Co-Occurring Driver Genomic Alterations in Advanced Non-Small-Cell Lung Cancer (NSCLC): A Retrospective Analysis.

Background: Actionable driver mutations account for 40-50% of NSCLC cases, and their identification clearly affects treatment choices and outcomes. Conversely, non-actionable mutations are genetic alterations that do not currently have established treatment implications. Among co-occurring alterations, the identification of concurrent actionable genomic alterations is a rare event, potentially impacting prognosis and treatment outcomes. Methods: We retrospectively evaluated the prevalence and patterns of concurrent driver genomic alterations in a large series of NSCLCs to investigate their association with clinicopathological characteristics, to assess the prognosis of patients whose tumor harbors concurrent alterations in the genes of interest and to explore their potential therapeutic implications. Results: Co-occurring driver alterations were identified in 26 out of 1520 patients with at least one gene alteration (1.7%). Within these cases, the incidence of concurrent actionable gene alterations was 39% (0.7% of the overall cohort). Among compound actionable gene mutations, EGFR was the most frequently involved gene (70%). The most frequent association was EGFR mutations with ROS1 rearrangement. Front-line targeted treatments were the preferred approach in patients with compound actionable mutations, with dismal median PFS observed (6 months). Conclusions: Advances in genomic profiling technologies are facilitating the identification of concurrent mutations. In patients with concurrent actionable gene alterations, integrated molecular and clinical data should be used to guide treatment decisions, always considering rebiopsy at the moment of disease progression.

Pneumonectomy for broncho-pulmonary carcinoids: a single centre analysis of surgical approaches and patient outcomes.

Background: Pneumonectomy is a radical surgical procedure associated with significant morbidity and mortality. Its application in the context of pulmonary neuroendocrine tumours, including carcinoid tumours, requires meticulous preoperative planning and intraoperative precision. This study aims to assess the safety and efficacy of pneumonectomy in the management of these rare and challenging neoplasms. Methods: A retrospective analysis of patients who underwent pneumonectomy for pulmonary carcinoid tumours at our institution over a specified period was conducted. Data regarding patient demographics, tumour characteristics, surgical techniques, intraoperative complications, perioperative management, and long-term outcomes were collected and analysed. Results: Between March 2001 and October 2022, 21 patients (7 male, 14 female) with carcinoid tumours underwent pneumonectomy on a total of 459 surgical operations for carcinoid. Preoperative bronchoscopic procedures were conducted in 90.4% of cases, leading to histological diagnoses for most. The median hospital stay was eight days, with no reported perioperative deaths. Median follow-up after surgery was 73 months, with a five-year overall survival of 65.4 months. Recurrences occurred in 28.6% of cases, primarily in atypical carcinoids. Conclusion: Despite the rarity of bronchial carcinoids, pneumonectomy is effective for low-grade malignancies, demonstrating positive short-and long-term outcomes. Radical lymph node dissection is fundamental in pathological staging and overall survival.

1000 Robotic-assisted lobectomies for primary lung cancer: 16 years single center experience.

OBJECTIVE: This study aimed at describing our high-volume single center experience in robotic-assisted thoracic surgery (RATS) to evaluate short outcome and feasibility of the technique, the adequacy of oncological results, and the learning curve. METHODS: We retrospectively analyzed data from 1000 consecutive patients who underwent lobectomy and systematic lymphadenectomy for primary lung cancer using RATS approach between May 2007 and May 2023. RESULTS: Nine-hundred ninety-seven patients (99.7 %) underwent lobectomy, whereas 3 (0.03 %) patients bilobectomy. Conversion rate to open surgery was 3.7 %. Minor complications occurred in 213 (21.3 %) patients, major complications in 29 patients (2.9 %). The 30-day and 90-day operative mortality was 0 % and 0.1 %, respectively. The median number of N1 + N2 stations resected was 5 (range 0-9), with a median number of 17 of N1 + N2 lymph nodes resected (range 0-55). The oncological outcome was evaluated only on the subgroup of patients (n = 895) with non-small cell lung cancer. Pathological lymph node upstaging from cN0 to pN1/pN2 was evident in 147 patients (17.3 %): 9 % from cN0 to pN1 and 7.1 % from cN0 to pN2. With a median follow-up of 3.9, 5-year OS and DFS were respectively 89.3 % and 83.6 % for stage I, 74 % and 66.5 % for stage II, and 61 % and 36.4 % for stage IIIA. CONCLUSIONS: Better vision and excellent instrument maneuverability of the robotic surgical system allowed excellent results in terms of early, adequate oncological outcome comparable to open surgery literature data, and acceptable learning curve. ULTRAMINI ABSTRACT: 1000 consecutive patients who underwent lobectomy and systematic lymphadenectomy for primary lung cancer using RATS approach have been analyzed with the aim to describe our high-volume single center experience, and to evaluate short outcome and feasibility of the technique, the adequacy of oncological results, and the learning curve.

How General and Inflammatory Status Impacts on the Prognosis of Patients Affected by Lung Cancer: State of the Art.

