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

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

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

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

Role of invasive mediastinal nodal staging in survival outcomes of patients with non-small cell lung cancer and without radiologic lymph node metastasis: a retrospective cohort study.

Background: Lung cancer diagnostic guidelines advocate for invasive mediastinal nodal staging (IMNS), but the survival benefits of this approach in patients with non-small cell lung cancer (NSCLC) without radiologic evidence of lymph node metastasis (rN0) remain uncertain. We aimed to investigate the impact of IMNS in patients with rN0 NSCLC by comparing the long-term survival between patients who underwent IMNS and those who did not (non-IMNS). Methods: In this retrospective cohort study, we included patients with NSCLC but without radiologic evidence of lymph node metastasis from the Registry for Thoracic Cancer Surgery and the clinical data warehouse at the Samsung Medical Centre, Republic of Korea between January 2, 2008 and December 31, 2016. We compared the 5-year overall survival (OS) rate as the primary outcome after propensity score matching between the IMNS and non-IMNS groups. The age, sex, performance statue, tumor size, centrality, solidity, lung function, FDG uptake in PET-CT, and histological examination of the tumor before surgery were matched. Findings: A total of 4545 patients (887 in the IMNS group and 3658 in the non-IMNS group) who received curative treatment for NSCLC were included in this study. By the mediastinal node dissection, the overall incidence of unforeseen mediastinal node metastasis (N2) was 7.2% (317/4378 patients). Despite the IMNS, 67% of pathological N2 was missed (61/91 patients with unforeseen N2). Based on propensity score matching, 866 patients each for the IMNS and non-IMNS groups were assigned. There was no significant difference in 5-year OS and recurrence-free survival (RFS) between two groups: 5-year OS was 73.9% (95% confidence interval, CI: 71%-77%) for IMNS and 71.7% (95% CI: 68.6%-74.9%; p = 0.23), for non-IMNS (hazard ratio, HR 0.90, 95% CI: 0.77-1.07), while 5-year RFS was 64.7% (95% CI: 61.5%-68.2%) and 67.5% (95% CI: 64.3%-70.9%; p = 0.35 (HR 1.08, 95% CI: 0.92-1.27), respectively. Moreover, the timing and locations of recurrence were similar in both groups. Interpretation: IMNS might not be required before surgery for patients with NSCLC without LN suspicious of metastasis. Further randomised trials are required to validate the findings of the present study. Funding: None.

Treatment Patterns and Outcomes of Anastomotic Leakage after Esophagectomy for Esophageal Cancer.

Background: Anastomotic leakage (AL) following esophagectomy represents a serious complication that often results in prolonged hospitalization and necessitates repeated interventions, including nothing-by-mouth (NPO) restriction, endoscopic vacuum therapy (EVT), or surgical repair. In this study, we evaluated the patterns and outcomes of AL treatment. Methods: We retrospectively reviewed the medical records of patients who underwent esophagectomy for esophageal cancer at a single center between 2003 and 2020. Of 3,096 examined cases, 181 patients (5.8%) with AL were included in the study: 114 patients (63%) with cervical anastomosis (CA) and 67 (37%) with intrathoracic anastomosis (TA). Results: The incidence of AL was 11.9% in the CA and 3.2% in the TA group (p<0.001). Among patients with CA who developed AL, 87 (76.3%) were managed with NPO, 15 (13.2%) with EVT, and 12 (10.5%) with surgical repair. Over 90% of patients with cervical AL resumed an oral diet by the time of discharge, regardless of treatment method. Among patients with TA and AL, 36 (53.7%) received NPO, 25 (37.7%) underwent EVT, and 6 (9%) required surgery. Of these, 34 patients who were managed with NPO and 19 with EVT could resume an oral diet. However, only 2 patients who underwent surgery resumed an oral diet, and 2 patients required additional EVT. Conclusion: Although patients with CA displayed a higher incidence of AL, their rate of successful oral intake exceeded that of those with TA, regardless of treatment method. Among patients exhibiting AL with TA, EVT was more commonly employed than in CA cases, and it appears effective.

