Clonally expanded EOMES+ Tr1-like cells in primary and metastatic tumors are associated with disease progression.

Regulatory T (Treg) cells are a barrier for tumor immunity and a target for immunotherapy. Using single-cell transcriptomics, we found that CD4+ T cells infiltrating primary and metastatic colorectal cancer and non-small-cell lung cancer are highly enriched for two subsets of comparable size and suppressor function comprising forkhead box protein P3+ Treg and eomesodermin homolog (EOMES)+ type 1 regulatory T (Tr1)-like cells also expressing granzyme K and chitinase-3-like protein 2. EOMES+ Tr1-like cells, but not Treg cells, were clonally related to effector T cells and were clonally expanded in primary and metastatic tumors, which is consistent with their proliferation and differentiation in situ. Using chitinase-3-like protein 2 as a subset signature, we found that the EOMES+ Tr1-like subset correlates with disease progression but is also associated with response to programmed cell death protein 1-targeted immunotherapy. Collectively, these findings highlight the heterogeneity of Treg cells that accumulate in primary tumors and metastases and identify a new prospective target for cancer immunotherapy.

Independent expression of circulating and tissue levels of PD-L1: correlation of clusters with tumor metabolism and outcome in patients with non-small cell lung cancer.

PURPOSE: To evaluate the clinical-pathological and prognostic significance of the circulating PD-L1 level in patients with surgically treated NSCLC, by combining data for PD-L1 expression with other immune-related markers and tumor metabolism. METHODS: Overall, 40 patients with resected NSCLC (stage Ia-IIIa) who had preoperative blood storage and underwent staging PET/CT were enrolled for the study. In all cases, we determined plasma levels of PD-L1 (pg/ml), immune-reactive areas (IRA %) covered by CD3, CD68, CD20, CD8, PD-1, and PD-L1 in the tumor specimen, and metabolic parameters on PET, i.e., SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Variables were statistically analyzed to establish their association with disease-free survival (DFS). RESULTS: The circulating levels of PD-L1 in the bloodstream could be determined in 38/40 (95%) samples. The mean and median expression levels were 34.86 pg/ml and 24.83 pg/ml, respectively. We did not find any statistically significant correlation between circulating PD-L1 and tissue expression of PD-L1/PD-1. Some mild degree of positive correlation was determined between tissue PD-L1 and SUVmax (ρ = 0.390; p = 0.0148). Hierarchical clustering combining circulating, tissue, and metabolic parameters identified clusters with high metabolic tumor burden or high expression of plasma PD-L1 levels (Z score ≥ 2) as having a poor DFS (p = 0.033). The multivariate analysis detected stage and metabolism (i.e., SUVmax and SUVpeak) as independent prognostic factors for DFS. CONCLUSION: Plasma levels of PD-L1 are independent of the expression of PD-1/PD-L1 in NSCLC tumor tissue and, when combined with other clinical-pathological parameters, allow for the identification of clusters with different outcomes.

Bronchopulmonary Carcinoids causing Cushing Syndrome: Results from a Multicentric Study Suggesting a More Aggressive Behavior.

OBJECTIVE: Cushing syndrome (CS) caused by bronchopulmonary carcinoids (BCs) is a very rare entity. The aim of this study was to revisit the features of a multicenter clinical series to identify significant prognostic factors. METHODS: From January 2002 to December 2013, the clinical and pathological data of 23 patients (treated in five different institutions) were retrospectively reviewed. Survival analysis was performed to explore the relative weight of potential prognostic factors. RESULTS: Median age and male/female ratio were 48 years and 14/9, respectively. Most (> 80%) of the patients presented with CS-related symptoms at diagnosis. Tumor location was peripheral in 13 patients (57%) and central in 10 (43%). All patients but two (treated with chemotherapy) underwent surgical resection with curative intent. Definitive cyto/histology was indicative of typical carcinoid (TC) in 16 cases (70%) and atypical carcinoid (AC) in 7 cases (30%). A complete remission of CS was obtained in 16 cases (70%). Lymph nodal involvement was detected in 11 cases (48%), with N2 disease occurring in 7 (∼ 30% of all cases). Four patients (22%) experienced a relapse of the disease after radical surgery. Overall 5-year survival (long-term survival, LTS) was 60%, better in TCs when compared with AC (LTS: 66 v s. 48%, p = 0.28). Log-rank analysis identified ECOG performance status, cTNM and cN staging, pTNM and pN staging, persistence of CS and relapses (local p = 0.006; distant p = 0.001) as significant prognostic factors in this cohort of patients. CONCLUSION: BCs causing CS are characterized by a high rate of lymph-nodal involvement, a suboptimal prognosis (5-year survival = 60%, 66% in TCs) and a remarkable risk of relapse even after radical resection. Advanced stage, lymph-nodal involvement and the persisting of the CS after treatment correlate with a poor prognosis.

