Yamazaki Haruhiko, Sugimori Makoto, Saito Aya
Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, 4-57 Urafunecho, Minami-Ku, Yokohama, Kanagawa, 232-0024, Japan.
Division of Cancer Genome Medicine, Genomics Laboratory, and Gastroenterology, Yokohama City University Medical Center, 4-57 Urafunecho, Minami-Ku, Yokohama, Kanagawa, 232-0024, Japan.
Surg Case Rep. 2024 Jul 17;10(1):171. doi: 10.1186/s40792-024-01971-1.
Pooled data analysis from three phase I/II larotrectinib clinical trials revealed that larotrectinib demonstrated rapid and durable disease control and a favorable safety profile for patients with neurotrophic-tropomyosin receptor kinase (NTRK) fusion positive thyroid carcinoma. Herein, we report the case of a patient with papillary thyroid carcinoma (PTC) and liver metastases who demonstrated a durable response to treatment with larotrectinib.
A 50-year-old female with PTC was referred to our hospital for postoperative observation. Computed tomography (CT) scan was performed to screen for distant metastasis, since thyroglobulin concentration increased gradually, and revealed multiple distant metastases, including multiple liver metastases. Radioactive iodine was administered at a dose of 100 mCi. However, uptake was observed only in the thyroid bed, and distant metastases had no avidity. As liver metastases progressed, lenvatinib (24 mg/day) was initiated after confirmation of liver metastases by liver biopsy 9 years and 1 month after the initial referral to our hospital. Since the multiple metastases became refractory for lenvatinib, the OncoGuide™ NCC Oncopanel System was performed, and the SQSTM1-NTRK1 gene fusion was confirmed. Larotrectinib was subsequently administered at a dose of 200 mg/day. The CT before the initiation of larotrectinib showed multiple liver metastases with a maximum diameter of 48 mm. The first CT evaluation at 1 month after the initiation of larotrectinib treatment showed that the tumor volume was reduced by 28% in the RECIST 1.1 criteria. After 3 months of larotrectinib treatment, a 38% reduction in the tumor volume was achieved as the best clinical response. The only side effect was grade 1 myalgia. At 12 months after the initiation of larotrectinib treatment, none of the lesions had progressed.
In conclusion, larotrectinib demonstrated effective antitumor activity against liver metastases of PTC, a relatively rare site of distant metastasis. Furthermore, the efficacy of larotrectinib was maintained, even though the patient had a history of multi-tyrosine kinase inhibitor treatment and a relatively infrequent fusion gene, SQSTM1-NTRK1.
三项I/II期拉罗替尼临床试验的汇总数据分析显示，拉罗替尼对神经营养性原肌球蛋白受体激酶（NTRK）融合阳性甲状腺癌患者显示出快速且持久的疾病控制效果以及良好的安全性。在此，我们报告一例乳头状甲状腺癌（PTC）伴肝转移患者对拉罗替尼治疗产生持久反应的病例。
一名患有PTC的50岁女性因术后观察被转诊至我院。由于甲状腺球蛋白浓度逐渐升高，进行了计算机断层扫描（CT）以筛查远处转移，结果显示存在多处远处转移，包括多处肝转移。给予100毫居里的放射性碘。然而，仅在甲状腺床观察到摄取，远处转移灶无摄取。随着肝转移进展，在初次转诊至我院9年1个月后经肝活检确诊肝转移后，开始使用乐伐替尼（24毫克/天）。由于多处转移对乐伐替尼耐药，进行了OncoGuide™ NCC Oncopanel系统检测，确认存在SQSTM1-NTRK1基因融合。随后给予拉罗替尼，剂量为200毫克/天。开始使用拉罗替尼前的CT显示多处肝转移，最大直径为48毫米。拉罗替尼治疗1个月后的首次CT评估显示，根据实体瘤疗效评价标准（RECIST）1.1，肿瘤体积缩小了28%。拉罗替尼治疗3个月后，肿瘤体积最大缩小38%，为最佳临床反应。唯一的副作用是1级肌痛。拉罗替尼治疗12个月后，所有病灶均未进展。
总之，拉罗替尼对PTC肝转移显示出有效的抗肿瘤活性，肝转移是相对少见的远处转移部位。此外，尽管该患者有多种酪氨酸激酶抑制剂治疗史且融合基因SQSTM1-NTRK1相对罕见，但拉罗替尼的疗效得以维持。
