Supplementary Material for: Benefit of continuation of low-dose imatinib for gastrointestinal stromal tumors despite adverse events with regular-dose imatinib

Tyrosine kinase inhibitors (TKIs) such as imatinib improve the prognosis of patients with gastrointestinal stromal tumors (GISTs). However, treatment options for GISTs are still limited, and the continuation of TKIs is difficult due to adverse events in some cases. The effectiveness of low-dose imatinib is unclear. We report two cases to show effectiveness of low-dose imatinib in patients with adverse events. The first case is a male in his early 60s with a history of intestinal GIST resection was diagnosed with recurrent GIST with peritoneal dissemination. He was started on low-dose imatinib (300 mg) because of a history of subconjunctival hemorrhage after receiving postoperative imatinib. Follow-up contrast-enhanced ultrasonography revealed that the tumors had shrunk in size and number after 2 months of treatment with 300-mg imatinib. He continued this treatment and showed partial response for 8 months. The second case is a female in her late 70s with rectal GIST was treated with imatinib 400 mg. Due to a severe skin lesion, she changed her treatment to sunitinib 2 months after initiation. However, new metastasis in the liver was confirmed after 4 months of administration of sunitinib. She underwent surgical resection of the rectal tumor to reduce the volume. After the surgery, low-dose imatinib (300 mg) with oral steroids was adopted. Follow-up confirmed the absence of recurrence at the rectum and no increase of hepatic tumor size for 18 months. Aggressive treatment with low-dose imatinib instead of discontinuation or alteration of treatment may benefit patients with unresectable and post-operative GISTs with sensible mutation to imatinib.酪氨酸激酶抑制剂（Tyrosine kinase inhibitors, TKIs）如伊马替尼（imatinib）可改善胃肠道间质瘤（gastrointestinal stromal tumors, GISTs）患者的预后。然而，胃肠道间质瘤的治疗选择仍较为有限，部分患者因不良反应难以维持TKIs治疗。低剂量伊马替尼的疗效尚不明确。本文报告两例病例，以展示低剂量伊马替尼在出现不良反应的患者中的治疗效果。第一例为60岁出头的男性患者，有肠道胃肠道间质瘤切除史，确诊为伴腹膜播散的复发性胃肠道间质瘤。因术后接受伊马替尼治疗后曾出现球结膜下出血，遂予低剂量伊马替尼（300 mg）治疗。随访行增强超声造影结果显示，接受300 mg伊马替尼治疗2个月后，肿瘤的大小与数量均较前缩小。患者持续接受该治疗方案，后续8个月均维持部分缓解（partial response）。第二例为70多岁的女性患者，患有直肠胃肠道间质瘤，初始接受400 mg伊马替尼治疗。因出现严重皮肤病变，于治疗启动2个月后更换为舒尼替尼（sunitinib）治疗。但在接受舒尼替尼治疗4个月后，确诊出现肝脏新发转移灶。患者遂接受直肠肿瘤切除术以缩减肿瘤负荷。术后采用联合口服糖皮质激素的低剂量伊马替尼（300 mg）治疗方案。经18个月随访，确认直肠部位无复发，肝脏肿瘤体积未出现增大。对于携带对伊马替尼敏感突变的不可切除及术后胃肠道间质瘤患者，采用低剂量伊马替尼替代停药或调整治疗方案的积极治疗策略，或可使患者获益。