Introduction: Tyrosine kinase inhibitors represent a better treatment in patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). Lenvatinib is usually well-tolerated, but sometimes, it is associated with serious and even life-threatening side effects. The aim of this study was to evaluate the prevalence of and the potential risk factors for fistula and/or organ perforation in RAI-R DTC patients treated with lenvatinib. Methods: This study included data from advanced and progressive RAI-R DTC patients treated with lenvatinib from February 2011 to February 2020 who were followed up at a single center. The clinical-pathological features and the biochemical and morphological results of the patients were collected at the time of starting lenvatinib and during the follow-up. Results: Fourteen of 95 (14.7%) locally advanced or metastatic RAI-R DTC patients treated with lenvatinib developed a fistula or organ perforation. Nine of 14 (64.3%) patients had tumor infiltration of the trachea, bronchus, esophagus, pleura, or bladder. Five of 14 (35.7%) had a bowel perforation, but only 2 had preexisting diverticulosis. Evaluation of the risk factors for developing a fistula or organ perforation showed that the presence of tumor infiltration and the tumor histology (papillary and poorly differentiated vs. follicular and Hurthle thyroid cancer) were significantly correlated with the development of a fistula or organ perforation (p = 0.003 and p = 0.02, respectively). In the subgroup of patients with tumor infiltration, we found that the papillary thyroid cancer histotype was the only potential predictor of fistula development. External beam radiation therapy (EBRT), the starting dose of lenvatinib, and the duration of treatment were not relevant for the development of fistula. Conclusions: In metastatic thyroid cancer patients treated with lenvatinib, the presence of tumor infiltration and histological type should be considered as potential risk factors for the development of fistula or organ perforation, although they do not represent an absolute contraindication. Although EBRT and the presence of diverticulosis were not significantly associated with the development of fistula and organ perforation, they should be regarded as potential additional reasons for the development of these complications. According to our findings, there is no reason to start lenvatinib at a lower daily dose when tumor infiltration is present.
Eur Thyroid J

中文翻译：

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乐伐替尼治疗放射性碘难治性甲状腺癌的患者发生瘘管或器官穿孔的患病率和危险因素

简介：酪氨酸激酶抑制剂代表了放射性碘难治性分化型甲状腺癌 (RAI-R DTC) 患者的更好治疗方法。乐伐替尼通常耐受性良好，但有时会出现严重甚至危及生命的副作用。本研究的目的是评估接受乐伐替尼治疗的 RAI-R DTC 患者瘘管和/或器官穿孔的患病率和潜在危险因素。方法：本研究纳入了 2011 年 2 月至 2020 年 2 月期间接受乐伐替尼治疗的晚期和进展性 RAI-R DTC 患者的数据，这些患者在单个中心进行了随访。在开始使用乐伐替尼时和随访期间收集患者的临床病理特征以及生化和形态学结果。结果：接受乐伐替尼治疗的 95 名（14.7%）局部晚期或转移性 RAI-R DTC 患者中有 14 名出现瘘管或器官穿孔。14 名患者中有 9 名（64.3%）存在气管、支气管、食道、胸膜或膀胱肿瘤浸润。14 人中有 5 人（35.7%）有肠穿孔，但只有 2 人有先前存在的憩室病。对发生瘘管或器官穿孔的危险因素的评估表明，肿瘤浸润的存在和肿瘤组织学（乳头状和低分化与滤泡状和 Hurthle 甲状腺癌）与瘘管或器官穿孔的发生显着相关（ p = 0.003 和p= 0.02，分别）。在肿瘤浸润患者亚组中，我们发现甲状腺乳头状癌组织型是瘘管发展的唯一潜在预测因子。外照射放疗（EBRT）、乐伐替尼的起始剂量和治疗持续时间与瘘管的发展无关。结论：在接受乐伐替尼治疗的转移性甲状腺癌患者中，肿瘤浸润的存在和组织学类型应被视为发生瘘管或器官穿孔的潜在危险因素，尽管它们并不代表绝对禁忌症。尽管 EBRT 和憩室病的存在与瘘管和器官穿孔的发展没有显着相关性，但它们应被视为这些并发症发展的潜在额外原因。根据我们的研究结果，当存在肿瘤浸润时，没有理由以较低的每日剂量开始使用乐伐替尼。
欧洲甲状腺杂志