Factors Associated with Postoperative Recurrence in Stage I to IIIA Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data.

Purpose: Recent development in perioperative treatment of resectable non-small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion: Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Clinical Utility of Tumor-Naïve Pre-surgical ctDNA Detection in Early-stage NSCLC.

PURPOSE: The use of tumor-informed circulating tumor DNA (ctDNA) testing in early-stage patients before surgery is limited mainly due to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected non-small cell lung cancer (NSCLC). METHOD: We analyzed pre-surgical plasma samples from 895 patients with EGFR and ALK-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histology, histological subtypes, and clinical-to-pathological TNM upstaging. RESULTS: Pre-surgical ctDNA detection was observed in 55 out of 414 (13%) patients with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (RFS) (2-year RFS 69% versus 91%; log-rank P<0.001), approaching that of clinical stage II LUAD. Pre-surgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict pre-surgical ctDNA detection. Moreover, pre-surgical ctDNA detection was predictive of the post-surgical discovery of IASLC G3 tumors (P<0.001) and pathological TNM upstaging (P<0.001). Notably, pre-surgical ctDNA detection strongly correlated with higher PD-L1 expression in tumors (positive rates 28% vs. 55%, P<0.001), identifying a subgroup likely to benefit from anti-PD-(L)-1 therapies. CONCLUSION: These findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need of tumor tissue profiling. Furthermore, it is clinically useful in identifying high-risk patients who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.

Enhancing Identification of High-Risk cN0 Lung Adenocarcinoma Patients Using MRI-Based Radiomic Features.

Purpose: To develop an MRI-based radiomics model to predict high-risk pathologic features for lung adenocarcinoma: micropapillary and solid pattern (MPsol), spread through air space (STAS), and poorly differentiated patterns. Materials and Methods: As a prospective study, we screened clinical N0 lung cancer patients who were surgical candidates and had undergone both 18F-fluorodeoxyglucose (FDG) positron emission tomography-CT (PET/CT) and chest CT from August 2018 to January 2020. We recruited patients meeting our proposed imaging criteria indicating high-risk, that is, poorer prognosis of lung adenocarcinoma, using CT and FDG PET/CT. If possible, these patients underwent an MRI examination from which we extracted 77 radiomics features from T1-contrast-enhanced and T2-weighted images. Additionally, patient demographics, SUVmax (maximum standardized uptake value) on FDG PET/CT, and the mean ADC value on DWI, were considered together to build prediction models for high-risk pathologic features. Results: Among 616 patients, 72 patients met the imaging criteria for high-risk lung cancer and underwent lung MRI. The MR-eligible group showed a higher prevalence of nodal upstaging (29.2% vs. 4.2%, p<0.001), vascular invasion (6.5% vs. 2.1%, p=0.011), high-grade pathologic features (p<0.001), worse 4-year disease free survival (p<0.001) compared with non-MR-eligible group. The prediction power for MR-based radiomics model predicting high-risk pathologic features was good, with mean area under the receiver operating curve (AUC) value measuring 0.751-0.886 in test sets. Adding clinical variables increased the predictive performance for MPsol and the poorly differentiated pattern using the 2021 grading system (AUC 0.860 and 0.907, respectively). Conclusion: Our imaging criteria can effectively screen high-risk lung cancer patients and predict high-risk pathologic features by our MR-based prediction model using radiomics.

Practice pattern and risk of not receiving planned surgery after neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma.

OBJECTIVES: Unlike the initial plan, some patients with oesophageal squamous cell carcinoma cannot or do not receive surgery after neoadjuvant chemoradiotherapy (nCRT). This study aimed to report the epidemiology of patients not receiving surgery after nCRT and to evaluate the potential risk of refusing surgery. METHODS: We analysed patients with clinical stage T3-T4aN0M0 or T1-T4aN1-N3M0 oesophageal squamous cell carcinoma who underwent nCRT as an initial treatment intent between January 2005 and March 2020. Patients not receiving surgery were categorized using predefined criteria. To evaluate the risk of refusing surgery, a propensity-matched comparison with those who received surgery was performed. Recurrence-free (RFS) and overall survival (OS) was compared between groups, according to clinical response to nCRT. RESULTS: Among the study population (n = 715), 105 patients (14.7%) eventually failed to reach surgery. There were three major patterns of not receiving surgery: disease progression before surgery (n = 25), functional deterioration at reassessment (n = 47), and patient's refusal without contraindications (n = 33). After propensity-score matching, the RFS curves of the surgery group and the refusal group were significantly different (P < 0.001), while OS curves were not significantly different (P = 0.069). In patients who achieved clinical complete response on re-evaluation, no significant difference in the RFS curves (P = 0.382) and in the OS curves (P = 0.290) was observed between the surgery group and the refusal group. However, among patients who showed partial response or stable disease on re-evaluation, the RFS and OS curves of the refusal group were overall significantly inferior compared to those of the surgery group (both P < 0.001). The 5-year RFS rates were 10.3% for the refusal group and 48.2% for the surgery group, and the 5-year OS rates were 8.2% for the refusal group and 46.1% for the surgery group. CONCLUSIONS: Patient's refusal remains one of the major obstacles in completing the trimodality therapy for oesophageal squamous cell carcinoma. Refusing surgery when offered may jeopardize oncological outcome, particularly in those with residual disease on re-evaluation after nCRT. These results provide significant implications for consulting patients who are reluctant to oesophagectomy after nCRT.

