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.

Implementation of an enhanced recovery protocol for lung volume reduction surgery: an observational cohort study.

OBJECTIVES: Lung volume reduction surgery (LVRS) is an established therapeutic option for advanced emphysema. To improve patients' safety and reduce complications, an enhanced recovery protocol (ERP) was implemented. This study aims to describe and evaluate the short-term outcome of this ERP. METHODS: This retrospective single-centre study included all consecutive LVRS patients (1 January 2017 until 15 September 2020). An ERP for LVRS was implemented and stepwise optimised from 1 August 2019, it consisted of changes in pre-, peri- and postoperative care pathways. Patients were compared before and after implementation of ERP. Primary outcome was incidence of postoperative complications (Clavien-Dindo), and secondary outcomes included chest tube duration, incidence of prolonged air leak (PAL), length of stay (LOS) and 90-day mortality. Lung function and exercise capacity were evaluated at 3 and 6 months post-LVRS. RESULTS: Seventy-six LVRS patients were included (pre-ERP: n=41, ERP: n=35). The ERP cohort presented with lower incidence of postoperative complications (42% vs 83%, P=0.0002), shorter chest tube duration (4 vs 12 days, P<0.0001) with a lower incidence of PAL (21% vs 61%, P=0.0005) and shorter LOS (6 vs 14 days, P<0.0001). No in-hospital mortality occurred in the ERP cohort versus 4 pre-ERP. Postoperative forced expiratory volume in 1 s was higher in the ERP cohort compared to pre-ERP at 3 months (1.35 vs 1.02 l) and at 6 months (1.31 vs 1.01 l). CONCLUSIONS: Implementation of ERP as part of a comprehensive reconceptualisation towards LVRS, demonstrated fewer postoperative complications, including PAL, resulting in reduced LOS. Improved short-term functional outcomes were observed at 3 and 6 months.

Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial.

Neoadjuvant chemoimmunotherapy improves pathologic complete response rate and event-free survival in patients with resectable non-small cell lung cancer (NSCLC) versus chemotherapy alone. NeoCOAST was the first randomized, multidrug platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathologic response (MPR) rate as the primary endpoint. Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti-PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). MPR rates were higher for patients in the combination arms versus durvalumab alone. Safety profiles for the combinations were similar to those of durvalumab alone. Multiplatform immune profiling suggested that improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune cell activation. SIGNIFICANCE: A neoadjuvant platform trial can rapidly generate clinical and translational data using candidate surrogate endpoints like MPR. In NeoCOAST, patients with resectable NSCLC had improved MPR rates after durvalumab plus oleclumab or monalizumab versus durvalumab alone and tumoral transcriptomic signatures indicative of augmented immune cell activation and function. See related commentary by Cooper and Yu, p. 2306. This article is featured in Selected Articles from This Issue, p. 2293.

Urgent lung volume reduction surgery is effective for secondary pneumothorax in emphysema patients.

Secondary pneumothorax due to emphysema can be life-threatening and requires surgery in most situations. Here, we extended lung resection to close the fistula using lung volume reduction surgery (LVRS). We present a patient with chronic obstructive pulmonary disease and secondary spontaneous pneumothorax referred after ineffective treatment by chemical pleurodesis. Urgent LVRS followed by elective LVRS was performed obtaining air-leak resolution and significantly improving pulmonary function and quality of life. We discuss the surgical technique and effectiveness of LVRS as a treatment for pneumothorax.

Minimally invasive sleeve lobectomy for centrally located lung cancer: A real-world study with propensity-score matching.

