Division of Medical Gastroenterology, Department of Internal Medicine, Sahlgrenska University Hospital, Blå Stråket 3, 413 35, Gothenburg, Sweden.
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Mol Diagn Ther. 2020 Apr;24(2):201-214. doi: 10.1007/s40291-020-00451-0.
Neoadjuvant tyrosine kinase inhibitor (TKI) therapy increases the chance of organ-preserving, radical resection in selected patients with gastrointestinal stromal tumors (GISTs). We aimed to evaluate systematic, immediate DNA sequencing of KIT and PDGFRA in pretreatment GIST tissue to guide neoadjuvant TKI therapy and optimize preoperative tumor response.
All patients who were candidates for neoadjuvant therapy of a suspected GIST [the study cohort (SC)] were prospectively included from January 2014 to March 2018. Patients were subjected to pretreatment endosonography-guided fine-needle biopsy (EUS-FNB) or transabdominal ultrasound-guided needle biopsy (TUS-NB), followed by immediate tumor DNA sequencing (< 2 weeks). A historic (2006-2013) reference cohort (RC) underwent work-up without sequencing before neoadjuvant imatinib (n = 42). The rate of optimal neoadjuvant therapy (Therapy) was calculated, and the induced tumor size reduction (Tumor Regression, %) was evaluated by computed tomography (CT) scan.
The success rate of pretreatment tumor DNA sequencing in the SC (n = 81) was 77/81 (95%) [EUS-FNB 71/74 (96%); TUS-NB 6/7 (86%)], with mutations localized in KIT (n = 58), PDGFRA (n = 18), or neither gene, wild type (n = 5). In patients with a final indication for neoadjuvant therapy, the Therapy was higher in the SC compared with the RC [61/63 (97%) versus 33/42 (79%), p = 0.006], leading to a significantly higher Tumor Regression in patients treated with TKI (27% vs. 19%, p = 0.015).
Pretreatment endosonography-guided biopsy sampling followed by immediate tumor DNA sequencing of KIT and PDGFRA is highly accurate and valuable in guiding neoadjuvant TKI therapy in GIST. This approach minimizes maltreatment with inappropriate regimens and leads to improved tumor size reduction before surgery.
新辅助酪氨酸激酶抑制剂（TKI）治疗增加了在选定的胃肠道间质瘤（GIST）患者中进行保器官、根治性切除的机会。我们旨在评估 KIT 和 PDGFRA 的预处理 GIST 组织的系统、即时 DNA 测序，以指导新辅助 TKI 治疗并优化术前肿瘤反应。
所有符合新辅助治疗疑似 GIST 的患者[研究队列（SC）]均于 2014 年 1 月至 2018 年 3 月前瞻性纳入。患者接受预处理内镜超声引导下细针活检（EUS-FNB）或经腹超声引导下针活检（TUS-NB），随后在<2 周内进行即时肿瘤 DNA 测序。历史性（2006-2013 年）参考队列（RC）在新辅助伊马替尼治疗前未经测序（n=42）。计算最佳新辅助治疗（治疗）的比例，并通过计算机断层扫描（CT）扫描评估诱导的肿瘤缩小（肿瘤退缩率，%）。
SC（n=81）预处理肿瘤 DNA 测序成功率为 77/81（95%）[EUS-FNB 71/74（96%）；TUS-NB 6/7（86%）]，突变定位于 KIT（n=58）、PDGFRA（n=18）或两种基因均未突变，野生型（n=5）。在最终需要新辅助治疗的患者中，SC 的治疗比例明显高于 RC[61/63（97%）与 33/42（79%），p=0.006]，导致 TKI 治疗患者的肿瘤退缩率显著更高[27%与 19%，p=0.015]。
预处理内镜超声引导活检采样后，即时进行 KIT 和 PDGFRA 的肿瘤 DNA 测序，在指导 GIST 新辅助 TKI 治疗方面具有高度的准确性和价值。这种方法最大限度地减少了不合适方案的过度治疗，并在手术前导致肿瘤体积缩小。
