Stage III NSCLC treatment options: too many choices.

Stage III nonsmall cell lung cancer (NSCLC) represents a wide range of tumour (T1 to T4) and nodal (N0 to N3) components, requiring variable management and a multidisciplinary approach. Recent advancements in minimally invasive techniques, molecular biology and novel drug discoveries have accelerated the refinement of stage III NSCLC management. The latest developments in staging include the forthcoming update of the nodal component in the 9th TNM (tumour-node-metastasis) edition, which emphasises the critical role for endobronchial ultrasonography in mediastinal staging. Recent treatment developments include the use of immunotherapy and targeted molecular therapy in both the neoadjuvant and adjuvant setting, either in combination with other modalities or used alone as consolidation. Surgical and radiotherapy advancements have further enhanced patient outcomes. These developments have significantly improved the prognosis for patients with stage III NSCLC. Fast-changing recommendations have also brought about a challenge, with clinicians facing a number of options to choose from. Therefore, a multimodal approach by a multidisciplinary team has become even more crucial in managing stage III NSCLC.

Why do patients stay in hospital after enhanced recovery thoracoscopic wedge resection? A prospective observational study.

OBJECTIVES: This single-centre prospective observational study aimed to investigate reasons for prolonged hospitalization [over the median length of stay (LOS)] after enhanced recovery thoracoscopic [ERAS 3-port video-assisted thoracoscopic surgery (VATS)] wedge resection. METHODS: All patients were evaluated twice-daily by an investigator for reasons of hospitalization. Each reason was analysed individually. Predictors for prolonged hospitalization were identified using a multivariable backward stepwise logistic regression model. RESULTS: A total of 150 consecutive patients (lymphadenectomy 8.7%) were included from November 2022 to December 2023, with a median LOS of 1 (interquartile range 1-2) day. Of these, 55 patients (36.7%) experienced prolonged hospitalization. The main reasons included postoperative pain (16.0%), air leak (14.7%) and social factors (14.7%), followed by oxygen dependency (7.3%), gastrointestinal factors (5.3%), urinary factors (4.7%), pneumonia (1.3%), pleural effusion (1.3%), chylothorax (0.7%), atrial fibrillation (0.7%), confusion (0.7%) and fatigue (0.7%). Multivariable analysis revealed that an increase in the percentage of predicted forced expiratory volume in 1 s (FEV1%pre) by 1% [odds ratio (OR) 0.41, P = 0.023) and percentage of predicted diffusing capacity for carbon monoxide (DLCO%pre) by 1% (OR 0.95, P = 0.002) decreased likelihood of prolonged hospitalization. Conversely, each additional pack-year (OR 1.01, P = 0.028) and living alone (OR 3.55, P = 0.005) increased the risk of prolonged hospitalization. CONCLUSIONS: Prolonged hospitalization (LOS > 1 day) after ERAS 3-port VATS wedge resection, with 8.7% lymphadenectomy, was mainly due to pain, air leak and social factors. Smokers with decreased FEV1%pre or DLCO%pre and patient living alone were at increased risk. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT06118593 (https://clinicaltrials.gov/study/NCT06118593?cond=why%20in%20hospital&rank=2).

Recurrence Rates and Patterns after Radical Resection of Lung Carcinoids.

Atypical lung carcinoid (AC) is widely accepted to recur more often after radical resection than typical lung carcinoid (TC). However, their recurrence rates have never been compared in a multi-state competing risks model. We retrospectively reviewed files from patients with AC and TC who had been radically resected at our European Neuroendocrine Tumor Society Center of Excellence between 2009 and 2020. We estimated the recurrence rates between the AC and TC patients counting unrelated death as a competing event using Aalen-Johansen estimates and compared them using a multi-state Cox model. Finally, we analyzed all AC and TC recurrences as to resection type, pathological stage, resection margin, recurrence site, and time to recurrence. The study included 217 patients, of whom 194 had TC and 23 had AC. The median follow-up was 9.4 years. The AC patients experienced recurrence at a higher rate (hazard ratio [HR] 16.0, 95% confidence interval [CI] 5.3-47.9, p < 0.001). Correspondingly, the 5- and 10-year recurrence rates were 18% and 32% for AC and merely 1.0% and 2.4% for TC. In patients without nodal involvement, AC recurred at a considerably higher rate (HR 41.2, 95% CI 8.7-194.8, p < 0.001) than TC. In both AC and TC, most recurrences were distant and occurred in patients with a resection margin less than 2 cm. We conclude that AC recurs more often than TC, even in patients without nodal involvement at surgery, suggesting that all AC patients regardless of their pathological stage should undergo close follow-up care after surgery.

