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.

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.

Anastomosis Complications after Bronchoplasty: Incidence, Risk Factors, and Treatment Options Reported by a Referral Cancer Center.

BACKGROUND: Sleeve lobectomy with bronchoplasty is a safe surgical technique for the management of lung cancer and endobronchial localization of extrapulmonary cancers. However, anastomotic complications can occur, and treatment strategies are not standardized. METHODS: Data from 280 patients subjected to bronchoplasty were retrospectively analyzed, focusing on surgical techniques, anastomotic complications, and their management. Multivariate analysis was performed, and Kaplan-Meier curves were used to determine survival. RESULTS: Ninety percent of 280 surgeries were for lung cancer. Anastomotic complications occurred in 6.42% of patients: late stenosis in 3.92% and broncho-pleural fistula in 1.78%. The median survival was 65.90 months (95% CI = 41.76-90.97), with no difference (p = 0.375) for patients with (51.28 months) or without (71.03 months) anastomotic complications. Mortality at 30 days was higher with anastomotic complications (16.7% vs. 3%, p = 0.014). Multivariable analysis confirmed pathological stage (N+) as a risk factor for anastomotic complications (p = 0.016). Our mortality (3.93%) and morbidity rate (41.78%) corresponded to recent series results. CONCLUSIONS: In our experience, surgery is preferred to avoid life-threatening complications in bronchopleural fistulas. Bronchoscopic balloon dilatation is preferred for benign strictures. The nodal stage is related to complications (p = 0.0014), reflecting the aggressiveness of surgery, which requires extended radical lymphadenectomy.

Predictors, surrogate, and patient-reported outcomes in immunotherapy and salvage surgery for unresectable lung cancer: a single-center retrospective study.

Medical treatment has changed drastically in recent years, especially for advanced stages of non-small-cell lung cancer (NSCLC), for which the development of immunotherapy and molecular targeted therapy significantly increased survival and quality of life. This single-center retrospective study aimed to analyze the outcome predictors, the surrogate outcomes, and the patient-reported outcomes after neoadjuvant immunotherapy for initially unresectable NSCLC. Patients affected by an initially unresectable NSCLC and identified between March 2014 and December 2021 who received immunotherapy alone or in combination with platinum-based chemotherapy and/or radiotherapy were collected. Overall survival (OS) and disease-free survival (DFS) were estimated according to the Kaplan-Meier method. Patient-reported outcomes were recorded using the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life (QoL) Group questionnaire-Lung Cancer 29 Module to compare differences in symptoms and QoL at two different times, 30 days and 1 year after surgery. Surgical, pathological records, and patient-reported outcomes (at 30 days and 1 year after surgery) were reviewed. Complete pathological remission was achieved in 7 patients (36.8%) and major pathological remission in 3 patients (15.7%). The median overall survival in the study group is 19 months (range: 2-57.4). Of 19 patients, 16 (84.2%) are alive to date, of which 2 (10.5%) have a local recurrence. At 30 days from surgery, the main symptoms reported by EORTC Module were coughing, shortness of breath, the side effect of treatment, fear of progression, and surgery-related problems. Induction immunotherapy with or without chemotherapy can be considered for unresectable locally advanced NSCLC, and after the downstaging, the possibility of surgery could be re-evaluated in a multidisciplinary setting with high rates of R0 resection. In this selected and highly motivated group of patients, the QoL and symptoms after salvage surgeries are acceptable and even better than those reported in the literature.

Diagnostic Performance and Cell Count of EBUS-TBNA Needle Gauges: A Prospective Trial.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic procedure for evaluating hilar and mediastinal lymphadenopathies and is the gold standard for lung cancer diagnosis and staging. Recent studies assessed the effectiveness of the 19-G flex needle in obtaining larger EBUS-TBNA samples, and prospective small series gave similar results in terms of diagnostic yield when testing different gauge needles. The lack of homogeneity between series and the small sample size of some prospective cohorts poses a limit to the validity of those results. This prospective controlled study compared the 19-G flex and 22-G needles in terms of diagnostic yield. An objective laboratory method was used to count cells and compare the two needles' cytologic yields. MATERIAL: A prospective controlled study was conducted on 90 patients undergoing EBUS-TBNA for the diagnosis of hilar and mediastinal lymphadenopathies. The institutional ethic committee (IEO573) approved the study, and informed consent was obtained from all patients. RESULTS: A total of 90 patients were enrolled in this study, 84.4% of whom were diagnosed with malignancy and 15.6% with non-neoplastic disease. Sensitivity for malignancy was 93.4% (CI: 87.4-97.1%) for the 19-G needle and 92.6% (CI: 86.3-96.5%) for the 22-G needle (p = 0.80). The percentage of malignant cells in the cell block was 63.9% and 61.5% for the 22-G and 19-G needles, respectively. The cell count assessed by flow cytometry was 2071 cells/µL (IQR: 600,2265) with the 22-G needle and 2761 cells/µL (IQR: 505,3250) with the 19-G needle (p = 0.79). The malignant cell count was 0.05 × 103 cells/µL with the 22-G and 0.08 × 103 cells/µL with the 19-G needle (p = 0.70). There was no difference in the presence of tissue cores in the samples, and rapid on-site evaluation (ROSE) cellularity was comparable between the two needles. CONCLUSIONS: The 19-G flex EBUS-TBNA needle is comparable to the 22-G needle in terms of diagnostic yield for cyto-histological evaluation of hilar and mediastinal lymphadenopathies. There is no difference between the 19-G and 22-G needle cell counts evaluated by flow cytometry.