Background: The safety, feasibility, and prognosis of sleeve lobectomy by minimally invasive surgery (MIS) remain to be validated. The purpose of this study was to investigate outcomes in real-world patients receiving minimally invasive sleeve lobectomy in a balanced large cohort. Methods: Between January 2013 and December 2018, 578 consecutive patients undergoing sleeve resection at a high-volume center were retrospectively analyzed. Surgical and oncologic outcomes were compared between MIS and thoracotomy patients after propensity-score matching (PSM). Results: MIS sleeve lobectomy was increasingly used as a time-trend in real-world. Before PSM, the MIS group had smaller tumor size, more T2-stage cases, and more right upper lobe sleeve lobectomies compared to the Open group. After 1:4 PSM by patient demographics and tumoral characteristics, 100 cases of MIS and 338 cases of Open sleeve lobectomy were further analyzed. Although median operation time was longer in the MIS group than in the Open group (170.5 minutes vs.149.5 minutes, P < 0.001), patients in MIS group had significantly less estimated intraoperative blood loss (100 ml vs. 200 ml, P = 0.003), shorter drainage duration (5 days vs. 6 days, P = 0.027) and less amount of drainage (1280 ml vs. 1640 ml, P < 0.001) after surgery. Complete resection rate, combined angioplasty, number of dissected lymph nodes, post-operative length of stay, postoperative morbidity and mortality rate, and application of adjuvant therapy were similar between the two matched groups. Conversion to open thoracotomy was necessary in 13.6% patients, but with similar perioperative outcomes compared to Open cases except for longer operation time. More lower lobe sleeve lobectomies were accomplished via robot-assisted thoracoscopic surgery than via video-assisted thoracoscopic surgery (40.0% vs. 12.0%, P = 0.017) in MIS patients. Five-year overall survivals (MIS vs. Open: 72.7% vs. 64.4%, P = 0.156) and five-year progression-free survivals (MIS vs. Open: 49.2% vs. 50.5%, P = 0.605) were similar between the two matched groups. Conclusions: MIS sleeve lobectomy is associated with similar or even better perioperative results and oncologic outcomes to open thoracotomy. Conversion to thoracotomy does not compromise perioperative outcomes. Robot surgery may be preferable for more complex sleeve resections.

Primary endpoints to assess the efficacy of novel therapeutic approaches in epidermal growth factor receptor-mutated, surgically resectable non-small cell lung cancer: A review.

While the discovery of oncogenic driver mutations has personalized the metastatic non-small cell lung cancer (NSCLC) treatment landscape with effective targeted therapies, implementation of new treatments in resectable NSCLC has been limited due to the long follow-up needed for overall survival (OS). Until recently, treatment for patients with early-stage resectable NSCLC has been limited to perioperative chemotherapy, which provides modest benefits. However, the regulatory acceptance of two surrogate endpoints for OS has allowed recent approval of both adjuvant osimertinib and atezolizumab, providing patients with new treatment options to improve outcomes. In phase 3 oncology trials, OS has historically been viewed as the gold-standard efficacy measure, but disease-free survival and event-free survival (EFS) are now validated surrogate endpoints for OS in clinical trials and should be considered when mature OS data is unavailable. Another potential surrogate endpoint in the adjuvant NSCLC setting is circulating tumor DNA (ctDNA)-based minimal residual disease (MRD), although prospective validation is needed. For neoadjuvant targeted therapies, EFS, major pathologic response and ctDNA-based MRD are potential surrogate endpoints. To fully translate the success of the personalized treatment advances in the metastatic setting to earlier-stage disease, prospective validation studies of these potential surrogate endpoints that can accelerate the evaluation of drug efficacy are needed. A collaborative effort is also needed from all clinical and regulatory parties to collate surrogate endpoint data for large-scale validation. In this review we discuss the trends in surrogate endpoints used in oncology trials, with a focus on considerations for selecting appropriate primary endpoints in early-stage resectable EGFR-mutant NSCLC, an area of unmet need for novel treatment options.

Surgical Outcomes of Video-Assisted versus Open Pneumonectomy for Lung Cancer: A Real-World Study.