Pulmonary cancer is often associated with systemic inflammation and poor nutritional status and these two aspects are strongly correlated and related to the scarce infiltration of a tumor by immune cells. We reviewed all English literature reviews from 2000 to 2024 from PubMed, Scopus and Google Scholar, including original articles, review articles, and metanalyses. We excluded non-English language articles and case reports/case series. Generally speaking, nutritional and inflammatory status largely affect medium and long-term prognosis in lung cancer patients. A correct stratification of patients could improve their preoperative general functional nutritional and inflammatory status, minimizing, therefore, possible treatment complications and improving long-term prognosis.

Comprehensive Pulmonary Rehabilitation for Patients with Malignant Pleural Mesothelioma: A Feasibility Pilot Study.

Malignant pleural mesothelioma (MPM) represents a significant health burden, with limited treatment options and poor prognosis. Despite advances in pharmacological and surgical interventions, the role of rehabilitation in MPM management remains underexplored. This study aims to assess the feasibility of a tailored pulmonary rehabilitation intervention addressing physical and respiratory function in MPM patients. A prospective pilot study was conducted on surgically treated MPM patients referred to a cardiopulmonary rehabilitation service. The intervention comprised multidisciplinary educational sessions, physical rehabilitation, and respiratory physiotherapy. Feasibility was evaluated based on dropout rates, adherence to the rehabilitation program, safety, and patient-reported outcomes. Twelve patients were initially enrolled, with seven completing the study. High adherence to physical (T1: 93.43%, T2: 82.56%) and respiratory (T1: 96.2%, T2: 92.5%) rehabilitation was observed, with minimal adverse events reported. Patient satisfaction remained high throughout the study (GPE scores at T1: 1.83 ± 1.17; T2: 2.0 ± 1.15), with improvements noted in physical function, pain management, and health-related quality of life. However, some issues, such as time constraints and lack of continuous supervision, were reported by participants. This pilot study demonstrates the feasibility and potential benefits of a tailored pulmonary rehabilitation intervention in MPM patients. Despite its promising outcomes, further research with larger samples is warranted to validate its efficacy and integrate rehabilitation as a component into the multidisciplinary management of MPM.

The Incidence of Winged Scapula after Thoracic Cancer Surgery: A Prospective Cohort Study.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths, and surgery is still the first treatment of choice in early and locally advanced cases. One of the iatrogenic complications is the serratus anterior palsy, which could lead to a winged scapula (WS). Unfortunately, the incidence of this deficit in thoracic surgery is unclear. Our primary aim was to determine the incidence of WS in lung cancer patients in a single-center experience. METHODS: We conducted a retrospective analysis of prospectively collected data with patients eligible for oncological thoracic surgery from March 2013 until January 2014. A physical evaluation of the WS was performed pre- and postoperatively, at the discharge and after 1 year of follow-up. RESULTS: A total of 485 patients were evaluated; 135 (27.8%) showed WS. Longer operative time (p < 0.0001), type of surgery (p < 0.0001), lymphadenectomy (p < 0.0001), and neoadjuvant treatment prior surgery (p = 0.0005) were significantly related to the WS injury. Multivariable analysis showed that type of surgery was significantly associated with WS (p < 0.0001). After 1 year, 41.6% still had WS. CONCLUSION: The incidence of WS was similar to the literature. As WS incidence is underdiagnosed, assessment and correct education about possible deficits or impairments should be improved. Moreover, when a minimally invasive approach is not planned, it is a good clinical practice to discuss surgical strategies with surgeons to reduce this deficit.

Resection to restoration: Assessing the synergy of polypropylene mesh (Marlex®) combined with methyl-methacrylate and latissimus dorsi flap for primary chest wall sarcomas.

BACKGROUND: Chest-wall sarcomas are treated with extensive resections and complex defect reconstruction to restore chest-wall integrity. It is a difficult surgical procedure that incorporates a multidisciplinary approach for the best outcome, preventing paradoxical chest movement issues and reducing complications. OBJECTIVE: We aimed to describe our experience of chest-wall reconstruction using polypropylene mesh (Marlex® Mesh) combined with methyl-methacrylate and soft-tissue coverage with a latissimus dorsi flap following sarcoma resection. PATIENTS AND METHODS: Among the 53 patients treated for primary chest-wall sarcomas at the European Institute of Oncology (IEO) in Milan, Italy, from 1998 to 2020, 14 cases underwent chest-wall resection and reconstruction using polypropylene mesh, methyl-methacrylate and the latissimus dorsi flap. Patients with locally advanced breast cancers, locally advanced lung cancers, squamous cell carcinomas, and other secondary chest-wall malignancies were excluded from the study, as were the patients with different types of chest-wall reconstruction. RESULTS: In this study, 14 patients (6 men and 8 women) with various primary chest-wall sarcomas were enrolled. On an average, 2 ribs (range: 1-5) were removed during the surgeries, and the chest-wall defects ranged from 20 to 150 cm2 with an average size of 73 cm2. The mean follow-up period for these patients was approximately 63.80 months CONCLUSION: The combination of Marlex® mesh filled with methyl-methacrylate and covered using latissimus dorsi myocutaneous flap provides safe, low-cost and effective single-stage chest-wall reconstruction after surgery for primary sarcomas.

