Department of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Clin Cancer Res. 2022 Jul 1;28(13):2890-2897. doi: 10.1158/1078-0432.CCR-21-4520.
Mesenchymal stem/stromal cell therapy may reduce radiation-induced xerostomia. We investigated the long-term safety of autologous adipose tissue-derived mesenchymal stem/stromal cell (ASC) injections into the submandibular glands.
An investigator-initiated, randomized, single-center, placebo-controlled trial. Previous patients with oropharyngeal squamous cell carcinoma with radiation-induced xerostomia were randomly (1:1) allocated to receive a 2.8 million ASCs/cm3 injection or placebo in both submandibular glands and followed for a minimum of 2 years. The primary endpoint was number of serious adverse events (SAE). Secondary endpoints included whole saliva flow rates and xerostomia-related symptoms. Data analysis was based on the intention-to-treat population using repeated measures mixed-effects linear models.
Thirty-three patients were randomized; 30 patients were treated (ASC group, n = 15; placebo group, n = 15). Long-term safety data were collected from all 30 patients. During follow-up, 6 of 15 (40%) of the ASC-treated patients versus 5 of 15 (33%) of the placebo patients experienced an SAE; no SAEs appeared to be treatment related. Unstimulated whole saliva flow rate increased to 0.20 and 0.16 mL/minute in the ASC and placebo group, respectively, yielding a 0.05 mL/minute (95% confidence interval: 0.00-0.10; P = 0.051) difference between groups. Patient-reported xerostomia symptoms diminished according to a decreased xerostomia questionnaire summary score of 35.0 and 45.1, respectively [-10.1 (-18.1 to -2.2); P = 0.013]. Three of the visual analog scale xerostomia measures indicated clinical benefit following use of ASC.
Our data show that ASC therapy is safe with a clinically relevant effect on xerostomia-related symptoms. Confirmation in larger randomized controlled trials is warranted.
间充质干细胞/基质细胞疗法可能减少放疗引起的口干症。我们研究了自体脂肪组织来源的间充质干细胞/基质细胞（ASC）注射到下颌下腺的长期安全性。
一项由研究者发起的、随机的、单中心、安慰剂对照试验。以前患有放射性口干症的口咽鳞状细胞癌患者随机（1:1）分配到接受 280 万 ASC/cm3 注射或安慰剂，分别在下颌下腺双侧注射，并随访至少 2 年。主要终点是严重不良事件（SAE）的数量。次要终点包括全唾液流率和口干相关症状。数据分析基于意向治疗人群，使用重复测量混合效应线性模型。
33 名患者被随机分配；30 名患者接受治疗（ASC 组 n=15；安慰剂组 n=15）。对所有 30 名患者进行了长期安全性数据收集。在随访期间，15 名 ASC 治疗患者中有 6 名（40%）和 15 名安慰剂患者中有 5 名（33%）发生 SAE；没有 SAE 似乎与治疗有关。未刺激的全唾液流率分别增加到 0.20 和 0.16 mL/min，ASC 和安慰剂组之间的差异为 0.05 mL/min（95%置信区间：0.00-0.10；P=0.051）。根据口干问卷总结评分分别减少 35.0 和 45.1，患者报告的口干症状减轻[10.1（-18.1 至-2.2）；P=0.013]。使用 ASC 后，3 项视觉模拟量表口干测量指标显示出临床获益。
我们的数据表明，ASC 治疗是安全的，对口干相关症状有明显的治疗效果。需要更大规模的随机对照试验来证实。