Whole-Section Landscape Analysis of Molecular Subtypes in Curatively Resected Small Cell Lung Cancer: Clinicopathologic Features and Prognostic Significance.

Despite the recognition of various molecular subtypes in small cell lung cancer (SCLC), most information has been derived from tissue microarrays or biopsy samples. Using whole sections of curatively resected SCLCs, we aimed to elucidate the clinicopathologic relevance and prognostic significance of the molecular subtypes. Whole-section immunohistochemistry was conducted for 73 resected SCLC samples using antibodies representative of molecular subtypes: ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1. Furthermore, multiplexed immunofluorescence was performed to evaluate the spatial relationship of YAP1 expression with other markers. The molecular subtype was correlated with clinical and histomorphologic features, and its prognostic role was explored in this cohort and validated in a previously published surgical cohort. Overall, the molecular subtypes were SCLC-A (54.8%), SCLC-N (31.5%), SCLC-P (6.8%), and SCLC-TN (triple negative, 6.8%). We found significant enrichment of SCLC-N (48.0%; P = .004) among combined SCLCs. Although a distinct subtype with high YAP1 expression was not found, YAP1 expression was reciprocal with ASCL1/NEUROD1 at the cellular level within tumors and was increased in areas with non-small cell-like morphology. Furthermore, the YAP1-positive SCLCs showed significantly increased recurrence at mediastinal lymph nodes (P = .047) and are an independent poor prognostic factor after surgery (adjusted hazard ratio, 2.87; 95% CI, 1.20-6.86; P = .017). The poor prognostic impact of YAP1 was also validated in the external surgical cohort. Our whole-section analysis in resected SCLCs reveals the highly heterogeneous nature of the molecular subtype and its clinicopathologic relevance. Although YAP1 is not a subtype delineator, YAP1 relates to the phenotypic plasticity of SCLC and may serve as a poor prognostic factor in resected SCLC.

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

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

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

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

The Role of Adjuvant Therapy Following Surgical Resection of Small Cell Lung Cancer: A Multi-Center Study.

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.

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

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

Prognostic Significance of FDG PET/CT in Esophageal Squamous Cell Carcinoma in the Era of the 8th AJCC/UICC Staging System.

Introduction: Recently, the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system was updated for its 8th edition. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a useful imaging tool to diagnose and predict prognoses for esophageal cancer. However, there was no previous study to explore the role of FDG PET/CT in the staging system based on the 8th edition. The prognostic value of FDG PET/CT was investigated in patients with esophageal squamous cell carcinoma (SqCC) considering the new 8th AJCC/UICC staging system. Methods: Subjects were 721 patients with esophageal SqCC undergoing pretherapeutic FDG PET/CT. Clinico-pathological variables and the maximum standardized uptake value (SUVmax) of the primary tumor were included in survival analysis. Subgroup analysis was performed to compare hazard ratios according to pathological stage and SUVmax. A new staging classification including FDG uptake was proposed. Results: In multivariate survival analysis, pathological stage and SUVmax of the primary tumor were selected as independent prognostic factors for overall survival in both the 7th and 8th editions. The proposed new staging system showed better discrimination for overall survival between stage I and II than did the conventional staging system (hazard ratios: 2.250 vs. 1.341). Conclusions: The FDG uptake of the primary tumor was found to be an independent prognostic factor along with pathological stage based on both 7th and 8th AJCC/UICC staging systems in patients with esophageal SqCC. The suggested new staging system including SUVmax was better for predicting prognoses than the conventional staging system.

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

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

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

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

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

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

Adjuvant Chemotherapy in Patients with Node-Negative Non-Small Cell Lung Cancer with Satellite Pulmonary Nodules in the Same Lobe.