BACKGROUND: The safety, feasibility and potential benefits of Video-assisted thoracoscopic surgery (VATS) pneumonectomy remain to be investigated. METHODS: Patients receiving VATS or Open pneumonectomy during the study period were included to compare surgical outcomes. Propensity-score matched (PSM) analysis was performed to eliminate potential biases. RESULTS: From 2013 to 2020, 583 consecutive patients receiving either VATS (105, 18%) or Open (478, 82%) pneumonectomy were included. Conversion from VATS to open was found in 20 patients (19.0%). The conversion patients had similar rates of major complications and perioperative mortality compared with the Open group. After PSM, 203 patients were included. No significant differences were observed in major complications and perioperative mortality between the two groups. For patients with stage pT2 tumors, the major complication rate in the VATS group was significantly lower than in the Open group (7.6% vs. 20.6%, p = 0.042). Compared with left pneumonectomy, the incidence of bronchopleural fistula (BPF) was significantly higher in right pneumonectomy for both VATS (0 vs. 16.7%, p = 0.005) and Open (0.7% vs. 6.5%, p = 0.002) approaches. CONCLUSIONS: Perioperative results of VATS pneumonectomy are non-inferior to those of the Open approach. Conversion to open surgery does not compromise perioperative outcomes. Patients with lower pT stage tumors who need pneumonectomy may benefit from VATS.

Proposal for a new local recurrence score in patients with recurrent malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma (MPM) is associated with high rates of local recurrence (LR) up to 75%. Second line treatment should be applied tailored to relapse pattern. We aimed to establish a new score for LR pattern with prognostic impact in this observational study of retrospective nature. Methods: MPM patients with LR after surgery, verified by serial imaging during follow-up visits or biopsy were included in a retrospective analysis using a new local recurrence score (LRS). We divided the thoracic cavity into six sections and calculated the LRS according to the tumor burden. We assessed the impact on survival after recurrence using cox regression model. Results: From 2001 until 2017, 128 consecutive MPM patients with LR who underwent macroscopic complete resection (MCR) by extrapleural pneumonectomy (EPP, n=61) or by (extended) pleurectomy/decortication [(E)PD, n=67], were included in the present analysis; 104 patients received second line therapy. Patients with chest wall (CW) recurrence had the shortest survival after recurrence (9 vs. 16 months, P=0.05) as well as patients with affected lymph nodes (LN) (9 vs. 17 months, P=0.02). In subgroup analysis, the (E)PD group had a significantly higher LRS (P≤0.001) despite a longer survival time after recurrence of 12.4 months (IQR, 6.45-20.32) compared to 9.3 months (IQR, 2.93-17.40, EPP group) (P=0.04). Patients with LRS ≤4 had a longer survival undergoing radiotherapy or local surgery for second line treatment whereas patients with LRS >4 only if they underwent chemotherapy. Conclusions: LRS might be a useful prognostic tool in MPM patients with LR after multimodality therapy to guide second line treatment allocation.

Extended resection for potentially operable patients with stage III non-small cell lung cancer after induction treatment.

OBJECTIVE: Surgical treatment of locally advanced non-small cell lung cancer including single or multilevel N2 remains a matter of debate. Several trials demonstrate that selected patients benefit from surgery if R0 resection is achieved. We aimed to assess resectability and outcome of patients with locally advanced clinical T3/T4 (American Joint Committee on Cancer 8th edition) tumors after induction treatment followed by surgery in a pooled analysis of 3 prospective multicenter trials. METHODS: A total of 197 patients with T3/T4 non-small cell lung cancer of 368 patients with stage III non-small cell lung cancer enrolled in the Swiss Group for Clinical Cancer Research 16/96, 16/00, 16/01 trials were treated with induction chemotherapy or chemoradiation therapy followed by surgery, including extended resections. Univariable and multivariable analyses were applied for analysis of outcome parameters. RESULTS: Patients' median age was 60 years, and 67% were male. A total of 38 of 197 patients were not resected for technical (81%) or medical (19%) reasons. A total of 159 resections including 36 extended resections were performed with an 80% R0 and 13.2% pathological complete response rate. The 30- and 90-day mortality were 3% and 7%, respectively, without a difference for extended resections. Morbidity was 32% with the majority (70%) of minor grading complications. The 3-, 5-, and 10-year overall survivals for extended resections were 61% (95% confidence interval, 43-75), 44% (95% confidence interval, 27-59), and 29.5% (95% confidence interval, 13-48), respectively. R0 resection was associated with improved overall survival (hazard ratio, 0.41; P < .001), but pretreatment N2 extension (177/197) showed no impact on overall survival. CONCLUSIONS: Surgery after induction treatment for advanced T3/T4 stage including single and multiple pretreatment N2 disease resulted in 80% R0 resection rate and 7% 90-day mortality. Favorable overall survival for extended and not extended resection was demonstrated to be independent of pretreatment N status.

