An Zhaojie, Tan Ming, Xia Yuxiang, Li Yong, Fan Liqiao, Zhao Qun, Zhang Zhidong, Tan Bibo, Liu Yu, Ma Zhixue, Wang Dong, Zhao Xuefeng
Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
J Gastrointest Oncol. 2022 Oct;13(5):2620-2625. doi: 10.21037/jgo-22-791.
Targeted therapy with tyrosine kinase inhibitors (TKIs) benefits most patients with stromal tumors; however, the effects of TKIs in patients with rare cases of gastrointestinal stromal tumors (GISTs) with platelet-derived growth factor receptor alpha () exon 12 mutations are unclear. Our report of a case treated with multiline TKIs (included ripretinib) may provide some experience into the future management of rare GIST with 12 exon mutation.
We report the case of a patient (42-year-old female) with a exon 12-mutated GIST who underwent multiple surgeries and multiple lines of TKI therapy. This patient had intra-abdominal recurrence after imatinib, which was used as the 1st-line targeted drug treatment for 7 months after radical surgery, and had widespread metastases in the abdominal cavity after sunitinib, which was used as the 2nd-line targeted drug treatment for 6 months after the second radical surgery. For this advanced GIST patient with extensive intraperitoneal metastasis and rare 12 exon mutation, we then selected ripretinib as the 3rd-line targeted drug therapy to treat the patient. Up to the last follow-up in September 2021, the patient continued to take drugs without obvious complaints of discomfort or adverse events.
This case showed that patients with exon 12-mutated GISTs are less likely to benefit from current conventional TKIs, and ripretinib treatment should be considered preferred to regorafenib or even sunitinib according to each patient's situation. However, the limitation of our case is that the patient's second recurrent lesion was not genetically tested to determine the presence of secondary mutation. Further, if a patient's tumor has a high risk of adverse biological behaviors, such as high mitotic figures, vascular tumor thrombus, succinate dehydrogenase B (SDHB) was negative, and regional lymph node metastasis, consideration should be given to shortening the postoperative follow-up interval to 2 months or even 1 month.
酪氨酸激酶抑制剂（TKIs）靶向治疗使大多数间质瘤患者获益；然而，TKIs 对罕见的血小板衍生生长因子受体α（）外显子 12 突变的胃肠道间质瘤（GISTs）患者的疗效尚不清楚。我们报告的一例接受多线 TKIs（包括瑞派替尼）治疗的病例可能为未来罕见的外显子 12 突变 GIST 的管理提供一些经验。
我们报告一例（42 岁女性）外显子 12 突变的 GIST 患者，该患者接受了多次手术和多线 TKI 治疗。该患者在伊马替尼治疗后出现腹腔内复发，伊马替尼在根治性手术后作为一线靶向药物治疗 7 个月，在舒尼替尼治疗后出现腹腔广泛转移，舒尼替尼在第二次根治性手术后作为二线靶向药物治疗 6 个月。对于这位有广泛腹膜转移且罕见外显子 12 突变的晚期 GIST 患者，我们随后选择瑞派替尼作为三线靶向药物治疗该患者。截至 2021 年 9 月的最后一次随访，患者继续服药，无明显不适或不良事件主诉。
该病例表明，外显子 12 突变的 GIST 患者从当前传统 TKIs 中获益的可能性较小，应根据每位患者的情况考虑将瑞派替尼治疗作为优于瑞戈非尼甚至舒尼替尼的首选。然而，我们病例的局限性在于患者的第二次复发病灶未进行基因检测以确定是否存在继发突变。此外，如果患者的肿瘤具有不良生物学行为的高风险，如高有丝分裂指数血管肿瘤血栓、琥珀酸脱氢酶 B（SDHB）阴性和区域淋巴结转移，则应考虑将术后随访间隔缩短至 2 个月甚至 1 个月。
