Protective effect of height on long-term survival of resectable lung cancer: a new feature of the lung cancer paradox.

INTRODUCTION: Unlike most malignancies, higher body mass index (BMI) is associated with a reduced risk of lung cancer and improved prognosis after surgery. However, it remains controversial whether height, one of determinants of BMI, is associated with survival independently of BMI and other confounders. METHODS: We extracted data on all consecutive patients with resectable non-small cell lung cancer included in Epithor, the French Society of Thoracic and Cardiovascular Surgery database, over a 16-year period. Height was analysed as a continuous variable, and then categorised into four or three categories, according to sex-specific quantiles. Cox proportional hazards regression was used to estimate the association of height with survival, adjusted for age, tobacco consumption, forced expiratory volume in one second (FEV1), WHO performance status (WHO PS), American Society of Anesthesiologists (ASA) score, extent of resection, histological type, stage of disease and centre as a random effect, as well as BMI in a further analysis. RESULTS: The study included 61 379 patients. Higher height was significantly associated with better long-term survival after adjustment for other variables (adjusted HR 0.97 per 10 cm higher height, 95% CI 0.95 to 0.99); additional adjustment for BMI resulted in an identical HR. The prognostic impact of height was further confirmed by stratifying by age, ASA class, WHO PS and histological type. When stratifying by BMI class, there was no evidence of a differential association (p=0.93). When stratifying by stage of disease, the prognostic significance of height was maintained for all stages except IIIB-IV. CONCLUSIONS: Our study shows that height is an independent prognostic factor of resectable lung cancer.

Impact of surgical approach on 90-day mortality after lung resection for nonsmall cell lung cancer in high-risk operable patients.

Introduction: Non-small cell lung cancer (NSCLC) is often associated with compromised lung function. Real-world data on the impact of surgical approach in NSCLC patients with compromised lung function are still lacking. The objective of this study is to assess the potential impact of minimally invasive surgery (MIS) on 90-day post-operative mortality after anatomic lung resection in high-risk operable NSCLC patients. Methods: We conducted a retrospective multicentre study including all patients who underwent anatomic lung resection between January 2010 and October 2021 and registered in the Epithor database. High-risk patients were defined as those with a forced expiratory volume in 1 s (FEV1) or diffusing capacity of the lung for carbon monoxide (DLCO) value below 50%. Co-primary end-points were the impact of risk status on 90-day mortality and the impact of MIS on 90-day mortality in high-risk patients. Results: Of the 46 909 patients who met the inclusion criteria, 42 214 patients (90%) with both preoperative FEV1 and DLCO above 50% were included in the low-risk group, and 4695 patients (10%) with preoperative FEV1 and/or preoperative DLCO below 50% were included in the high-risk group. The 90-day mortality rate was significantly higher in the high-risk group compared to the low-risk group (280 (5.96%) versus 1301 (3.18%); p<0.0001). In high-risk patients, MIS was associated with lower 90-day mortality compared to open surgery in univariate analysis (OR=0.04 (0.02-0.05), p<0.001) and in multivariable analysis after propensity score matching (OR=0.46 (0.30-0.69), p<0.001). High-risk patients operated through MIS had a similar 90-day mortality rate compared to low-risk patients in general (3.10% versus 3.18% respectively). Conclusion: By examining the impact of surgical approaches on 90-day mortality using a nationwide database, we found that either preoperative FEV1 or DLCO below 50% is associated with higher 90-day mortality, which can be reduced by using minimally invasive surgical approaches. High-risk patients operated through MIS have a similar 90-day mortality rate as low-risk patients.

Immune changes in hilar tumor draining lymph nodes following node sparing neoadjuvant chemoradiotherapy of localized cN0 non-small cell lung cancer.