The Smokers Health Multiple ACtions (SMAC-1) Trial: Study Design and Results of the Baseline Round.

BACKGROUND: Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer deaths. Even more so, it is a key risk factor for many other cancers and cardiovascular and pulmonary diseases. The Smokers health Multiple ACtions (SMAC-1) trial aimed to demonstrate the feasibility and effectiveness of an integrated program based on the early detection of smoking-related thoraco-cardiovascular diseases in high-risk subjects, combined with primary prevention. A new multi-component screening design was utilized to strengthen the framework on conventional lung cancer screening programs. We report here the study design and the results from our baseline round, focusing on oncological findings. METHODS: High-risk subjects were defined as being >55 years of age and active smokers or formers who had quit within 15 years (>30 pack/y). A PLCOm2012 threshold >2% was chosen. Subject outreach was streamlined through media campaign and general practitioners' engagement. Eligible subjects, upon written informed consent, underwent a psychology consultation, blood sample collection, self-evaluation questionnaire, spirometry, and LDCT scan. Blood samples were analyzed for pentraxin-3 protein levels, interleukins, microRNA, and circulating tumor cells. Cardiovascular risk assessment and coronary artery calcium (CAC) scoring were performed. Direct and indirect costs were analyzed focusing on the incremental cost-effectiveness ratio per quality-adjusted life years gained in different scenarios. Personalized screening time-intervals were determined using the "Maisonneuve risk re-calculation model", and a threshold <0.6% was chosen for the biennial round. RESULTS: In total, 3228 subjects were willing to be enrolled. Out of 1654 eligible subjects, 1112 participated. The mean age was 64 years (M/F 62/38%), with a mean PLCOm2012 of 5.6%. Former and active smokers represented 23% and 77% of the subjects, respectively. At least one nodule was identified in 348 subjects. LDCTs showed no clinically significant findings in 762 subjects (69%); thus, they were referred for annual/biennial LDCTs based on the Maisonneuve risk (mean value = 0.44%). Lung nodule active surveillance was indicated for 122 subjects (11%). Forty-four subjects with baseline suspicious nodules underwent a PET-FDG and twenty-seven a CT-guided lung biopsy. Finally, a total of 32 cancers were diagnosed, of which 30 were lung cancers (2.7%) and 2 were extrapulmonary cancers (malignant pleural mesothelioma and thymoma). Finally, 25 subjects underwent lung surgery (2.25%). Importantly, there were zero false positives and two false negatives with CT-guided biopsy, of which the patients were operated on with no stage shift. The final pathology included lung adenocarcinomas (69%), squamous cell carcinomas (10%), and others (21%). Pathological staging showed 14 stage I (47%) and 16 stage II-IV (53%) cancers. CONCLUSIONS: LDCTs continue to confirm their efficacy in safely detecting early-stage lung cancer in high-risk subjects, with a negligible risk of false-positive results. Re-calculating the risk of developing lung cancer after baseline LDCTs with the Maisonneuve model allows us to optimize time intervals to subsequent screening. The Smokers health Multiple ACtions (SMAC-1) trial offers solid support for policy assessments by policymakers. We trust that this will help in developing guidelines for the large-scale implementation of lung cancer screening, paving the way for better outcomes for lung cancer patients.

