Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review.
Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review.
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DOI：
10.18632/oncotarget.25257
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发表时间：
2018-05-08
期刊：
影响因子：
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通讯作者：
Takahashi K
中科院分区：
文献类型：
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作者：
Watanabe J;Togo S;Sumiyoshi I;Namba Y;Suina K;Mizuno T;Kadoya K;Motomura H;Iwai M;Nagaoka T;Sasaki S;Hayashi T;Uekusa T;Abe K;Urata Y;Sakurai F;Mizuguchi H;Kato S;Takahashi K
抗间变性淋巴瘤激酶 (ALK) 靶向治疗可显着改善 ALK 重排肺腺癌 (Ad-LC) 患者的治疗反应。已有少数伴有 ALK 重排的鳞状细胞肺癌 (Sq-LC) 病例报道；然而，ALK 抑制剂治疗后的临床病理特征和临床结果尚不清楚。我们在本研究中通过回顾性比较 5 名 ALK 重排 Sq-LC 患者与 ALK 重排 Ad-LC 患者的临床特征并评估 ALK 抑制剂应答者和无应答者的代表性病例来解决这一问题。 Sq-LC 中 ALK 重排的发生率为 1.36%。 Sq-LC 中使用克唑替尼初始治疗后的无进展生存期 (PFS) 显着短于具有 ALK 重排的 Ad-LC (p = 0.033)。通过荧光原位杂交 (FISH) 检测的两个 ALK 重排阳性/免疫组织化学阴性病例对克唑替尼没有反应，并且艾来替尼治疗 ALK 重排 Sq-LC 后 PFS 降低 (p = 0.045)。重新活检显示，对色瑞替尼有反应的人携带 L1196M 突变，该突变会导致对其他 ALK 抑制剂产生耐药性。然而，尽管 FISH 阳性循环肿瘤细胞和循环游离 DNA 中存在 ALK 重排，并且不存在 ALK 抑制剂耐药性突变，但无反应者对所有 ALK 抑制剂均具有耐药性。这些结果表明，对于 ALK 重排的 Sq-LC 患者来说，ALK 抑制剂仍然是一种合理的治疗选择，这些患者的预后比 ALK 重排的 Ad-LC 患者更差，并且耐药机制具有异质性。此外，肿瘤科医生应根据临床病理特征意识到 ALK 重排 Sq-LC 的可能性，并根据再活检结果规划二线治疗策略，以改善患者预后。
Anti-anaplastic lymphoma kinase (ALK)-targeted therapy dramatically improves therapeutic responses in patients with ALK-rearranged lung adenocarcinoma (Ad-LC). A few cases of squamous cell lung carcinoma (Sq-LC) with ALK rearrangement have been reported; however, the clinicopathological features and clinical outcomes following treatment with ALK inhibitors are unknown. We addressed this in the present study by retrospectively comparing the clinical characteristics of five patients with ALK-rearranged Sq-LC with those of patients with ALK-rearranged Ad-LC and by evaluating representative cases of ALK inhibitor responders and non-responders. The prevalence of ALK rearrangement in Sq-LCs was 1.36%. Progression-free survival (PFS) after initial treatment with crizotinib was significantly shorter in Sq-LC than in Ad-LC with ALK rearrangement (p = 0.033). Two ALK rearrangements assayed by fluorescence in situ hybridization (FISH)-positive/immunohistochemistry-negative cases did not respond to crizotinb, and PFS decreased following alectinib treatment of ALK-rearranged Sq-LC (p = 0.045). A rebiopsy revealed that responders to ceritinib harbored the L1196M mutation, which causes resistance to other ALK inhibitors. However, non-responders were resistant to all ALK inhibitors, despite the presence of ALK rearrangement in FISH-positive circulating tumor cells and circulating free DNA and absence of the ALK inhibitor resistance mutation. These results indicate that ALK inhibitors remain a reasonable therapeutic option for ALK-rearranged Sq-LC patients who have worse outcomes than ALK-rearranged Ad-LC patients and that resistance mechanisms are heterogeneous. Additionally, oncologists should be aware of the possibility of ALK-rearranged Sq-LC based on clinicopathological features, and plan second-line therapeutic strategies based on rebiopsy results in order to improve patient outcome.