OBJECTIVES: Since video-assisted thoracic surgery (VATS) was first performed in the early 1990s, there have been many developments, and the conversion rate has decreased over the years. This article highlights the specific outcomes of patients undergoing conversion to thoracotomy despite initially scheduled VATS lung resection. METHODS: We retrospectively reviewed 501 patients who underwent thoracoscopic anatomic lung resection (i.e. lobectomy, segmentectomy or bilobectomy) between 1 January 2012 and 1 August 2017 at our institution. We explored the risk factors for surgical conversion and adverse events occurring in patients who underwent conversion to thoracotomy. RESULTS: A total of 44/501 patients underwent conversion during the procedure (global rate: 8.8%). The main reasons for conversion were (i) anatomical variation, adhesions or unexpected tumour extension (37%), followed by (ii) vascular causes (30%) and (iii) unexpected lymph node invasion (20%). The least common reason for conversion was technical failure (13%). We could not identify any specific risk factors for conversion. The global complication rate was significantly higher in converted patients (40.9%) than in complete VATS patients (16.8%) (P = 0.001). Postoperative atrial fibrillation was a major complication in converted patients (18.2%) [odds ratio (OR) 5.09, 95% confidence interval (CI) 1.80–13.27; P = 0.001]. Perioperative mortality was higher in the conversion group (6.8%) than in the VATS group (0.2%) (OR 33.3, 95% CI 3.4–328; P = 0.003). CONCLUSIONS: Through the years, the global conversion rate has dramatically decreased to <10%. Nevertheless, patients who undergo conversion represent a high-risk population in terms of complications (40.9% vs 16.8%) and perioperative mortality (6.8% vs 0.2%).

Occult micrometastases can be missed by routine pathological analysis. Mapping of the pulmonary lymphatic system by near-infrared (NIR) fluorescence imaging can identify the first lymph node relay. This sentinel lymph node (SLN) can be analyzed by immunohistochemistry (IHC), which may increase micrometastasis detection and improve staging. This study analyzed the feasibility and safety of identifying SLNs in thoracic surgery by NIR fluorescence imaging in non-small cell lung cancer (NSCLC). This was a prospective, observational, single-center study. Eighty adult patients with suspected localized stage NSCLC (IA1 to IIA) were included between December 2020 and May 2022. All patients received an intraoperative injection of indocyanine green (ICG) directly in the peri tumoural area or by electromagnetic navigational bronchoscopy (ENB). The SLN was then assessed using an infrared fluorescence camera. SLN was identified in 60 patients (75%). Among them, 36 SLNs associated with a primary lung tumor were analyzed by IHC. Four of them were invaded by micrometastases (11.1%). In the case of pN0 SLN, the rest of the lymphadenectomy was cancer free. The identification of SLNs in thoracic surgery by NIR fluorescence imaging seems to be a feasible technique for improving pathological staging.

Synthetic 3D multicellular systems derived from patient tumors, or tumoroids, have been developed to complete the cancer research arsenal and overcome the limits of current preclinical models. They aim to represent the molecular and structural heterogeneity of the tumor micro-environment, and its complex network of interactions, with greater accuracy. They are more predictive of clinical outcomes, of adverse events, and of resistance mechanisms. Thus, they increase the success rate of drug development, and help clinicians in their decision-making process. Lung cancer remains amongst the deadliest of diseases, and still requires intensive research. In this review, we analyze the merits and drawbacks of the current preclinical models used in lung cancer research, and the position of tumoroids. The introduction of immune cells and healthy regulatory cells in autologous tumoroid models has enabled their application to most recent therapeutic concepts. The possibility of deriving tumoroids from primary tumors within reasonable time has opened a direct approach to patient-specific features, supporting their future role in precision medicine.

Patient-derived tumoroid (PDT) has been developed and used for anti-drug screening in the last decade. As compared to other existing drug screening models, a PDT-based in vitro 3D cell culture model could preserve the histological and mutational characteristics of their corresponding tumors and mimic the tumor microenvironment. However, few studies have been carried out to improve the microvascular network connecting the PDT and its surrounding microenvironment, knowing that poor tumor-selective drug transport and delivery is one of the major reasons for both the failure of anti-cancer drug screens and resistance in clinical treatment. In this study, we formed vascularized PDTs in six days using multiple cell types which maintain the histopathological features of the original cancer tissue. Furthermore, our results demonstrated a vascular network connecting PDT and its surrounding microenvironment. This fast and promising PDT model opens new perspectives for personalized medicine: this model could easily be used to test all therapeutic treatments and could be connected with a microfluidic device for more accurate drug screening.

In recent years, targeted therapy and immunotherapy have been demonstrated to improve survival in non-operable, non-small cell lung cancer (NSCLC) patients. The results of salvage lung resection in patients with initially unresectable advanced NSCLC after immune checkpoint inhibitor (ICI) or Target Therapy (TT) treatment remain unclear. This study aimed to define the outcomes of patients undergoing salvage surgery in a multi-center real-life setting. An international multicenter retrospective cohort study was conducted. Patients included in the study were judged inoperable, according to a multidisciplinary tumor board decision, before being submitted to ICI or TKI treatment. The rate of complications, the overall survival (OS), and progression-free survival (PFS) were compared. Crude and Multivariable-adjusted analysis were conducted. Nighty-eight patients affected by NSCLC were included in the study. Most patients were female (N = 50-51 %), and the median age at surgery was 62 years. While ICI was performed in 29 patients (30 %), TT was done in 45 (46 %), and ICI plus chemotherapy in 24 (24 %). The inoperability was determined by metastatic disease in 43 cases (44 %), N2-N3 advanced disease in 18 (18 %), local invasiveness in 10 (10 %), a combination of local invasiveness and N-status in 26 (27 %), and other reasons in 1 case (1 %). Overall, the complication rate was 30 %, the mortality rate was 1 %, and the median LOS was 6 days. No residual lung disease (ypT0) was observed in 30 patients (31 %). The 5-year OS was 74 %, while the 5-year PFS was 44 %. Performing sublobar resections was an independent adverse prognostic factor in the multivariable analysis for survival (P < 0.01), while the pathological complete response (pCR) was an independent prognostic predictor of improved survival (P = 0.025). On multivariable analysis performing a sublobar resection (P < 0.01), an increasing ypT stage (P < 0.01), and postoperative therapy (P < 0.01) were independent prognostic predictors, correlating with impaired disease progression. Patients selected for Salvage Surgery after ICI or TT have reasonable post-operative and long-term outcomes. In this context, Salvage Surgery could be proposed in selected patients after a careful multidisciplinary evaluation.