晚期分化型甲状腺癌颈部放疗缩野的区域控制与毒性：一项回顾性队列研究

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中文摘要

背景： 对于高危、大体残留、未切除或复发的分化型甲状腺癌（DTC），当不建议进一步手术时，外照射放疗（RT）具有指征。尽管RT可改善区域控制时间（LRC），但头颈部毒性仍是一个重要问题。在晚期DTC中，缩野能否在维持肿瘤控制的同时减轻毒性仍不明确。
方法： 在这项回顾性队列研究中，1999年至2023年在一家三级中心连续治疗的327例非间变性、非髓样DTC患者中，有284例可获得详细RT计划。治疗野分类为：全面（双侧中央区及双侧颈部）、同侧（中央区加同侧颈部）或中央（仅中央区）。急性毒性定义为RT开始后90天内的最严重级别（CTCAE），此后为晚期毒性（RTOG）。区域复发时间（LRR）采用累积发生率函数评估，将无LRR死亡作为竞争风险。总体中位随访时间为8.9年（四分位距5.3-12.7年）。
结果： 在284例患者中，103例（36%）接受全面野，116例（41%）接受同侧野，65例（23%）接受中央野。各组在急性≥2级毒性方面存在差异：口干症（全面36%、同侧17%、中央16%，p=0.002）、吞咽困难（全面58%、同侧48%、中央36%，p=0.02）、声音改变（全面39%、同侧22%、中央28%，p=0.02）和乏力（全面41%、同侧28%、中央22%，p=0.02）。晚期≥2级吞咽困难也存在差异（全面23%、同侧6%、中央8%，p=0.0004）。经皮内镜下胃造瘘管置入在全面野中高于中央野（p=0.0003）和同侧野（p=0.019）。野内失败率分别为全面野11/103（10.7%）、同侧野11/116（9.5%）、中央野5/65（7.7%），各组LRC无差异（p=0.88）。6例接受中央野RT的患者发生野外侧颈部复发，均成功通过手术挽救。
结论： 在适当选择的DTC患者中，逐步缩小RT野与急性和晚期毒性发生率显著降低相关，且未损害LRC。这些发现支持个体化野选择，并强调RT缩野在该人群中的潜在作用。需要前瞻性多中心研究来证实这些发现。

英文摘要

BACKGROUND: External beam radiotherapy (RT) is indicated for high-risk, gross residual, unresected, or recurrent differentiated thyroid cancer (DTC) when further surgery is not recommended. Although RT improves time to locoregional control (LRC), head and neck toxicities remain a significant concern. Whether field reduction can lessen toxicity while maintaining tumor control in advanced DTC remains undefined.
METHODS: In this retrospective cohort study, detailed RT plans were available for 284 of 327 consecutive nonanaplastic, nonmedullary DTC patients treated from 1999 to 2023 at a single tertiary center. Treatment fields were classified as: comprehensive (bilateral central compartment and bilateral necks), ipsilateral (central compartment plus ipsilateral neck), or central (central compartment only). Acute toxicities were defined as the worst grade within 90 days of RT start (CTCAE) and late toxicities thereafter (RTOG). Time to locoregional recurrence (LRR) was assessed using cumulative incidence functions, treating death without LRR as a competing risk. Overall median follow-up was 8.9 years (interquartile range 5.3-12.7 years).
RESULTS: Among 284 patients, 103 (36%) received comprehensive, 116 (41%) ipsilateral, and 65 (23%) central fields. Group differences in acute grade ≥ 2 toxicities were observed in xerostomia (36% comprehensive, 17% ipsilateral, 16% central, p = 0.002), dysphagia (58% comprehensive, 48% ipsilateral, 36% central, p = 0.02), voice changes (39% comprehensive, 22% ipsilateral, 28% central, p = 0.02) and fatigue (41% comprehensive, 28% ipsilateral, 22% central, p = 0.02). Also differing was late grade ≥ 2 dysphagia (23% comprehensive, 6% ipsilateral, 8% central, p = 0.0004). Percutaneous endoscopic gastrostomy tube placement was higher in comprehensive versus central (p = 0.0003) and ipsilateral (p = 0.019) fields. In-field failure rates were 11/103 (10.7%) for comprehensive, 11/116 (9.5%) for ipsilateral, and 5/65 (7.7%) for central fields, with no difference in LRC across groups (p = 0.88). Six patients with central RT developed out-of-field lateral neck recurrences, all successfully salvaged with surgery.
CONCLUSIONS: Progressive RT field reduction in appropriately selected DTC patients was associated with significantly lower rates of acute and late toxicities without compromising LRC. These findings support individualized field selection and highlight the potential role of RT field de-escalation in this population. Prospective multicenter studies are needed to confirm these findings.