Abstract:Background: We hypothesized that video-assisted thoracic surgery (VATS) lung metastasectomy under non-intubated anesthesia may have a lesser immunological and inflammatory impact than the same procedure under general anesthesia. Methods: Between December 2005 and October 2015, 55 patients with pulmonary oligometastases (at the first episode) successfully underwent VATS metastasectomy under non-intubated anesthesia. Lymphocytes subpopulation and interleukins 6 and 10 were measured at different intervals and matched with a control group composed of 13 patients with similar clinical features who refused non-intubated surgery. Results:The non-intubated group demonstrated a lesser reduction of natural killer lymphocytes at 7 days from the procedure (p = 0.04) compared to control. Furthermore, the group revealed a lesser spillage of interleukin 6 after 1 (p = 0.03), 7 (p = 0.04), and 14 (p = 0.05) days. There was no mortality in any groups. Major morbidity rate was significantly higher in the general anesthesia group 3 (5%) vs. 3 (23%) (p = 0.04). The median hospital stay was 3.0 vs. 3.7 (p = 0.033) days, the estimated costs with the non-intubated procedure was significantly lower, even excluding the hospital stay. Conclusions: VATS lung metastasectomy in non-intubated anesthesia had significantly lesser impact on both immunological and inflammatory response compared to traditional procedure in intubated general anesthesia.

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Introduction: The standard surgical procedures for patients with early-stage NSCLC is lobectomy-associated radical lymphadenectomy performed by using the thoracotomy approach. In the last few years, minimally invasive techniques have increasingly strengthened their role in lung cancer treatment, especially in the early stage of the disease. Although the lobectomy technique has been accepted, controversy still surrounds lymph node dissection. In our study, we analyze the rate of upstaging early non-small cell lung cancer patients who underwent radical surgical treatment using the robotic and the VATS techniques compared to the standard thoracotomy approach.Methods and Materials: We retrospectively reviewed patients who underwent a lobectomy and radical lymphadenectomy at our Institute between 2010 and 2019. We selected 505 patients who met the inclusion criteria of the study: 237 patients underwent robotic surgery, 158 patients had thoracotomy, and 110 patients were treated with VATS. We analyzed the demographic features between the groups as well as the nodal upstaging rate after pathological examination, the number of dissected lymph nodes and the ratio of dissected lymph nodes to metastatic lymph nodes of the three groups.Results: The patients of the three groups were homogenous with respect to age, sex, and histology. The postoperative major morbidity rate was significantly higher in the thoracotomy group, and hospital stay was significantly longer. The percentage of the mediastinal nodal upstaging rate and the number of dissected lymph nodes was significantly higher in the robotic group compared with the VATS group. The ratio of dissected lymph nodes to metastatic lymph nodes was significantly lower compared with the VATS group and the thoracotomy group.Discussion: The prognostic impact of the R(un) status is still highly debated. A surgical approach that allows better results in terms of resection has still not been defined. Our results show that robotic surgery is a safe and feasible approach especially regarding the accuracy of mediastinal lymphadenectomy. These findings can lead to defining a more precise pathological stage of the disease and, if necessary, to more accurate postoperative treatment.

Background: While the thoracotomy approach was considered the gold standard until two decades ago, robotic surgery has increasingly strengthened its role in lung cancer treatment, improving patients’ peri-operative outcomes. In this study, we report our experience in robotic lobectomy for early-stage non-small cell lung cancer, with particular attention to oncological outcomes and nodal upstaging rate. Methods: We retrospectively reviewed patients who underwent lobectomy and radical lymphadenectomy at our Institute between 2016 and 2020. We selected 299 patients who met the inclusion criteria of the study. We analyzed the demographic features of the groups as well as their nodal upstaging rate after pathological examination. Then, we analyzed disease-free and overall survival of the entire enrolled patient population and we compared the same oncological outcomes in the upstaging and the non-upstaging group. Results: A total of 299 patients who underwent robotic lobectomy were enrolled. After surgery, 55 patients reported nodal hilar or mediastinal upstaging. The 3-year overall survival of the entire population was 82.8%. The upstaging group and the non-upstaging group were homogeneous for age, gender, smoking habits, clinical stage, tumor site, tumor histology. The non-upstaging group had better OS (p = 0.004) and DFS (p < 0.0001). Conclusion: Our results show that robotic surgery is a safe and feasible approach for the treatment of early-stage NSCLC, especially for its accuracy in mediastinal lymphadenectomy. The oncological outcomes were encouraging and consistent with previous findings.