BACKGROUND: According to the eighth TNM (tumor-node-metastasis) staging system, the presence of separate tumor nodules in the same lobe is designated as a T3 descriptor. However, it remains unclear whether adjuvant chemotherapy confers survival advantages in this setting. METHODS: We retrospectively identified 142 pathologic T3N0M0 patients with additional pulmonary nodules in the same lobe from a single-institutional database from 2004 to 2019. The main outcomes were overall survival and recurrence-free survival. Multivariable Cox regression was used to identify the benefit of adjuvant chemotherapy while adjusting for other variables. RESULTS: Sixty-one patients received adjuvant chemotherapy (adjuvant group) and 81 patients did not receive adjuvant therapy after surgery (surgery-only group). There were no demonstrable differences between the 2 groups regarding hospital mortality and postoperative complications, indicating that treatment selection had not significantly occurred. However, the use of adjuvant chemotherapy was associated with improved 5-year overall survival (70% vs. 59%, p=0.006) and disease-free survival (60% vs. 46%, p=0.040). A multivariable Cox model demonstrated that adjuvant chemotherapy was associated with a survival advantage (adjusted hazard ratio, 0.54; p<0.001). In exploratory analyses of subgroups, the effect of adjuvant chemotherapy seemed to be insufficient in those with small main tumors (<4 cm). CONCLUSION: Adjuvant chemotherapy was associated with better survival in T3 cancers with an additional tumor nodule in the same lobe. However, the role of adjuvant chemotherapy in patient subgroups with small tumors or those without risk factors should be determined via large studies.

Role of Recurrent Laryngeal Nerve Lymph Node Dissection in Surgery of Early-Stage Esophageal Squamous Cell Carcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The efficacy of adjuvant chemotherapy with capecitabine and cisplatin after surgery in locally advanced esophageal squamous cell carcinoma: a multicenter randomized phase III trial.

There is limited evidence for the effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma (ESCC). This study aimed to assess whether adjuvant capecitabine and cisplatin improve survival compared to surgery alone among patients with locally advanced ESCC. This is a multicenter randomized controlled trial. Patients were eligible if they underwent curative resection for ESCC staged T2-4 or N1 and M0 according to the TNM cancer staging system sixth edition. The intervention group received four cycles of adjuvant chemotherapy (capecitabine: 1,000 mg/m 2 b.i.d for 14 days, and intravenous cisplatin: 75 mg/m2 at day 1, every 3 weeks). A total of 136 patients were randomly assigned to either the adjuvant chemotherapy group (n = 68) or surgery-alone group (n = 68). Seven patients who rejected chemotherapy after randomization were excluded from the final analysis. The cumulative incidence of recurrence within 18 months after surgery was significantly lower in the adjuvant chemotherapy group than in the surgery-alone group (hazard ratio [HR]: 0.49; 95% confidence interval (CI): 0.25-0.95]. However, the 5- and 10-year disease-free survival did not differ between treatment groups (HR: 0.84; 95% CI: 0.53-1.34 and HR: 0.76; 95% CI: 0.50-1.18, respectively). Adjuvant chemotherapy after curative resection in patients with locally advanced ESCC reduced early recurrence but had no statistically significant increase in the long-term disease-free survival. Due to the limited sample size of this study, additional randomized controlled trials with larger sample sizes are necessary.

Conditional Survival of Patients Who Underwent Curative Resection for Esophageal Squamous Cell Carcinoma.

OBJECTIVE: To analyze conditional survival estimates of patients with esophageal cancer who underwent curative resection. SUMMARY BACKGROUND DATA: Conditional survival reflects dynamic prognosis updated to the current status and is a more relevant indicator for current healthcare and life decisions. METHODS: This study included 1883 patients who underwent complete resection for esophageal squamous cell carcinoma at a tertiary cancer center from 1994 to 2016. We calculated 5-year (5Y) conditional overall survival (COS), conditional recurrence-free survival (CRFS), and conditional relative survival (CRS) estimates from diagnosis to 5 years of survival. RESULTS: The 5Y COS, CRFS, and CRS increased from 63.7%, 65.2%, and 70.2% at diagnosis to 75.8%, 91.9%, and 86.4 at 5 years after diagnosis, respectively. While there were large differences with different stages (stage I, II, III) at diagnosis (81.2%, 64.9%, and 37.3% for COS; 85.1, 65.1%, and 67.9% for CRFS; 89.2%, 72.1%, and 41.1% for CRS), the gap decreased with time; rates were similar after 5 years (77.1%, 75.7%, and 72.6% for COS; 91.7%, 90.6%, and 94.5% for CRFS, and 89.3%, 85.4%, and 78.3% in CRS, respectively). The 5Y COS, CRFS, and CRS were persistently lower in older patients even after 5 years. CONCLUSIONS: Conditional survival estimates generally increase over time, and the largest improvements were observed for patients with advanced stage. Availability of updated prognosis at various time points allows clinicians to better guide their patients. Our results also imply substantial residual risk of recurrence and sustained excess mortality compared to the general population even after 5 years.

