Impact of bronchoscopic lung volume reduction with endobronchial valves on dynamic hyperinflation: Results from the PIERCE study.

BACKGROUND AND OBJECTIVE: Dynamic hyperinflation (DH) is a major marker of exertional dyspnoea in severe emphysema. We hypothesized that bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBVs) decreases DH. METHODS: In this prospective bi-centre study from both Toulouse and Limoges Hospitals, we assessed DH during an incremental cycle ergometry before and 3 months after EBVs treatment. The primary objective was to observe the change in inspiratory capacity (IC) at isotime. Target lobe volume reduction (TLVR) and changes in residual volume (RV), forced expiratory volume in one-second (FEV1 ), mMRC, 6 minutes walking distance (6MWD), BODE and other dynamic measures like tele-expiratory volume (EELV) were also analysed. RESULTS: Thirty-nine patients were included, of whom thirty-eight presented DH. IC and EELV at isotime significantly improved (+214 mL, p = 0.004; -713 mL, p Ë‚ 0.001, respectively). Mean changes were +177 mL for FEV1 (+19%, p < 0.001), -600 mL for RV (p < 0.0001), +33 m for 6MWD (p < 0.0001), respectively. Patients who responded on RV (>430 mL decrease) and FEV1 (>12% gain) had better improvements compared to non-responders (+368 mL vs. +2 mL; +398 mL vs. -40 mL IC isotime, respectively). On the opposite, in patients who responded on DH (>200 mL IC isotime increase), changes in TLV (-1216 mL vs. -576 mL), FEV1 (+261 mL vs. +101 mL), FVC (+496 mL vs. +128 mL) and RV (-805 mL vs. -418 mL) were greater compared to non-responders. CONCLUSIONS: DH decreases after EBVs treatment, and this improvement is correlated with static changes.

Retrospective Assessment of Complementary Liquid Biopsy on Tissue Single-Gene Testing for Tumor Genotyping in Advanced NSCLC.

Biomarker testing is key for non-small cell lung cancer (NSCLC) management and plasma based next-generation sequencing (NGS) is increasingly characterized as a non-invasive alternative. This study aimed to evaluate the value of complementary circulating tumor DNA (ctDNA) NGS on tissue single-gene testing (SGT). Ninety-one advanced stage NSCLC patients with tumor genotyping by tissue SGT (3 genes) followed by ctDNA (38 genes amplicon panel) were included. ctDNA was positive in 47% (n = 43) and identified a targetable biomarker in 19 patients (21%). The likelihood of positivity on ctDNA was higher if patients had extra-thoracic disease (59%) or were not under active treatment (59%). When compared to SGT, ctDNA provided additional information in 41% but missed a known alteration in 8%. Therapeutic change for targeted therapy based on ctDNA occurred in five patients (5%), while seven patients with missed alterations on ctDNA had EGFR mutations or ALK fusions. The median turnaround time of ctDNA was 10 days (range 6-25), shorter (p = 0.002) than the cumulative delays for the tissue testing trajectory until biomarker availability (13 d; range 7-1737). Overall, the results from this study recapitulate the potential and limitations of ctDNA when used complementarily to tissue testing with limited biomarker coverage.

Endobronchial valves: 1st Multicenter retrospective study on the 2-step approach.

BACKGROUND: Although the endobronchial valves (EBV) were successfully developed as treatment for severe emphysema, its main complication, pneumothorax, remained an important concern. OBJECTIVE: To assess whether the placement of Zephyr© endobronchial valves throughout 2 procedures instead of 1 minor the frequency of pneumothorax without lowering the benefits of such treatment. METHODS: This retrospective study was conducted in 15 pulmonology department in France. All the patients met the inclusion criteria of the recommendation set by the expert panel on the Endoscopic Lung Volume Reduction (ELVR) updated in 2019. As recommended, all the scan were analyzed with the StratX© (PulmonX Corporation, Redwood city, CA) protocol, and completed by a Chartis© (PulmonX Corporation, Redwood city, CA) in case of questionable fissure. During the first procedure, all but the most proximal sub-segment of the targeted lobe were occluded. One month after, EBV were placed in the bronchus of the last subsegment. All patients were evaluated before and 3 months after the second procedure. RESULTS: Between March 2019 and December 2020, 96 patients received EBV treatment. 12 patients (12.5%) presented a pneumothorax (3 after the 1st step and 9 after the 2nd procedure). Beside pneumothorax, the main adverse event was exacerbation (10.4%) and pneumonia (4.1%). No death were reported. Significant improvement were found for FEV1 (14.6 ± 25.3%), RV (- 0.69 ± 2.1 L), 6MWT (34.8 ± 45.9 m), BODE Score (-1.41 ± 1.41pts), and mMRC scale (-0.85 ± 0.7pts). These results are compared not only to the results previously published using the usual approach but also to our previous publication evaluating the 2-step approach. Some patients presented authentic segmental atelectasis despite infralobar treatment. CONCLUSION: Placing EBV during 2 procedures instead of one led to a significant decrease of post treatment pneumothoraces without increasing the rate of other complications. It does not seem to alter the benefits of such therapy for severe emphysema. These results must be confirmed by launching a multicenter, prospective, randomized, controlled study to compare the frequency of pneumothorax and the efficacy of this new approach with the usual one-time procedure.

