Elisa Capizzi1, Filippo Gustavo Dall'Olio2, Elisa Gruppioni1, Francesca Sperandi2, Annalisa Altimari1, Francesca Giunchi1, Michelangelo Fiorentino3, Andrea Ardizzoni2. 1. Laboratory of Oncologic Molecular Pathology, St.Orsola Teaching Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. 2. Department of Medical Oncology, St.Orsola Teaching Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. 3. Laboratory of Oncologic Molecular Pathology, St.Orsola Teaching Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. Electronic address: michelangelo.fiorentino@unibo.it.
Abstract
OBJECTIVES: Patients harboring rearrangements of the ROS1 gene are eligible for first-line therapy with Crizotinib, which represents the best available treatment option. Diagnostic criteria, based on break-apart fluorescence in situ hybridization, were mirrored from ALK by analogy and include tumors with 5' deletions. However, the probability of response to Crizotinib in patients with 5' deletion in ROS1 is unknown given the rarity of this condition. MATERIALS AND METHODS: We hereby describe clinical outcome of 8 NSCLC patients harboring a 5' deletion at FISH treated with Crizotinib RESULTS: Three out of 4 cases whose 5' deletion was confirmed by NGS as a ROS1/EZR fusion displayed an objective response to Crizotinib while a case with ROS1/SDC4 fusion did not. By contrast, among the 4 cases where NGS did not detect ROS1 gene fusions only 2 patients responded to crizotinib therapy with one also harboring a concomitant EML4-ALK rearrangement. CONCLUSION: 5' ROS1 deletions detected by FISH are associated with a high chance of response to Crizotinib in NSCLC, similarly to canonical ROS1 split-apart FISH rearrangements. However, the confirmation of the ROS1 gene fusion with at least another method, such as NGS, seems beneficial in order to define the ROS1 fusion partner and to avoid possible false positive results.
OBJECTIVES:Patients harboring rearrangements of the ROS1 gene are eligible for first-line therapy with Crizotinib, which represents the best available treatment option. Diagnostic criteria, based on break-apart fluorescence in situ hybridization, were mirrored from ALK by analogy and include tumors with 5' deletions. However, the probability of response to Crizotinib in patients with 5' deletion in ROS1 is unknown given the rarity of this condition. MATERIALS AND METHODS: We hereby describe clinical outcome of 8 NSCLCpatients harboring a 5' deletion at FISH treated with Crizotinib RESULTS: Three out of 4 cases whose 5' deletion was confirmed by NGS as a ROS1/EZR fusion displayed an objective response to Crizotinib while a case with ROS1/SDC4 fusion did not. By contrast, among the 4 cases where NGS did not detect ROS1 gene fusions only 2 patients responded to crizotinib therapy with one also harboring a concomitant EML4-ALK rearrangement. CONCLUSION: 5' ROS1 deletions detected by FISH are associated with a high chance of response to Crizotinib in NSCLC, similarly to canonical ROS1 split-apart FISH rearrangements. However, the confirmation of the ROS1 gene fusion with at least another method, such as NGS, seems beneficial in order to define the ROS1 fusion partner and to avoid possible false positive results.