The Swiss Approach - feasibility of a national low-dose CT lung cancer screening program.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in Switzerland. Despite this, there is no lung cancer screening program in the country. In the United States, low-dose computed tomography (LDCT) lung cancer screening is partially established and endorsed by guidelines. Moreover, evidence is growing that screening reduces lung cancer-related mortality and this was recently shown in a large European randomized controlled trial. Implementation of a lung cancer screening program, however, is challenging and depends on many country-specific factors. The goal of this article is to outline a potential Swiss lung cancer screening program. FRAMEWORK: An exhaustive literature review on international screening models as well as interviews and site visits with international experts were initiated. Furthermore, workshops and interviews with national experts and stakeholders were conducted to share experiences and to establish the basis for a national Swiss lung cancer screening program. SCREENING APPROACH: General practitioners, pulmonologists and the media should be part of the recruitment process. Decentralisation of the screening might lead to a higher adherence rate. To reduce stigmatisation, the screening should be integrated in a "lung health check". Standardisation and a common quality level are mandatory. The PLCOm2012 risk calculation model with a threshold of 1.5% risk for developing cancer in the next six years should be used in addition to established inclusion criteria. Biennial screening is preferred. LUNG RADS and NELSON+ are applied as classification models for lung nodules. CONCLUSION: Based on data from recent studies, literature research, a health technology assessment, the information gained from this project and a pilot study the Swiss Interest Group for lung cancer screening (CH-LSIG) recommends the timely introduction of a systematic lung cancer screening program in Switzerland. The final decision is for the Swiss Cancer Screening Committee to make.

Surgical resection of Masaoka stage III thymic epithelial tumours with great vessels involvement: a retrospective multicentric analysis from the European Society of Thoracic Surgeons thymic database.

OBJECTIVES: The aim of this study was to analyse the outcomes of an international cohort of patients affected by Masaoka stage III thymic epithelial tumours with vascular involvement and treated by surgery. METHODS: Study design was the observational multicentre retrospective cohort study. Data were extracted from the European Society of Thoracic Surgeons thymic database; additional variables were collected. Inclusion criteria were as follows: stage III (Masaoka-Koga) thymic epithelial tumours; surgery with radical intention; clinical or pathological great vessels involvement; and radiologically suspected or diagnosed intraoperatively. Outcome items were analysed. RESULTS: Sixty-five patients submitted to surgery from 2001 to 2017 fulfilled inclusion criteria. Thymoma and thymic carcinoma patients did not differ for demographics and clinical characteristics. The majority of great vessel treated were superior vena cava or innominate veins (72.3%). Eleven patients (16.9%) had postoperative cardiopulmonary complications; vascular stenosis was observed in 3 patients (4.6%). The multivariable Cox analysis for disease-free survival showed an increased hazard of recurrence for thymic carcinoma (hazard ratio = 3.59; 95% confidence interval: 1.66-7.78, P = 0.001). The 1-, 3-, 5- and 10-year overall survival rates were 0.86, 0.84, 0.81, and 0.53, respectively. There was no significant difference in overall survival according to resection status or between thymoma and thimic carcinoma. The univariable Cox regression model did not show an increased hazard of death for myasthenic patients considering all resection status and for patients who received neoadjuvant therapy. CONCLUSIONS: We observed that clinical outcomes of patients treated for stage III thymic epithelial tumours with vascular involvement are satisfactory suggesting to increase the confidence in dealing with these complex surgeries. Complete resection should be achieved, even though extensive vascular reconstructions are required.

Quality of Life Is Not Deteriorated After Extrapleural Pneumonectomy vs. (Extended) Pleurectomy/Decortication in Patients With Malignant Pleural Mesothelioma.