Comparative Analysis of Clinical Characteristics and Prognosis Between Primary Lung Cancers Identified as Screening Detected and Incidentally Detected Pulmonary Nodules.

BACKGROUND/AIM: Although the importance of low-dose computed tomography (LDCT) screening is increasingly emphasized and implemented, many lung cancers continue to be incidentally detected during routine medical practices, and data on incidentally detected lung cancer (IDLC) remain scarce. This study aimed to investigate the clinical characteristics and prognosis of IDLCs by comparing them with screening-detected lung cancers (SDLCs). PATIENTS AND METHODS: In this retrospective study, subjects with cT1 (≤3 cm) pulmonary nodules detected on baseline computed tomography (CT), later pathologically confirmed as primary lung cancer in 2015, were included. Patients were categorized into IDLC and SDLC groups based on the setting of the first pulmonary nodule detection. RESULTS: Out of 457 subjects, 129 (28.2%) were IDLCs and 328 (71.8%) were SDLCs. The IDLC group, consisted of older individuals with a higher prevalence of smokers and underlying pulmonary disease, compared to the SDLC group. Adenocarcinomas were more frequently detected in SDLCs (87.5%) than in IDLCs (76.7%, p<0.001). The time to treatment initiation (TTI) and 5-year overall survival (OS) rates were similar. Multivariate analyses revealed underlying interstitial lung disease, DLCO, solidity of nodules and TNM stage as independent risk factors associated with mortality. Less than 30% of study participants would have been eligible for the current lung cancer screening program. CONCLUSION: The IDLC group was associated with older age, higher rate of smokers, underlying pulmonary disease, and non-adenocarcinoma histology. However, prognosis was similar to that of the SDLC group, attributable to the similarity in TNM stage, strict adherence to guidelines, and short TTI. Furthermore, less than 30% of the participants would have been suitable for the existing lung cancer screening program, indicating a potential need to reconsider the scope for screening candidates.

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.

Adjuvant Pembrolizumab in Patients with Stage IIIA/N2 Non-Small Cell Lung Cancer Completely Resected after Neoadjuvant Concurrent Chemoradiation: A Prospective, Open-Label, Single-Arm, Phase 2 Trial.

Purpose: Optimal treatment for stage IIIA/N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). Materials and Methods: In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to two years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Results: Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), 9 (26%), and 4 (12%) had a tumor proportion score of <1%, 1-50%, and ≥50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a five-year DFS rate of 29%. The OS rate was 86% at two years and 76% at five years. Patients with tumor recurrence within six months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Conclusion: Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

Lung cancer-specific symptoms and fear of cancer recurrence among recurrence-free non-small cell lung cancer survivors.

PURPOSE: Lung cancer survivors have more psychosocial problems, including depression and anxiety disorder, than other cancer survivors. Lung cancer-specific symptoms, such as cough, dyspnea, or pain in chest, might increase FCR among survivors. We aimed to evaluate the association between lung cancer-specific symptoms and FCR among recurrence-free non-small cell lung cancer (NSCLC) survivors. METHODS: This is a cross-sectional study. Recurrence-free NSCLC survivors were recruited from January to October 2020 at a tertiary hospital in Seoul, Korea. We measured FCR using the Korean version of FCRI-SF and categorized them into three groups: non-clinical FCR (nFCR, < 13), subclinical FCR (sFCR, 13 to 21), and clinical FCR (cFCR, ≥ 22). Lung cancer-specific symptoms were measured using the Korean version of EORTC QLQ-LC13 and EORTC QLQ-C30. RESULTS: A total of 727 survivors were enrolled. One-third (30.8%) of survivors reported sFCR, and 19.7% had cFCR. In a multivariate analysis, survivors with severe pain in chest were 4.7 times (95% CI: 2.4-9.0) more likely to experience cFCR compared to those without it. Mild dyspnea (OR 1.7, 95% CI: 1.1-2.7) and mild dysphagia (OR 2.4, 95% CI: 1.3-4.4) were associated with cFCR. Survivors with sFCR (Coef. - 6.3, 95% CI: - 9.8, - 2.8) and cFCR (Coef. - 11.3, 95% CI: - 15.5, - 7.2) had poorer quality of life compared to survivors with nFCR. CONCLUSION: NSCLC survivors were experiencing lung cancer-specific symptoms even a few years after treatment, which were associated with cFCR, resulting in poor HRQoL. It is necessary to develop a lung cancer-specific symptom checklist and use it during even long-term surveillance.