Predicting complication risks after sleeve lobectomy for non-small cell lung cancer.

Background: Sleeve lobectomy is a challenging procedure with a high risk of postoperative complications. To facilitate surgical decision-making and optimize perioperative treatment, we developed risk stratification models to quantify the probability of postoperative complications after sleeve lobectomy. Methods: We retrospectively analyzed the clinical features of 691 non-small cell lung cancer (NSCLC) patients who underwent sleeve lobectomy between July 2016 and December 2019. Logistic regression models were trained and validated in the cohort to predict overall complications, major complications, and specific minor complications. The impact of specific complications in prognostic stratification was explored via the Kaplan-Meier method. Results: Of 691 included patients, 232 (33.5%) developed complications, including 35 (5.1%) and 197 (28.5%) patients with major and minor complications, respectively. The models showed robust discrimination, yielding an area under the receiver operating characteristic (ROC) curve (AUC) of 0.853 [95% confidence interval (CI): 0.705-0.885] for predicting overall postoperative complication risk and 0.751 (95% CI: 0.727-0.762) specifically for major complication risks. Models predicting minor complications also achieved good performance, with AUCs ranging from 0.78 to 0.89. Survival analyses revealed a significant association between postoperative complications and poor prognosis. Conclusions: Risk stratification models could accurately predict the probability and severity of complications in NSCLC patients following sleeve lobectomy, which may inform clinical decision-making for future patients.

Long-term outcomes of lung transplantation with ex vivo lung perfusion technique.

Ex vivo lung perfusion (EVLP) has demonstrated encouraging short- and medium-term outcomes with limited data available on its long-term outcomes. This study assesses (1) EVLP long-term outcomes and (2) EVLP era-based sub-analysis in addition to secondary outcomes of recipients with EVLP-treated donor lungs compared with recipients of conventionally preserved donor lungs in unmatched and propensity score-matched cohorts. Double lung transplants performed between 1st January 2012 and 31st December 2021 were included. A total of 57 recipients received EVLP-treated lungs compared to 202 unmatched and 57 matched recipients who were subjected to non-EVLP-treated lungs. The EVLP group had a significantly lower mean PaO2/FiO2 ratio and significantly higher mean BMI than the non-EVLP group in the unmatched and matched cohorts. The proportion of smoking history in the unmatched cohort was significantly higher in the EVLP group, while a similar smoking history was demonstrated in the matched cohorts. No difference was demonstrated in overall freedom from death and retransplantation between the groups in the unmatched and matched cohorts (unmatched: hazard ratio (HR) 1.28, 95% confidence interval (CI) 0.79-2.07, P = 0.32; matched: HR 1.06, 95% CI 0.59-1.89). P = 0.89). In the unmatched cohort, overall freedom from chronic allograft dysfunction (CLAD) was significantly different between the groups (HR 1.64, 95% CI 1.07-2.52, P = 0.02); however, the cumulative CLAD incidence was similar (HR 0.72, 95% CI 0.48-1.1, P = 0.13). In the matched cohort, the overall freedom from CLAD (HR 1.69, 95% CI 0.97-2.95, P = 0.06) and cumulative CLAD incidence (HR 0.91, 95% CI 0.37-2.215, P = 0.83) were similar between the groups. The EVLP era sub-analysis of the unmatched cohort in 2012-2014 had a significantly higher cumulative CLAD incidence in the EVLP group; however, this was not demonstrated in the matched cohort. All secondary outcomes were similar between the groups in the unmatched and matched cohorts. In conclusion, transplantation of marginal donor lungs after EVLP evaluation is non-detrimental compared to conventionally preserved donor lungs in terms of mortality, retransplantation, cumulative CLAD incidence, and secondary outcomes. Although the unmatched EVLP era of 2012-2014 had a significantly higher cumulative CLAD incidence, no such finding was demonstrated in the matched cohort of the same era.