Background: Extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) is highly abandoned due to high morbidity and mortality rates and impaired quality of life (QoL). However, there are still rare indications for this intervention. The aim of this longitudinal prospective study was to monitor QoL and lung function in patients undergoing EPP and compare the outcomes with extended pleurectomy/decortication [(E)PD]. Methods: Between June 2013 and June 2017, 42 patients underwent induction chemotherapy followed by either EPP (n = 7) or (E)PD (n = 35). All patients filled out the EORTC QLC-C15-PAL, -LC13, and SF-36 self-rating questionnaires pre-operatively, 6 weeks and 4 months after the operation. Additionally, lung function was measured pre-operatively and 4 months post-operatively. Results: We observed no significant differences in all QoL categories (general global health, pain, and dyspnea) between both surgical procedures, over the whole observation period. Moreover, a general tendency toward restoration of the pre-operative QoL status was documented at 4 months after the both operations. Forced expiratory volume in 1 s (FEV1) showed a significant decrease after surgery in both the groups [EPP group p = 0.06 and (E)PD group p < 0.001]; also, the forced volume vital capacity (FVC) significantly decreased (EPP group p = 0.046 P/D group <0.001). Diffusion capacity did not show significant changes. Conclusion: According to these results, QoL is no longer severely impaired after EPP compared with EPD, and therefore should not be used as an argument against EPP in principle. However, indication has to be carefully evaluated for each patient.

Implementing CT tumor volume and CT pleural thickness into future staging systems for malignant pleural mesothelioma.

OBJECTIVES: Tumor thickness and tumor volume measured by computed tomography (CT) were suggested as valuable prognosticator for patients' survival diagnosed with malignant pleural mesothelioma (MPM). The purpose was to assess the accuracy of CT scan based preoperatively measured tumor volume and thickness compared to actual tumor weight of resected MPM specimen and pathologically assessed tumor thickness, as well as an analysis of their impact on overall survival (OS). METHODS: Between 09/2013-08/2018, 74 patients were treated with induction chemotherapy followed by (extended) pleurectomy/decortication ((E)PD). In 53 patients, correlations were made between CT-measured volume and -tumor thickness (cTV and cTT) and actual tumor weight (pTW) based on the available values. Further cTV and pT/IMIG stage were correlated using Pearson correlation. Overall survival (OS) was calculated with Kaplan Meier analysis and tested with log rank test. For correlation with OS Kaplan-Meier curves were made and log rank test was performed for all measurements dichotomized at the median. RESULTS: Median pathological tumor volume (pTV) and pTW were 530 ml [130 ml - 1000 ml] and 485 mg [95 g - 982 g] respectively. Median (IQR) cTV was 77.2 ml (35.0-238.0), median cTT was 9.0 mm (6.2-13.7). Significant association was found between cTV and pTV (R = 0.47, p < 0.001) and between cTT and IMIG stage (p = 0,001) at univariate analysis. Multivariate regression analysis revealed, that only cTV correlates with pTV. Median follow-up time was 36.3 months with 30 patients dead at the time of the analysis. Median OS was 23.7 months. 1-year and 3-year survival were 90 and 26% respectively and only the cTV remained statistically associated with OS. CONCLUSION: Preoperatively assessed CT tumor volume and actual tumor volume showed a significant correlation. CT tumor volume may predict pathological tumor volume as a reflection of tumor burden, which supports the integration of CT tumor volume into future staging systems.

Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA.

Osimertinib is a third-generation, irreversible oral EGFR-tyrosine kinase inhibitor), that potently inhibits EGFR-tyrosine kinase inhibitor-sensitizing mutations and T790M resistance mutations together with efficacy in CNS metastases in patients with non-small-cell lung cancer (NSCLC). Here we describe the rationale and design for the Phase III NeoADAURA study (NCT04351555), which will evaluate neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone prior to surgery, in patients with resectable stage II-IIIB N2 EGFR mutation-positive NSCLC. The primary end point is centrally assessed major pathological response at the time of resection. Secondary end points include event-free survival, pathological complete response, nodal downstaging at the time of surgery, disease-free survival, overall survival and health-related quality of life. Safety and tolerability will also be assessed. Trial Registration number: NCT04351555 (ClinicalTrials.gov).