Background: While much progress has been accomplished in the understanding of radiation-induced immune effects in tumors, little is known regarding the mechanisms involved at the tumor draining lymph node (TDLN) level. The objective of this retrospective study was to assess the immune and biological changes arising in non-involved TDLNs upon node sparing concurrent chemoradiotherapy (CRT) of non-small cell lung cancer (NSCLC) tumors. Methods: Patients with proven localized (cN0M0) NSCLC, treated by radical surgery plus lymph node dissection with (CRT+) or without (CRT-) neoadjuvant chemoradiotherapy, whereby radiotherapy was targeted on the primary tumor with no significant incidental irradiation of the non-involved TDLN station (stations XI), were identified. Bulk RNA sequencing of TDLNs was performed and data were analyzed based on differential gene expression (DGE) and gene sets enrichment. Results: Sixteen patients were included and 25 TDLNs were analyzed: 6 patients in the CRT+ group (12 samples) and 10 patients in the CRT- group (13 samples). Overall, 1001 genes were differentially expressed between the two groups (CRT+ and CRT-). Analysis with g-profiler revealed that gene sets associated with antitumor immune response, inflammatory response, hypoxia, angiogenesis, epithelial mesenchymal transition and extra-cellular matrix remodeling were enriched in the CRT+ group, whereas only gene sets associated with B cells and B-cell receptor signaling were enriched in the CRT- group. Unsupervised dimensionality reduction identified two clusters of TDLNs from CRT+ patients, of which one cluster (cluster 1) exhibited higher expression of pathways identified as enriched in the overall CRT+ group in comparison to the CRT- group. In CRT+ cluster 1, 3 out of 3 patients had pathological complete response (pCR) or major pathological response (MPR) to neoadjuvant CRT, whereas only 1 out of 3 patients in the other CRT+ cluster (cluster 2) experienced MPR and none exhibited pCR. Conclusion: Neoadjuvant node sparing concurrent CRT of NSCLC patients is associated with distinct microenvironment and immunological patterns in non-involved TDLNs as compared to non-involved TDLNs from patients with non-irradiated tumors. Our data are in line with studies showing superiority of lymph node sparing irradiation of the primary tumor in the induction of antitumor immunity.

Medico-economic impact of thoracoscopy versus thoracotomy in lung cancer: multicentre randomised controlled trial (Lungsco01).

BACKGROUND: Lungsco01 is the first study assessing the real benefits and the medico-economic impact of video-thoracoscopy versus open thoracotomy for non-small cell lung cancer in the French context. METHODS: Two hundred and fifty nine adult patients from 10 French centres were randomised in this prospective multicentre randomised controlled trial, between July 29, 2016, and November 24, 2020. Survival from surgical intervention to day 30 and later was compared with the log-rank test. Total quality-adjusted-life-years (QALYs) were calculated using the EQ-5D-3L®. For medico-economic analyses at 30 days and at 3 months after surgery, resources consumed were valorised (€ 2018) from a hospital perspective. First, since mortality was infrequent and not different between the two arms, cost-minimisation analyses were performed considering only the cost differential. Second, based on complete cases on QALYs, cost-utility analyses were performed taking into account cost and QALY differential. Acceptability curves and the 95% confidence intervals for the incremental ratios were then obtained using the non-parametric bootstrap method (10,000 replications). Sensitivity analyses were performed using multiple imputations with the chained equation method. RESULTS: The average cumulative costs of thoracotomy were lower than those of video-thoracoscopy at 30 days (€9,730 (SD = 3,597) vs. €11,290 (SD = 4,729)) and at 3 months (€9,863 (SD = 3,508) vs. €11,912 (SD = 5,159)). In the cost-utility analyses, the incremental cost-utility ratio was €19,162 per additional QALY gained at 30 days (€36,733 at 3 months). The acceptability curve revealed a 64% probability of efficiency at 30 days for video-thoracoscopy, at a widely-accepted willingness-to-pay threshold of €25,000 (34% at 3 months). Ratios increased after multiple imputations, implying a higher cost for video-thoracoscopy for an additional QALY gain (ratios: €26,015 at 30 days, €42,779 at 3 months). CONCLUSIONS: Given our results, the economic efficiency of video-thoracoscopy at 30 days remains fragile at a willingness-to-pay threshold of €25,000/QALY. The economic efficiency is not established beyond that time horizon. The acceptability curves given will allow decision-makers to judge the probability of efficiency of this technology at other willingness-to-pay thresholds. TRIAL REGISTRATION: NCT02502318.

Mortality and failure-to-rescue major complication trends after lung cancer surgery between 2005 and 2020: a nationwide population-based study.