Impact of Margin Distance on Locoregional Recurrence and Survival After Thoracoscopic Segmentectomy.

BACKGROUND: This study aimed to identify the impact of margin distance on locoregional recurrence (LRR) and survival outcomes after thoracoscopic segmentectomy for non-small cell lung cancer. METHODS: We retrospectively analyzed data from prospectively collected consecutive thoracoscopic segmentectomies in a single center from January 2008 to February 2023. The restricted cubic spline of the adjusted Cox regression model for LRR displayed the breakpoint of margin distance. The Kaplan-Meier estimator with log-rank test evaluated the overall survival between the 2 groups stratified by the breakpoint, and the Aalen-Johansen estimator with the Gray test assessed the LRR-free survival and lung cancer-specific survival in the competing model. RESULTS: The study included 155 patients. LRR was observed in 22 patients (14.2%), with a median time to LRR of 17.1 months (interquartile range, 6.3-26.3 months). Margin distance was found to be a predictor for LRR (hazard ratio, 0.92; P = .033). The identified breakpoint for margin distance in this cohort was 19.8 mm. Compared with this cutoff, a margin distance of 15 mm increased the risk of LRR by 65%, whereas 25 mm decreased the risk to LRR with 31%. A segmentectomy with a margin distance ≥20 mm resulted in significant improvements in overall survival (P = .020), lung cancer-specific survival (P = .010), and LRR-free survival (P < .001) compared with cases with a margin distance of <20 mm. CONCLUSIONS: Margin distance ≥20 mm decreased LRR and improved survival outcomes for thoracoscopic segmentectomy in this study.

Impact of number of dissected lymph nodes on recurrence and survival following thoracoscopic segmentectomy for clinical stage I non-small cell lung cancer.

OBJECTIVE: This study aimed to identify the impact of number of dissected lymph nodes during thoracoscopic segmentectomy on recurrence and survival of clinical stage I non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We retrospectively analysed data from prospectively collected consecutive thoracoscopic segmentectomies conducted between June 2008 and September 2023 at a single institution. Kaplan-Meier analysis with log-rank test assessed OS. Fine-Gray's test assessed specific death in a competing risk model. The logistic regression model was utilized to predict recurrence, while the Cox regression model was employed to analyse overall survival (OS). Subgroup and sensitivity analyses were performed. RESULTS: A total of 227 patients were included in the final analyses. The mean follow-up was 38.4 months (standard deviation 35.8). Among all patients, 37 patients (16.3 %) experienced recurrence and 51 (22.5 %) deceased during the follow-up period. The median number of dissected lymph nodes was 9 (interquartile range (IQR) 6-12). No statistical difference in recurrence rate and 5-year OS was observed between cases with dissected lymph nodes > 9 and ≤ 9 (14.6 % vs. 17.6 %, p = 0.549; 75.5 % vs. 69.5 %, p = 0.760). On multivariable analysis, body mass index (odds ratio [OR] 1.15, p = 0.002), Charlson Comorbidity index (OR 1.28, p = 0.002), synchronous pulmonary cancer (OR 3.05, p = 0.019), and tumour size (OR 1.04, p = 0.044) increased of the recurrence rate, while percentage of predicted forced expiratory volume in 1 s (hazard ratio (HR) 1.09, p = 0.048), history of smoking (HR 1.02, p = 0.009), and solid nodule (HR 1.56, p = 0.010) was related to poorer survival. CONCLUSIONS: In this study, number of dissected lymph nodes did not impact recurrence rate or overall survival after thoracoscopic segmentectomy for clinical stage I NSCLC.

Postoperative outcomes in patients with diabetes after enhanced recovery thoracoscopic lobectomy.