Surgically Treated pT2aN0M0 (Stage IB) Non-Small Cell Lung Cancer: A 20-Year Single-Center Retrospective Study.

Introduction The suitability of adjuvant therapy (AT) in patients with stage IB non-small cell lung cancer (NSCLC) is still under debate considering the cost-benefit ratio between improvement in survival and side effects. We retrospectively evaluated survival and incidence of recurrence in radically resected stage IB NSCLC, to determine whether AT could significantly improve prognosis. Methods Between 1998 and 2020, 4692 consecutive patients underwent lobectomy and systematic lymphadenectomy for NSCLC. Two hundred nineteen patients were pathological T2aN0M0 (>3 and ≤4 cm) NSCLC 8th TNM. None received preoperative or AT. Overall survival (OS), cancer specific survival (CSS) and the cumulative incidence of relapse were plotted and log-rank or Gray's tests were used to assess the difference in outcome between groups. Results The most frequent histology was adenocarcinoma (66.7%). Median OS was 146 months. The 5-, 10-, and 15-year OS rates were 79%, 60%, and 47%, whereas the 5-, 10-, and 15-year CSS were 88%, 85%, and 83%, respectively. OS was significantly related to age (p < 0.001) and cardiovascular comorbidities (p = 0.04), whereas number of LNs removed was an independent prognostic factor of CSS (p = 0.02). Cumulative incidence of relapse at 5-, 10-, and 15-year were 23%, 31%, and 32%, respectively, and significantly related to the number of LNs removed (p = 0.01). Patients with more than 20 LNs removed and clinical stage I had a significantly lower relapse (p = 0.02). Conclusions Excellent CSS, up to 83% at 15-year, and relatively low risk of recurrence for stage IB NSCLC (8th TNM) patients suggested that AT for those patients could be reserved only for very selected high-risk cases.

miRNome profiling of lung cancer metastases revealed a key role for miRNA-PD-L1 axis in the modulation of chemotherapy response.

Locally advanced non-small cell lung cancer (NSCLC) is frequent at diagnosis and requires multimodal treatment approaches. Neoadjuvant chemotherapy (NACT) followed by surgery is the treatment of choice for operable locally advanced NSCLC (Stage IIIA). However, the majority of patients are NACT-resistant and show persistent lymph nodal metastases (LNmets) and an adverse outcome. Therefore, the identification of mechanisms and biomarkers of NACT resistance is paramount for ameliorating the prognosis of patients with Stage IIIA NSCLC. Here, we investigated the miRNome and transcriptome of chemo-naïve LNmets collected from patients with Stage IIIA NSCLC (N = 64). We found that a microRNA signature accurately predicts NACT response. Mechanistically, we discovered a miR-455-5p/PD-L1 regulatory axis which drives chemotherapy resistance, hallmarks metastases with active IFN-γ response pathway (an inducer of PD-L1 expression), and impacts T cells viability and relative abundances in tumor microenvironment (TME). Our data provide new biomarkers to predict NACT response and add molecular insights relevant for improving the management of patients with locally advanced NSCLC.

Correction to: Cover always the bronchial stump! A flap could prevent catastrophic complications even in complete broncho­pleural fistula.

[This corrects the article DOI: 10.1007/s12055-022-01386-3.].

Cover always the bronchial stump! A flap could prevent catastrophic complications even in complete broncho-pleural fistula.

