The Prognostic Role of the Number of Involved Structures in Thymic Epithelial Tumors: Results from the ESTS Database.

BACKGROUND: The role of the number of involved structures (NIS) in thymic epithelial tumors (TETs) has been investigated for inclusion in future staging systems, but large cohort results still are missing. This study aimed to analyze the prognostic role of NIS for patients included in the European Society of Thoracic Surgeons (ESTS) thymic database who underwent surgical resection. METHODS: Clinical and pathologic data of patients from the ESTS thymic database who underwent surgery for TET from January 2000 to July 2019 with infiltration of surrounding structures were reviewed and analyzed. Patients' clinical data, tumor characteristics, and NIS were collected and correlated with CSS using Kaplan-Meier curves. The log-rank test was used to assess differences between subgroups. A multivariable model was built using logistic regression analysis. RESULTS: The final analysis was performed on 303 patients. Histology showed thymoma for 216 patients (71.3%) and NET/thymic carcinoma [TC]) for 87 patients (28.7%). The most frequently infiltrated structures were the pleura (198 cases, 65.3%) and the pericardium in (185 cases, 61.1%), whereas lung was involved in 96 cases (31.7%), great vessels in 74 cases (24.4%), and the phrenic nerve in 31 cases (10.2%). Multiple structures (range, 2-7) were involved in 183 cases (60.4%). Recurrence resulted in the death of 46 patients. The CSS mortality rate was 89% at 5 years and 82% at 10 years. In the univariable analysis, the favorable prognostic factors were neoadjuvant therapy, Masaoka stage 3, absence of metastases, absence of myasthenia gravis, complete resection, thymoma histology, and no more than two NIS. Patients with more than two NIS presented with a significantly worse CSS than patients with no more than two NIS (CSS 5- and 10-year rates: 9.5% and 83.5% vs 93.2% and 91.2%, respectively; p = 0.04). The negative independent prognostic factors confirmed by the multivariable analysis were incomplete resection (hazard ratio [HR] 2.543; 95% confidence interval [CI] 1.010-6.407; p = 0.048) and more than two NIS (HR 1.395; 95% CI 1.021-1.905; p = 0.036). CONCLUSIONS: The study showed that more than two involved structures are a negative independent prognostic factor in infiltrative thymic epithelial tumors that could be used for prognostic stratification.

Multi-omics integrative modelling for stereotactic body radiotherapy in early-stage non-small cell lung cancer: clinical trial protocol of the MONDRIAN study.

BACKGROUND: Currently, main treatment strategies for early-stage non-small cell lung cancer (ES-NSCLC) disease are surgery or stereotactic body radiation therapy (SBRT), with successful local control rates for both approaches. However, regional and distant failure remain critical in SBRT, and it is paramount to identify predictive factors of response to identify high-risk patients who may benefit from more aggressive approaches. The main endpoint of the MONDRIAN trial is to identify multi-omic biomarkers of SBRT response integrating information from the individual fields of radiomics, genomics and proteomics. METHODS: MONDRIAN is a prospective observational explorative cohort clinical study, with a data-driven, bottom-up approach. It is expected to enroll 100 ES-NSCLC SBRT candidates treated at an Italian tertiary cancer center with well-recognized expertise in SBRT and thoracic surgery. To identify predictors specific to SBRT, MONDRIAN will include data from 200 patients treated with surgery, in a 1:2 ratio, with comparable clinical characteristics. The project will have an overall expected duration of 60 months, and will be structured into five main tasks: (i) Clinical Study; (ii) Imaging/ Radiomic Study, (iii) Gene Expression Study, (iv) Proteomic Study, (v) Integrative Model Building. DISCUSSION: Thanks to its multi-disciplinary nature, MONDRIAN is expected to provide the opportunity to characterize ES-NSCLC from a multi-omic perspective, with a Radiation Oncology-oriented focus. Other than contributing to a mechanistic understanding of the disease, the study will assist the identification of high-risk patients in a largely unexplored clinical setting. Ultimately, this would orient further clinical research efforts on the combination of SBRT and systemic treatments, such as immunotherapy, with the perspective of improving oncological outcomes in this subset of patients. TRIAL REGISTRATION: The study was prospectively registered at clinicaltrials.gov (NCT05974475).

