Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
Drugs. 2012 Oct 22;72(15):1953-63. doi: 10.2165/11635590-000000000-00000.
One randomized trial has found that adjuvant treatment with imatinib for gastrointestinal stromal tumour (GIST) 3 cm or larger in diameter prolongs recurrence-free survival, and another trial has reported that 3 years of adjuvant imatinib improves both recurrence-free and overall survival compared with 1 year of imatinib in high-risk GIST. The US National Comprehensive Cancer Network now recommends consideration of adjuvant imatinib for at least 3 years for patients with a high risk of GIST recurrence. Estimation of the risk of GIST recurrence is mandatory when considering adjuvant therapy. The risk varies greatly from negligible risk (tumours smaller than 1 cm) to 90% or greater risk (large tumours with frequent mitoses). The risk of recurrence can be estimated using one of the three validated risk stratification schemes, the National Institutes of Health (NIH) consensus risk criteria, the Armed Forces Institute of Pathology criteria or the modified NIH criteria, which have roughly similar prognostic accuracy, or with nomograms or prognostic contour maps. Patients with an intermediate risk may pose a problem when considering adjuvant therapy because few research data are available. The decision about whether or not to treat these patients with adjuvant imatinib can be solved using the modified NIH risk stratification criteria, since, with these criteria, patients with intermediate risk have similar outcomes to those with low risk, leaving only patients with high risk for consideration of adjuvant therapy. Analysis of tumour tissue for KIT and PDGFRA mutations is recommended to exclude patients with imatinib-insensitive mutations from adjuvant therapy (notably patients with PDGFRA substitution mutation D842V), and those with neurofibromatosis-1-associated wild-type GIST. The standard daily dose of adjuvant imatinib is 400 mg, but it is unknown whether this dose is optimal. Some patients, such as those with KIT exon 9 mutation, might benefit from a higher dose. While the optimal duration of adjuvant therapy is also unknown, 3 years of adjuvant imatinib is currently a reasonable choice. Early detection and management of imatinib side effects is likely important for achieving high compliance. Repeat imaging of the abdomen with CT or MRI during adjuvant imatinib and after its completion is also likely to be beneficial, since most patients whose GIST recurs after adjuvant treatment respond to reinstitution of imatinib, and the presence of a small tumour burden when imatinib is reinstituted may reduce the likelihood of rapid emergence of a second mutation that confers imatinib resistance.
一项随机试验发现，对于直径为 3cm 或更大的胃肠道间质瘤（GIST），辅助用伊马替尼治疗可延长无复发生存期，另一项试验报道，与 1 年的伊马替尼相比，3 年的辅助伊马替尼治疗可改善高风险 GIST 的无复发生存期和总生存期。美国国家综合癌症网络现在建议对于 GIST 复发风险高的患者，至少考虑辅助用伊马替尼 3 年。当考虑辅助治疗时，必须评估 GIST 复发的风险。风险差异很大，从无风险（肿瘤小于 1cm）到 90%或更高风险（有频繁有丝分裂的大肿瘤）。可以使用三种经验证的风险分层方案之一来估计复发风险，即美国国立卫生研究院（NIH）共识风险标准、武装部队病理研究所标准或改良 NIH 标准，这些方案的预后准确性大致相似，也可以使用列线图或预后轮廓图。当考虑辅助治疗时，中间风险的患者可能会带来问题，因为可用的研究数据很少。可以使用改良 NIH 风险分层标准来解决是否用辅助伊马替尼治疗这些患者的问题，因为根据这些标准，中间风险的患者与低风险患者的结局相似，只需要考虑高风险患者进行辅助治疗。建议分析肿瘤组织中的 KIT 和 PDGFRA 突变，以排除无辅助治疗敏感性的突变患者（特别是 PDGFRA 取代突变 D842V 的患者）和伴有神经纤维瘤病 1 相关野生型 GIST 的患者。建议从辅助治疗中排除无辅助治疗敏感性突变的患者（特别是 PDGFRA 取代突变 D842V 的患者）和伴有神经纤维瘤病 1 相关野生型 GIST 的患者。推荐用伊马替尼进行辅助治疗的标准日剂量为 400mg，但尚不清楚该剂量是否最佳。一些患者，如 KIT 外显子 9 突变患者，可能受益于更高的剂量。虽然辅助治疗的最佳持续时间也未知，但目前 3 年的辅助伊马替尼是一个合理的选择。早期发现和管理伊马替尼的副作用可能对提高依从性很重要。在辅助伊马替尼期间和完成后用 CT 或 MRI 重复腹部成像也可能有益，因为大多数在辅助治疗后 GIST 复发的患者对重新开始伊马替尼治疗有反应，当重新开始伊马替尼治疗时肿瘤负荷较小可能会降低迅速出现赋予伊马替尼耐药性的第二个突变的可能性。