Broncho-pleural fistula after pneumonectomy is a life-threatening condition with very high mortality rate, even if detected early. All symptomatic patients should be treated immediately. The diagnosis in the absence of symptoms poses the real difficulties of management. Early detection of asymptomatic post-pneumonectomy broncho-pleural fistula is usually fortuitous. The use of bronchoscopy allows direct and accurate evaluation of the stump. This reported case allows us to make several considerations on the treatment of fistulas, but above all to consider that the systematic bronchial stump coverage is fundamental not only for preventing fistulas, but also for limiting their enlargement and communication with the residual cavity, in order to prevent catastrophic complications.

Long-term clinical outcomes and prognostic factors of upfront surgery as a first-line therapy in biopsy-proven clinical N2 non-small cell lung cancer.

Background: Multimodality therapy offers the best opportunity to improve pathological N2 non-small cell lung cancer (NSCLC) prognosis. This paper aimed to evaluate the long-term clinical outcomes and the prognostic factors of upfront surgery as first-line therapy in biopsy-proven clinical N2. Methods: Retrospective review of biopsy-proven cN2 NSCLC patients operated between 2007 and 2017. Upfront surgery was considered if the primary tumour was deemed completely resectable, with mediastinal nodal involvement confined to a single station and no preoperative evidence of extranodal tumour invasion. Results: Two hundred eighty-five patients who underwent radical resections were included. One hundred fifty-nine patients (55.8%) received induction chemotherapy. At follow-up completion, 127 (44.6%) patients had died. For the induction chemotherapy group, the median overall survival (OS) was 49 months [95% confidence interval (CI): 38-70 months], and the 5-year OS was 44.4%. The median and 5-year OS for the up front surgery group was 66 months (95% CI: 40-119 months) and 66.3%, respectively. There were no statistically significant differences between treatment approaches (p = 0.48). One hundred thirty-four patients (47.0%) developed recurrence. The recurrence-free survival (RFS) at 5 years was 17% (95% CI: 11-25%) for induction chemotherapy and 22% (95% CI: 9-32%) for upfront surgery; there were no statistically significant differences between groups (p = 0.93). No significant differences were observed based on the clinical N status (OS, p = 0.36; RFS, p = 0.65). Conclusions: Upfront surgery as first-line therapy for biopsy-proven cN2 NSCLC showed favourable clinical outcomes, similar to those obtained after induction chemotherapy followed by surgery. Therefore, it should be considered one of the multimodality treatment options in resectable N2 NSCLC.

The Interdisciplinary Management of Lung Cancer in the European Community.

Lung cancer continues to be the largest cause of cancer-related mortality among men and women globally, accounting for around 27% of all cancer-related deaths. Recent advances in lung cancer medicines, particularly for non-small-cell lung cancer (NSCLC), have increased the need for multidisciplinary disease care, thereby enhancing patient outcomes and quality of life. Different studies in the European community have evaluated the impact of multidisciplinary care on outcomes for lung cancer patients, including its impact on survival, adherence to guideline treatment, utilization of all treatment modalities, timeliness of treatment, patient satisfaction, quality of life, and referral to palliative care. This publication will examine the roles and duties of all multidisciplinary members and the influence of multidisciplinary care on lung cancer outcomes in Europe. Multidisciplinary treatment is the foundation of lung cancer treatment. The optimal setting for interdisciplinary collaboration between specialists with complementary functions is multidisciplinary meetings. Multidisciplinary care in lung cancer facilitates the delivery of a high-quality service, which may improve lung cancer patients' survival, utilization of all treatment modalities, adherence to guideline management, and quality of life, despite the fact that only limited observational data have demonstrated these results. To confirm the relationship between multidisciplinary treatment and improved lung cancer patient outcomes, however, further research is required.

Preliminary Results of Robotic Lobectomy in Stage IIIA-N2 NSCLC after Induction Treatment: A Case Control Study.

Despite there already being many studies on robotic surgery as a minimally invasive approach for non-small-cell lung cancer (NSCLC) patients, the use of this technique for stage III disease is still poorly described. These are the preliminary results of our prospective study on the safety and effectiveness of robotic approaches in patients with locally advanced NSCLC in terms of postoperative complications and oncological outcomes. Since 2016, we prospectively investigated 19 consecutive patients with NSCLC stage IIIA-pN2 (diagnosed by EBUS-TBNA) who underwent lobectomy and radical lymph node dissection with robotic approaches after induction treatment. Furthermore, we matched a case-control study with 46 patients treated with open surgery during the same period of time, with similar age, comorbidities, clinical stage and tumor size. The individual matched population was composed of 16 robot-assisted thoracic surgeries and 16 patients who underwent open surgery. The median time range of resection was inferior in the open group compared to robotic lobectomy (243 vs. 161 min; p < 0.001). Lymph node resection and positivity were not significantly different (p = 0.96 and p = 0.57, respectively). Moreover, no difference was observed for PFS (p = 0.16) or OS (p = 0.41). In conclusion, we demonstrated that the early outcomes and oncological results of N2-patients after robotic lobectomy were similar to those who had open surgery. Considering the advantages of minimally invasive surgery, robot-assisted lobectomy appears to be a safe approach to patients with locally advanced diseases.