Risk Factor Analysis of Morbidity and 90-Day Mortality of Curative Resection in Patients with Stage IIIA-N2 Non-Small Cell Lung Cancer after Induction Concurrent Chemoradiation Therapy.

Background: Major pulmonary resection after neoadjuvant concurrent chemoradiation therapy (nCCRT) is associated with a substantial risk of postoperative complications. This study investigated postoperative complications and associated risk factors to facilitate the selection of suitable surgical candidates following nCCRT in stage IIIA-N2 non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of patients diagnosed with clinical stage IIIA-N2 NSCLC who underwent surgical resection following nCCRT between 1997 and 2013. Perioperative characteristics and clinical factors associated with morbidity and mortality were analyzed using univariable and multivariable logistic regression. Results: A total of 574 patients underwent major lung resection after induction CCRT. Thirty-day and 90-day postoperative mortality occurred in 8 patients (1.4%) and 41 patients (7.1%), respectively. Acute respiratory distress syndrome (n=6, 4.5%) was the primary cause of in-hospital mortality. Morbidity occurred in 199 patients (34.7%). Multivariable analysis identified significant predictors of morbidity, including patient age exceeding 70 years (odds ratio [OR], 1.8; p=0.04), low body mass index (OR, 2.6; p=0.02), and pneumonectomy (OR, 1.8; p=0.03). Patient age over 70 years (OR, 1.8; p=0.02) and pneumonectomy (OR, 3.26; p<0.01) were independent predictors of mortality in the multivariable analysis. Conclusion: In conclusion, the surgical outcomes following nCCRT are less favorable for individuals aged over 70 years or those undergoing pneumonectomy. Special attention is warranted for these patients due to their heightened risks of respiratory complications. In high-risk patients, such as elderly patients with decreased lung function, alternative treatment options like definitive CCRT should be considered instead of surgical resection.

Prognostic impact of muscle mass loss in elderly patients with oesophageal cancer receiving neoadjuvant chemoradiation therapy.

BACKGROUND: We aimed to identify the impact of muscle mass on locally advanced oesophageal cancer (LAEC) in elderly patients receiving neoadjuvant chemoradiation therapy (NACRT). METHODS: We reviewed the medical records of 345 patients diagnosed with LAEC who underwent NACRT and surgery. Physical variables, including height, weight, skeletal muscle mass, and laboratory values, were obtained before and after NACRT. Body mass index (BMI, kg/m2), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were calculated as height/(weight)2, ANC/ALC, platelet count/ALC, and (10 × albumin + 0.05 × ALC), respectively. The cutoff for low muscle mass was 43.0 cm2/m2 for BMI below 25 kg/m2 and 53.0 cm2/m2 for BMI 25 kg/m2 or higher. The skeletal muscle index (SMI) was defined as skeletal muscle area/(height)2 (cm2/m2). The ΔSMI (%/50 days) was defined as (SMI after NACRT - SMI before NACRT)/interval (days) × 50 (days) to compare changes over the same period. The excessive muscle loss (EML) group was defined as patients with ΔSMI ≤-10% following NACRT. An elderly patient was defined as aged ≥65 years. The primary outcome measure was overall survival (OS). RESULTS: During a median follow-up of 32.8 months (range, 2.0-176.2), 192 patients died, with a median OS of 50.2 months. Elderly patients did not show inferior OS (young vs. elderly, 57.7% vs. 54.0% at 3 years, P = 0.247). 71.0% and 87.2% of all patients had low muscle mass before and after NACRT, respectively, which was not associated with OS (P = 0.270 and P = 0.509, respectively). Inflammatory (NLR and PLR) and nutritional index (PNI) values or their changes did not correlate with OS. However, the EML group had worse OS (41.6% vs. 63.2% at 3 years, P < 0.0001). In the multivariate analysis, EML was also a significant prognostic factor for OS. In the subgroup analysis by age, EML was a strong prognostic factor for OS in the elderly group. The 3-year OS was 36.8% in the EML group and 64.9% in the non-EML group (P < 0.0001) in elderly patients, and 47.4% and 62.1% (P = 0.063) in the young patients. In multivariate analysis of each subgroup, EML remained prognostic only in the elderly group (P = 0.008). CONCLUSIONS: EML may be strongly associated with a deteriorated OS in elderly patients undergoing NACRT, followed by surgery for LAEC. The strategies for decreasing muscle loss in these patients should be investigated.

