Ballal Sanjana, Yadav Madhav Prasad, Satapathy Swayamjeet, Roesch Frank, Chandekar Kunal R, Martin Marcel, Shakir Mohammad, Agarwal Shipra, Rastogi Sameer, Moon Euy Sung, Bal Chandrasekhar
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.
Department of Chemistry-TRIGA, Johannes Gutenberg University, Mainz, Germany.
Thyroid. 2025 Feb;35(2):188-198. doi: 10.1089/thy.2024.0229. Epub 2025 Jan 27.
The study aimed to analyze the long-term outcomes of [Lu]Lu-DOTAGA.FAPi dimer therapy in individuals diagnosed with radioiodine-resistant (RAI-R) follicular cell-derived thyroid cancer. In this retrospective study, 73 patients with RAI-R follicular thyroid carcinoma who had undergone multiple lines of previous treatments were included. Following [Ga]Ga-DOTA.SA.FAPi positron emission tomography-computed tomography scan, among the 73 patients, 65 received [Lu]Lu-DOTAGA.FAPi dimer monotherapy with a median activity of 5.5 GBq per cycle at 8-week intervals. The remaining eight patients underwent tandem [Lu]Lu/[Ac]Ac-DOTAGA.FAPi dimer therapy, consisting of a median of two cycles of [Lu]Lu-DOTAGA.FAPi dimer followed by one cycle of [Ac]Ac-DOTAGA.FAPi dimer, also at 8-week intervals. The primary endpoint included progression-free survival (PFS) and overall survival (OS). Secondary endpoints included PERCIST criteria response assessment and safety assessment according to Common Terminology Criteria for Adverse Events (V5.0). We enrolled 37 female and 36 male patients, with a mean age of 54.3 years (range: 27 - 80 years). The patients received a median cumulative activity of 22.2 GBq (range, 4 GBq-55.5 GBq) of [Lu]Lu-DOTAGA-FAPi dimer over one to nine cycles, with a median of three cycles. Among 73 patients, 20 died and 16 deaths were due to thyroid cancer. Nineteen patients experienced disease progression, with an estimated median PFS of 29 months [CI 14-34 months]. The estimated median OS was 32 months [CI 21-40 months]. Four patients (5.4%) encountered grade III anemia, primarily linked to bone metastasis in three cases and neck tumor mass bleed in one. Grade III thrombocytopenia occurred in three patients (4%). No grade III renal or hepatotoxicity was observed. In this study, [Lu]Lu-DOTAGA.FAPi dimer therapy showed promising safety and efficacy in aggressive, radioiodine-resistant thyroid cancer, achieving a median PFS and OS of 29 and 32 months, respectively, with manageable adverse events. Confirmation of our findings is needed from prospective clinical trials comparing [Lu]Lu-DOTAGA.FAPi dimer therapy to other treatments.
本研究旨在分析[镥]镥-DOTAGA.FAPi二聚体疗法对诊断为放射性碘难治性（RAI-R）滤泡细胞源性甲状腺癌患者的长期疗效。在这项回顾性研究中，纳入了73例接受过多种前期治疗的RAI-R滤泡性甲状腺癌患者。在[镓]镓-DOTA.SA.FAPi正电子发射断层扫描-计算机断层扫描后，73例患者中，65例接受了[镥]镥-DOTAGA.FAPi二聚体单药治疗，每8周为一个周期，中位活度为5.5GBq。其余8例患者接受了[镥]镥/[锕]锕-DOTAGA.FAPi二聚体序贯治疗，包括中位两个周期的[镥]镥-DOTAGA.FAPi二聚体，随后是一个周期的[锕]锕-DOTAGA.FAPi二聚体，同样每8周为一个周期。主要终点包括无进展生存期（PFS）和总生存期（OS）。次要终点包括根据实体瘤疗效评价标准（PERCIST）进行的疗效评估以及根据不良事件通用术语标准（V5.0）进行的安全性评估。我们纳入了37例女性和36例男性患者，平均年龄54.3岁（范围：27 - 80岁）。患者在1至9个周期内接受了[镥]镥-DOTAGA-FAPi二聚体的中位累积活度为22.2GBq（范围，4GBq - 55.5GBq），中位周期数为3个周期。73例患者中，20例死亡，16例死于甲状腺癌。19例患者出现疾病进展，估计中位PFS为29个月[可信区间14 - 34个月]。估计中位OS为32个月[可信区间21 - 40个月]。4例患者（5.4%）出现3级贫血，其中3例主要与骨转移有关，1例与颈部肿瘤肿块出血有关。3例患者（4%）出现3级血小板减少。未观察到3级肾毒性或肝毒性。在本研究中，[镥]镥-DOTAGA.FAPi二聚体疗法在侵袭性放射性碘难治性甲状腺癌中显示出有前景的安全性和疗效，中位PFS和OS分别达到29个月和32个月，不良事件可控。需要通过前瞻性临床试验将[镥]镥-DOTAGA.FAPi二聚体疗法与其他治疗方法进行比较，以证实我们的研究结果。