Prospective evaluation of EBUS-TBNA specimens for programmed death-ligand 1 expression in non-small cell lung cancer patients: a pilot study.

OBJECTIVE: EBUS-TBNA cytological sampling is routinely performed for pathological diagnosis, mediastinal staging, and molecular testing in lung cancer patients. EBUS-TBNA samples are not formally accepted for testing programmed death-ligand 1 (PD-L1) expression. The objective of the study was to compare the feasibility, reproducibility, and accuracy of PD-L1 expression assessment in cytological specimens and histological samples. METHODS: We prospectively collected histological (transbronchial forceps biopsy) and cytological (EBUS-TBNA) samples from peribronchial neoplastic lesions during an endoscopic procedure at the same target lesion for the pathological diagnosis and molecular assessment of stage IV non-small cell lung cancer (NSCLC). RESULTS: Fifteen patients underwent the procedure. Adequate cytological samples (at least 100 neoplastic cells) were obtained in 12 cases (92.3%). Assessment of PD-L1 expression was similar between histological and cytological samples (agreement rate = 92%). Sensitivity and diagnostic accuracy of EBUS-TBNA cytological specimens were 88.9% and 100%, respectively. CONCLUSIONS: The evaluation of PD-L1 expression in EBUS-TBNA cytological specimens is feasible and presents good reproducibility when compared with routine histological samples. EBUS-TBNA cytological samples could be used for the assessment of PD-L1 expression in patients with NSCLC as a minimally invasive approach in stage IV NSCLC cancer patients.

Genomic Characterization of Concurrent Alterations in Non-Small Cell Lung Cancer (NSCLC) Harboring Actionable Mutations.

An increasing number of driver genomic alterations with potential targeted treatments have been identified in non-small cell lung cancer (NSCLC). Much less is known about the incidence and different distribution of concurrent alterations, as identified by comprehensive genomic profiling in oncogene-addicted NSCLCs. Genomic data from advanced NSCLC consecutively analyzed using a broad next-generation sequencing panel were retrospectively collected. Tumors harboring at least one main actionable gene alteration were categorized according to the presence/absence of concurrent genomic aberrations, to evaluate different patterns among the main oncogene-addicted NSCLCs. Three-hundred-nine actionable gene alterations were identified in 284 advanced NSCLC patients during the study period. Twenty-five tumor samples (8%) displayed concurrent alterations in actionable genes. Co-occurrences involving any pathogenic variant or copy number variation (CNV) were identified in 82.8% of cases. Overall, statistically significant differences in the number of concurrent alterations, and the distribution of TP53, STK11, cyclines and receptor tyrosin kinase (RTK) aberrations were observed across the eight actionable gene groups. NGS analyses of oncogene-addicted NSCLCs showed a different distribution and pattern of co-alteration profiles. Further investigations are needed to evaluate the prognostic and treatment-related impact of these concurrent alterations, hooked to the main gene aberrations.

The Impact of Multidisciplinary Team Meetings on Patient Management in Oncologic Thoracic Surgery: A Single-Center Experience.

BACKGROUND: the aim of this paper is to quantify multidisciplinary team meeting (MDT) impact on the decisional clinical pathway of thoracic cancer patients, assessing the modification rate of the initial out-patient evaluation. METHODS: the impact of MDT was classified as follows: confirmation: same conclusions as out-patient hypothesis; modification: change of out-patient hypothesis; implementation: definition of a clear clinical track/conclusion for patients that did not receive any clinical hypothesis; further exams required: the findings that emerged in the MDT meeting require further exams. RESULTS: one thousand consecutive patients evaluated at MDT meetings were enrolled. Clinical settings of patients were: early stage lung cancer (17.4%); locally advanced lung cancer (27.4%); stage IV lung cancer (9.8%); mesothelioma (1%); metastases to the lung from other primary tumors (4%); histologically proven or suspected recurrence from previous lung cancer (15%); solitary pulmonary nodule (19.2%); mediastinal tumors (3.4%); other settings (2.8%). CONCLUSIONS: MDT meetings impact patient management in oncologic thoracic surgery by modifying the out-patient clinical hypothesis in 10.6% of cases; the clinical settings with the highest decisional modification rates are "solitary pulmonary nodule" and "proven or suspected recurrence" with modification rates of 14.6% and 13.3%, respectively.

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.