Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, 200 First Street S.W, Rochester, MN, 55905, USA.
Curr Treat Options Oncol. 2021 Mar 20;22(5):37. doi: 10.1007/s11864-021-00837-0.
Treatment with the tyrosine kinase inhibitor (TKI), imatinib is the standard first-line treatment for metastatic gastrointestinal stromal tumors (GISTs). Unfortunately, acquired c-kit mutations cause secondary resistance to imatinib in a median of 18-24 months. Sunitinib and regorafenib are multi-kinase inhibitors that can be used as second-line or third-line therapy in imatinib-resistant or -intolerant GISTs, respectively. Ripretinib (a switch-control tyrosine kinase inhibitor) has recently been approved for fourth-line treatment in metastatic GIST. The TKI avapritinib has been approved for metastatic GIST harboring the imatinib-resistant PDGFRA exon 18 mutation. Although TKI therapies have revolutionized the treatment of metastatic GISTs, they cannot cure metastatic GISTs. Therefore, cytoreductive surgery is of considerable interest and has been accordingly investigated. Retrospective non-randomized studies demonstrated the feasibility and safety of continuous TKI therapy and surgical resection. Most studies demonstrate response to TKI therapy, completeness of resection, extent of disease, and surgical complexity as predictors of outcomes. Most TKIs can be stopped shortly before surgery and restarted shortly after. There is no known survival benefit from debulking operations or R2 resections and this should not be considered. However, debulking/palliative surgery may be necessary for patients with complications of hemorrhage, pain, or intestinal obstruction. SDH-deficient GISTs have an indolent natural history despite metastatic disease and may be another uncommon subgroup that would benefit from surgical debulking (R2 resection). At the time of operation, care should be taken to avoid tumor rupture. After surgical resection, patients should resume tyrosine kinase inhibitor (TKI) therapy as soon as possible and be monitored for disease progression. In all patients with metastatic GIST, the decision to pursue metastasectomy for GIST should be made in a multidisciplinary setting and be individualized according to patient age, comorbidities, functional status, symptoms, mutation status, extent of disease, completeness of resection, TKI response, and goals of the patient.
针对转移性胃肠间质瘤（GIST），采用酪氨酸激酶抑制剂（TKI）伊马替尼治疗是标准的一线治疗方法。不幸的是，继发性 c-kit 突变导致对伊马替尼的获得性耐药，中位时间为 18-24 个月。舒尼替尼和瑞戈非尼分别是多激酶抑制剂，可作为伊马替尼耐药或不耐受的 GIST 的二线或三线治疗药物。 Ripretinib（一种开关控制酪氨酸激酶抑制剂）最近被批准用于转移性 GIST 的四线治疗。TKI 阿伐替尼已被批准用于携带伊马替尼耐药 PDGFRA 外显子 18 突变的转移性 GIST。尽管 TKI 治疗方法彻底改变了转移性 GIST 的治疗方法，但它们不能治愈转移性 GIST。因此，细胞减灭术引起了相当大的兴趣，并进行了相应的研究。回顾性非随机研究证明了连续 TKI 治疗和手术切除的可行性和安全性。大多数研究表明 TKI 治疗的反应、切除的完整性、疾病的程度和手术的复杂性是预测结果的因素。大多数 TKI 可以在手术前短时间内停止，并在手术后短时间内重新开始。减瘤手术或 R2 切除术并没有生存获益，因此不应考虑。然而，对于有出血、疼痛或肠梗阻并发症的患者，减瘤/姑息性手术可能是必要的。尽管存在转移性疾病，但 SDH 缺陷型 GIST 具有惰性的自然病史，可能是另一个从手术减瘤（R2 切除术）中获益的罕见亚组。在手术时，应注意避免肿瘤破裂。手术后，患者应尽快恢复酪氨酸激酶抑制剂（TKI）治疗，并监测疾病进展。对于所有转移性 GIST 患者，应在多学科环境中做出是否进行 GIST 转移切除术的决定，并根据患者年龄、合并症、功能状态、症状、突变状态、疾病程度、切除的完整性、TKI 反应和患者目标进行个体化。