The approval of osimertinib for adjuvant treatment of stage I–II–III EGFR-mutated NSCLC (early stage) represents a paradigm shift, raising the question of whether other genotype-matched therapeutics approved for advanced-stage NSCLC can also provide clinical benefit in the adjuvant setting. However, there is a paucity of real-world data on the prevalence of actionable genomic alterations (GAs) in early-stage NSCLC. We used next-generation sequencing, complemented by immunohistochemistry and fluorescence in situ hybridization, to screen our single-institution cohort of 1961 NSCLC consecutive cases for actionable molecular targets. The prevalence of actionable GAs was comparable in early versus advanced-stage NSCLC, the only exception being KRAS mutations (more frequent in early-stage cases). Consistent with advanced-stage tumors being more aggressive, co-occurrence of TP53 and EGFR GAs as well as copy number gains were less frequent in early-stage tumors. EGFR mutations and high expression of PD-L1 were inversely associated, whereas KRAS mutations and high PD-L1 reactivity showed positive association. Recapitulating advanced-stage tumors, early-stage NSCLC had the highest share of EGFR mutations in lepidic and acinar subtypes. Resected lepidic tumors contained the highest proportion of the KRAS G12C actionable variant. These results, obtained with routine diagnostic technologies in an unselected clinical setting, provide a significant addition of real-world data in early-stage NSCLC.

Next-generation sequencing has become a cornerstone in clinical oncology practice and is recommended for the appropriate use of tailored therapies in NSCLC. While NGS has already been standardised in advanced-stage NSCLC, its use is still uncommon in the early stages. The recent approval of Osimertinib for resected EGFR-mutated NSCLC in an adjuvant setting has launched the hypothesis that other targeted therapies used in metastatic patients can also lead to improved early-stage outcomes of NSCLC. The impact of molecular biomarkers on the prognosis of patients undergoing radical surgery for NSCLC is still unclear. Notably, the heterogeneous populations included in the studies that analysed surgical patients could be the main reason for these results. In this review, we report the most important studies that analysed the impact of principal molecular biomarkers on the survival outcomes of patients who underwent radical surgery for NSCLC.

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Objective To investigate risk factors for nodal upstaging in patients with lung carcinoids and to understand which type of lymphadenectomy is most appropriate. Methods Data regarding patients with lung carcinoids, who underwent surgical resection and lymphadenectomy in five institutions from January 1, 2005 to December 31, 2019, were collected and retrospectively analyzed. Clinical and pathological tumor characteristics were correlated to analyze lymph node upstaging. Results The analysis was conducted on 283 patients. Pathology showed 230 typical and 53 atypical carcinoids. Nodal and mediastinal upstaging occurred in 33 (11.6%) and 16 (5.6%) patients, respectively. At the univariable analysis, nodal upstaging was significantly correlated with central location (p = 0.003), atypical histology (p < 0.001), pT dimension (p = 0.004), and advanced age (p = 0.043). The multivariable analysis confirmed atypical histology (odds ratio [OR]: 11.030; 95% confidence interval [CI]: 4.837−25.153, p < 0.001) and central location (OR: 3.295; 95% CI: 1.440−7.540, p = 0.005) as independent prognostic factors for nodal upstaging. Atypical histology (p < 0.001), pT dimension (p = 0.036), number of harvested lymph node stations (p = 0.047), and type of lymphadenectomy (p < 0.001) correlated significantly with mediastinal upstaging. The multivariable analysis confirmed atypical histology (OR: 5.408; 95% CI: 1.391−21.020, p = 0.015) and pT (OR: 1.052; 95% CI: 1.021−1.084, p = 0.001) as independent prognostic factors. Conclusion Atypical histology, dimension, and central location are associated with a high‐risk for occult hilo‐mediastinal metastases, and mediastinal radical dissection may predict nodal upstaging. Thus, we suggest radical mediastinal lymph node dissection in high‐risk tumors, reserving sampling, or lobe‐specific dissection in peripheral, small typical carcinoids.