[Strategy for molecular testing in pulmonary carcinoma]. / Stratégie de testing moléculaire des carcinomes pulmonaires.

Nowadays, the analysis of theranostic molecular markers is central in the management of lung cancer. As those tumors are diagnosed in two third of the cases at an advanced stage, molecular screening is frequently performed on "small samples". The screening strategy starts by an accurate histopathological characterization, including on biopsies or cytological specimens. WHO 2015 provided a new classification for small biopsy and cytology, defining categories such as non-small cell carcinoma (NSCC), favor adenocarcinoma (TTF1 positive), or favor squamous cell carcinoma (p40 positive). Only the NSCC tumors, non-squamous, are eligible to molecular testing. A strategy aiming at tissue sparing for the small biopsies has to be organized. Tests corresponding to available drugs are prioritized. Blank slides will be prepared for immunohistochemistry and in situ hybridization based tests such as ALK. DNA will then be extracted for the other tests, EGFR mutation screening first associated or not to KRAS. Then, the emerging biomarkers (HER2, ROS1, RET, BRAF…) as well as potentially other markers in case of clinical trials, can been tested. The spread of next generation sequencing technologies, with a very sensitive all-in-one approach will allow the identification of minority clones. Eventually, the development of liquid biopsies will provide the opportunity to monitor the apparition of resistance clones during treatment. This non-invasive approach allows patients with a contraindication to perform biopsy or with non-relevant biopsies to access to molecular screening.

Radial-EBUS and virtual bronchoscopy planner for peripheral lung cancer diagnosis: How it became the first-line endoscopic procedure.

BACKGROUND: Various advanced bronchoscopy methods have been developed to reach peripheral lung lesions (PLL). In a large cohort, we aimed to assess a standardized procedure of first-line radial-endobronchial ultrasound (r-EBUS) and virtual bronchoscopy planner for the diagnosis of peripheral lung cancer. METHODS: This retrospective, single center study included patients who had r-EBUS-guided bronchoscopy for the diagnosis of a PLL between 2008 and 2019. Cases without a final diagnosis of cancer or follow-up were excluded. RESULTS: Between 2008 and 2019, 2735 patients had a r-EBUS procedure, among whom 1627 had a final diagnosis of cancer and were included in the present study. Over the 12-year study period, r-EBUS became the first-line endoscopic procedure to assess PLL (25% as first-line bronchoscopy in 2008 vs. 92% in 2019). The frequency of the bronchus sign decreased from 2009 to 2019 (100% to 80%; p = 0.001), whereas US visualization of the lesion remained stable (88%). The median number of biopsies increased from two (2008 to 2014) to four (2015 to 2019) (p < 0.0001), with the same diagnostic efficiency (74% total and 80% when a bronchus sign was present). Of the 651 adenocarcinomas, molecular analysis was possible in 86%. PD-L1 expression analysis was possible in 81% of cases. During the study period, the lifetime of the radial probe increased from 57 procedures to 77 procedures/probe. CONCLUSION: Because r-EBUS and VB planner is easy to perform under local anesthesia, inexpensive and efficient it can be used as a first-line procedure to assess peripheral lung cancer.

Incomplete Carney Triad: A Surgical Case of a Rare Syndrome.

We describe a 36-year-old woman with multiple gastric gastrointestinal stromal tumors, hepatic and lymphatic metastasis, and a mediastinal paraganglioma as a presentation of an incomplete Carney triad. We present our therapeutic approach, with emphasis on the surgical and oncologic specificities of this syndrome.

Surgical or medical strategy for locally-advanced, stage IIIA/B-N2 non-small cell lung cancer: Reproducibility of decision-making at a multidisciplinary tumor board.