Lay abstract A plain language version of this article is available and is published alongside the paper online: www.futuremedicine.com/doi/suppl/10.2217/fon-2021-0549.

SAKK 16/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non-Small-Cell Lung Cancer-A Multicenter Single-Arm Phase II Trial.

PURPOSE: For patients with resectable stage IIIA(N2) non-small-cell lung cancer, neoadjuvant chemotherapy with cisplatin and docetaxel followed by surgery resulted in a 1-year event-free survival (EFS) rate of 48% in the SAKK 16/00 trial and is an accepted standard of care. We investigated the additional benefit of perioperative treatment with durvalumab. METHODS: Neoadjuvant treatment consisted of three cycles of cisplatin 100 mg/m2 and docetaxel 85 mg/m2 once every 3 weeks followed by two doses of durvalumab 750 mg once every 2 weeks. Durvalumab was continued for 1 year after surgery. The primary end point was 1-year EFS. The hypothesis for statistical considerations was an improvement of 1-year EFS from 48% to 65%. RESULTS: Sixty-eight patients were enrolled, 67 were included in the full analysis set. Radiographic response rate was 43% (95% CI, 31 to 56) after neoadjuvant chemotherapy and 58% (95% CI, 45 to 71) after sequential neoadjuvant immunotherapy. Fifty-five patients were resected, of which 34 (62%) achieved a major pathologic response (MPR; ≤ 10% viable tumor cells) and 10 (18%) among them a complete pathologic response. Postoperative nodal downstaging (ypN0-1) was observed in 37 patients (67%). Fifty-one (93%) resected patients had an R0 resection. There was no significant effect of pretreatment PD-L1 expression on MPR or nodal downstaging. The 1-year EFS rate was 73% (two-sided 90% CI, 63 to 82). Median EFS and overall survival were not reached after 28.6 months of median follow-up. Fifty-nine (88%) patients had an adverse event grade ≥ 3 including two fatal adverse events that were judged not to be treatment-related. CONCLUSION: The addition of perioperative durvalumab to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small-cell lung cancer is safe and exceeds historical data of chemotherapy alone with a high MPR and an encouraging 1-year EFS rate of 73%.

Two centres experience of lung cancer resection in patients with advanced non-small cell lung cancer upon treatment with immune checkpoint inhibitors: safety and clinical outcomes.

OBJECTIVES: Recent trials have begun to explore immune checkpoint inhibitors for non-small cell lung cancer in the neoadjuvant setting, but data on tumour response and surgical outcome remain limited. METHODS: Retrospective evaluation of clinical data from patients with non-small cell lung cancer treated with immune checkpoint inhibitors followed by lung resection was performed at 2 large volume institutions (1 North American, 1 European). Data were analysed using Chi-squared, Fisher's and Wilcoxon rank-sum tests where appropriate. RESULTS: Thirty-seven patients were identified from 2017 to 2019. Forty-nine per cent were Stage IIIB and IV. Forty-six per cent received immunotherapy alone and 54% in combination with chemo- and/or radiotherapy. Sixteen per cent of cases were successfully performed minimally invasively. Twenty patients were operated with lobectomy (6 of these with wedges or segments of a neighbouring lobe, 2 with sleeve resections and 1 with a chest wall resection), 4 with bilobectomies, 11 with pneumonectomy (including 5 extrapleural pneumonectomies and 1 atrial resection) and 1 with a wedge resection. Overall, 10 patients (27%) developed postoperative complications and the 90-day mortality was zero. One-year recurrence-free survival was 73% for stage II/IIIA and 55% for stage IIIB/stage IV. The major pathologic response rate was 34%. CONCLUSION: In this retrospective study, lung resection after immunotherapy (alone or in combination) is safe, although often requires complex surgery. Due to increasing number of clinical trials adopting immunotherapy in the neoadjuvant setting, it is likely that this therapy will become part of standard of care. Immunotherapy may also allow surgery to have a role for selected patients with advanced disease.

