Therapeutic bronchoscopy for malignant central airway obstructions caused by non-bronchogenic cancers: Results from the EpiGETIF registry.

BACKGROUND AND OBJECTIVE: Little is known about malignant central airway obstruction (MCAO) complicating the metastatic spread of non-bronchogenic solid cancers (NBC) and their bronchoscopic management. This study aimed to describe the epidemiology of this population and determine prognostic factors before therapeutic bronchoscopy (TB). METHODS: In this multicenter study using the EpiGETIF registry, we analysed patients treated with TB for MCAO caused by NBC between January 2019 and December 2022. RESULTS: From a database of 2389 patients, 436 patients (18%) with MCAO and NBC were identified. After excluding patients with direct local invasion, 214 patients (8.9%) were analysed. The main primaries involved were kidney (17.8%), colon (16.4%), sarcoma (15.4%), thyroid (8.9%) and head and neck (7.9%) cancers. Most patients (63.8%) had already received one or more lines of systemic treatment. Obstructions were purely intrinsic in 58.2%, extrinsic in 11.1% and mixed in 30.8%. Mechanical debulking was used in 73.4% of cases, combined with thermal techniques in 25.6% of cases. Airway stenting was required in 38.4% of patients. Median survival after TB was 11.2 months, influenced by histology (p = 0.002), performance status (p = 0.019), initial hypoxia (HR 1.45 [1.01-2.18]), prior oncologic treatment received (HR 1.82 [1.28-2.56], p < 0.001) and assessment of success at the end of the procedure (HR 0.66 [0.44-0.99], p < 0.001). Complications rate was 8.8%, mostly mild, with no procedure-related mortality. CONCLUSION: TB for MCAO caused by a NBC metastasis provides rapid improvement of symptoms and prolonged survival. Patients should be promptly referred by medical oncologists for bronchoscopic management based on the prognostic factors identified.

Therapeutic bronchoscopy for malignant central airway obstruction: Introduction to the EpiGETIF registry.

BACKGROUND AND OBJECTIVE: EpiGETIF is a web-based, multicentre clinical database created in 2019 aiming for prospective collection of data regarding therapeutic rigid bronchoscopy (TB) for malignant central airway obstruction (MCAO). METHODS: Patients were enrolled into the registry from January 2019 to November 2022. Data were prospectively entered through a web-interface, using standardized definitions for each item. The objective of this first extraction of data was to describe the population and the techniques used among the included centres to target, facilitate and encourage further studies in TB. RESULTS: Overall, 2118 patients from 36 centres were included. Patients were on average 63.7 years old, mostly male and smokers. Most patients had a WHO score ≤2 (70.2%) and 39.6% required preoperative oxygen support, including mechanical ventilation in 6.7%. 62.4% had an already known histologic diagnosis but only 46.3% had received any oncologic treatment. Most tumours were bronchogenic (60.6%), causing mainly intrinsic or mixed obstruction (43.3% and 41.5%, respectively). Mechanical debulking was the most frequent technique (67.3%), while laser (9.8%) and cryo-recanalization (2.7%) use depended on local expertise. Stenting was required in 54.7%, silicone being the main type of stent used (55.3%). 96.3% of procedure results were considered at least partially successful, resulting in a mean 4.1 points decrease on the Borg scale of dyspnoea. Complications were noted in 10.9%. CONCLUSION: This study exposes a high volume of TB that could represent a good source of future studies given the dismal amount of data about the effects of TB in certain populations and situations.

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.

Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital.

