Comparison of the treatment outcomes of different neoadjuvant chemoradiotherapy regimens for resectable locally advanced esophageal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by radical esophagectomy is the standard treatment for locally advanced esophageal squamous cell cancer (LA-ESCC). However, various nCRT regimens have been used and their comparative efficacy and safety remain unclear. METHODS: Patients with histologically confirmed LA-ESCC who underwent nCRT followed by radical esophagectomy between January 2016 and February 2022 were enrolled in our study. Three different nCRT regimens were retrospectively compared: Conventional radiotherapy (RT) + cisplatin/5-fluorouracil (FP) (Conv-FP), hypofractionated RT + FP (Hypo-FP), and regimens from the CROSS trial (CROSS). The overall survival (OS), pathological complete response (pCR) rates, toxicities, and treatment compliance were analyzed. RESULTS: Among the 600 patients, 225 received Conv-FP, 255 received Hypo-FP, and 120 received the CROSS regimen. OS at 1 year were 78.7%, 83.9%, and 88.1% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (p < 0.001). The pCR rates were 30.6%, 33.9%, and 35.0%, respectively (p = 0.653). The overall incidence of grade 3 toxicities was 10.2%. Hematologic and non-hematologic toxicities of grade ≥ 3 were observed in 8.4% and 11.4%, 0% and 7.6%, 5.5% and 0.8% in Conv-FP, Hypo-FP, and CROSS, respectively (p = 0.002 and 0.030). Weight loss > 5% was observed in 44.0%, 51.4%, and 32.5%, respectively (p < 0.001). In the multivariate analysis, clinical T-stage (p = 0.004), N-stage (p = 0.012), the use of FP chemotherapy regimen (p = 0.013), surgical resection (p < 0.001), hematologic toxicity (p = 0.001), and weight loss (p = 0.004) were significantly associated with poor OS. CONCLUSION: The choice of nCRT regimen did not significantly affect the pCR rates in patients with LA-ESCC. However, the CROSS regimen demonstrated better OS and lower toxicity, suggesting it may be the optimal treatment option among the groups. SYNOPSIS: This study compared three different neoadjuvant chemoradiotherapy (nCRT) regimens for locally advanced esophageal squamous cell cancer (LA-ESCC): Conventional radiotherapy (RT) + cisplatin/5-fluorouracil (FP), hypofractionated RT + FP, and regimens from the CROSS trial. The overall survival (OS), pathological complete response (pCR) rates, toxicities, and treatment compliance were analyzed. Results showed that the choice of nCRT regimen did not significantly affect pCR rates, but the CROSS regimen showed better OS and lower toxicity, suggesting it may be the optimal treatment option. DATA AVAILABILITY: Data availability is limited due to institutional data protection law and confidentiality of patient data.

Salvage Radiotherapy for Loco-Regional Recurrence of Esophageal Cancer Following Surgery.

Purpose: There is few evidence regarding the optimal salvage treatment options for loco-reginal recurrence of esophageal cancer. This study aimed to evaluate the clinical outcomes of salvage radiotherapy (RT) in patients with loco-regional recurrence (LRR) after surgery for esophageal cancer. Materials and Methods: We retrospectively reviewed 147 esophageal cancer patients who received salvage RT for loco-regional recurrence between 1996 and December 2019. A total dose of 60 Gy in 20 fractions was used for RT alone and 60-70 Gy in 30-35 fractions for concurrent chemoradiotherapy (CCRT). Results: The patients' median age was 65 (41-86). The median disease-free interval (DFI) was 13.5 months (1.0 to 97.4 months). After a median 18.8 months follow-up, the 2-year overall survival (OS) and progression-free survival (PFS) rates were 38.1% and 25.9%, respectively. The median OS and PFS were 18.8 and 8.4 months, respectively. The CCRT could not improve OS compared to RT (p=0.336), but there was a trend of better PFS in the CCRT group. Regarding toxicities, the rate of grade 3 or higher toxicity was 10.9% occurring in 16 patients, and it was higher in patients who received CCRT than in the RT alone group (19.6% vs. 6.3%, p=0.023). Conclusion: Salvage RT alone as well as CCRT could be effective in patients with locoregionally recurrent esophageal cancer.

Comparison of the Oncologic Outcomes for Patients with Middle to Lower Esophageal Squamous Cell Carcinoma Undergoing Surgical Treatment Using the Ivor-Lewis or McKeown Operation.