OBJECTIVES: To estimate the evolution of quality indicators (30-day mortality and failure-to-rescue) inpatients who underwent lung cancer surgery in France over the past 15 years and to study the potential influencing factors. DESIGN: Retrospective cohort study using data from the French hospital database (PMSI). SETTING: Nationwide population-based study. PARTICIPANTS: All patients who underwent pulmonary resection for lung cancer in France (2005-2020) were included (N=1 57 566). Characteristics of patients (age, gender, comorbidities), surgery (surgical approach, type of resection, extent of resection) and hospital (type of hospital, hospital volume for pulmonary resections) were retrieved. PRIMARY AND SECONDARY OUTCOME MEASURES: We studied two outcome indicators: 30-day mortality and failure-to-rescue. We used regression-based techniques (including interrupted time-series) to assess the effects of patient and hospital characteristics on 30-day mortality and failure-to-rescue (number of deaths among patients with at least one major postoperative complication within the 30 days after surgery), adjusting for case mix. RESULTS: The 30-day mortality rate increased from 3.8% in 2005 to 4.9% in 2010 and then decreased to 2.9% in 2020. The failure-to-rescue rate decreased from 12.2% in 2005 to 7.1% in 2020. The pneumonectomy rate decreased significantly over time (18.1% in 2005 to 4.8% in 2020) and had the greatest contribution on the reduction of mortality between two periods (2005-2010/2015-2020). The use of video-assisted thoracoscopic surgery or robot-assisted surgery had a great influence on the reduction of mortality (16% of the observed difference in mortality) between the two periods, as did hospital volume. CONCLUSIONS: The change in surgical practices, particularly the reduction in pneumonectomies, could be one of the main reasons for reduction in postoperative mortality and failure-to-rescue in France since 2011. Hospital volume is another important factor in reducing postoperative mortality. Our study should encourage the use of technological or organisational innovation, such as changes in surgical practice and cancer surgery authorisations, to improve quality of care.

Impact of robotic access on outcomes after lung cancer surgery in France: Analysis from the Epithor database.

Introduction: We aimed to compare postoperative outcomes after pulmonary resection for lung cancer after open thoracotomy (OT), video-assisted (VATS), and robotic-assisted (RA) thoracic surgery using a propensity score analysis. Methods: From 2010 to 2020, 38,423 patients underwent resection for lung cancer. In total, 58.05% (n = 22,306) were operated by thoracotomy, 35.35% (n = 13,581) by VATS, and 6.6% (n = 2536) by RA. A propensity score was used to create balanced groups with weighting. End points were in-hospital mortality, postoperative complications, and length of hospital stay, reported by odds ratios (ORs) and 95% confidence intervals (CIs). Results: VATS decreased in-hospital mortality compared with OT (OR, 0.64; 95% CI, 0.58-0.79; P < .0001) but not compared with RA (OR, 1.09; 95% CI, 0.77-1.52; P = .61). VATS reduced major postoperative complications compared with OT (OR, 0.83; 95% CI, 0.76-0.92; P < .0001) but not RA (OR, 1.01; 95% CI, 0.84-1.21; P = .17). VATS reduced prolonged air leaks rate compared with OT (OR, 0.9; 95% CI, 0.84-0.98; P = .015) but not RA (OR, 1.02; 95% CI, 0.88-1.18; P = .77). As compared with OT, VATS and RA decreased the incidence of atelectasis (respectively: OR, 0.57; 95% CI, 0.50-0.65; P < .0001 and OR, 0.75; 95% CI, 0.60-0.95; P = .016); the incidence of pneumonia (OR, 0.75; 95% CI, 0.67-0.83; P < .0001 and OR, 0.62; 95% CI, 0.50-0.78; P < .0001); and the number of postoperative arrhythmias (OR, 0.69; 95% CI, 0.61-0.78; P < .0001 and OR, 0.75; 95% CI, 0.59-0.96; P = .024). Both VATS and RA resulted in shorter hospital stays (-1.91 days [-2.24; -1.58]; P < .0001 and -2.73 days [-3.1; -2.36]; P < .0001, respectively). Conclusions: RA appeared to decrease postoperative pulmonary complications as well as VATS compared with OT. VATS decreased postoperative mortality as compared with RA and OT.

Diffusion of Minimally Invasive Approach for Lung Cancer Surgery in France: A Nationwide, Population-Based Retrospective Cohort Study.