Background: In the context of personalized medicine, screening patients to identify targetable molecular alterations is essential for therapeutic decisions such as inclusion in clinical trials, early access to therapies, or compassionate treatment. The objective of this study was to determine the real-world impact of routine incorporation of FoundationOne analysis in cancers with a poor prognosis and limited treatment options, or in those progressing after at least one course of standard therapy. Methods: A FoundationOneCDx panel for solid tumor or liquid biopsy samples was offered to 204 eligible patients. Results: Samples from 150 patients were processed for genomic testing, with a data acquisition success rate of 93%. The analysis identified 2419 gene alterations, with a median of 11 alterations per tumor (range, 0-86). The most common or likely pathogenic variants were on TP53, TERT, PI3KCA, CDKN2A/B, KRAS, CCDN1, FGF19, FGF3, and SMAD4. The median tumor mutation burden was three mutations/Mb (range, 0-117) in 143 patients with available data. Of 150 patients with known or likely pathogenic actionable alterations, 13 (8.6%) received matched targeted therapy. Sixty-nine patients underwent Molecular Tumor Board, which resulted in recommendations in 60 cases. Treatment with genotype-directed therapy had no impact on overall survival (13 months vs. 14 months; p = 0.95; hazard ratio = 1.04 (95% confidence interval, 0.48-2.26)]. Conclusions: This study highlights that an organized center with a Multidisciplinary Molecular Tumor Board and an NGS screening system can obtain satisfactory results comparable with those of large centers for including patients in clinical trials.

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.

Neoadjuvant durvalumab for resectable non-small-cell lung cancer (NSCLC): results from a multicenter study (IFCT-1601 IONESCO).

BACKGROUND: The IONESCO (IFCT-1601) trial assessed the feasibility of neoadjuvant durvalumab, for early-stage resectable non-small-cell lung cancer (NSCLC). METHODS: In a multicenter, single-arm, phase II trial, patients with IB (≥4 cm)-IIIA, non-N2, resectable NSCLC received three doses of durvalumab (750 mg every 2 weeks) and underwent surgery between 2 and 14 days after the last infusion. The primary endpoint was the complete surgical resection rate. Secondary endpoints included tumor response rate, major histopathological response (MPR: ≤10% remaining viable tumor cells), disease-free survival (DFS), overall survival (OS), durvalumab-related safety, and 90-day postoperative mortality (NCT03030131). RESULTS: Forty-six patients were eligible (median age 60.9 years); 67% were male, 98% were smokers, and 41% had squamous cell carcinoma. Regarding tumor response, 9% had a partial response, 78% had stable disease, and 13% had progressive disease. Among the operated patients (n=43), 41 achieved complete resection (89%, 95% CI 80.1% to 98.1%)), and eight achieved MPR (19%). The 12-month median OS and DFS rates were 89% (95% CI 75.8% to 95.3%) and 78% (95% CI 63.4% to 87.7%), respectively (n=46). The median follow-up was 28.4 months (12.8-41.1). All patients in whom MPR was achieved were disease-free at 12 months compared to only 11% of those with >10% residual tumor cells (p=0.04). No durvalumab-related serious or grade 3-5 events were reported. The unexpected 90-day postoperative mortality of four patients led to premature study termination. None of these four deaths was considered secondary to direct durvalumab-related toxicity. CONCLUSIONS: Neoadjuvant durvalumab given as monotherapy was associated with an 89% complete resection rate and an MPR of 19%. Despite an unexpectedly high rate of postoperative deaths, which prevented us from completing the trial, we were able to show a significant association between MPR and DFS.

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.

Pneumatocoeles after bronchoscopic lung volume reduction with valves.

Pneumatocoele is a very rare complication of Zephyr EBV, probably due to chest tube insertion and suction of a trapped and emphysematous lung. Complete healing and functional improvements are possible without the need for valve removal. https://bit.ly/2K84Vjl.

Effectiveness and safety of nivolumab in the treatment of lung cancer patients in France: preliminary results from the real-world EVIDENS study.

EVIDENS is an ongoing, prospective, non-interventional study evaluating the effectiveness and safety of nivolumab in lung cancer patients in France (ClinicalTrials.gov NCT03382496). Adults with a pathologically confirmed diagnosis of lung cancer and initiating treatment with nivolumab were recruited from 146 sites in France. This analysis included only patients with non-small cell lung cancer (NSCLC) who received ≥1 nivolumab infusion, and evaluated patient characteristics at the time of nivolumab initiation and its effectiveness and safety after a median follow-up of 18 months. A total of 1,420 patients with NSCLC were included, most of whom had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (82.9%), non-squamous histology (69.2%) and stage IV disease (91.4%). Brain metastases were present in 19.9% of patients. Nivolumab was a second-line or ≥third-line regimen in 73.6% and 26.1% of patients, respectively. Almost all patients had prior chemotherapy (99.7%). Median overall survival was 11.2 months (95% confidence interval [CI]: 10.0-12.4). ECOG PS, smoking status, corticosteroids at baseline, epidermal growth factor receptor mutation status, presence of symptomatic brain metastases and treatment-related adverse events (TRAEs) were independent predictors of survival. Grade 3 and 4 TRAEs were reported in 105 (7.4%) and 12 (0.8%) patients, respectively; no treatment-related deaths were reported. Preliminary results of the EVIDENS study confirm the effectiveness and safety of nivolumab, mostly in pre-treated advanced NSCLC patients, with similar benefits to those observed in the phase III randomized clinical trials, despite a broader study population.