Robotic thymectomy in thymic tumours: a multicentre, nation-wide study.

OBJECTIVES: Robotic thymectomy has been suggested and considered technically feasible for thymic tumours. However, because of small-sample series and the lack of data on long-term results, controversies still exist on surgical and oncological results with this approach. We performed a large national multicentre study sought to evaluate the early and long-term outcomes after robot-assisted thoracoscopic thymectomy in thymic epithelial tumours. METHODS: All patients with thymic epithelial tumours operated through a robotic thoracoscopic approach between 2002 and 2022 from 15 Italian centres were enrolled. Demographic characteristics, clinical, intraoperative, postoperative, pathological and follow-up data were retrospectively collected and reviewed. RESULTS: There were 669 patients (307 men and 362 women), 312 (46.6%) of whom had associated myasthenia gravis. Complete thymectomy was performed in 657 (98%) cases and in 57 (8.5%) patients resection of other structures was necessary, with a R0 resection in all but 9 patients (98.6%). Twenty-three patients (3.4%) needed open conversion, but no perioperative mortality occurred. Fifty-one patients (7.7%) had postoperative complications. The median diameter of tumour resected was 4 cm (interquartile range 3-5.5 cm), and Masaoka stage was stage I in 39.8% of patients, stage II in 56.1%, stage III in 3.5% and stage IV in 0.6%. Thymoma was observed in 90.2% of patients while thymic carcinoma occurred in 2.8% of cases. At the end of the follow-up, only 2 patients died for tumour-related causes. Five- and ten-year recurrence rates were 7.4% and 8.3%, respectively. CONCLUSIONS: Through the largest collection of robotic thymectomy for thymic epithelial tumours we demonstrated that robot-enhanced thoracoscopic thymectomy is a technically sound and safe procedure with a low complication rate and optimal oncological outcomes.

Lung Cancer Screening: The European Perspective.

Several randomized and observational studies on lung cancer screening held in Europe significantly contributed to the knowledge on low-dose computed tomography screening targets in high-risk individuals with smoking history and older than 50 years. In particular, steps forward have been made in the field of risk modeling, screening interval, diagnostic protocol with volumetry, optimization, overdiagnosis estimation, oncological outcome, oncological risk due to radiation exposure, recruitment, and communication strategy.

Prolonged air leak after robotic lung resection: a narrative review.

Background and Objective: Prolonged air leak (PAL) following lung resection is related to an increase in morbidity and both direct and indirect costs. In recent years, robotic-assisted thoracic surgery (RATS) has proved to be a safe technique with comparable perioperative outcomes of video-assisted thoracic surgery (VATS), optimal oncological results, and potential advantages in case of sublobar resection. We here focus on the incidence and clinical impact of PAL in the field of robotic surgery and discuss the therapeutic strategies currently available. Methods: We conducted a search on PubMed/MEDLINE and Scopus database from inception until May 27th 2022 to select the relevant literature published in English exploring the occurrence of PAL following RATS. Key Content and Findings: The implementation of robotic surgery led to a significant reduction in PAL occurrence after pulmonary resection compared to open thoracotomy, while there is still no clear advantage with respect to VATS. However, the enhanced dexterity and improved visualization of the robot seem to particularly valuable in case of sublobar lung resection, especially complex ones. Accurate selection of patients based on the presence of risk factors allows the implementation of intraoperative measures in order to reduce the occurrence of PAL. Conclusions: Robotic lung resection is a safe technique, advantageous compared to traditional open thoracotomy in terms of PAL occurrence reduction and it is a valid alternative to manual VATS. Moreover, with the extension of indications for sublobar resection in the treatment of early stage lung cancer, RATS may prove to be the technique of choice thanks to its intrinsic advantages.

A Risk Model to Predict the Delivery of Adjuvant Chemotherapy Following Lung Resection in Patients With Pathologically Positive Lymph Nodes.