BACKGROUND: The minimally invasive approach (MIA) has gained popularity thanks to its efficacy and safety. Our work consisted of evaluating the diffusion of the MIA in hospitals and the variability of this approach (within and between regions). METHODS: All patients who underwent limited resection or lobectomy for lung cancer in France were included from the national hospital administrative database (2013-2020). We described between-hospital differences in the MIA rate over four periods (2013-2014, 2015-2016, 2017-2018, and 2019-2020). The potential influence of the hospital volume, hospital type, and period on the adjusted MIA rate was estimated by a multilevel linear regression. RESULTS: From 2013 to 2020, 77,965 patients underwent a lobectomy or limited resection for lung cancer. The rate of the MIA increased significantly over the four periods (50% in 2019-2020). Variability decreased over time in 7/12 regions. The variables included in the multilevel model were significantly related to the adjusted rate of the MIA. Variability between regions was considerable since 18% of the variance was due to systematic differences between regions. CONCLUSIONS: We confirm that the MIA is part of the surgical techniques used on a daily basis for the treatment of lung cancer. However, this technology is mostly used by surgeons in high volume institutions.

Multimodality therapy for lung cancer invading the chest wall: A study of the French EPITHOR database.

OBJECTIVES: According to a nation-based study, we intend to report the data of the patients operated on for lung cancer invading the chest wall, taking into consideration the completion of induction chemotherapy (Ind_CT), induction radiochemotherapy (Ind_RCT) or no induction therapy (0_Ind). MATERIALS AND METHODS: All patients with a primary lung cancer invading the chest wall who underwent radical resection from 2004 to 2019 were included. Superior sulcus tumors were excluded. RESULTS: Overall, 688 patients were included: 522 operated without induction therapy, 101 with Ind_CT and 65 with Ind_RCT. Postoperative 90-day mortality was 10.7% in the 0_Ind group, 5.0% in the Ind_CT group, 7.7% in the Ind_RCT group (p = 0.17). Incomplete resection rate was 14.0% in the 0_Ind group, 6.9% in the Ind_CT group, 6.2% in the Ind_RCT group (p = 0.04). In the 0_Ind group, 70% of the patients received adjuvant therapies. Overall survival (OS) analysis disclosed the best long-term outcomes in the Ind_RCT group (5-year OS probability: 56.5% versus 40.0% and 40.5% for 0_Ind and Ind_CT groups, respectively; p = 0.035). At multivariable analysis, Ind_RCT (HR = 0.571; p = 0.008), age > 60 years old (HR = 1,373; p = 0.005), male sex (HR = 1.710; p < 0.001), pneumonectomy (HR = 1.368; p = 0.025), pN2 status (HR = 1.981; p < 0.001), ≥3 resected ribs (HR = 1.329; p = 0.019), incomplete resection (HR = 2.284; p < 0.001) and lack of adjuvant therapy (HR = 1.959; p < 0.001) were associated with OS. Ind_CT was not associated with survival (HR = 0.848; p = 0.257). CONCLUSION: Induction chemoradiation therapy seems to improve survival. Therefore, the present results should be confirmed by a prospective randomized trial testing the benefit of induction radiochemotherapy for NSCLC invading the chest wall.

Is there variation between hospitals within each region in postoperative mortality for lung cancer surgery in France? A nationwide study from 2013 to 2020.

Introduction: The practice of thoracic surgery for lung cancer is subject to authorization in France. We evaluated the performance of hospitals using 30-day post-operative mortality as a quality indicator, estimating its distribution within each region and measuring its variability between regions. Material and methods: All data for patients who underwent pulmonary resection for lung cancer in France (2013-2020) were collected from the national hospital administrative database. Thirty-day mortality was defined as any patient who died in hospital (including transferred patients) within the first 30 days after the operation and those who died later during the initial hospitalization. The Standardized Mortality ratio (SMR) was the smoothed, adjusted, hospital-specific mortality rate divided by the expected mortality. To describe the variation in hospital mortality between hospitals in each region, we used different commonly used indicators of variation such as coefficients of variation (CV), interquartile interval or range (IQR), extreme ratio, and systematic component of variance (SCV). Results: In 2013-2020, 87,232 patients underwent lung resection for cancer in France. The number of deaths was 2,537, a rate of 2.91%. The median SMR of 199 hospitals was 0.99 with an IQR of 0.86 to 1.18 and a CV of 0.25. Among the regions that had the most hospitals performing lung resections for cancer, the extreme ratio was >2, which means that the maximum value is twice as high as the minimum value. The SCV between hospitals was >10 for two of these regions, which is considered indicative of very high variation. For the other regions (with few hospitals performing lung resections for cancer), the variation between hospitals was lower. Globally, the variability between regions concerning the SMR was moderate, 6% of the variance was due to differences across regions. On the contrary, the hospital volume was significantly related to the SMR (p = 0.003) with a negative linear trend, whatever the region. Conclusion: This work shows significant differences in the practices of the various hospitals within regions. However, overall, the variability in the 30-day mortality rate between regions was moderate. Our findings raises questions regarding the regionalization of major surgical procedures in France.

