdivided into four categories: single-station N2 without N1 (N2a1), single-station N2 with N1 (N2a2), multiple-station N2 with single zone involvement (single-zone N2b), and multiple-station N2 with multiple zone involvement (multi-zone N2b). LN zones included in the subdivision of N2 disease were upper mediastinal, lower mediastinal, aortopulmonary, and subcarinal. Results: Among 996 eligible patients, 211 (21.2%), 394 (39.6%), and 391 (39.3%) were confirmed to have pN2a1, pN2a2, and pN2b disease, respectively. In multivariable analysis after adjustment for sex, age, pT category, and adjuvant chemotherapy, overall survival was significantly better with single-zone N2b disease (n=125, 12.6%) than with multi-zone N2b disease (n=266, 26.7%) (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49 to 0.90; p=0.009) and was comparable to that of N2a2 disease (HR, 1.12; 95% CI, 0.83 to 1.49; p=0.46). Conclusion Prognosis of single-zone LN metastasis was better than that of multiple-zone LN metastasis in patients with N2b NSCLC. Along with the station-based N descriptors, zone-based descriptors might ensure optimal staging, enabling the most appropriate decision-making on adjuvant therapy for patients with pN2 NSCLC.

Background: This study aimed to examine the clinical implications of selective station 4L lymph node dissection (S4L-LND) on survival in non-small cell lung cancer (NSCLC) and to evaluate its potential advantages. Methods: We enrolled patients with primary left-sided NSCLC who underwent upfront video-assisted thoracoscopic surgery with R0 resection including lobectomy and segmentectomy, with or without S4L-LND, at our institution between January 2007 and December 2021. Following 1:1 propensity score matching (PSM), we compared overall survival (OS) and recurrence-free survival (RFS) between patients with and without S4L-LND. Results: The study included 2,601 patients, of whom 1,126 underwent S4L-LND and 1,475 did not. PSM yielded 1,036 patient pairs. Among those who underwent S4L-LND, 87 (7.7%) exhibited S4L-LN involvement. Neither OS (p=0.12) nor RFS (p=0.24) differed significantly between matched patients with and without S4L-LND. In patients with S4L-LN involvement, metastases were more common in the left upper lobe (LUL) than in the left lower lobe (LLL) (3.6% vs. 2.0%, p=0.061). Metastasis became significantly more frequent with more advanced clinical N (cN) stage (cN0, 2.3%; cN1, 5.8%; cN2, 32.6%; p<0.001). Multivariate logistic regression analysis revealed that cN stage and tumor location were independently associated with S4L-LN involvement (p<0.001 for both). Conclusion OS and RFS did not differ significantly between matched patients with and without S4L-LND. Among participants with S4L-LN involvement, metastases occurred more frequently in the LUL than the LLL, and their incidence increased significantly with more advanced cN stage. Thus, patients with LUL or advanced cN lung cancers may benefit from S4L-LND.

Background: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). Methods: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. Results: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment,AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. Conclusion VT can be considered as an adjustment factor for risk assessment in the secondtrimester serum screening test.

Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/ AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.

Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.