Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Ann Surg Oncol. 2021 Mar;28(3):1731-1739. doi: 10.1245/s10434-020-09023-2. Epub 2020 Aug 17.
While numerous factors affect prognosis in papillary thyroid carcinoma (PTC), the comparative impact of histologic grade has not been well described. Moreover, indications for external beam radiation therapy (EBRT) remain imprecise. We evaluate clinicopathologic characteristics and outcomes for PTC stratified by grade.
We profiled histologic grade for PTC (well differentiated, moderately differentiated, poorly differentiated) via hospital (National Cancer Database) and population-based (Surveillance, Epidemiology, and End Results) registries. Cox regression was used to adjust for clinicopathologic covariates. Statistical interactions between subtypes and the effect of EBRT on survival were assessed.
Collectively, worsening clinicopathologic factors (age, tumor size, extrathyroidal extension, nodal spread, M1 disease) and outcomes (disease-free survival, overall survival) correlated with less differentiated state, across all histologic grades (p < 0.001). Multivariable analysis showed escalating hazard with loss of differentiation relative to well-differentiated PTC (moderately differentiated hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.04-1.41, p = 0.02; poorly differentiated HR 2.62, 95% CI 2.23-3.08, p < 0.001). Correspondingly, greater survival benefit was associated with EBRT for poorly differentiated cases (HR 0.36, 95% CI 0.18-0.72, p = 0.004). This finding was upheld after landmark analysis to address potential immortal time bias (HR 0.37, 95% CI 0.17-0.80, p = 0.01).
Worsening histologic grade in PTC is independently associated with parallel escalation in mortality risk, on a scale approximating or surpassing established thyroid cancer risk factors. On preliminary analysis, EBRT was associated with improved survival in the most aggressive or least differentiated subvariants. Further investigation is warranted to examine the efficacy of EBRT for select poorly differentiated thyroid carcinomas.
虽然许多因素都会影响甲状腺乳头状癌（papillary thyroid carcinoma，PTC）的预后，但组织学分级的相对影响尚未得到很好的描述。此外，外照射放射治疗（external beam radiation therapy，EBRT）的适应证也不明确。我们评估了按分级分层的 PTC 的临床病理特征和结局。
我们通过医院（国家癌症数据库）和人群（监测、流行病学和最终结果）登记处对 PTC 的组织学分级（分化良好、中度分化、低分化）进行了分析。Cox 回归用于调整临床病理协变量。评估了亚型之间的统计学相互作用以及 EBRT 对生存的影响。
总体而言，随着年龄、肿瘤大小、甲状腺外扩散、淋巴结转移、M1 疾病等临床病理因素的恶化（无病生存率、总生存率）与分化程度较差相关，所有组织学分级均如此（p<0.001）。多变量分析显示，与分化良好的 PTC 相比，分化程度降低的风险逐渐升高（中度分化的危险比[HR] 1.21，95%置信区间[CI] 1.04-1.41，p=0.02；低分化 HR 2.62，95%CI 2.23-3.08，p<0.001）。相应地，EBRT 与低分化病例的生存获益更大（HR 0.36，95%CI 0.18-0.72，p=0.004）。在解决潜在的不朽时间偏倚的里程碑分析后，这一发现得到了支持（HR 0.37，95%CI 0.17-0.80，p=0.01）。
PTC 组织学分级恶化与死亡率的平行升高独立相关，其严重程度近似或超过已确立的甲状腺癌危险因素。初步分析表明，EBRT 与最具侵袭性或分化最差的亚变异型的生存改善相关。需要进一步研究来检查 EBRT 对某些低分化甲状腺癌的疗效。