BACKGROUND: Diabetes is considered a general surgical risk factor, but with few data from enhanced recovery (ERAS) otherwise known to improve outcome. Therefore, this study aimed to investigate postoperative outcomes of patients with diabetes who underwent video-assisted thoracoscopic surgery (VATS) lobectomy in an established ERAS setting. METHODS: We retrospectively analysed outcome data (hospital stay (LOS), readmissions, and mortality) from a prospective database with consecutive unselected ERAS VATS lobectomies from 2012 to 2022. Complete follow-up was secured by the registration system in East Denmark. RESULTS: We included 3164 patients of which 323 had diabetes, including 186 treated with insulin and antidiabetic medicine, 35 with insulin only and 102 with antidiabetic medicine only. The median LOS was 3 days, stable over the study period. There were no differences in terms of LOS, postoperative complications, readmissions or 30 days alive and out of hospital. Patients with diabetes had significantly higher 30- and 90-day mortality rates compared to those without diabetes (p < .001), but also had higher preoperative comorbidity. Preoperative HbA1c levels did not correlate with postoperative outcomes. CONCLUSION: In an ERAS setting, diabetes may not increase the risk for prolonged LOS, complications, and readmissions after VATS lobectomy, however with higher 30- and 90-day mortality probably related to more preoperative comorbidities.

In-hospital thromboprophylaxis variation and the risk of venous thromboembolism after lung cancer surgery: a nationwide cohort study.

OBJECTIVES: Venous thromboembolic event (VTE) is a severe complication in patients with lung cancer undergoing thoracic surgery. Nevertheless, because of insufficient evidence, there are no clear guidelines, and VTE prophylaxis practices vary widely. This nationwide cohort study was a comparative study investigating VTE risk in surgical departments that routinely administered in-hospital thromboprophylaxis with low-molecular-weight heparin compared to those that did not. METHODS: We identified all patients with non-small-cell lung cancer (NSCLC) who underwent surgery in Denmark during 2010-2021. Thoracic surgery was exclusively performed in the 4 university hospitals. Three hospitals implemented in-hospital thromboprophylaxis as standard care since 2000, while the fourth adopted this practice in September 2016. VTE events were assessed at 6-month follow-up according to hospital and study period, using an inverse probability of treatment weighting approach. RESULTS: We identified 9615 patients. During 6-month follow-up, a total of 190 VTE events were observed, resulting in a weighted rate of 4.5 events per 100 person-years and an absolute risk of 2.2%. There was no clear trend according to hospital site or use of in-hospital thromboprophylaxis with a 2.2% risk in the hospital not using thromboprophylaxis compared to 1.7-3.1% in those that did. CONCLUSIONS: Use of in-hospital thromboprophylaxis did not affect the risk of VTE after surgery for NSCLC, suggesting that relying solely on in-hospital thromboprophylaxis may be insufficient to mitigate VTE risk in these patients. Further research is warranted to investigate the potential benefits of extended thromboprophylaxis in reducing VTE risk in selected NSCLC surgical patients.

Risk of Venous Thromboembolism in Patients With Stage III and IV Non-Small-Cell Lung Cancer: Nationwide Descriptive Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) is a common complication in patients starting cancer therapies for non-small-cell lung cancer (NSCLC). We examined the risk and timing of VTE in patients with stage IIIA, IIIB to C, and stage IV NSCLC according to received cancer treatments. MATERIALS AND METHODS: A nationwide registry-based cohort study of patients recorded in the Danish Lung Cancer Registry (2010-2021) followed for 1 year after entry into the registry to assess the incidence of VTE. The Aalen-Johansen estimator was used to calculate the risk of VTE after treatment commencement with chemotherapy, radiotherapy, chemoradiation, immunotherapy, and targeted therapy. RESULTS: Among the 3475 patients with stage IIIA, 4047 with stage IIIB to C, and 18,082 patients with stage IV cancer, the 1-year risk of VTE was highest in the first 6 months and varied markedly by cancer stage and cancer treatment. In stage IIIA, VTE risk was highest with chemotherapy (3.9%) and chemoradiation (4.1%). In stage IIIB to C, risks increased with chemotherapy (5.2%), immunotherapy (9.4%), and targeted therapy (6.0%). Stage IV NSCLC showed high risk with targeted therapy (12.5%) and immunotherapy (12.2%). The risk was consistently higher for pulmonary embolism than deep vein thrombosis. CONCLUSION: VTE risks vary substantially according to cancer treatments and cancer stages. The highest risk was observed in the initial 6 months of therapy initiation. These insights emphasize the need for tailored risk assessment and vigilance in managing VTE complications in patients with NSCLC. Further research is needed to optimize individual thromboprophylaxis strategies for patients with unresectable and metastatic NSCLC.