To investigate factors associated with the ability to receive adjuvant chemotherapy in patients with pathological N1 and N2 stage after anatomic lung resections for non-small cell lung cancer (NSCLC). Multicenter retrospective analysis on 707 consecutive patients found pathologic N1 (pN1) or N2 (pN2) disease following anatomic lung resections for NSCLC (2014-2019). Multiple imputation logistic regression was used to identify factors associated with adjuvant chemotherapy and to develop a model to predict the probability of starting this treatment. The model was externally validated in a population of 253 patients. In the derivation set, 442 patients were pN1 and 265 pN2. 58% received at least 1 cycle of adjuvant chemotherapy. The variables significantly associated with the probability of starting chemotherapy after multivariable regression analysis were: younger age (p < 0.0001), Body Mass Index (BMI) (p = 0.031), Forced Expiratory Volume in 1 second (FEV1) (p = 0.037), better performance status (PS) (p < 0.0001), absence of chronic kidney disease (CKD) (p = 0.016), resection lesser than pneumonectomy (p = 0.010). The logit of the prediction model was: 6.58 -0.112 x age +0.039 x BMI +0.009 x FEV1 -0.650 x PS -1.388 x CKD -0.550 x pneumonectomy. The predicted rate of adjuvant chemotherapy in the validation set was 59.2 and similar to the observed 1 (59%, p = 0.87) confirming the model performance in external setting. This study identified several factors associated with the probability of initiating adjuvant chemotherapy after lung resection in node-positive patients. This information can be used during preoperative multidisciplinary meetings and patients counseling to support decision-making process regarding the timing of systemic treatment.

Mitral Valve Systolic Anterior Motion in Robotic Thoracic Surgery as the Cause of Unexplained Hemodynamic Shock: From a Case Report to Recommendations.

Robotic major lung resection for lung cancer carries a risk for intraoperative hemodynamic instability. Systolic anterior motion (SAM) of the mitral valve is a rare and often misrecognized cause of intraoperative hemodynamic instability. If not promptly recognized, SAM leads to a complicated perioperative course. Here, we report for the first time a case of a patient with SAM with a severe degree of left ventricular outflow obstruction (LVOTO) undergoing robotic lung lobectomy and its challenging intraoperative management. A 70-year-old man undergoing robotic left upper lobectomy developed immediately after the induction of general anesthesia hemodynamic instability due to SAM-related LVOTO. The diagnosis was possible, thanks to the use of transesophageal echocardiography (TEE). The treatment strategies applied were preload optimization without fluid overload, ultra-short-acting beta-blockers, and vasopressors. Peripheral nerve blockades were preferred over epidural analgesia to avoid vasodilatation. The patient reported a good quality of recovery and no pain the day after surgery. The management of patients with higher risk of SAM and LVOTO development during robotic thoracic surgery requires a dedicated and skilled team together with high-impact treatment strategies driven by TEE. Since current guidelines do not recommend the use of TEE, even for patients with higher cardiac risk undergoing noncardiac surgery, the present case report may stimulate interest in future recommendations.

Venoarterial Extracorporeal Membrane Oxygenation Support in Lung Cancer Resection.

Cardiovascular comorbidities often prevent patients with otherwise resectable early-stage lung cancer from undergoing surgery due to prohibitive perioperative risk. Here we describe the intraoperative use of venoarterial (VA) extracorporeal membrane oxygenation in a stage cIIA lung cancer patient with arterial infiltration and severe postischemic dilated cardiomyopathy (ejection fraction, 0.23) undergoing left upper lobectomy with pulmonary artery angioplasty. Providing intraoperative cardiovascular and respiratory function support, venoarterial extracorporeal membrane oxygenation represents a suitable option for patients with heart failure, ensuring an adequate hemodynamic profile and reducing the risk of complications. Thus, these otherwise inoperable patients can be offered a potentially curative surgical resection of the malignancy.

Surgical and Oncological Outcomes of En-Bloc Resection for Malignancies Invading the Thoracic Spine.