Thoracoscopic Vs Open Surgery Following Neoadjuvant Chemoradiation for Clinical N2 Lung Cancer.

We evaluated the feasibility of video-assisted thoracoscopic surgery (VATS) following neoadjuvant concurrent chemoradiotherapy (nCCRT) for N2 non-small-cell lung cancer (NSCLC). We retrospectively reviewed patients with clinical N2 NSCLC who underwent lobectomy and lymph node dissection after nCCRT. The patients were matched using a propensity score based on age, sex, pulmonary function test, histologic type, clinical T factor, and method of N-staging. A total of 385 patients were enrolled between June 2012 and July 2017 (35 VATS, 350 open). After propensity matching (31 VATS, 112 open), the VATS group showed a significantly lower major complication rate (≥ grade II Clavien-Dindo classification; 9.7% vs 30.4%, P = 0.036). No significant differences were found between 2 group of 5-year survival rates (77.1% for the VATS group, 59.9% for the open group; P = 0.276) and recurrence-free survival rates (66.3% for the VATS group, 54.6% for the open group; P = 0.354). In multivariable analysis, VATS did not affect overall survival and recurrence-free survival. VATS was comparable to open thoracotomy in patients with clinical N2 NSCLC after nCCRT without compromising oncologic efficacy.

Pragmatic role of noncontrast magnetic resonance lymphangiography in postoperative chylothorax or cervical chylous leakage as a diagnostic and preprocedural planning tool.

OBJECTIVES: To define the roles of noncontrast magnetic resonance lymphangiography (MRL) in the management of postoperative chylothorax or cervical chylous leakage. METHODS: A total of 50 consecutive patients underwent noncontrast MRL, intranodal lymphangiography, and thoracic duct embolization between May 2016 and April 2020. Their mean age was 62.6 years ± 10.3 (SD) years, and 35 of the participants were men. Conventional lymphangiographic images were sufficient in quality as a reference for the evaluation of diagnostic accuracy of leakage and location in 35 patients (70%) and for evaluation of anatomic details of the thoracic duct and jugulovenous junction in 34 patients (68%). RESULTS: MRL showed that the sensitivity, specificity, and positive and negative predictive values for leakage detection were 100%, 97.1%, 100%, and 100%, respectively, and the concordance rate was 97.14% (95% confidence interval [CI], 85.08-99.93%; p < .001). Leakage location was concordant between MRL and conventional lymphangiography in 27 patients (77.1%, 27/35). Regarding anatomical details of the thoracic duct, variation of the thoracic duct was missed in 11.7% of patients (4/34). The jugulovenous junction was observed in 91.1% (31/34), and its opening into the central vein was depicted in 76.4% (26/34). The concordance rate was between 76.47 and 91.18. CONCLUSIONS: Noncontrast MRL has a high sensitivity for the detection of postoperative thoracic and cervical chylous leakage but is suboptimal for the localization of the leak and depiction of anatomical details of the thoracic duct. This method is worthy of consideration as either a decision-making or planning tool for subsequent interventions. KEY POINTS: • Noncontrast MRL provides limited resolution images of CLS but has a high sensitivity for the detection of postoperative chylous leakage in the thoracic and neck regions. • Noncontrast MRL is suboptimal for depicting anatomic details in the thoracic duct and jugulovenous junction but can play a role as a decision-making and a planning tool for subsequent lymphatic interventions.