Prognostic score and sex-specific nomograms to predict survival in resectable lung cancer: A French nationwide study from the Epithor cohort database.

Background: Prognostic assessment in patients undergoing cancer treatments is of paramount importance to plan subsequent management. In resectable lung cancer availability of an easy-to use nomogram to predict long-term outcome would be extremely useful to identify high-risk patients in the era of perioperative targeted and immune therapies. Methods: We retrieved clinical, surgical and pathological data of all consecutive patients included in Epithor, the database of French Society of Thoracic and Cardiovascular Surgery, and operated on between 2003 and 2020 for non-small cell lung cancer in a curative intent. The primary endpoint was overall survival up to 5 years. We assessed prognostic significance of available variables using Cox modelling, in the whole dataset, and in men and in women separately, and performed temporal validation. Finally, we constructed two sex-specific nomograms. Survivals by fifths of score were assessed in the development and temporal validation sets. Findings: The study included 62,633 patients (43,551 men and 19,082 women). Median survival time was 9.2 years. Nine factors had strong prognostic impact and were used to construct nomograms. The optimism-corrected c statistic for the prognostic score was 0.689 in the development sample, and 0.726 (95% CI 0.718-0.735) in the temporal validation sample. All differences between adjacent fifths of score were significant (P < 0.0001). Figures of 3-year OS by fifths of score were 92.2%, 83.0%, 74.3%, 64.0%, and 43.4%, respectively, in the development set and 93.3%, 88.4%, 81.0%, 73.7%, 55.7% in the temporal validation set. Performance of score was maintained when stratifying by stage of diseases. Interpretation: In the present work, we report evidence that long-term overall survival after resection of NSCLC can be predicted by an easy to construct and use composite score taking into account both host and tumour related factors. Funding: Epithor is funded by FSTCVS.

Impact of the SARS-CoV-2 Epidemic on Lung Cancer Surgery in France: A Nationwide Study.

Few studies have investigated the link between SARS-CoV-2 and health restrictions and its effects on the health of lung cancer (LC) patients. The aim of this study was to assess the impact of the SARS-CoV-2 epidemic on surgical activity volume, postoperative complications and in-hospital mortality (IHM) for LC resections in France. All data for adult patients who underwent pulmonary resection for LC in France in 2020, collected from the national administrative database, were compared to 2018-2019. The effect of SARS-CoV-2 on the risk of IHM and severe complications within 30 days among LC surgery patients was examined using a logistic regression analysis adjusted for age, sex, comorbidities and type of resection. There was a slight decrease in the volume of LC resections in 2020 (n = 11,634), as compared to 2018 (n = 12,153) and 2019 (n = 12,227), with a noticeable decrease in April 2020 (the peak of the first wave of epidemic in France). We found that SARS-CoV-2 (0.43% of 2020 resections) was associated with IHM and severe complications, with, respectively, a sevenfold (aOR = 7.17 (3.30-15.55)) and almost a fivefold (aOR = 4.76 (2.31-9.80)) increase in risk. Our study suggests that LC surgery is feasible even during a pandemic, provided that general guidance protocols edited by the surgical societies are respected.

The Reality of Lung Cancer Paradox: The Impact of Body Mass Index on Long-Term Survival of Resected Lung Cancer. A French Nationwide Analysis from the Epithor Database.

Obesity could have a protective effect in patients with lung cancer. We assessed the prognostic role of preoperative BMI on survival in patients who underwent lung resection for NSCLC. A total of 54,631 consecutive patients with resectable lung cancer within a 15-year period were extracted from Epithor (the French Society of Thoracic and Cardiovascular Surgery database). Patient subgroups were defined according to body mass index (BMI): underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obese (BMI ≥ 30 kg/m2). Underweight was associated with lower survival (unadjusted HRs 1.24 (1.16-1.33)) compared to normal weight, whereas overweight and obesity were associated with improved survival (0.95 (0.92-0.98) and 0.88 (0.84-0.92), respectively). The impact of BMI was confirmed when stratifying for sex or Charlson comorbidities index (CCI). Among patients with obesity, a higher BMI was associated with improved survival. After adjusting for period of study, age, sex, WHO performance status, CCI, side of tumor, extent of resection, histologic type, and stage of disease, the HRs for underweight, overweight, and obesity were 1.51 (1.41-1.63), 0.84 (0.81-0.87), and 0.80 (0.76-0.84), respectively. BMI is a strong and independent predictor of survival in patients undergoing surgery for NSCLC.

