Evaluation of Overall Survival in Patients With Anaplastic Thyroid Carcinoma, 2000-2019
Evaluation of Overall Survival in Patients With Anaplastic Thyroid Carcinoma, 2000-2019
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DOI：
10.1001/jamaoncol.2020.3362
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发表时间：
2020-09-01
期刊：
影响因子：
28.4
通讯作者：
Zafereo, Mark
中科院分区：
文献类型：
--
作者：
Maniakas, Anastasios;Dadu, Ramona;Zafereo, Mark
本队列研究的数据来自一家三级医疗机构，旨在评估新出现的靶向治疗、免疫治疗、手术和放射治疗是否与甲状腺间变性癌患者的总生存期相关。重要性甲状腺间变性癌（ATC）从诊断时起的中位总生存期（OS）为4个月，疾病特异性死亡率接近100%。治疗的最新重大进展与OS之间的关联尚未得到评估。目的评价近20年来ATC患者的OS率。设计、设置和参与者：在一家三级医疗机构进行的回顾性队列研究。纳入了2000年1月至2019年10月期间组织病理学证实ATC的患者，并根据就诊日期分为3组：2000-2013年、2014-2016年和2017-2019年。主要结果和测量不同治疗时期和不同治疗（包括靶向治疗、免疫治疗和手术）之间的总生存率比较。结果在479例接受ATC评估的患者（246例男性[51%];中位年龄65.0 [范围，21.1-92.6]岁）中，52例（11%）为IVA期，172例（36%）为IVB期，255例（53%）为IVC期。整个队列的中位OS为0.79年（9.5个月），范围为0.01 - 16.63。1年和2年的OS为35%（95% CI，29%-42%）和18%（95% CI，13%-23%），2000-2013年组（n = 227），47%（95% CI，36%-56%）和25%（95% CI，17%-34%），2014-2016年组（n = 100）和59%（95% CI，49%-67%）和42%（95% CI，30%-53%）（n = 152）（P < .001）。与2000-2013年患者相比，2017-2019年组的风险比为0.50（95% CI，0.38-0.67）（P < .001）。与OS改善相关的因素包括靶向治疗（风险比，0.49; 95%CI，0.39-0.63; P < .001），在靶向治疗基础上增加免疫治疗，（风险比，0.58; 95% CI，0.36-0.94; P = 0.03）和新辅助BRAF导向治疗后手术（风险比，0.29; 95% CI，0.10-0.78; P = 0.02）。新辅助BRAF导向治疗后接受手术的患者（n = 20）的1年生存率为94%，中位随访时间为1.21年。结论和相关性在这项跨越近20年的大型单机构队列研究中，患者管理的变化似乎与生存率的显著增加相关。无法治疗的ATC时代正逐渐被基于分子的个性化治疗所取代，包括手术和放射治疗在内的多学科治疗相结合。问题：靶向治疗、免疫治疗、手术和放射治疗的使用是否与改善甲状腺未分化癌（ATC）患者的总生存率相关？在这项涵盖479例ATC患者的单机构队列研究中，1年和2年生存率从2000-2013年的35%和18%（n = 227）显著增加到2014-2016年的47%和25%（n = 100），2017-2019年（n = 152）分别为59%和42%。这项研究表明，ATC可以有效地治疗高度专业化的分子为基础的个性化治疗，并在适当的时候手术，无论疾病阶段。
This cohort study of data from a single tertiary care institution assesses whether emerging use of targeted therapy, immunotherapy, surgery, and radiation therapy are associated with overall survival in patients with anaplastic thyroid carcinoma.Importance Anaplastic thyroid carcinoma (ATC) historically has a 4-month median overall survival (OS) from time of diagnosis, with disease-specific mortality approaching 100%. The association between recent major advancements in treatment and OS has yet to be evaluated. Objective To evaluate rates of OS in patients with ATC over the last 2 decades. Design, Setting, and Participants Retrospective cohort study in a single tertiary care institution. Patients with histopathological confirmation of ATC from January 2000 to October 2019 were included and divided into 3 groups according to date of presentation: 2000-2013, 2014-2016, and 2017-2019. Main Outcomes and Measures Overall survival compared among different treatment eras and differing therapies, including targeted therapy, immunotherapy, and surgery. Results Of 479 patients (246 men [51%]; median age, 65.0 [range, 21.1-92.6] years) with ATC evaluated, 52 (11%) were stage IVA, 172 (36%) stage IVB, and 255 (53%) stage IVC at presentation. The median OS of the entire cohort was 0.79 years (9.5 months), ranging from 0.01 to 16.63. The OS at 1 and 2 years was 35% (95% CI, 29%-42%) and 18% (95% CI, 13%-23%) in the 2000-2013 group (n = 227), 47% (95% CI, 36%-56%) and 25% (95% CI, 17%-34%) in the 2014-2016 group (n = 100), and 59% (95% CI, 49%-67%) and 42% (95% CI, 30%-53%) in the 2017-2019 group (n = 152), respectively (P < .001). The hazard ratio was 0.50 (95% CI, 0.38-0.67) for the 2017-2019 group compared with the 2000-2013 patients (P < .001). Factors associated with improved OS included targeted therapy (hazard ratio, 0.49; 95% CI, 0.39-0.63; P < .001), the addition of immunotherapy to targeted therapy (hazard ratio, 0.58; 95% CI, 0.36-0.94; P = .03), and surgery following neoadjuvant BRAF-directed therapy (hazard ratio, 0.29; 95% CI, 0.10-0.78; P = .02). Patients undergoing surgery following neoadjuvant BRAF-directed therapy (n = 20) had a 94% 1-year survival with a median follow-up of 1.21 years. Conclusion and Relevance In this large single-institution cohort study spanning nearly 20 years, changes in patient management appear to be associated with significant increase in survival. The era of untreatable ATC is progressively being replaced by molecular-based personalized therapies, with integration of multidisciplinary therapies including surgery and radiation therapy.Question Is emerging use of targeted therapy, immunotherapy, surgery, and radiation therapy associated with improved overall survival in patients with anaplastic thyroid carcinoma (ATC)? Findings In this single-institution cohort study of 479 patients with ATC spanning nearly 20 years, 1- and 2-year survival significantly increased from 35% and 18% in the 2000-2013 era (n = 227) to 47% and 25% in the 2014-2016 era (n = 100), and 59% and 42% in the 2017-2019 era (n = 152), respectively. Meaning This study suggests that ATC may be effectively treated with highly specialized molecular-based personalized therapies, and surgery when appropriate, regardless of disease stage.