OBJECTIVE(S): There is still limited data in the literature concerning the survival of patients with tumors of the thoracic spine. In this study, we analyzed clinical features, perioperative and long-term outcomes in patients who underwent vertebrectomy for cancer. Furthermore, we evaluated the survival and surgical complications. METHODS: We retrospectively reviewed all cases of thoracic spinal tumors treated by the same team between 1998 and 2018. We divided them into three groups according to type of tumor (primary vertebral, primary lung and metastases) and compared outcomes. For each patient, Overall Survival (OS) and Cumulative Incidence of Relapse (CIR) were estimated. Complications and survival were analyzed using a logistic model. RESULTS: Seventy-two patients underwent thoracic spine surgery (40 in group 1, 16 in each group 2 and 3). Thirty patients died at the end of the observation at a mean follow up time of 60 months (41%). The 5-year overall survival was 72% (95% CI: 0.52-0.84), 20% (95% CI: 0.05-0.43) and 27% (95% CI: 0.05-0.56) for each group, respectively. CIR of group 3 was higher (HR 2.57, 95% CI: 1.22-5.45, p = 0.013). The logistic model revealed that age was related to complications (p = 0.04), while surgery for a type 3 tumor was related to mortality (p = 0.02). CONCLUSIONS: Although the cohort size was limited, primary vertebral tumors displayed the best 5-y-OS with an acceptable complications rate. The indication of surgery should be advised by a multidisciplinary team and only for selected cases. Finally, the use of a combined approach does not increase the risk of complications.

Overview of the outcomes of robotic segmentectomy and lobectomy.

Segmentectomy has gained popularity in the latest years as a valid alternative to lobectomy. Initially reserved to patient unfit for lobar lung resection, this procedure is now offered also in selected patient with <2 cm peripheral lung cancer confined to an anatomic segment with no nodal involvement on preoperative evaluation. The introduction of screening with low-dose CT chest scan allowed the identification of lung cancer at early stages, making possible to schedule a more conservative lung surgery. A major improvement came also from minimally invasive surgery (MIS), reducing complication rate with comparable survival rates when compared to open surgery. However, due to long learning curve and uncomfortable instruments handling of video-assisted thoracoscopy, many surgeons still prefer to perform segmentectomies through a thoracotomy and thus increasing perioperative morbidity and leading to post-thoracotomy syndrome due to rib-spreading. Robotic assisted thoracic surgery (RATS) can avoid this throwback, combining the handling of open surgery with lesser invasiveness of thoracoscopy. Although literature has given strong evidences in favour of robotic lobectomies, data are still limited regarding segmentectomies performed with this technique. Moreover, no results are still available from the two ongoing randomized controlled trials comparing segmentectomy to lobectomy and so the latter represent the oncologically proper procedure for lung cancer along with lymph-node dissection. In this review we analyse the literature currently available on outcomes of lobar and sublobar anatomical resection performed by RATS, with a brief mention of the existing surgical techniques of port positioning and the costs of this procedure.

Lung cancer screening: who pays? Who receives? The European perspectives.

Lung cancer is the leading cause of cancer-related death worldwide, and its early detection is critical to achieving a curative treatment and to reducing mortality. Low-dose computed tomography (LDCT) is a highly sensitive technique for detecting noninvasive small lung tumors in high-risk populations. We here analyze the current status of lung cancer screening (LCS) from a European point of view. With economic burden of health care in most European countries resting on the state, it is important to reduce costs of screening and improve its effectiveness. Current cost-effectiveness analyses on LCS have indicated a favorable economic profile. The most recently published analysis reported an incremental cost-effectiveness ratio (ICER) of €3,297 per 1 life-year gained adjusted for the quality of life (QALY) and €2,944 per life-year gained, demonstrating a 90% probability of ICER being below €15,000 and a 98.1% probability of being below €25,000. Different risk models have been used to identify the target population; among these, the PLCOM2012 in particular allows for the selection of the population to be screened with high sensitivity. Risk models should also be employed to define screening intervals, which can reduce the general number of LDCT scans after the baseline round. Future perspectives of screening in a European scenario are related to the will of the policy makers to implement policy on a large scale and to improve the effectiveness of a broad screening of smoking-related disease, including cardiovascular prevention, by measuring coronary calcium score on LDCT. The employment of artificial intelligence (AI) in imaging interpretation, the use of liquid biopsies for the characterization of CT-detected undetermined nodules, and less invasive, personalized surgical treatments, will improve the effectiveness of LCS.