Thymomectomy plus total thymectomy versus simple thymomectomy for early-stage thymoma without myasthenia gravis: a European Society of Thoracic Surgeons Thymic Working Group Study.

OBJECTIVES: Resection of thymic tumours including the removal of both the tumour and the thymus gland (thymothymectomy; TT) is the procedure of choice and is recommended in most relevant articles in the literature. Nevertheless, in recent years, some authors have suggested that resection of the tumour (simple thymomectomy; ST) may suffice from an oncological standpoint in patients with early-stage thymoma who do not have myasthenia gravis (MG) (non-MG). The goal of our study was to compare the short- and long-term outcomes of ST versus TT in non-MG early-stage thymomas using the European Society of Thoracic Surgeons thymic database. METHODS: A total of 498 non-MG patients with pathological stage I thymoma were included in the study. TT was performed in 466 (93.6%) of 498 patients who had surgery with curative intent; ST was done in 32 (6.4%). The completeness of resection, the rate of complications, the 30-day mortality, the overall recurrence and the freedom from recurrence were compared. We performed crude and propensity score-adjusted comparisons by surgical approach (ST vs TT). RESULTS: TT showed the same rate of postoperative complications, 30-day mortality and postoperative length of stay as ST. The 5-year overall survival rate was 89% in the TT group and 55% in the ST group. The 5-year freedom from recurrence was 96% in the TT group and 79% in the ST group. CONCLUSION: Patients with early-stage thymoma without MG who have a TT show significantly better freedom from recurrence than those who have an ST, without an increase in postoperative morbidity rate.

CD26 as a target against fibrous formation in chronic airway rejection lesions.

AIMS: Chronic lung allograft dysfunction (CLAD) after lung transplantation (Tx) is the clinical result of chronic airway rejection lesions (CARL), histomorphologically described as either obliterative remodeling of small airways or alveolar fibroelastosis, or as a combination of both. We here investigated the CD26-inhibitory effect on CD26-expressing CARL. MAIN METHODS: CARL were induced by BALB/c â†’ C57BL/6 mouse Tx under mild immunosuppression. CARL-related pro-fibrotic mediators were determined by RT-qPCR and western blotting (WB), EMT and ERK markers by WB. CD26 co-expression by immunofluorescence. CD26 was inhibited by Vildagliptin, gene depleted by CD26-/- mice. Primary lung fibroblasts were employed for ex vivo analyses. Samples from lung transplant patients with CLAD were analyzed by immunohistochemistry. KEY FINDINGS: CARL revealed a significantly higher expression of profibrotic proteins vs. normal lungs (p < 0.05). CD26 and EMT co-expressed in CARL with significantly higher Vimentin, Slug, Hif-1α, α-SMA expression vs. normal lungs (p < 0.05). Vildagliptin decreased the expression of α-SMA and N-cadherin in wild type (WT) lung fibroblasts (p < 0.05). Primary lung fibroblasts from WT and CD26-/- mice treated with TGF-ß1, IFN-γ, and FGF showed a reduction of EMT protein expression, proliferation, and reduced activation of ERK in CD26-/- mice vs. WT mice. CD26-positive cells were found in patient samples with CLAD in areas of loose fibrosis, but not in areas of dense fibrosis. SIGNIFICANCE: CD26 is expressed in CARL-developing lung transplants and CD26-inhibition downregulates fibrosis-forming mediators and fibroblast proliferation. CD26 thus qualifies as a target to attenuate the development of CARL mainly via modulation of ERK and the EMT pathway.

Lung Volume Reduction Surgery in Patients with Homogeneous Emphysema.

Randomized controlled trials have demonstrated that lung volume reduction surgery (LVRS) improves exercise capacity, lung function, and quality of life in patients with heterogenous emphysema on computed tomographic and perfusion scan. However, most patients have a nonheterogenous type of destruction. These patients, summarized under "homogeneous emphysema," may also benefit from LVRS as long they are severely hyperinflated, and adequate function is remaining with a diffusing capacity of the lungs for carbon monoxide greater than 20% and no pulmonary hypertension. Surgical mortality is low when patients are well selected.