Bilateral endobronchial valves treatment for severe emphysema.

Bilateral endobronchial valves treatment can lead to additional significant benefits in patients who respond to the first procedure and have a clear target lobe on both lungs but increases the rate of complications https://bit.ly/3J0mZ8h.

Two-Stage Bronchoscopic Endobronchial Valve Treatment Can Lead to Progressive Lung Volume Reduction and May Decrease Pneumothorax Risk.

Background: Since successful development of endobronchial valves (EBV) as treatment for severe emphysema, its main complication, pneumothorax, remains an important concern. Objective: We hypothesized that a two-step EBV implantation, during two distinct iterative procedures could lead to a more progressive target lobe volume reduction (TLVR) and thus ipsilateral lobe re-expansion, resulting in a significant decrease in the pneumothorax rate. Methods: This retrospective bi-center study carried out by Limoges and Toulouse University Hospitals included patients following the inclusion criteria established by the BLVR expert panel. All patients were treated by two distinct procedures: first, EBVs were placed in all but the most proximal segment or sub-segment. The remaining segment was treated subsequently. All patients had a complete evaluation before treatment, and 3 months after the second procedure. Results: Out of 58 patients included, only 4 pneumothoraxes (7%) occurred during the study. The other complications were pneumonia and severe COPD exacerbation (8.6% and 13.7% of patients, respectively). Significant improvement was found for FEV1 (+19.6 ± 25%), RV (-468 ± 960mL), 6MWD (30 ± 85m), BODE Index (-1.4 ± 1.8 point) and TLVR (50.6 ± 35.1%). Significant TLVR (MCID) was obtained in 74.1% of patients (43/58). Conclusion: This new approach using EBV could reduce the incidence of pneumothorax without increasing other complication rates. Clinical and physiological outcomes are similar to those reported in studies using the conventional single-step treatment.

Neutrophil-to-lymphocyte ratio evolution is an independent predictor of early progression of second-line nivolumab-treated patients with advanced non-small-cell lung cancers.

INTRODUCTION: Although second-line immunotherapy obtained better outcomes than chemotherapy for patients with advanced non-small-cell lung cancers (NSCLCs), it is expensive and only a minority of patients seem to benefit, based on early tumor progression post-immunotherapy. Notable host inflammation, characterized by biomarkers (e.g. neutrophil-to-lymphocyte ratio (NLR])), prolongs overall survival (OS) of surgery-, chemotherapy- and immunotherapy-treated patients. To our knowledge, no previous studies used biomarker evolution to analyze the immunotherapy impact on host inflammation. Immunotherapy mainly exerts its activity by lymphocyte reactivation. METHODS: This retrospective study was conducted on patients, selected by their progression status just before their 4th nivolumab injection, and treated at Bordeaux and Limoges University Hospitals. A comparative group of at least 1-year responders was also selected. Clinical parameters and hematological data just before the 1st (baseline) and 4th nivolumab infusions were collected to calculate the NLR change (ΔNLR) between those two infusions. The combined impact of the different known prognostic factors was also analyzed with multivariable analyses. RESULTS: Fifty-nine patients were included. The 29 early progressors had significantly more frequent ΔNLR > 1 (p = 0.0007), OR 18.08 [95% CI 2.96-246.24] with progressive disease as best response to prior treatment line (p = 0.0014). ΔNLR < 1 prolonged OS (HR 0.001 [0.0007-0.18], p = 0.001); as did a partial response to prior line of systemic treatment (HR 0.14 [0.03--0.56], p = 0.005). CONCLUSION: Based on selected early progressors given second-line immunotherapy for advanced NSCLC, progression as best response to prior treatment and ΔNLR > 1 characterized the early progressors and shortened OS after starting nivolumab. This phenomenon questions nivolumab utility in patients with a major host neutrophil inflammation.