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首页> 外文期刊>Lung Cancer: Targets and Therapy >Symptomatic CNS Radiation Necrosis Requiring Neurosurgical Resection During Treatment with Lorlatinib in ALK-Rearranged NSCLC: A Report of Two Cases
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Symptomatic CNS Radiation Necrosis Requiring Neurosurgical Resection During Treatment with Lorlatinib in ALK-Rearranged NSCLC: A Report of Two Cases

机译：症状CNS放射性坏死要求神经外科在洛尔拉替尼治疗期间在ALK重新排列的NSCLC中：两种情况的报告

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摘要

Central nervous system (CNS) metastasis carries a significant morbidity and mortality in anaplastic lymphoma kinase ( ALK )-rearranged non-small cell lung cancer (NSCLC). Next-generation ALK tyrosine kinase inhibitors (TKIs) are highly CNS-penetrant and have demonstrated remarkable intracranial activity across clinical studies, and yet radiation remains the mainstay of treatment modality against CNS metastasis. We have previously reported alectinib can induce CNS radiation necrosis even after a remote history of radiation (7 years post-radiation). Lorlatinib is another potent next-generation ALK TKI that can overcome many ALK resistance mutations and has been shown to have excellent activity in patients with baseline CNS metastasis. Here we report two ALK -rearranged NSCLC patients who developed radiation necrosis shortly after initiating lorlatinib following progression on the sequential treatment of crizotinib, alectinib, and brigatinib. In both cases, radiation necrosis is evidenced by serial MRI images and histological examination of the resected CNS metastasis that had previously been radiated. Our cases highlight the importance of recognizing CNS radiation necrosis that may mimic disease progression in ALK -rearranged NSCLC treated with and potentially precipated by next-generation ALK TKIs.
机译：中枢神经系统（CNS）转移在促进淋巴瘤激酶（ALK）中具有显着的发病率和死亡率 - 再抑制非小细胞肺癌（NSCLC）。下一代ALK酪氨酸激酶抑制剂（TKIS）是高度CNS - 渗透性，并且在临床研究中表现出显着的颅内活动，但辐射仍然是对CNS转移的治疗方式的主干。我们以前报道过inectinib即使在辐射的远程历史之后也可以诱导CNS放射坏死（辐射后7年）。 Lorlatinib是另一种有效的下一代ALK TKI，可以克服许多抗抗原突变，并且已被证明在基线CNS转移患者中具有优异的活性。在这里，我们报告了两种Alk -rearranged NSCLC患者，在进行中，在进行克里齐替尼，莱切韦和Brigatinib的顺序治疗后发起Lorlatinib后不久发育了放射坏死。在这两种情况下，串行MRI图像和先前辐射的切除的CNS转移的组织学检查证明了放射性坏死。我们的案例突出了识别CNS放射性坏死的重要性，这些坏死可能模仿疾病进展的Alk -rearranged NSClc，并可能由下一代ALK TKI沉淀。

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