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.

Staging of nutrition disorders in non-small-cell lung cancer patients: utility of skeletal muscle mass assessment.

BACKGROUND: An international consensus proposed in 2011 a definition and classification system for cachexia (CAX), mainly based on weight loss, sarcopenia [skeletal muscle mass (SMM) loss], inflammation, and anorexia. The aim of this study was to stage CAX in non-small-cell lung cancer (NSCLC) patients by using a classification based on the Fearon criteria and supported by quantifiable parameters. METHODS: This was a cross-sectional and non-interventional multicentre study. SMM was assessed by analysing L3 computed tomography-scan images. Patients completed the anorexia/CAX subscale of the Functional Assessment of Anorexia/Cachexia Therapy, EORTC QLQ-C30 quality of life (QoL) and International Physical Activity Questionnaire (IPAQ). RESULTS: Patients were recruited in 56 sites. The analysis population comprised 531 patients, and SMM was assessed in 312 patients. Male patients were 66.5%, with a mean (SD) age of 65.2 (10.0) years, 79.9% were PS 0-1, and the tumour stage was mainly IIIB-IV (87.3%). Overall, 38.7% of patients had CAX, 33.8% pre-CAX, and 0.9% refractory CAX. Molecular tumour profiles were significantly associated with the presence of CAX: 23.9% in EGFR, ALK, ROS1, BRAF, or HER2+ patients, 41.4% in K-RAS+, and 43.2% in patients with no molecular abnormality (P = 0.003). The more advanced the CAX stage, the poorer the scores of functional items of the QoL (P < 0.001) and International Physical Activity Questionnaire (P < 0.001). Sarcopenia was present in 66.7% of CAX and 68.5% of pre-CAX patients. Overall, 43.8% of pre-CAX patients had only sarcopenia with limited weight loss (≤2%) and no anorexia. CONCLUSIONS: This is the first study to show the distribution of CAX in a population of NSCLC patients and an association between molecular abnormality in NSCLC and CAX. The original Fearon classification for CAX stages was supported by the associated functional QoL scores and physical activity levels, resulting in a clinically relevant system for detection of early stages of CAX.

Renal insufficiency is the leading cause of double maintenance (bevacizumab and pemetrexed) discontinuation for toxicity to advanced non-small cell lung cancer in real world setting.

OBJECTIVES: In advanced non-small cell lung cancer (NSCLC), maintenance therapy has emerged as a novel therapeutic reference for patients with non-progressive disease after platinum-based induction chemotherapy. However, the use of double maintenance (DM) with pemetrexed and bevacizumab is still being evaluated in terms of its clinical benefits and safety profile. The objective of this retrospective study was to describe the reasons for DM discontinuation in a real-world setting. MATERIALS AND METHODS: Patients with advanced non-squamous NSCLC were eligible if they had received at least 4 cycles of induction chemotherapy, followed by at least 1 cycle of DM. They were identified by using the oncology pharmacy database of 17 French centers. RESULTS: Eighty-one patients who began a DM after induction chemotherapy were identified from September 2009 to April 2013. Among the 78 patients who had stopped DM at the time of the analysis, the main reasons for discontinuation were disease progression (42%), adverse events (33%), and personal preference (8%). The most frequent toxicity responsible for DM discontinuation was renal insufficiency (54%). CONCLUSION: For patients with advanced NSCLC eligible for DM therapy, a particular attention should be paid to potential renal failure. Kidney function should be monitored carefully before and during DM to detect and manage early this adverse event.