Interest of anatomical segmentectomy over lobectomy for lung cancer: a nationwide study.

BACKGROUND: Anatomical segmentectomy is an alternative to lobectomy for early-stage lung cancer (LC) or in patients at high risk. The main objective of this study was to compare the morbidity and mortality associated with these two types of pulmonary resection using data from the French National Epithor database. METHODS: All patients who underwent lobectomy or segmentectomy for early-stage LC from January 1st 2014 to December 31st 2016 were identified in the Epithor database. The primary endpoint was morbidity; the secondary endpoint was postoperative mortality. Propensity score matching was implemented and used to balance groups. The results were reported as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: During the study period, 1,604 segmentectomies (9.78%) and 14,786 lobectomies (90.22%) were performed. After matching, the segmentectomy group experienced significantly less atelectasis (OR 0.54; 95% CI: 0.4-0.75, P<0.0001), pneumonia (OR 0.72; 95% CI: 0.55-0.95, P=0.02), prolonged air leaks (OR 0.75; 95% CI: 0.64-0.89, P=0.001) or bronchopleural fistula (OR 0.35; 95% CI: 0.14-0.83, P=0.017), and fewer patients had at least one complication (OR 0.7; 95% CI: 0.62-0.78, P<0.0001). According to the Clavien-Dindo classification, postoperative complications were significantly less severe in the segmentectomy group (OR 0.52; 95% CI: 0.37-0.74, P<0.0001). There was no significant difference in postoperative mortality at 30 days (OR 0.67; 95% CI: 0.38-1.20, P=0.18), 60 days (OR 0.78; 95% CI: 0.42-1.47, P=0.4), or 90 days (OR 0.77; 95% CI: 0.45-1.34, P=0.36). CONCLUSIONS: Anatomical segmentectomy is an alternative surgical approach that could reduce postoperative morbidity, but it does not appear to affect mortality.

Guidelines on enhanced recovery after pulmonary lobectomy.

OBJECTIVE: To establish recommendations for optimisation of the management of patients undergoing pulmonary lobectomy, particularly Enhanced Recovery After Surgery (ERAS). DESIGN: A consensus committee of 13 experts from the French Society of Anaesthesia and Intensive Care Medicine (Soci,t, franOaise d'anesth,sie et de r,animation, SFAR) and the French Society of Thoracic and Cardiovascular Surgery (Soci,t, franOaise de chirurgie thoracique et cardiovasculaire, SFCTCV) was convened. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence. METHODS: Five domains were defined: 1) patient pathway and patient information; 2) preoperative management and rehabilitation; 3) anaesthesia and analgesia for lobectomy; 4) surgical strategy for lobectomy; and 5) enhanced recovery after surgery. For each domain, the objective of the recommendations was to address a number of questions formulated according to the PICO model (Population, Intervention, Comparison, Outcome). An extensive literature search on these questions was carried out and analysed using the GRADE® methodology. Recommendations were formulated according to the GRADE® methodology, and were then voted by all experts according to the GRADE grid method. RESULTS: The SFAR/SFCTCV guideline panel provided 32 recommendations on the management of patients undergoing pulmonary lobectomy. After two voting rounds and several amendments, a strong consensus was reached for 31 of the 32 recommendations and a moderate consensus was reached for the last recommendation. Seven of these recommendations present a high level of evidence (GRADE 1+), 23 have a moderate level of evidence (18 GRADE 2+ and 5 GRADE 2-), and 2 correspond to expert opinions. Finally, no recommendation was provided for 2 of the questions. CONCLUSIONS: A strong consensus was expressed by the experts to provide recommendations to optimise the whole perioperative management of patients undergoing pulmonary lobectomy.

Monitoring HSP70 exosomes in cancer patients' follow up: a clinical prospective pilot study.