BACKGROUND: Stage IIIA/B-N2 is a very heterogeneous group of patients and accounts for one third of NSCLC at diagnosis. The best treatment strategy is established at a Multidisciplinary Tumor Board (MTB): surgical resection with neoadjuvant or adjuvant therapy versus definitive chemoradiation with immune checkpoint inhibitors consolidation. Despite the crucial role of MTBs in this complex setting, limited data is available regarding its performances and the reproducibility of the decision-making. METHODS: Using a large cohort of IIIA/B-N2 NSCLC patients, we described patient's characteristics and treatment strategies established at the initial MTB: with a "surgical strategy" group, for potentially resectable disease, and a "medical strategy" group for non-resectable patients. A third group consisted of patients who were not eligible for surgery after neoadjuvant treatment and switched from the surgical to the medical strategy. We randomly selected 30 cases (10 in each of the 3 groups) for a blinded re-discussion at a fictive MTB and analyzed the reproducibility and factors associated with treatment decision. RESULTS: Ninety-seven IIIA/B-N2 NSCLC patients were enrolled between June 2017 and December 2019. The initial MTB opted for a medical or a surgical strategy in 44% and 56% of patients respectively. We identified histology, tumor size and localization, extent of lymph node involvement and the presence of bulky mediastinal nodes as key decision-making factors. Thirteen patients were not eligible for surgical resection after neoadjuvant therapy and switched for a medical strategy. Overall concordance between the initial decision and the re-discussion was 70%. The kappa correlation coefficient was 0.43. Concordance was higher for patients with limited mediastinal node invasion. Survival did not appear to be impacted by conflicting decisions. CONCLUSIONS: Reproducibility of treatment decision-making for stage IIIA/B-N2 NSCLC patients at a MTB is moderate but does not impact survival.

Virtual Bronchoscopy Planner and Radial-EBUS Guided Biopsy for Organizing Pneumonia Diagnosis.

BACKGROUND: The diagnosis of organizing pneumonia (OP) often requires histological confirmation. The aim of this retrospective study was to evaluate the diagnostic yield and complication rate of radial endobronchial ultrasound (r-EBUS) for OP. METHODS: All patients who had r-EBUS as a first diagnostic procedure for a peripheral pulmonary lesion at Rouen University Hospital, France, between April 2008 and December 2020 were included. Cases without a final diagnosis of OP or follow-up were excluded. Patients, lesions, and r-EBUS characteristics were retrospectively analyzed. RESULTS: 2735 r-EBUS procedures were performed, and 33 cases with final OP could be analyzed. Procedures were performed under local anesthesia in 28/33 cases (85%). Among the 33 final OP cases, 17 were considered cryptogenic, and 16 secondary. The lesions were patchy alveolar opacities in 23 cases (70%), masses or pulmonary nodules in 8 cases (24%), and diffuse infiltrative opacities in 2 cases (6%). A bronchus sign on CT scan was found in all cases. In 22 cases (67%), a histopathological diagnosis was obtained from the r-EBUS samples. In 4 cases (12%), histopathological diagnosis was made by surgery, and in 7 cases (21%) the diagnosis was made based on clinical, radiological, and evolution features. An ultrasound image was found in 100% (22/22) of cases in the r-EBUS positive (r-EBUS+) group vs. 60% (6/10) in the r-EBUS negative (r-EBUS-) group, respectively (p < 0.002). The diagnostic yield of r-EBUS for OP was 67% and increased to 79% (22/28) when an ultrasound image was obtained. The median time between CT scan and r-EBUS procedure was 14 days (3-94): 11.5 days in the r-EBUS+ group and 22 days in the r-EBUS- group (p < 0.0001). No severe complications were reported. CONCLUSION: r-EBUS, when performed shortly after a CT scan showing a bronchus sign, is an efficient and safe technique for OP diagnosis.

Electromagnetic navigation bronchoscopy localization of lung nodules for thoracoscopic resection.

BACKGROUND: Thoracoscopic localization of small peripheral pulmonary nodules is a concern. Failure can lead to larger parenchymal resection or conversion to thoracotomy. This study evaluates our experience in preoperative electromagnetic navigation bronchoscopy-guided localization of small peripheral lung lesions. METHODS: From January 2017 to March 2020 clinical, radiographic, surgical, and pathological data of patients who underwent electromagnetic navigation bronchoscopy (ENB)-guided methylene blue pleural marking of highly suspected pulmonary lesions before a full thoracoscopic resection were evaluated. Localization was performed for solid or mixed subpleural nodules measuring <10 mm, solid nodules measuring <20 mm located at more than 1 cm from the pleura and any pure ground glass opacity. Successful localization was defined as successful identification and thoracoscopic resection of target lesions. RESULTS: Forty-eight patients were included: 30 solid nodules (63%), 12 pure GGO (25%) and 6 mixed (13%). The median largest diameter at CT-scan was 11 mm (IQR, 9-14 mm) while the median distance from the pleural surface was 12 mm (IQR, 6-16 mm). The median ENB length was 25 min (19-33 min). Localization procedure was successful in 45 cases (94%). No procedural-related complications were reported. CONCLUSIONS: ENB is a safe and accurate preoperative procedure to localize small lung peripheral lesions. The high successful rate, the absence of related complications, the possibility of performing the procedure in the same operating room with a single general anesthesia, make ENB-guided dye marking an advantageous tool for thoracoscopic pulmonary resection.