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.

Role of bronchoscopy for respiratory involvement in granulomatosis with polyangiitis and microscopic polyangiitis.

Objectives: This study describes data from bronchoscopy performed at the diagnosis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: We conducted a retrospective study between 2004 and 2019 in patients aged >18 years with a diagnosis of microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) who underwent bronchoscopy at onset of the disease. We collected bronchoalveolar lavage (BAL) and histological findings obtained during bronchoscopy. Results: 274 patients with AAV were identified. Among 92 bronchoscopies, 62 were performed at diagnosis, and 58 procedures were finally analysed. Cough was more frequent in patients with MPA than GPA (p=0.02). The presence of endobronchial lesions (24.1%) was found to be significantly associated with GPA (p<0.0001) and proteinase 3-ANCA (p=0.01). The most frequent endobronchial lesions were inflammation and hyperaemia of the bronchial mucosa (50%), followed by stenoses (28%), ulcerations (21%) and mass-like granulomatosis (7%). The diagnostic yield of bronchial biopsies was useful for visible lesions (66.6% versus 0%; p=0.006). On BAL, diffuse alveolar haemorrhage (DAH) was detected in 31 (53.4%) patients and was more frequent in MPA patients (70.4% versus 38.7%; p=0.016). In 16.1% of DAH cases, BAL confirmed the diagnosis despite the absence of clinical or biological arguments. The incidence of microbial infections on BAL (38%) was similar between MPA and GPA (p=0.54). Conclusion: Bronchoscopy is an informative procedure at the onset of AAV disease in patients with respiratory manifestations. Endobronchial lesions are more frequently found in GPA and should be biopsied. BAL can be used to confirm DAH or diagnose superadded infection.

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 and molecular analysis of lung cancers associated with fibrosing interstitial lung disease.

BACKGROUND: Interstitial lung disease is a heterogeneous group of diseases, some of which are known to present an independent risk factor for lung cancer. Its pathophysiological mechanism has not been fully elucidated and therapeutic management is also complex. We aim to both describe a cohort of patients with lung cancer associated with pre-existing fibrosing interstitial lung disease and to characterize their molecular profile. METHODS: We conducted a retrospective, single centre cohort study, at Toulouse University Hospital. Immuno-histochemical (PD-L1, CD8) and molecular analysis was performed on archived tumour sample. Molecular signalling pathways involved were analysed with the Reactome Pathway Database. RESULTS: Forty-nine patients were analysed. Most common histology was adenocarcinoma (65,3%), followed by squamous cell carcinoma (30.6%). Idiopathic pulmonary fibrosis (30,6%) and interstitial lung disease associated with connective tissue disease (22,4%) were mostly diagnosed. Usual interstitial pneumonia dominated the scans patterns. A high proportion of early tumour stages was observed and overall survival was 34,5 months. In metastatic stages response rate to first line chemotherapy was 38% and overall survival was 11,2 months. Main cause of death was complex cancer progression. PD-L1 expression (n=23) was low (0%) to intermediate (1-49%). Tumour mutational burden was low in 69,2% of analysed cases (n=12) and microsatellite status was stable in all cases (n=13). Sample genotyping (n=14) showed frequent involvement of the TP53 gene and the implication of signalling pathways common to fibrotic processes such as TGFß and PI3K/AKT. CONCLUSIONS: We suggest a particular phenotype of lung cancer associated with fibrosing interstitial lung disease that could provide the basis for specific therapeutic strategies.

Impact of pulmonary hypertension on lung cancer management.

INTRODUCTION: The diagnosis and management of lung cancer is challenging among patients followed-up for pulmonary hypertension (PH). Many interventional procedures are not suitable for severely ill patients, thus limiting the diagnosis and treatment of cancer. We report on patients diagnosed with both conditions in our Institution. METHODS: We conducted a retrospective observational cohort study at Toulouse University Hospital. We analysed both management and outcome for patients followed-up for precapillary PH following diagnosis of primary lung cancer. RESULTS: Out of 764 patients followed-up for PH, 25 went on to develop bronchopulmonary neoplasia. The median age was 69 years with a predominance of males (56%) and smokers (92%). Fifty-two percent had group 1 PH and 36% severe group 3 PH. The comorbidity burden was high and 76% were oxygen-dependent. Twenty-eight percent of patients were considered ineligible for tissue biopsy, the diagnosis being made by a multidisciplinary team (MDT) based on radio-clinical presentation. Fifty-four percent of patients did not benefit from any treatment. Sixteen percent of pulmonary diagnostic procedures were associated with complications (severe hypoxaemia, intra-alveolar hemorrhage, haemothorax). Patients were undertreated compared to disease stage guidelines (2 surgical procedures for 9 localised stages). Median survival after cancer diagnosis was 6 months. CONCLUSION: The management of lung cancer is complex in PH patients. The high rate of complications during the diagnosis and therapy steps coupled with very poor patient outcome for both conditions should prompt physicians to thoroughly discuss the benefit/risk benefit in each case.

Feasibility of comprehensive genotyping specimens from radial endobronchial ultrasonography and electromagnetic navigation bronchoscopy.

INTRODUCTION: Mini-invasive bronchoscopic techniques (such as radial endobronchial ultrasonography (rEBUS) and electromagnetic navigation (EMN)) have been developed to reach the peripheral lung but result in small samples. The feasibility of an adequate molecular testing from these specimens has been very little studied. METHODS: We retrospectively reviewed EMN and rEBUS procedures performed in patients diagnosed with lung cancer in our institution in 2017 and 2018. We analysed the sensitivity for rEBUS and EMN and each sampling method, and the feasibility of a comprehensive molecular testing. RESULTS: In total, 317 rEBUS and 14 EMN were performed. Median sizes of tumours were 16 and 32 mm for EMN and rEBUS, respectively. Overall sensitivity for rEBUS and EMN was 84.3%. Cytology was found to be complementary with biopsies, with 13.3% of cancer diagnosed on cytology while biopsies were negative. Complication rate was 2.4% (pneumothorax 1.5%, mild haemoptysis 0.9%). Genotyping (immunohistochemistry for ROS1 and ALK followed by fluorescence in situ hybridisation if positive and hybrid capture next-generation sequencing covering 48 genes), when ordered (n=188), was feasible in 69.1% (EGFR 17.7%, KRAS 31.7%, BRAF 4.8%, ALK 1.2%, MET 3.1%, HER2 0.8%). PD-L1 (programmed death-ligand 1) expression, when ordered (n=232), could be analysed in 94% of cases. Overall, 56.9% (33 out of 58) of patients for whom genotyping was not feasible underwent a second sampling (12 pretreatment, 21 at progression), allowing for the detection of six actionable genotypes (five EGFR, one MET). CONCLUSION: rEBUS and EMN are sensitive and safe procedures that result in limited samples, often not suitable for genotyping, highlighting the importance of integrating liquid biopsy in routine testing.

Bronchoscopic Treatment of Endobronchial Inflammatory Myofibroblastic Tumors.

Endobronchial localizations of inflammatory myofibroblastic tumors are very unusual. We report the multimodal, bronchoscopic management of 3 cases, offering durable local control in all cases (including 2 patients who were definitively cured). Although surgery is usually considered the gold standard, therapeutic bronchoscopy should probably be considered as a frontline option for proximal lesions with limited base (< 10 mm2) because of uncommon metastatic spread and delayed local recurrence. Of note, 1 of our cases is a rare airway case after allograft hematopoietic stem cell transplant.