Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
JAMA Oncol. 2020 May 1;6(5):706-713. doi: 10.1001/jamaoncol.2019.6851.
While well-differentiated papillary thyroid carcinoma (WDPTC) outcomes have been well characterized, the prognostic implications of more aggressive variants are far less defined. The rarity of these subtypes has led to their consolidation as intermediate risk for what are in fact likely heterogeneous diseases.
To analyze incidence, clinicopathologic characteristics, and outcomes for aggressive variants of papillary thyroid carcinoma (PTC).
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 2000 to 2016 from hospital-based and population-based US cancer registries to analyze aggressive PTC variants, including diffuse sclerosing (DSV), tall-cell (TCV), insular, and poorly differentiated (PDTC) subtypes. These variants were compared against WDPTC and anaplastic cases. Data analysis was conducted from January 2019 to October 2019.
Age-adjusted incidence was calculated via annual percentage change (APC) using the weighted least-squares method. Overall survival and disease-specific survival were analyzed via Cox regression. Propensity-score matching was used to adjust survival analyses for clinical and demographic covariates.
Collectively, 5447 aggressive PTC variants were identified (including 415 DSV, 3339 TCV, 362 insular, and 1331 PDTC cases), as well as 35 812 WDPTC and 2249 anaplastic cases. Over the study period, a substantial increase in aggressive variant incidence was observed (APC, 9.1 [95% CI, 7.33-10.89]; P < .001), surpassing the relative increases observed in WDPTC (APC, 5.1 [95% CI, 3.98-6.12]; P < .001) and anaplastic cases (APC, 1.9 [95% CI, 0.75-3.05]; P = .003; parallelism P < .007). Survival varied markedly based on histologic subtype, with a wide spectrum of mortality risk noted; 10-year overall survival was 85.4% (95% CI, 84.6%-86.3%) in WDPTC, 79.2% (95% CI, 73.6%-85.3%) in DSV, 71.9% (95% CI, 68.4%-75.6%) in TCV, 45.1% (95% CI, 40.2%-50.6%) in PDTC, 27.9% (95% CI, 20.0%-38.9%) in the insular variant, and 8.9% (95% CI, 7.5%-10.6%) in anaplastic cases (P < .001). These differences largely persisted even after adjusting for inherent differences in baseline characteristics by multivariable Cox regression and propensity-score matching.
An upsurge in aggressive PTC incidence was observed at a rate beyond that seen in WDPTC or anaplastic thyroid carcinoma. Moreover, long-term survival outcomes for aggressive PTC subgroups exhibit heterogeneous clinical behavior and a wide range of mortality risk, suggesting that treatment should be tailored to specific histologic subtypes. Given increasing prevalence and disparate outcomes, further investigation to identify optimal therapeutic strategies is needed in these diverse, understudied populations.
虽然已经很好地描述了分化良好的甲状腺乳头状癌 (WDPTC) 的预后，但更具侵袭性的变体的预后意义却远未确定。这些亚型的罕见性导致它们被合并为中间风险，而实际上它们可能是异质性疾病。
分析侵袭性甲状腺乳头状癌 (PTC) 变体的发病率、临床病理特征和结局。
设计、地点和参与者：本队列研究使用了 2000 年至 2016 年来自基于医院和基于人群的美国癌症登记处的数据，分析了侵袭性 PTC 变体，包括弥漫性硬化 (DSV)、高细胞 (TCV)、胰岛和低分化 (PDTC) 亚型。这些变体与 WDPTC 和间变性病例进行了比较。数据分析于 2019 年 1 月至 2019 年 10 月进行。
使用加权最小二乘法计算年龄调整后的发病率，通过年度百分比变化 (APC) 计算。通过 Cox 回归分析总生存率和疾病特异性生存率。使用倾向评分匹配来调整生存分析的临床和人口统计学协变量。
共发现 5447 例侵袭性 PTC 变体（包括 415 例 DSV、3339 例 TCV、362 例胰岛和 1331 例 PDTC 病例），以及 35812 例 WDPTC 和 2249 例间变性病例。在研究期间，侵袭性变体的发病率显著增加（APC，9.1 [95%CI，7.33-10.89]；P<0.001），超过了 WDPTC（APC，5.1 [95%CI，3.98-6.12]；P<0.001）和间变性病例（APC，1.9 [95%CI，0.75-3.05]；P=0.003；平行性 P<0.007）的相对增加。根据组织学亚型，生存率差异显著，死亡率风险范围广泛；WDPTC 的 10 年总生存率为 85.4%（95%CI，84.6%-86.3%），DSV 为 79.2%（95%CI，73.6%-85.3%），TCV 为 71.9%（95%CI，68.4%-75.6%），PDTC 为 45.1%（95%CI，40.2%-50.6%），胰岛变体为 27.9%（95%CI，20.0%-38.9%），间变性病例为 8.9%（95%CI，7.5%-10.6%）（P<0.001）。即使在多变量 Cox 回归和倾向评分匹配后调整了基线特征的固有差异，这些差异在很大程度上仍然存在。
侵袭性 PTC 发病率的上升速度超过了 WDPTC 或间变性甲状腺癌的上升速度。此外，侵袭性 PTC 亚组的长期生存结果表现出异质性的临床行为和广泛的死亡率风险，这表明治疗应针对特定的组织学亚型进行调整。鉴于发病率不断上升和不同的预后结果，需要在这些不同的、研究不足的人群中进一步研究以确定最佳治疗策略。
