1 Department of Radiation Oncology, Endocrine Service, Memorial Sloan Kettering Cancer Center , New York, New York.
2 Department of Surgical Oncology, University of Groningen, University Medical Center Groningen , The Netherlands .
Thyroid. 2018 Sep;28(9):1180-1189. doi: 10.1089/thy.2018.0214.
Differentiated thyroid cancer typically has an indolent clinical course but can cause significant morbidity by local progression. Oncologic surgical resection can be technically difficult due to the proximity to critical normal structures in the neck. Our objective was to review the safety, feasibility, and outcomes of definitive-intent intensity-modulated radiation therapy (IMRT) and to analyze whether patients receiving concurrent chemotherapy (CC-IMRT) had higher rates of disease control and survival over IMRT alone in patients with unresectable or gross residual disease (GRD).
Eighty-eight patients with GRD or unresectable nonanaplastic, nonmedullary thyroid cancer treated with definitive-intent IMRT between 2000 and 2015 were identified. Local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Kaplan-Meier method. Univariate and multivariate analyses using cox regression were used to determine the impact of clinical conditions and treatment on LPFS, DMFS, and OS.
Of the 88 patients identified, 45 (51.1%) were treated CC-IMRT and 43 (48.9%) were treated with IMRT alone. All patients treated with CC-IMRT received weekly doxorubicin (10 mg/m). The median follow-up among surviving patients was 40.3 months and 29.2 months for all patients. The LPFS at 4 years was 77.3%. Patients receiving CC-IMRT had higher LPFS compared with IMRT alone (CC-IMRT 85.8% vs. IMRT 68.8%, p = 0.036). The 4-year OS was 56.3% for all patients. Patients treated with CC-IMRT had higher OS compared to patients treated with IMRT alone (CC-IMRT 68.0% vs. IMRT 47.0%, p = 0.043). On multivariate analysis, receipt of concurrent chemotherapy was associated with a lower risk of death (HR 0.395, p = 0.019) and lower risk of local failure (HR 0.306, p = 0.042). Grade 3+ acute toxicities occurred in 23.9% of patients, the most frequent being dermatitis (18.2%) and mucositis (9.1%). 17.1% of patients required a percutaneous endoscopic gastrostomy (PEG) tube during or shortly after completion of RT, with 10.1% of patients needing a PEG more than 12 months after therapy. The rates of acute and late toxicities were not statistically higher in the CC-IMRT cohort, although trends towards higher toxicity in the CC-IMRT were present for dermatitis and PEG requirement.
IMRT is a safe and effective means to achieve local control in patients with unresectable or incompletely resected nonanaplastic, nonmedullary thyroid cancer. Concurrent doxorubicin was not associated with worse toxicity and should be considered in these patients given its potential to improve local control and overall survival.
分化型甲状腺癌通常具有惰性的临床病程，但由于颈部邻近重要的正常结构，局部进展可导致显著的发病率。由于肿瘤靠近颈部的关键正常结构，因此肿瘤的外科切除术在技术上可能具有难度。我们的目的是回顾明确意向强度调制放射治疗（IMRT）的安全性、可行性和结果，并分析在无法切除或存在大量残留疾病（GRD）的患者中，接受同步化疗（CC-IMRT）的患者与单纯 IMRT 相比，疾病控制和生存率是否更高。
在 2000 年至 2015 年间，共确定了 88 例接受明确意向 IMRT 治疗的 GRD 或无法切除的非未分化、非髓样甲状腺癌患者。使用 Kaplan-Meier 方法评估局部无进展生存率（LPFS）、远处无转移生存率（DMFS）和总生存率（OS）。使用 Cox 回归进行单变量和多变量分析，以确定临床状况和治疗对 LPFS、DMFS 和 OS 的影响。
在确定的 88 例患者中，45 例（51.1%）接受 CC-IMRT 治疗，43 例（48.9%）接受单纯 IMRT 治疗。所有接受 CC-IMRT 治疗的患者均接受每周多柔比星（10mg/m2）治疗。在幸存患者中，中位随访时间为 40.3 个月，所有患者的中位随访时间为 29.2 个月。4 年 LPFS 为 77.3%。与单纯 IMRT 相比，接受 CC-IMRT 的患者 LPFS 更高（CC-IMRT 85.8% vs. IMRT 68.8%，p=0.036）。所有患者的 4 年 OS 为 56.3%。与单纯 IMRT 相比，接受 CC-IMRT 的患者 OS 更高（CC-IMRT 68.0% vs. IMRT 47.0%，p=0.043）。多变量分析显示，同步化疗的接受与死亡风险降低（HR 0.395，p=0.019）和局部失败风险降低相关（HR 0.306，p=0.042）。23.9%的患者发生 3 级以上急性毒性反应，最常见的是皮炎（18.2%）和粘膜炎（9.1%）。17.1%的患者在放疗期间或放疗后需要经皮内镜胃造口术（PEG）管，其中 10.1%的患者在治疗后 12 个月以上需要 PEG 管。CC-IMRT 组的急性和迟发性毒性反应发生率并无统计学意义更高，但在 CC-IMRT 中，皮炎和 PEG 需求的毒性反应趋势更高。
IMRT 是一种安全有效的方法，可在无法切除或不完全切除的非未分化、非髓样甲状腺癌患者中实现局部控制。同步多柔比星治疗并不会导致更严重的毒性反应，鉴于其改善局部控制和总生存率的潜力，应在这些患者中考虑使用。