Assessment of Quality Outcomes and Learning Curve for Robot-Assisted Minimally Invasive McKeown Esophagectomy.

BACKGROUND: This study aimed to identify the results of the quality assessment and the learning curve of robot-assisted minimally invasive McKeown esophagectomy (RAMIE-MK). METHODS: The study retrospectively reviewed the data of 400 consecutive patients with esophageal cancer who underwent RAMIE-MK by a single surgeon from November 2015 to March 2019. Cumulative summation analysis of the learning curve was performed. The patients were divided into decile cohorts of 40 cases to minimize demographic deviations and to maximize the power of detecting statistically significant changes in performance. RESULTS: The 90-day mortality rate for all the patients was 0.5% (2 cases). The authors' experience was divided into the ascending phase (40 cases), the plateau phase (175 cases), and the descending phase (185 cases). After 40 cases, significant improvements in operative time (328 vs. 251 min; P = 0.019), estimated blood loss (350 vs. 200 ml; P = 0.031), and conversion rates (12.5% vs. 2.5%; P < 0.001) were observed. After 80 cases, a decrease in the rates of anastomotic leakage (22.5% vs. 8.1%; P = 0.001) and vocal cord palsy (31.3% vs. 18.4%; P = 0.024) was observed. The number of harvested lymph nodes increased after 40 cases (13 vs. 23; P < 0.001), especially for lymph nodes along the recurrent laryngeal nerve (3.0 vs. 6.0; P < 0.001). CONCLUSIONS: The learning phase of RAMIE-MK consists of 40 cases, and quality outcomes can be improved after 80 procedures. Several turning points related to the optimization of surgical outcomes can be used as benchmarks for surgeons performing RAMIE-MK.

Preliminary Results of Extracorporeal Membrane Oxygenation Assisted Tracheal Sleeve Pneumonectomy for Cancer.

OBJECTIVE: Tracheal sleeve pneumonectomy is a challenge in lung cancer management and in achieving long-term oncological results. In November 2018, we started a prospective study on the role of extracorporeal membrane oxygenation (ECMO) in tracheal sleeve pneumonectomy. We aim to present our preliminary results. METHODS: From November 2018 to November 2019, six patients (three men and three women; median age: 61 years) were eligible for tracheal sleeve pneumonectomy for lung cancer employing the veno-venous ECMO during tracheobronchial anastomosis. RESULTS: Only in one patient, an intrapericardial pneumonectomy without ECMO support was performed, but cannulas were maintained during surgery. The median length of surgery was 201 minutes (range: 162-292 minutes), and the average duration of the apneic phase was 38 minutes (range: 31-45 minutes). No complications correlated to the positioning of the cannulas were recorded. There was only one major postoperative complication (hemothorax). At the time of follow-up, all patients were alive; one patient alive with bone metastasis was being treated with radiotherapy. CONCLUSION: ECMO-assisted oncological surgery was rarely described, and its advantages include hemodynamic stability with low bleeding complications and a clean operating field. As suggested by our preliminary data, ECMO-assisted could be a useful alternative strategy in select lung cancer patients.

Treatment of Chylothorax after Lung Resection: Indications, Timing, and Outcomes.

BACKGROUND: Chylothorax following pulmonary resection and lymphadenectomy for cancer is a potential severe complication in thoracic surgery. In the present study, we investigated the efficacy of the nonsurgical approach as well as the need for reoperation after conservative approach failure. METHODS: Chylothorax was diagnosed when chylous leakage from the chest drainage was observed and confirmed by the presence of triglycerides in the pleural fluid. We initially treated all the patients conservatively with complete oral intake cessation and total parenteral nutrition; if drainage output remained more than 800 mL/d after the first 5 days or major pleural effusion was observed at chest X-ray after chest tube removal, surgical treatment of chylothorax was indicated. RESULTS: Between January 1998 and December 2018, 5,072 patients underwent standard anatomical resection and mediastinal lymph node dissection for cancer at our institution. Among them, 30 patients (0.6%) developed chylothorax: 20 patients were effectively treated only by nil per os and low-fat diet, while 10 patients (33.3%) required surgical treatment. Mean age was 63 years; there were 24 male patients (80%); right-sided chylothorax was more frequent than left-sided chylothorax (22 vs. 8, respectively) although not statistically significant (p = 0.38); the only factor that seems to influence the need for reoperation is chylothorax flow rate during conservative treatment (p = 0.06). CONCLUSION: Conservative treatment is effective in the case of low flow-rate chylothorax (< 800 mL/d); in the case of a higher flow rate, surgical exploration is needed and thoracic duct ligation-with or without lymphatic sites clipping-provides definitive lymphostasis.

