Laboratory of Oncologic Molecular Pathology, St.Orsola Teaching Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.
Department of Medical Oncology, St.Orsola Teaching Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.
Lung Cancer. 2019 Sep;135:88-91. doi: 10.1016/j.lungcan.2019.07.017. Epub 2019 Jul 17.
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.
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.
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.
ROS1 基因重排的患者有资格接受克唑替尼的一线治疗，这是最佳的治疗选择。诊断标准基于分离荧光原位杂交（FISH），与间变性淋巴瘤激酶（ALK）类似，包括 5' 缺失的肿瘤。然而，由于这种情况罕见，ROS1 5' 缺失患者对克唑替尼的反应率尚不清楚。
我们在此描述了 8 例经 FISH 检测到 5' 缺失的 NSCLC 患者接受克唑替尼治疗的临床结果。
4 例经 NGS 证实为 ROS1/EZR 融合的病例中有 3 例对克唑替尼有客观反应，而 ROS1/SDC4 融合的病例则没有。相比之下，在 NGS 未检测到 ROS1 基因融合的 4 例病例中，只有 2 例对克唑替尼治疗有反应，其中 1 例还伴有 EML4-ALK 重排。
FISH 检测到的 5'ROS1 缺失与 NSCLC 中对克唑替尼高度应答相关，与经典的 ROS1 分离 FISH 重排相似。然而，为了确定 ROS1 融合伙伴并避免可能的假阳性结果，至少使用另一种方法（如 NGS）确认 ROS1 基因融合似乎是有益的。