Efficacy of avoiding chest drains after video-assisted thoracoscopic surgery wedge resection: protocol for a randomised controlled trial.

INTRODUCTION: The use of routine postoperative chest drains after video-assisted thoracoscopic surgery (VATS) of the lung is a practice based on tradition with the aim of draining fluid and air. However, new evidence suggests that chest drains can be avoided in selected cases. With this randomised controlled trial, we wish to establish the efficacy and safety of avoiding postoperative chest drains compared with routine postoperative chest drains. METHODS AND ANALYSIS: This is a two-centre randomised controlled trial without allocation concealment, but where randomisation occurs after the end of procedure leaving operative personnel blinded during surgery. The sample size is calculated to show a difference in pain measurements using the Numeric Rating Scale under different circumstances and at different time points to show superiority of the intervention. The trial is pragmatic by design to reflect the daily clinical scenario and with the aim of increasing the external validity of the results. ETHICS AND DISSEMINATION: Approval by the local ethics committees has been obtained for both sites. The study was registered with ClinicalTrials.gov (NCT05358158) prior to inclusion. The results of the trial will be disseminated by publication in an international journal and presentation at major international thoracic surgical meetings. ARTICLE SUMMARY: This is a randomised controlled trial estimating the effects of avoiding a chest drain after VATS wedge resection of the lung on pain, total morphine use, quality of life and complications. TRIAL REGISTRATION NUMBER: NCT05358158.

Prognostic Thresholds of Mitotic Count and Ki-67 Labeling Index for Recurrence and Survival in Lung Atypical Carcinoids.

Atypical carcinoid (AC) is a rare neuroendocrine neoplasm of the lung, which exhibits a varying malignant potential. In this study, we aimed to identify the prognostic thresholds of the mitotic count and Ki-67 labeling index for recurrence and survival in AC. We retrospectively reviewed 78 patients who had been radically resected for AC and calculated said thresholds using time-dependent receiver operating characteristic curves and the Youden index. We then dichotomized the patients into groups of above or below these thresholds and estimated the cumulative incidences of the groups using the Aalen-Johansen estimator. We compared the groups using univariable and multivariable Fine-Gray subdistribution hazard models. Our findings show that more patients recurred and died from this disease if their mitotic count exceeded three and four mitoses per 2 mm2, respectively, or if their Ki-67 labeling index exceeded 14% and 11%, respectively. Both thresholds independently predicted survival (p < 0.001 and p = 0.015, respectively). These thresholds may serve as a valuable tool for clinicians and researchers in making treatment plans and predicting outcomes for patients with AC.

Readmission after enhanced recovery video-assisted thoracoscopic surgery wedge resection.