Surgical Treatment of Bilateral Lung Cancers: Long-Term Outcomes and Prognostic Factors.

BACKGROUND: Bilateral lung neoplasms are becoming more common, but distinguishing two primary lung cancers from metastatic disease can be difficult and only long-term follow-up after treatment can disclose the real behavior of the disease.The present study aimed to identify the appropriate candidates for bilateral surgical resections from the perspective of short-term postoperative complications and long-term outcomes. METHODS: Two hundred and fifteen consecutive patients undergoing bilateral pulmonary resection for lung cancers over a 20-year period were analyzed. Preoperative patient characteristics were noted, including demographic information, operative details, pathologic information including histology and tumor stage according to the eighth edition of the tumor nodes metastases staging system, and the use of neoadjuvant or adjuvant treatments. RESULTS: Patients receiving the second pulmonary resection more than 24 months from the first procedure as well as patients receiving bilateral lobectomies had higher overall 3-, 5-, and 10-year survival rates compared with the others. CONCLUSION: Patients receiving the second resection more than 24 months from the first procedure have the best long-term results irrespective of the type of resection.

Ten Years' Experience in Robotic-Assisted Thoracic Surgery for Early Stage Lung Cancer.

BACKGROUND: This study analyzed the short- and long-term outcomes of robotic-assisted thoracic surgery (RATS) for early stage non-small cell lung cancer (NSCLC). METHODS: From November 2006 to December 2016, we performed 363 RATS procedures. This study retrospectively reviewed 339 patients who underwent RATS for clinical stages I (n = 318) or II (n = 21) NSCLC. RESULTS: Twenty-nine patients underwent segmentectomy, 307 lobectomy, and 3 pneumonectomy. Conversion occurred in 22 patients (6.5%): 15 (4.4%) due to technical issues, 4 (1.2%) for oncological reasons, and 3 (0.9%) for bleeding. The median number of N1 and N2 stations resected was 2 and 3, respectively, and the median number of N1 and N2 lymph nodes resected was 9 and 6, respectively. Median operative time was 192 minutes for lobectomy, 172 minutes for segmentectomy, and 275 minutes for pneumonectomy. Median length of hospital stay was 5 days (2-191). The most common postoperative complication was prolonged air leak (12.1%). Major complications occurred in eight patients (2.4%). The 30-day and 90-day operative mortality was 0% and 0.3%, respectively. Two and 5-year cancer-specific survival rate was 96.1% and 91.5%, respectively. Five-year survival rate was 96.2% for patients who underwent segmentectomy, and 89.1% for lobectomy. All three patients who underwent pneumonectomy were alive at 5 years with no disease. CONCLUSIONS: Besides the well-known short-term outcomes showing very low morbidity and mortality rates, mediastinal lymph node dissection during RATS adequately assesses lymph node stations detecting occult lymph node metastasis and leading to excellent oncologic results. However, these results await longer follow-up studies.

Prevention of Atrial Fibrillation in High-risk Patients Undergoing Lung Cancer Surgery: The PRESAGE Trial.

OBJECTIVE: We performed a prospective, randomized clinical study to assess whether prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, reduces the incidence of postoperative atrial fibrillation. BACKGROUND: Postoperative atrial fibrillation is a well recognized complication after lung cancer surgery, with an incidence as high as 30%. Perioperative increase of NT-proBNP has been demonstrated to be a strong independent predictor of postoperative atrial fibrillation in this setting. METHODS: NT-proBNP concentration was measured 24 hours before surgery and soon after surgery in 1116 patients. Three hundred twenty (29%) patients showed a high NT-proBNP value and were enrolled: 108 were assigned to the metoprolol group, 102 to the losartan group, and 110 to the control group. RESULTS: Overall, the incidence of postoperative atrial fibrillation was 20% (n = 64); it was significantly lower in the metoprolol and losartan groups compared with the control group [6%, 12%, and 40%, respectively; relative risk 0.19, 95% confidence intervals (CIs), 0.09-0.37; P < 0.001 in the metoprolol group; and 0.29, 95% CI, 0.16-0.52; P < 0.001 in the losartan group). No significant difference was found when the metoprolol and losartan groups were directly compared (P = 0.21). CONCLUSIONS: A prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with high NT-proBNP levels, significantly reduced the occurrence of postoperative atrial fibrillation.