Differentiation Between Invasive Adenocarcinoma and Focal Interstitial Fibrosis among Persistent Pulmonary Part-solid Nodules: With Emphasis on the CT Morphologic Analysis.

PURPOSE: Focal interstitial fibrosis (FIF) manifesting as a persistent part-solid nodule (PSN) has been mistakenly treated surgically due to similar imaging features to invasive adenocarcinoma (ADC). The purpose of this study was to observe predictive imaging features correlated with FIF through CT morphologic analysis. MATERIALS AND METHODS: From January 2009 to December 2020, 44 patients with surgically proven FIF in a single institution were enrolled and compared with 88 ADC patients through propensity score matching. Patient characteristics and CT morphologic analysis of persistent PSNs were used to identify predictive imaging features of FIF. Receiver operating characteristic (ROC) curve analysis was used to quantify the performance of imaging features. RESULTS: A total of 132 patients with 132 PSNs (44 FIF, 88 ADC; mean age, 67.7±7.58; 75 females) were involved in our analysis. Multivariable analysis demonstrated that preserved peritumoral vascular margin (preserved vascular margin), preserved secondary pulmonary lobule margin (preserved lobular margin), and lower coronal to axial ratio (C/A ratio; cutoff: 1.005) were significant independent predictors of FIF (P<0.05). ROC curve analysis to evaluate the predictive value of the logistic model based on the imaging features of FIF, and the AUC value was 0.881. CONCLUSION: CT imaging features of preserved vascular margin, preserved lobular margin, and lower C/A ratio (cutoff, <1.005) might be helpful imaging features in discriminating FIF over ADC among persistent PSN in clinical practice.

Comprehensive analysis of transcription factor-based molecular subtypes and their correlation to clinical outcomes in small-cell lung cancer.

BACKGROUND: Recent 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 pairing multi-omics data with immunohistochemistry (IHC) to elucidate the underlying characteristics associated with differences in clinical outcomes between subtypes. METHODS: IHC (n = 252), target exome sequencing (n = 422), and whole transcriptome sequencing (WTS, n = 189) data generated from 427 patients (86.4% males, 13.6% females) with SCLC were comprehensively analysed. The differences in the mutation profile, gene expression profile, and inflammed signatures were analysed according to the IHC-based molecular subtype. FINDINGS: IHC-based molecular subtyping, comprised of 90 limited-disease (35.7%) and 162 extensive-disease (64.3%), revealed a high incidence of ASCL1 subtype (IHC-A, 56.3%) followed by ASCL1/NEUROD1 co-expressed (IHC-AN, 17.9%), NEUROD1 (IHC-N, 12.3%), POU2F3 (IHC-P, 9.1%), triple-negative (IHC-TN, 4.4%) subtypes. IHC-based subtype showing high concordance with WTS-based subtyping and non-negative matrix factorization (NMF) clusterization method. IHC-AN subtype resembled IHC-A (rather than IHC-N) in terms of both gene expression profiles and clinical outcomes. Favourable median overall survival was observed in IHC-A (15.2 months) compared to IHC-N (8.0 months, adjusted HR 2.3, 95% CI 1.4-3.9, p = 0.002) and IHC-P (8.3 months, adjusted HR 1.7, 95% CI 0.9-3.2, p = 0.076). Inflamed tumours made up 25% of cases (including 53% of IHC-P, 26% of IHC-A, 17% of IHC-AN, but only 11% of IHC-N). Consistent with recent findings, inflamed tumours were more likely to benefit from first-line immunotherapy treatment than non-inflamed phenotype (p = 0.002). INTERPRETATION: 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, real-world Asian/non-Western patient cohort, showing high concordance with the previous NMF-based SCLC model. In addition, we revealed underlying biological pathway activities, immunogenicity, and treatment outcomes based on molecular subtype, possibly related to the difference in clinical outcomes, including immunotherapy response. FUNDING: This work was supported by AstraZeneca, Future Medicine 2030 Project of the Samsung Medical Center [grant number SMX1240011], the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) [grant number 2020R1C1C1010626] and the 7th AstraZeneca-KHIDI (Korea Health Industry Development Institute) oncology research program.