Endoscopic Lipofilling for the Treatment of Bronchopleural Fistulas After Anatomic Lung Resection.

A bronchopleural fistula is a potentially fatal complication of anatomic lung resection surgery. Bronchoscopy has been described in the treatment of small-caliber fistulas. An endoscopic procedure based on instillation of mesenchymal stem cells for the treatment of bronchopleural fistula has recently been successful. Fat tissue is rich in mesenchymal stem cells, and we describe a technique based on the instillation of autologous fat (lipofilling) for the treatment of bronchopleural fistulas. The procedure was applied to 8 subjects affected by bronchopleural fistulas that were greater than 8 mm in diameter, and saw resolution in all cases.

Multi-Step Combined Upfront Surgery for Locally Advanced Paravertebral Sarcoma: A Case Report.

Background: Paravertebral localization of primary undifferentiated pleomorphic sarcoma (UPS) with bone and vascular involvement is infrequent and challenging. Multi-step surgical procedure has been described as a feasible and effective option to achieve sustained local tumor control. Methods: We report on a 62-year old man with paravertebral UPS infiltrating the aortic wall and the 9th thoracic vertebra who underwent a multi-step surgical procedure aimed at achieving oncologic radicality through a coordinated effort between thoracic, vascular and spinal surgeons. After balancing the risks and benefits of perioperative therapies, upfront surgery was performed including aortic resection with bypass grafting followed by a triple en bloc vertebrectomy with tumor excision. Mid-term follow-up (22 months) is then provided. Results: The combined procedure achieved oncological radicality and no local recurrence in the mid-term. No major complications occurred. Conclusions: Multi-step and multi-specialty surgery is a feasible and effective strategy to treat primary UPS in unfavorable localization. A strategic cooperation between surgeons and a multidisciplinary tumor board is required to define an optimal, personalized treatment strategy in sarcoma patients.

Subpopulations of Circulating Cells with Morphological Features of Malignancy Are Preoperatively Detected and Have Differential Prognostic Significance in Non-Small Cell Lung Cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) frequently presents when surgical intervention is no longer feasible. Despite local treatment with curative intent, patients might experience disease recurrence. In this context, accurate non-invasive biomarkers are urgently needed. We report the results of a pilot study on the diagnostic and prognostic role of circulating tumor cells (CTCs) in operable NSCLC. METHODS: Blood samples collected from healthy volunteers (n = 10), nodule-negative high-risk individuals enrolled in a screening program (n = 7), and NSCLC patients (n = 74) before surgery were analyzed (4 mL) for the presence of cells with morphological features of malignancy enriched through the ISET® technology. RESULTS: CTC detection was 60% in patients, while no target cells were found in lung cancer-free donors. We identified single CTCs (sCTC, 46%) and clusters of CTCs and leukocytes (heterotypic clusters, hetCLU, 31%). The prevalence of sCTC (sCTC/4 mL ≥ 2) or the presence of hetCLU predicted the risk of disease recurrence within the cohort of early-stage (I-II, n = 52) or advanced stage cases (III-IVA, n = 22), respectively, while other tumor-related factors did not inform prognosis. CONCLUSIONS: Cancer cell hematogenous dissemination occurs frequently in patients with NSCLC without clinical evidence of distant metastases, laying the foundation for the application of cell-based tests in screening programs. CTC subpopulations are fine prognostic classifiers whose clinical validity should be further investigated in larger studies.

Quality of Life, Postoperative Pain, and Lymph Node Dissection in a Robotic Approach Compared to VATS and OPEN for Early Stage Lung Cancer.