Chest wall resection and reconstruction for locally recurrent breast cancer: From technical aspects to biological assessment.

INTRODUCTION: Breast cancer is the leading cause of cancer death among women in the industrialized countries. The incidence of local recurrences after mastectomy and breast-conserving therapy varies between 5% and 40% depending on risk factors and primary therapy. METHODS: From April 1999 to April 2011, 40 patients underwent chest wall resection and reconstruction for locally recurrent breast carcinoma with chest wall invasion. The main goal of surgery was local disease control to palliate clinical symptoms. RESULTS: Local radical resection was achieved in 26 patients (65%). One, 2 and 5 year overall survival rates were 94.4%, 82.0% and 68.5%; 1, 2 and 5 year disease-free survival rates were 94.4%, 73.6% and 45.5% respectively. Univariate analysis indicated age (p = 0.002) and synchronous distant metastases (p = 0.020) as factors having a negative impact on overall survival; multivariate analysis disclosed age (p = 0.052) and synchronous metastases (p = 0.059) as factors with a slight negative impact on overall survival. Older age was associated with improved overall survival. Univariate analysis indicated synchronous distant metastases (p = 0.029) and the need of post resectional additional treatments (p = 0.022) as factors adversely conditioning disease-free survival or time to progression; multivariate analysis disclosed the need of post resectional additional treatments (p = 0.036) as the only factor adversely conditioning disease-free survival or time to progression. CONCLUSIONS: Chest wall resection and reconstruction for locally recurrent breast cancer is a feasible and safe procedure providing adequate local disease control and an excellent palliation of very disabling symptoms in a selected group of patients.

Recent advances in lung cancer research: unravelling the future of treatment.

Lung cancer, a multifaceted disease, demands tailored therapeutic approaches due to its diverse subtypes and stages. This comprehensive review explores the intricate landscape of lung cancer research, delving into recent breakthroughs and their implications for diagnosis, therapy, and prevention. Genomic profiling and biomarker identification have ushered in the era of personalised medicine, enabling targeted therapies that minimise harm to healthy tissues while effectively combating cancer cells. The relationship between pulmonary tuberculosis and lung cancer is examined, shedding light on potential mechanisms linking these two conditions. Early detection methods, notably low-dose computed tomography scans, have significantly improved patient outcomes, emphasising the importance of timely interventions. There has been a growing interest in segmentectomy as a surgical intervention for early-stage lung cancer in recent years. Immunotherapy has emerged as a transformative approach, harnessing the body's immune system to recognise and eliminate cancer cells. Combining immunotherapy with traditional treatments, such as chemotherapy and targeted therapies, has shown enhanced efficacy, addressing the disease's heterogeneity and overcoming drug resistance. Precision medicine, guided by genomic profiling, has enabled the development of targeted therapies like tyrosine kinase inhibitors, offering personalised treatments tailored to individual patients. Challenges such as drug resistance and limited accessibility to advanced therapies persist, emphasising the need for collaborative efforts and innovative technologies like artificial intelligence. Despite challenges, ongoing interdisciplinary collaborations and technological advancements offer hope for a future where lung cancer is treatable and preventable, reducing the burden on patients and healthcare systems worldwide.

The Role of Adjuvant Chemotherapy in pN1 (IIB/IIIA) NSCLC Patients Who Undergo Pneumonectomy: Is It Still Justified in the Modern Era?

