Department of Radiation Oncology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Gyeonggi-do, Republic of Korea.
Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea.
Int J Radiat Oncol Biol Phys. 2021 Jun 1;110(2):462-472. doi: 10.1016/j.ijrobp.2020.12.047. Epub 2021 Jan 4.
To study the hypothyroidism risk after adjuvant radiation therapy (RT) and the association of different RT targets with hypothyroidism risk.
We studied 4073 women treated with adjuvant RT for breast cancer from 2007 to 2016. The primary endpoint was hypothyroidism development after RT. Patients were divided and analyzed into 3 groups: whole breast (WB)-alone (n = 2468), regional node irradiation (RNI)-Lv.4 (n = 215; cranial border at the subclavian artery, according to the European Society for Radiotherapy and Oncology consensus guideline), and RNI-supraclavicular lymph node (SCL) (n = 1390; cranial border at the cricoid cartilage). In general, RNI-Lv.4 was used in the patients with high-risk pN0 and pN1 breast cancer. In auxiliary analysis, the mean thyroid dose was estimated in each group (total n = 600, 200 from each group). All the doses were converted to the equivalent dose in 2 Gy fractions (EQD2) with α/β ratios of 3.
The median follow-up duration was 84 months (WB-alone, 84 months; RNI-Lv.4, 44 months; RNI-SCL, 91 months). The 3-year hypothyroidism incidence rate differed significantly between the RNI-SCL and WB-alone groups (2.2% vs 0.8%; Bonferroni corrected P [Pc] < .001) but not between the RNI-Lv.4 and WB-alone groups (0.9% vs 0.8%; Pc > .05). The Cox model revealed an adjusted hazard ratio of 2.25 (95% CI, 1.49-3.38) for RNI-SCL vs WB-alone, 1.69 (95% CI, 1.12-2.56) for adjuvant systemic therapies, and 2.07 (95% CI, 1.07-3.99) for age <60 years. In the subgroup analysis, the hypothyroidism risk became more prominent in patients aged <60 years. The mean exposure doses to the thyroid were 0.23 versus 1.93 versus 7.89 Gy (EQD2) for the WB-alone versus RNI-Lv.4 versus RNI-SCL groups (P < .001). No statistically different locoregional recurrence rates were seen between groups (5-year rate: <3%).
The risk of hypothyroidism increases after RNI-SCL for breast cancer but not after RNI-Lv 4. These data support routine contouring of the thyroid in the RNI setting, and future studies are required to develop optimal dose-volume constraints.
研究辅助放疗（RT）后发生甲状腺功能减退症的风险，以及不同 RT 靶区与甲状腺功能减退症风险的关系。
我们研究了 2007 年至 2016 年间接受辅助 RT 的 4073 例乳腺癌女性患者。主要终点是 RT 后甲状腺功能减退症的发展。患者分为 3 组：全乳腺（WB）-单纯照射组（n = 2468）、区域淋巴结照射（RNI）-Lv.4 组（n = 215；颅边界位于锁骨下动脉，根据欧洲放射肿瘤学会共识指南）、RNI-锁骨上淋巴结（SCL）组（n = 1390；颅边界位于环状软骨）。一般来说，RNI-Lv.4 用于高危 pN0 和 pN1 乳腺癌患者。在辅助分析中，估计了每组的平均甲状腺剂量（总 n = 600，每组 200）。所有剂量均转换为等效剂量 2 Gy 分数（EQD2），α/β 比为 3。
中位随访时间为 84 个月（WB-单纯照射组，84 个月；RNI-Lv.4 组，44 个月；RNI-SCL 组，91 个月）。RNI-SCL 组与 WB-单纯照射组的 3 年甲状腺功能减退症发生率差异有统计学意义（2.2% vs 0.8%；Bonferroni 校正后 P[Pc] <.001），但 RNI-Lv.4 组与 WB-单纯照射组差异无统计学意义（0.9% vs 0.8%；Pc >.05）。Cox 模型显示，与 WB-单纯照射组相比，RNI-SCL 组的调整后危险比为 2.25（95%CI，1.49-3.38），辅助全身治疗为 1.69（95%CI，1.12-2.56），年龄 <60 岁为 2.07（95%CI，1.07-3.99）。在亚组分析中，年龄 <60 岁的患者甲状腺功能减退症风险更为显著。WB-单纯照射组、RNI-Lv.4 组和 RNI-SCL 组的甲状腺平均暴露剂量分别为 0.23Gy、1.93Gy 和 7.89Gy（EQD2）（P <.001）。各组间局部区域复发率无统计学差异（5 年率：<3%）。
乳腺癌患者行 RNI-SCL 后甲状腺功能减退症的风险增加，但行 RNI-Lv.4 后则不增加。这些数据支持在 RNI 治疗中常规勾画甲状腺，未来需要进一步研究以制定最佳的剂量体积限制。