Exosomes are nanovesicles released by all cells that can be found in the blood. A key point for their use as potential biomarkers in cancer is to differentiate tumour-derived exosomes from other circulating nanovesicles. Heat shock protein-70 (HSP70) has been shown to be abundantly expressed by cancer cells and to be associated with bad prognosis. We previously showed that exosomes derived from cancer cells carried HSP70 in the membrane while those from non-cancerous cells did not. In this work, we opened a prospective clinical pilot study including breast and lung cancer patients to determine whether it was possible to detect and quantify HSP70 exosomes in the blood of patients with solid cancers. We found that circulating exosomal HSP70 levels, but not soluble HSP70, reflected HSP70 content within the tumour biopsies. Circulating HSP70 exosomes increased in metastatic patients compared to non-metastatic patients or healthy volunteers. Further, we demonstrated that HSP70-exosome levels correlated with the disease status and, when compared with circulating tumour cells, were more sensitive tumour dissemination predictors. Finally, our case studies indicated that HSP70-exosome levels inversely correlated with response to the therapy and that, therefore, monitoring changes in circulating exosomal HSP70 might be useful to predict tumour response and clinical outcome.

Validation and update of the thoracic surgery scoring system (Thoracoscore) risk model.

OBJECTIVES: The performance of prediction models tends to deteriorate over time. The purpose of this study was to update the Thoracoscore risk prediction model with recent data from the Epithor nationwide thoracic surgery database. METHODS: From January 2016 to December 2017, a total of 56 279 patients were operated on for mediastinal, pleural, chest wall or lung disease. We used 3 recommended methods to update the Thoracoscore prediction model and then proceeded to develop a new risk model. Thirty-day hospital mortality included patients who died within the first 30 days of the operation and those who died later during the same hospital stay. RESULTS: We compared the baseline patient characteristics in the original data used to develop the Thoracoscore prediction model and the validation data. The age distribution was different, with specifically more patients older than 65 years in the validation group. Video-assisted thoracoscopy accounted for 47% of surgeries in the validation group compared but only 18% in the original data. The calibration curve used to update the Thoracoscore confirmed the overfitting of the 3 methods. The Hosmer-Lemeshow goodness-of-fit test was significant for the 3 updated models. Some coefficients were overfitted (American Society of Anesthesiologists score, performance status and procedure class) in the validation data. The new risk model has a correct calibration as indicated by the Hosmer-Lemeshow goodness-of-fit test, which was non-significant. The C-index was strong for the new risk model (0.84), confirming the ability of the new risk model to differentiate patients with and without the outcome. Internal validation shows no overfitting for the new model. CONCLUSIONS: The new Thoracoscore risk model has improved performance and good calibration, making it appropriate for use in current clinical practice.

Comparison of Epithor clinical national database and medico-administrative database to identify the influence of case-mix on the estimation of hospital outliers.

BACKGROUND: The national Epithor database was initiated in 2003 in France. Fifteen years on, a quality assessment of the recorded data seemed necessary. This study examines the completeness of the data recorded in Epithor through a comparison with the French PMSI database, which is the national medico-administrative reference database. The aim of this study was to demonstrate the influence of data quality with respect to identifying 30-day mortality hospital outliers. METHODS: We used each hospital's individual FINESS code to compare the number of pulmonary resections and deaths recorded in Epithor to the figures found in the PMSI. Centers were classified into either the good-quality data (GQD) group or the low-quality data (LQD) group. To demonstrate the influence of case-mix quality on the ranking of centers with low-quality data, we used 2 methods to estimate the standardized mortality rate (SMR). For the first (SMR1), the expected number of deaths per hospital was estimated with risk-adjustment models fitted with low-quality data. For the second (SMR2), the expected number of deaths per hospital was estimated with a linear predictor for the LQD group using the coefficients of a logistic regression model developed from the GQD group. RESULTS: Of the hospitals that use Epithor, 25 were classified in the GQD group and 75 in the LQD group. The 30-day mortality rate was 2.8% (n = 300) in the GQD group vs. 1.9% (n = 181) in the LQD group (P <0.0001). The between-hospital differences in SMR1 appeared substantial (interquartile range (IQR) 0-1.036), and they were even higher in SMR2 (IQR 0-1.19). SMR1 identified 7 hospitals as high-mortality outliers. SMR2 identified 4 hospitals as high-mortality outliers. Some hospitals went from non-outlier to high mortality and vice-versa. Kappa values were roughly 0.46 and indicated moderate agreement. CONCLUSION: We found that most hospitals provided Epithor with high-quality data, but other hospitals needed to improve the quality of the information provided. Quality control is essential for this type of database and necessary for the unbiased adjustment of regression models.