PDF(Pubmed)
Abstract：
UNASSIGNED: Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor arising in the gut, most commonly stomach or small bowel. The most common driver mutations are KIT and PDGFRA which can be treated with imatinib or avapritinib (for PDGFRA D842V-mutant GIST), respectively. BRAF V600E mutant GISTs are rare and these do not respond to imatinib. Multiple clinical trials have shown antitumor effects with dabrafenib in BRAF-mutant melanoma and a few case reports have demonstrated treatment of BRAF V600E mutant GIST with a BRAF kinase inhibitor.
UNASSIGNED: We present a case of a 67-year-old woman diagnosed with high-risk GIST following initial resection. She was initially treated with adjuvant imatinib which was discontinued after 7 months because molecular analysis of her tumor showed the absence of KIT and PDGFRA mutations and a BRAF V600E mutation. When her disease progressed, she was started on sunitinib and subsequently regorafenib. Both agents were discontinued due to severe palmar-plantar erythrodysesthesia and clinical progression. She was subsequently started on dabrafenib based on the presence of a BRAF V600E mutation; this therapy led to a partial response. Her disease remained stable on this medication for 19 months before progression and addition of trametinib to her treatment. Her disease continued to progress and she was switched to everolimus with mixed response before re-challenging with dabrafenib and trametinib. Her imaging showed a mixed response to the re-challenge before progressing after 5 months and transitioning to hospice.
UNASSIGNED: We describe an uncommon molecular subtype of GIST with a BRAF V600E mutation. As expected, her disease was resistant to standard GIST therapy, however there was notable tumor regression following treatment with dabrafenib. This case shows the importance of molecular testing in GIST and adds to the current body of literature on the treatment of BRAF-mutant GIST.
UNASSIGNED: We present a case of a 67-year-old woman diagnosed with high-risk GIST following initial resection. She was initially treated with adjuvant imatinib which was discontinued after 7 months because molecular analysis of her tumor showed the absence of KIT and PDGFRA mutations and a BRAF V600E mutation. When her disease progressed, she was started on sunitinib and subsequently regorafenib. Both agents were discontinued due to severe palmar-plantar erythrodysesthesia and clinical progression. She was subsequently started on dabrafenib based on the presence of a BRAF V600E mutation; this therapy led to a partial response. Her disease remained stable on this medication for 19 months before progression and addition of trametinib to her treatment. Her disease continued to progress and she was switched to everolimus with mixed response before re-challenging with dabrafenib and trametinib. Her imaging showed a mixed response to the re-challenge before progressing after 5 months and transitioning to hospice.
UNASSIGNED: We describe an uncommon molecular subtype of GIST with a BRAF V600E mutation. As expected, her disease was resistant to standard GIST therapy, however there was notable tumor regression following treatment with dabrafenib. This case shows the importance of molecular testing in GIST and adds to the current body of literature on the treatment of BRAF-mutant GIST.
摘要：
■胃肠道间质瘤（GIST）是一种罕见的发生在肠道的间充质肿瘤，最常见的是胃或小肠。最常见的驱动突变是KIT和PDGFRA，可以用伊马替尼或阿瓦替尼治疗（对于PDGFRAD842V突变型GIST），分别。BRAFV600E突变GIST是罕见的，这些对伊马替尼没有反应。多项临床试验已显示dabrafenib在BRAF突变型黑色素瘤中的抗肿瘤作用，并且一些病例报告已证明用BRAF激酶抑制剂治疗BRAFV600E突变型GIST。
■我们介绍了一例67岁女性初次切除后诊断为高危GIST的病例。她最初用佐剂伊马替尼治疗，7个月后停药，因为她的肿瘤的分子分析显示不存在KIT和PDGFRA突变以及BRAFV600E突变。当她的疾病进展时，她开始服用舒尼替尼,随后服用瑞戈非尼.由于严重的掌足红感觉障碍和临床进展，两种药物均被停用。随后，基于BRAFV600E突变的存在，她开始接受dabrafenib治疗；这种治疗导致部分反应。在病情进展和治疗中加入曲美替尼之前，她的疾病在该药物下保持稳定19个月。她的疾病继续进展，在用达布拉非尼和曲美替尼重新挑战之前，她以混合反应改用依维莫司。她的影像学显示，在5个月后进展并过渡到临终关怀之前，对再次挑战的反应是混合的。
■我们描述了一种罕见的具有BRAFV600E突变的GIST分子亚型。不出所料,她的疾病对标准GIST治疗有抗药性,然而，使用dabrafenib治疗后，肿瘤明显消退。该病例显示了分子检测在GIST中的重要性，并增加了目前关于BRAF突变GIST治疗的文献。
■我们介绍了一例67岁女性初次切除后诊断为高危GIST的病例。她最初用佐剂伊马替尼治疗，7个月后停药，因为她的肿瘤的分子分析显示不存在KIT和PDGFRA突变以及BRAFV600E突变。当她的疾病进展时，她开始服用舒尼替尼,随后服用瑞戈非尼.由于严重的掌足红感觉障碍和临床进展，两种药物均被停用。随后，基于BRAFV600E突变的存在，她开始接受dabrafenib治疗；这种治疗导致部分反应。在病情进展和治疗中加入曲美替尼之前，她的疾病在该药物下保持稳定19个月。她的疾病继续进展，在用达布拉非尼和曲美替尼重新挑战之前，她以混合反应改用依维莫司。她的影像学显示，在5个月后进展并过渡到临终关怀之前，对再次挑战的反应是混合的。
■我们描述了一种罕见的具有BRAFV600E突变的GIST分子亚型。不出所料,她的疾病对标准GIST治疗有抗药性,然而，使用dabrafenib治疗后，肿瘤明显消退。该病例显示了分子检测在GIST中的重要性，并增加了目前关于BRAF突变GIST治疗的文献。