We compare the perioperative course, postoperative pain, and quality-of-life (QOL) in patients undergoing anatomic resections of early-stage lung cancer by means of robotic surgery (RATS), video-assisted thoracic surgery (VATS), or muscle-sparing thoracotomy (OPEN); 169 consecutive patients with known/suspected lung cancer, candidates to anatomic resection, were enrolled in a single-center prospective study from April 2016 to December 2018. EORTC QLQ-C30 and QLQ-LC13 scores were obtained preoperatively and, at three time points, postoperatively. RATS and VATS groups were matched for ASA scores, while RATS and open surgery were matched for gender, ASA score, cancer stage, and tumor size; 58 patients underwent open surgery, 58 had VATS, and 53 had RATS. Hospital stay was shorter after RATS than OPEN (median 4.5 versus 5; p = 0.047). Comparing matched RATS and VATS groups, the number of hilar lymph nodes and nodal stations removed was significantly higher in the former approach (p = 0.01 vs. p < 0.0001); conversely, pain at 2 weeks was slightly lower after VATS (p = 0.004). No significant difference was observed in conversions, complications, duration of surgery, and postoperative hospitalization. The robotic approach was superior to OPEN in terms of QOL, pain, and length of postoperative stay and showed improved lymph node dissection compared to VATS.

Perioperative Outcome of Robotic Approach Versus Manual Videothoracoscopic Major Resection in Patients Affected by Early Lung Cancer: Results of a Randomized Multicentric Study (ROMAN Study).

INTRODUCTION: We report the results of the first prospective international randomized control trial to compare the perioperative outcome and surgical radicality of the robotic approach with those of traditional video-assisted surgery in the treatment of early-stage lung cancer. METHODS: Patients with clinical stage T1-T2, N0-N1 non-small cell lung cancer (NSCLC) were randomly assigned to robotic-assisted thoracoscopic surgery (RATS) or video-assisted thoracic surgery (VATS) resection arms. The primary objective was the incidence of adverse events including complications and conversion to thoracotomy. The secondary objectives included extent of lymph node (LN) dissection and other indicators. RESULTS: This trial was closed at 83 cases as the probability of concluding in favor of the robot arm for the primary outcome was null according to the observed trend. In this study, we report the results of the analysis conducted on the patients enrolled until trial suspension. Thirty-nine cases were randomized in the VATS arm and 38 in the robotic arm. Six patients were excluded from analysis. Despite finding no difference between the two arms in perioperative complications, conversions, duration of surgery, or duration of postoperative stay, a significantly greater degree of LN assessment by the robotic technique was observed in regards to the median number of sampled LN stations [6, interquartile range (IQR) 4-6 vs. 4, IQR 3-5; p = 0.0002], hilar LNs (7, IQR 5-10 vs. 4, IQR 2-7; p = 0.0003), and mediastinal LNs (7, IQR 5-10 vs. 5, IQR 3-7; p = 0.0001). CONCLUSIONS: The results of this trial demonstrated that RATS was not superior to VATS considering the perioperative outcome for early-stage NSCLC, but the robotic approach allowed an improvement of LN dissection. Further studies are suggested to validate the results of this trial. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT02804893.

Distinguishing multiple lung primaries from intra-pulmonary metastases and treatment implications.

INTRODUCTION: The distinction between multiple primary lung cancers and intra-pulmonary metastases has been extensively investigated because of its important clinical and therapeutic implications. AREAS COVERED: Rapidly improving imaging technology and genomic analysis has led to a finer discrimination between multiple primary lung tumors and pulmonary metastases. However, over the past few decades, standardized criteria for the identification of multiple lung tumors have been lacking. Therefore, in 2017 a multidisciplinary international committee composed of the Union for International Cancer Control (UICC), American Joint Committee on Cancer (AJCC) and International Association for the Study of Lung Cancer (IASLC) addressed this problem when drawing up the 8th edition of TMN stage classification, that now represents a specific consensus on this topic. The most advanced diagnostic strategies associated with screening allow for the detection of early stage synchronous lung cancers. EXPERT OPINION: Although diagnostic confirmation relies on pathologic and clinical examination, new molecular analyses help in the discrimination between primary and secondary tumors. The treatment of multiple primary lung tumors remains, whenever possible, a local treatment based on surgical resection, providing the absence of distant or local (lymph node) metastases.