BACKGROUND: The upper mediastinum is the most common metastatic site of esophageal squamous cell carcinoma (ESCC), and complete dissection of this region is important for oncologic reasons. This study aimed to compare the oncologic outcomes and completeness of upper mediastinal dissection for ESCC patients undergoing the Ivor-Lewis (IL) or McKeown (MK) operations. METHODS: Between 2013 and 2018, 680 patients (IL, 433; MK, 247) underwent upfront esophagectomy with two-field lymph node (LN) dissection for mid-to-lower ESCCs. Propensity score-matching (1:1 ratio) was performed to minimize the effects of confounding factors. RESULTS: The mean age was 64.5 ± 8.8 years, and 635 (93.4%) of the patients were male. The median follow-up period was 71.66 months (interquartile range [IQR], 59.60-91.04 months). The IL group had a higher mean age, lower body mass index, higher proportion of advanced T and N, and higher adjuvant therapy rates, but these differences were well-balanced after propensity score-matching. The mean number of dissected LNs at the mediastinum and at the right recurrent laryngeal nerve (RLN) were similar between the two groups after matching, whereas the IL group exhibited a slightly greater number of dissected LNs at the left RLN. Among the matched patients, the IL and MK groups exhibited similar 5-year overall survival (OS: 75.1% vs 78.0%; p = 0.368). The multivariate model showed no differences in OS, disease-free survival, or recurrence-free survival for locoregional, upper mediastinum, or neck between the two groups. CONCLUSIONS: This study suggests that both the IL and MK operations are oncologically feasible for patients with mid-to-lower ESCC.

Clinical Utility of Tumor-Naïve Presurgical Circulating Tumor DNA Detection in Early-Stage NSCLC.

OBJECTIVES: The use of tumor-informed circulating tumor DNA (ctDNA) testing in patients with early-stage disease before surgery is limited, mainly owing 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 NSCLC. METHOD: We analyzed presurgical plasma samples from 895 patients with EGFR and anaplastic lymphoma kinase-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histologic diagnosis, histologic subtypes, and clinical-to-pathologic TNM upstaging. RESULTS: Presurgical ctDNA detection was observed in 55 of 414 patients (13%) with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (2-year recurrence-free survival 69% versus 91%; log-rank p < 0.001), approaching that of clinical stage II LUAD. Presurgical 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 presurgical ctDNA detection. Moreover, presurgical ctDNA detection was predictive of the postsurgical discovery of International Association for the Study of Lung Cancer grade 3 tumors (p < 0.001) and pathologic TNM upstaging (p < 0.001). Notably, presurgical ctDNA detection strongly correlated with higher programmed death-ligand 1 expression in tumors (positive rates 28% versus 55%, p < 0.001), identifying a subgroup likely to benefit from anti-programmed death-ligand 1 therapies. CONCLUSION: These findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need for tumor tissue profiling. Furthermore, it is clinically useful in identifying patients at high risk who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.

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.

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.

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.

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.

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.

Emulating trial to evaluate the effectiveness of routine supportive care on mortality among cancer patients experiencing distress at the time of diagnosis.

INTRODUCTION: Few studies have evaluated the effectiveness of interventions for distress during cancer diagnosis on clinical outcomes in a real-world setting. We aimed to evaluate whether routine information and psychosocial support to patients experiencing distress at the time of diagnosis could decrease the risk of mortality within 1 and 3 years after diagnosis. MATERIAL AND METHODS: We conducted a retrospective cohort study of 4880 newly diagnosed cancer patients who reported distress scores of ≥4 using the tablet or kiosk-based screening between July 2014 and December 2017 at a university-affiliated cancer center in Seoul, South Korea. We performed an emulated target trial with two groups: those that received information and psychosocial support and those that did not. Cox proportional hazards models were used to identify the associations between information and psychosocial support and all-cause mortality. RESULTS: Of all the patients, 16.6 % had routine information and psychosocial support. The hazard ratio (HR) for one-year mortality comparing participants with information and psychosocial support to those without it were 0.73 (95 % confidence interval (CI) = 0.54, 0.99). Age < 50 and 50 - <60 group had a stronger effect of information and psychosocial support on reducing mortality within one-year than these in age ≥ 60 (p for interaction = 0.03). In terms of three-year mortality, the HR comparing participants with information and psychosocial support to those without it was 0.93 (95 % CI = 0.76, 1.14). CONCLUSION: This large-scale real-world study suggests that timely psychosocial care benefits newly diagnosed cancer patients who had distress during pre-treatment period.

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.

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.