BACKGROUND: Despite the implementation of Enhanced Recovery After Surgery (ERAS) programs, surgical stress continues to influence postoperative rehabilitation, including the period after discharge. However, there is a lack of data available beyond the point of discharge following video-assisted thoracoscopic surgery (VATS) wedge resection. Therefore, the objective of this study is to investigate incidence and risk factors for readmissions after ERAS VATS wedge resection. METHODS: A retrospective analysis was performed on data from prospectively collected consecutive VATS wedge resections from June 2019 to June 2022. We evaluated main reasons related to wedge resection leading to 90-day readmission, early (occurring within 0-30 days postoperatively) and late readmission (occurring within 31-90 days postoperatively). To identify predictors for these readmissions, we utilized a logistic regression model for both univariable and multivariable analyses. RESULTS: A total of 850 patients (non-small cell lung cancer 21.5%, metastasis 44.7%, benign 31.9%, and other lung cancers 1.9%) were included for the final analysis. Median length of stay was 1 day (IQR 1-2). During the postoperative 90 days, 86 patients (10.1%) were readmitted mostly due to pneumonia and pneumothorax. Among the cohort, 66 patients (7.8%) had early readmissions primarily due to pneumothorax and pneumonia, while 27 patients (3.2%) experienced late readmissions mainly due to pneumonia, with 7 (0.8%) patients experiencing both early and late readmissions. Multivariable analysis demonstrated that male gender, pulmonary complications, and neurological complications were associated with readmission. CONCLUSIONS: Readmission after VATS wedge resection remains significant despite an optimal ERAS program, with pneumonia and pneumothorax as the dominant reasons. Early readmission was primarily associated with pneumothorax and pneumonia, while late readmission correlated mainly with pneumonia.

Complication rates rise with age and Haller index in minimally invasive correction of pectus excavatum: A high-volume, single-center retrospective cohort study.

OBJECTIVES: The study objectives were to describe the compounded complication rate of minimally invasive repair of pectus excavatum, identify predisposing risk factors, and evaluate the optimal timing of correction. Minimally invasive repair of pectus excavatum is the standard treatment for pectus excavatum and consists of 2 invasive procedures, for example, correction with bar insertion followed by bar removal after 2 to 3 years. METHODS: A retrospective cohort study identifying children, adolescents, and adults of both genders corrected for pectus excavatum with minimally invasive repair of pectus excavatum between 2001 and 2022. Information on complications related to bar insertion and removal procedures for each individual patient was compiled into a compounded complication rate. Complication severities were categorized according to the Clavien-Dindo classification. RESULTS: A total of 2013 patients were corrected by minimally invasive repair of pectus excavatum with a median age (interquartile range) for correction of 16.6 (5) years. Overall compounded complication rate occurred at a frequency of 16.4%, of which 9.3% required invasive reinterventions (Clavien-Dindo classification ≥IIIa). The complication rate related to bar insertion was 2.6-fold higher compared with bar removal (11.8% vs 4.5%, respectively). Multivariable analysis revealed age (adjusted odds ratio, 1.05; P < .001), precorrection Haller Index (adjusted odds ratio, 1.10; P < .033), and early-phase institutional experience (adjusted odds ratio, 1.59; P < .002) as independent predisposing risk factors. The optimal age of correction was 12 years, and the compounded complication rate correlated exponentially with age with a doubling time of 7.2 years. Complications increased 2.2-fold when the Haller index increased to 5 or more units. CONCLUSIONS: Minimally invasive repair of pectus excavatum is associated with a high compounded complication rate that increases exponentially with age and high Haller Index. Consequently, we recommend repair during late childhood and early adolescence, and emphasize the importance of informing patients and relatives about the significant risks of adult correction as well as the need of 2 consecutive procedures taking the complication profile into account before planning surgery.

Ready to Go Home? Nurses' Perspectives of Prolonged Admission for Patients Undergoing Video-Assisted Thoracic Surgery for Non-Small-Cell Lung Cancer in Denmark.

Enhanced recovery after surgery programs with median postoperative hospitalization of 2 days improve outcomes after lung cancer surgery. This article explores nursing care practices for patients with lung cancer who remain hospitalized despite having recovered somatically. Qualitative focus group interviews were conducted with 16 nurses. Ricoeur's phenomenological hermeneutics underpins the methodology applied in this study, and we relied on Benner and Wrubel's theory. The nurses emphasized that the thoughts of patients with a recent lung cancer diagnosis revolve around more than the surgery. Nursing comprises not only practicalities but also attending to patients' stress and their coping with being struck with lung cancer and having undergone surgery. A counterculture emerged to counteract the logic of productivity, indicating that caring as a worthy end in itself may be underestimated in protocol-driven care. Prolonging hospitalization largely depends on clinical judgment. The nurses' aim is not to keep patients in the hospital but to avoid any needless suffering, allowing them to reclaim the primacy of caring.