Clinicopathologic Features and Response to Therapy of NRG1 Fusion-Driven Lung Cancers: The eNRGy1 Global Multicenter Registry.

PURPOSE: Although NRG1 fusions are oncogenic drivers across multiple tumor types including lung cancers, these are difficult to study because of their rarity. The global eNRGy1 registry was thus established to characterize NRG1 fusion-positive lung cancers in the largest and most diverse series to date. METHODS: From June 2018 to February 2020, a consortium of 22 centers from nine countries in Europe, Asia, and the United States contributed data from patients with pathologically confirmed NRG1 fusion-positive lung cancers. Profiling included DNA-based and/or RNA-based next-generation sequencing and fluorescence in situ hybridization. Anonymized clinical, pathologic, molecular, and response (RECIST v1.1) data were centrally curated and analyzed. RESULTS: Although the typified never smoking (57%), mucinous adenocarcinoma (57%), and nonmetastatic (71%) phenotype predominated in 110 patients with NRG1 fusion-positive lung cancer, further diversity, including in smoking history (43%) and histology (43% nonmucinous and 6% nonadenocarcinoma), was elucidated. RNA-based testing identified most fusions (74%). Molecularly, six (of 18) novel 5' partners, 20 unique epidermal growth factor domain-inclusive chimeric events, and heterogeneous 5'/3' breakpoints were found. Platinum-doublet and taxane-based (post-platinum-doublet) chemotherapy achieved low objective response rates (ORRs 13% and 14%, respectively) and modest progression-free survival medians (PFS 5.8 and 4.0 months, respectively). Consistent with a low programmed death ligand-1 expressing (28%) and low tumor mutational burden (median: 0.9 mutations/megabase) immunophenotype, the activity of chemoimmunotherapy and single-agent immunotherapy was poor (ORR 0%/PFS 3.3 months and ORR 20%/PFS 3.6 months, respectively). Afatinib achieved an ORR of 25%, not contingent on fusion type, and a 2.8-month median PFS. CONCLUSION: NRG1 fusion-positive lung cancers were molecularly, pathologically, and clinically more heterogeneous than previously recognized. The activity of cytotoxic, immune, and targeted therapies was disappointing. Further research examining NRG1-rearranged tumor biology is needed to develop new therapeutic strategies.

A formalized transition program for cystic fibrosis: A 10-year retrospective analysis of 97 patients in Lyon.

INTRODUCTION: The prognosis of people diagnosed with cystic fibrosis (CF) has dramatically improved over the past decade in France, largely due to advances in CF care management, including an emphasis on chronic maintenance medications. Currently, the majority of French CF patients are adults, which means that they went through a transition process from receiving care at a pediatric CF center to receiving care at an adult CF center. To determine the impact of the transfer on clinical evolution, we report the transition procedure of our CF center in Lyon. MATERIALS AND METHODS: From January 2006 to December 2016, 97 CF patients underwent a standardized process of transitioning from the pediatric to the adult CF center in Lyon. We compared the clinical evolution of these patients during three periods, starting the year before transition and ending the year after transition. Clinical data taken into account were forced expiratory volume in 1 s (FEV1 in liters), body mass index (BMI in kg/m2 ), pulmonary colonization, number of antibiotic courses, number of days of hospitalization per year, and outpatient visits per year. RESULTS: No significant differences were observed between respiratory and nutritional status, respiratory microbiome, number of antibiotic courses, or number of hospitalizations or visits when comparing the threeperiods of observation around transition (the year before, the first year after, and the second year after transfer). CONCLUSION: The standardized transition procedure used in Lyon is associated with the clinical stability of our CF patients.

Evolution and Predictive Factors of Improvement of Obstructive Sleep Apnea in an Obese Population After Bariatric Surgery.

STUDY OBJECTIVES: Our objectives were to determine in an obese population (body mass index > 35 kg/m²) the number of patients, after gastric bypass (GBP), who no longer met French Ministry of Health criteria for utilizing positive airway pressure (PAP), and the predictive factors of obstructive sleep apnea (OSA) improvement. METHODS: Between June 2012 and August 2014 we diagnosed OSA in 129 incident patients requiring PAP therapy before GBP. A postoperative sleep recording was undertaken for 44 of these patients after a weight loss of at least 10%. RESULTS: Most of the patients showed severe OSA with a mean [standard deviation] apnea-hypopnea index (AHI) of 52.8 [23.8] events/h. The body mass index was 46.1 [5.1] kg/m². All the patients were treated via PAP and most of them via auto-titrating PAP with a range of 4-16 cmH2O. Following the GBP, in 31 patients (70.5%) OSA was improved, allowing PAP to be stopped (AHI < 15 events/h). The Epworth Sleepiness Scale score, the modified Medical Research Council dyspnea scale, the loudness of snoring, and sleep structure were improved. AHI was decreased by a mean of 40.9 [22.4] events/h (P < .001). In a multivariate logistic regression model, age (P = .018) and sleep oxygen desaturation index (P = .049) appeared to predict improvement of OSA. CONCLUSIONS: After GBP, 70.5% of the patients no longer met French Ministry of Health criteria for utilizing PAP, allowing discontinuation of this treatment. At diagnosis, a younger age and a less severe sleep oxygen desaturation were predictive factors of this improvement.