INTRODUCTION: We aimed to assess our 25-year experience in order to evaluate the role of adjuvant chemotherapy in patients who undergo pneumonectomy for pN1 NSCLC. MATERIALS AND METHODS: We retrospectively reviewed the outcomes and medical records of patients undergoing pneumonectomy for NSCLC with pathological diagnosis of pN1, excluding all patients who underwent neoadjuvant treatment. We compared patients treated with adjuvant chemotherapy with patients who did not undergo neoadjuvant treatment during a follow-up soon after surgery. Gray's test was used to assess differences in the cumulative incidence of relapse or CSS between the different groups. Kaplan-Meier methods were used for drawing overall survival (OS) plots. In order to assess differences in survival between the groups, the log-rank test was used. The cumulative incidence of relapse, CSS, and OS were calculated at 1, 2, 3, 4, and 5 years of follow-up. RESULTS: The 30-day and 90-day mortality rates of our cohort were 6% and 11,6%. Excluding the first three months after surgery (deaths linked to postoperative comorbidity), after 5 years we found no significant differences between the two cohorts (adjuvant CT and no adjuvant CT) in terms of the overall survival (OS) (p: 0.31), cancer-specific survival (CSS) (p: 0.59), disease-free survival (DFS) (p: 0.94), and relapse rate (p: 0.76). CONCLUSIONS: Patients with pN1 NSCLC that was completely resected through pneumonectomy and radical lymphadenectomy may represent a particular cohort, which could be strictly followed up without adjuvant chemotherapy.

Revamping Non-Small Cell Lung Cancer Treatments in Stages II and III: Preparing Healthcare for Cutting-Edge Immuno-Oncology Regimens.

Non-small cell lung cancer (NSCLC) poses a significant challenge in clinical oncology, necessitating continual refinement of treatment approaches in stages II and III. Recent advancements have highlighted the potential of neoadjuvant therapy in optimising patient outcomes. Biomarker testing guides neoadjuvant therapy decisions, including epidermal growth factor receptor (EGFR) mutation and programmed death-ligand 1 (PD-L1) expression testing. Neoadjuvant therapy aims to improve oncological outcomes by treating micrometastatic disease and assessing tumour response before surgery. Disease-free survival is a surrogate endpoint for overall survival in both neoadjuvant and adjuvant settings. Multidisciplinary collaboration is crucial for individualised treatment planning and optimising patient care. The management of NSCLC requires a comprehensive approach, integrating expertise across disciplines and tailoring treatment strategies to individual patient needs. Neoadjuvant therapy shows promise in improving long-term outcomes, with biomarker testing guiding treatment decisions. Challenges such as defining borderline resectability and differentiating pseudoprogression highlight the need for ongoing research and collaboration.

The role of the surgical volume for clinical outcomes in VATS lobectomy for lung cancer: a national large database multicenter analysis.

Improving the quality of lung cancer care at a cost that can be sustained is a hotly debated issue. High-risk, low-volume procedures (such as lung resections) are believed to improve significantly when centralised in high-volume centres. However, limited evidence exists to support volume requirements in lung cancer surgery. On the other hand, there was no evidence that the number of lung resections affected either the short-term perioperative results or the long-term cost. Using data from an extensive nationwide registry, this study investigated the correlations between surgical volumes and selected perioperative outcomes. A retrospective analysis of a prospectively filled national registry that follows stringent quality assurance and security procedures was conducted to ensure data accuracy and security. Patients who underwent VATS lobectomy from 2014 to 2019 at the participating centres were included. Selected perioperative outcomes were reported. Total direct hospital cost is measured at discharge for hospitalisations with a primary diagnosis of lung cancer, hospital stay costs, and postoperative length of hospital stay after lobectomy. After the propensity score matched, centres were divided into three groups according to the surgical volume of the unit where VATS lobectomies were performed (high-volume centre: > 500 lobectomies; medium-volume centre: 200-500 lobectomies; low-volume centre: < 200 lobectomies). 11,347 patients were included and matched (low-volume center = 2890; medium-volume center = 3147; high-volume center = 2907). The mean operative time density plot (Fig. 1A) showed no statistically significant difference (p = 0.67). In contrast, the density plot of the harvested lymph nodes (Fig. 1B) showed significantly higher values in the high-volume centres (p = 0.045), albeit without being clinically significant. The adjusted rates of any and significant complications were higher in the low-volume centre (p = 0.034) without significantly affecting the length of hospital stay (p = 0.57). VATS lobectomies for lung cancer in higher-volume centres seem associated with a statistically significantly higher number of harvested lymph nodes and lower perioperative complications, yet without any significant impact in terms of costs and resource consumption. These findings may advise the investigation of the learning curve effect in a complete economic evaluation of VATS lobectomy in lung cancer. Fig. 1 The mean operative time density plot showed no statistically significant difference (p = 0.67).