再分化治疗 (RDT) 可以恢复分化甲状腺癌 (DTC) 细胞对放射性碘 (RAI) 的摄取，从而为先前的 RAI 难治性 (RAIR) 疾病提供挽救性 I-131 治疗。本研究评估了接受 RDT 的患者的临床结果，并确定了 RDT 后 RAI 恢复的预测临床病理特征。这是一个回顾性病例系列，涉及 2017 年至 2022 年间在 Mayo Clinic 接受 RDT 的 33 名 RECIST 进展性转移性 RAIR-DTC 患者罗切斯特。所有患者均接受基因组分析，并接受单独的 MEK、RET 或 ALK 抑制剂或联合 BRAF-MEK 抑制剂治疗 4 周。第 3 周，转移灶中 RAI 亲和力增加的患者接受高剂量 I-131 治疗。全面审查基线和临床病理结果。在 33 名患者中，57.6% 在 RDT（再分化亚组）后恢复了 RAI 摄取。 42.1% (8/19) 患有乳头状甲状腺癌 (PTC)，100% (4/4) 患有侵袭性包膜滤泡变异型 PTC (IEFV-PTC)，100% (7/7) 患有滤泡性甲状腺癌 (FTC) 再分化。所有 (11/11) RAS 突变肿瘤均重新分化，而 BRAF 突变疾病为 38.9% (7/18)（6 个 PTC 和 1 个 IEFV-PTC）。 76.5% (13/17) 的再分化患者和 66.7% (8/12) 的非再分化患者达到疾病稳定 (SD) 或非完全缓解/非进展性疾病的最佳总体 RECIST 缓解。单独使用药物三周后，两个亚组的肿瘤平均缩小 12%。经过高剂量 I-131 治疗后的再分化亚组在 RDT 后 6 个月时肿瘤平均减少了 20%。两组在无进展生存期（PFS）、开始全身治疗的时间和任何额外治疗的时间方面没有统计学上的显着差异。在整个队列中，6.1% (2/33) 经历了组织学转化为甲状腺未变性癌，15.1% (5/33) 死亡，所有患者在 RDT 后均已重新分化并接受 I-131 治疗。RDT 有可能恢复 RAI 亲和力和在特定的 RAIR-DTC 患者中，特别是那些具有 RAS 驱动的“滤泡”表型的患者中，I-131 治疗后诱导 RECIST 反应。在 PTC 患者中，再分化亚组和非再分化亚组之间评估的临床结果均无统计学差异。需要进一步的研究来更好地描述 RDT 后高剂量 RAI 的长期生存和/或安全性结果，特别是它是否可能与组织学间变性转化相关。

Redifferentiation therapy (RDT) can restore radioactive iodine (RAI) uptake in differentiated thyroid cancer (DTC) cells to enable salvage I-131 therapy for previously RAI refractory (RAIR) disease. This study evaluated the clinical outcomes of patients that underwent RDT and identified clinicopathologic characteristics predictive of RAI restoration following RDT.This is a retrospective case series of 33 patients with RECIST-progressive metastatic RAIR-DTC who underwent RDT between 2017 and 2022 at the Mayo Clinic Rochester. All patients underwent genomic profiling and received MEK, RET or ALK inhibitors alone or combination BRAF-MEK inhibitors for 4 weeks. At week 3, those with increased RAI avidity in metastatic foci received high dose I-131 therapy. Baseline and clinicopathologic outcomes were comprehensively reviewed.Of the 33 patients, 57.6% had restored RAI uptake following RDT (Redifferentiated subgroup). 42.1% (8/19) with papillary thyroid cancers (PTC), 100% (4/4) with invasive encapsulated follicular variant PTCs (IEFV-PTC), and 100% (7/7) with follicular thyroid cancers (FTC) redifferentiated. All (11/11) RAS mutant tumors redifferentiated compared to 38.9% (7/18) with BRAF mutant disease (6 PTC and 1 IEFV-PTC). 76.5% (13/17) of redifferentiated and 66.7% (8/12) of non-redifferentiated patients achieved a best overall RECIST response of stable disease (SD) or non-complete response/non-progressive disease. Both subgroups had a median 12% tumor shrinkage at three weeks on drug(s) alone. The redifferentiated subgroup, following high dose I-131 therapy, achieved an additional median 20% tumor reduction at 6 months after RDT. There were no statistically significant differences between both groups in progression free survival (PFS), time to initiation of systemic therapy and time to any additional therapy. Of the entire cohort, 6.1% (2/33) experienced histologic transformation to anaplastic thyroid cancer and 15.1% (5/33) died, all had redifferentiated following RDT and received I-131 therapy.RDT has the potential to restore RAI avidity and induce RECIST responses following I-131 therapy in select patients with RAIR-DTC, particularly those with RAS-driven 'follicular' phenotypes. In patients with PTC, none of the evaluated clinical outcomes differed statistically between the redifferentiated and non-redifferentiated subgroups. Further studies are needed to better characterize the long-term survival and/or safety outcomes of high-dose RAI following RDT, particularly whether it could be associated with histologic anaplastic transformation.