Assessment of pulmonary vascular anatomy: comparing augmented reality by holograms versus standard CT images/reconstructions using surgical findings as reference standard.

BACKGROUND: We compared computed tomography (CT) images and holograms (HG) to assess the number of arteries of the lung lobes undergoing lobectomy and assessed easiness in interpretation by radiologists and thoracic surgeons with both techniques. METHODS: Patients scheduled for lobectomy for lung cancer were prospectively included and underwent CT for staging. A patient-specific three-dimensional model was generated and visualized in an augmented reality setting. One radiologist and one thoracic surgeon evaluated CT images and holograms to count lobar arteries, having as reference standard the number of arteries recorded at surgery. The easiness of vessel identification was graded according to a Likert scale. Wilcoxon signed-rank test and κ statistics were used. RESULTS: Fifty-two patients were prospectively included. The two doctors detected the same number of arteries in 44/52 images (85%) and in 51/52 holograms (98%). The mean difference between the number of artery branches detected by surgery and CT images was 0.31 ± 0.98, whereas it was 0.09 ± 0.37 between surgery and HGs (p = 0.433). In particular, the mean difference in the number of arteries detected in the upper lobes was 0.67 ± 1.08 between surgery and CT images and 0.17 ± 0.46 between surgery and holograms (p = 0.029). Both radiologist and surgeon showed a higher agreement for holograms (κ = 0.99) than for CT (κ = 0.81) and found holograms easier to evaluate than CTs (p < 0.001). CONCLUSIONS: Augmented reality by holograms is an effective tool for preoperative vascular anatomy assessment of lungs, especially when evaluating the upper lobes, more prone to anatomical variations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04227444 RELEVANCE STATEMENT: Preoperative evaluation of the lung lobe arteries through augmented reality may help the thoracic surgeons to carefully plan a lobectomy, thus contributing to optimize patients' outcomes. KEY POINTS: • Preoperative assessment of the lung arteries may help surgical planning. • Lung artery detection by augmented reality was more accurate than that by CT images, particularly for the upper lobes. • The assessment of the lung arterial vessels was easier by using holograms than CT images.

Multicentre retrospective analysis on pulmonary metastasectomy: an European perspective.

OBJECTIVES: To assess the current practice of pulmonary metastasectomy at 15 European Centres. Short- and long-term outcomes were analysed. METHODS: Retrospective analysis on patients ≥18 years who underwent curative-intent pulmonary metastasectomy (January 2010 to December 2018). Data were collected on a purpose-built database (REDCap). Exclusion criteria were: previous lung/extrapulmonary metastasectomy, pneumonectomy, non-curative intent and evidence of extrapulmonary recurrence at the time of lung surgery. RESULTS: A total of 1647 patients [mean age 59.5 (standard deviation; SD = 13.1) years; 56.8% males] were included. The most common primary tumour was colorectal adenocarcinoma. The mean disease-free interval was 3.4 (SD = 3.9) years. Relevant comorbidities were observed in 53.8% patients, with a higher prevalence of metabolic disorders (32.3%). Video-assisted thoracic surgery was the chosen approach in 54.9% cases. Wedge resections were the most common operation (67.1%). Lymph node dissection was carried out in 41.4% cases. The median number of resected lesions was 1 (interquartile range 25-75% = 1-2), ranging from 1 to 57. The mean size of the metastases was 18.2 (SD = 14.1) mm, with a mean negative resection margin of 8.9 (SD = 9.4) mm. A R0 resection of all lung metastases was achieved in 95.7% cases. Thirty-day postoperative morbidity was 14.5%, with the most frequent complication being respiratory failure (5.6%). Thirty-day mortality was 0.4%. Five-year overall survival and recurrence-free survival were 62.0% and 29.6%, respectively. CONCLUSIONS: Pulmonary metastasectomy is a low-risk procedure that provides satisfactory oncological outcomes and patient survival. Further research should aim at clarifying the many controversial aspects of its daily clinical practice.

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 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.

Advances in lung cancer surgery: the role of segmentectomy in early-stage management.

INTRODUCTION: The evolving landscape of surgical interventions for early-stage non-small cell lung cancer (NSCLC) necessitates a reassessment of the traditional gold standard of lobectomy versus emerging sublobar resections, prompting this critical narrative review. AREAS COVERED: This review encompasses recent randomized controlled trials, notably JCOG0802/WJOG4607L and CALGB140503, comparing lobectomy and sublobar resections for early-stage NSCLC, focusing on tumor size and recurrence rates. It also discusses the importance of individualized decision-making, future research avenues, and technological advancements in lung cancer surgery. EXPERT OPINION: In this rapidly evolving field, sublobar resections emerge as a viable alternative to lobectomy for tumors smaller than 2 cm in early-stage NSCLC, necessitating precise patient selection and ongoing technological advancements to optimize outcomes.