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.

Contralateral Pulmonary Resection after Pneumonectomy.

Background: Contralateral pulmonary resection after pneumonectomy presents considerable challenges, and few reports in the literature have described this procedure. Methods: We retrospectively reviewed the medical records of all patients who underwent contralateral lung resection following pneumonectomy for any reason at our institution between November 1994 and December 2020. Results: Thirteen patients (9 men and 4 women) were included in this study. The median age was 57 years (range, 35-77 years), and the median preoperative forced expiratory volume in 1 second was 1.64 L (range, 1.17-2.12 L). Contralateral pulmonary resection was performed at a median interval of 44 months after pneumonectomy (range, 6-564 months). Surgical procedures varied among the patients: 10 underwent single wedge resection, 2 were treated with double wedge resection, and 1 underwent lobectomy. Diagnoses at the time of contralateral lung resection included lung cancer in 7 patients, lung metastasis from other cancers in 3 patients, and tuberculosis in 3 patients. Complications were observed in 4 patients (36%), including acute kidney injury, pneumothorax following chest tube removal, pneumonia, and prolonged air leak. No cases of operative mortality were noted. Conclusion: In carefully selected patients, contralateral pulmonary resection after pneumonectomy can be accomplished with acceptable operative morbidity and mortality.

Surgical outcomes and survival following esophagectomy for squamous cell carcinoma with or without liver cirrhosis: retrospective cohort study.

BACKGROUND AND AIMS: Esophageal squamous cell carcinoma (ESCC) shares common risk factors with liver cirrhosis (LC). The influence of LC in patients with ESCC has not been fully investigated. This study aimed to investigate the postoperative and long-term survival outcomes of esophagectomy for ESCC according to LC presence. METHODS: Among patients who underwent curative-intent surgery for ESCC between 1994 and 2018, 121 patients with Child-Pugh class A LC and 2810 patients without LC were compared. RESULTS: Among the LC patients, 73 (60.3%) were diagnosed with LC before surgery and 48 (39.7%) were diagnosed intraoperatively. There were no significant differences in baseline characteristics between patients with LC and those without LC. However, intraoperative blood loss was higher, and operation time, hospital stay, and ICU stay were longer in patients with LC than in those without LC. Moreover, the reoperation, 30-day morbidity (60.6 vs. 73.6%, P =0.006) and 90-day mortality (2.2 vs. 4.9%, P =0.049) were significantly higher in patients with LC. The 5-year overall survival (OS) rate was significantly higher in patients without LC than in those with LC. After adjusting the confounding variables, LC was an adverse risk factor of OS (hazard ratio 1.402, P =0.004). Among patients with LC, the Model of End-Stage Liver Disease score was related to the development of complications of grade more than III (odds ratio 1.459, P =0.013). CONCLUSION: ESCC patients with Child-Pugh class A LC have high incidences of postoperative morbidity and mortality, and poor OS. Thus, careful patient selection, meticulous operation, and careful postoperative care are needed.

Supporting Life Adjustment in Patients With Lung Cancer Through a Comprehensive Care Program: Protocol for a Controlled Before-and-After Trial.

BACKGROUND: Lung cancer diagnosis affects an individual's quality of life as well as physical and emotional functioning. Information on survivorship care tends to be introduced at the end of treatment, but early intervention may affect posttreatment adjustment. However, to the best of our knowledge, no study has explored the effect of early information intervention on the return to work, family, and societal roles of lung cancer survivors. OBJECTIVE: We report the study protocol of a comprehensive care prehabilitation intervention designed to facilitate lung cancer survivors' psychological adjustment after treatment. METHODS: A comprehensive care program was developed based on a literature review and a qualitative study of patients with lung cancer and health professionals. The Lung Cancer Comprehensive Care Program consists of educational videos and follow-up visits by a family medicine physician. To prevent contamination, the control group received routine education, whereas the intervention group received routine care and intervention. Both groups completed questionnaires before surgery (T0) and at 1-month (T1), 6-month (T2), and 1-year (T3) follow-up visits after surgery. The primary outcome was survivors' psychological adjustment to cancer 6 months after pulmonary resection. RESULTS: The historical control group (n=441) was recruited from September 8, 2021, to April 20, 2022, and the intervention group (n=350) was recruited from April 22, 2022, to October 17, 2022. All statistical analyses will be performed upon completion of the study. CONCLUSIONS: This study examined the effectiveness of an intervention that provided general and tailored informational support to lung cancer survivors, ranging from before to the end of treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05078918; https://clinicaltrials.gov/ct2/show/NCT05078918. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54707.

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.