Endosonography and pretreatment tumor profiling - from sampling, staining, to sequencing
Sammanfattning: Background and aims: Endosonography-guided fine needle aspiration (EUS-FNA) is imperfect in diagnosing solid pancreatic lesions (SPL) and subepithelial lesions (SEL) including gastrointestinal stromal tumors (GIST). In GISTs, imatinib therapy is effective only in variants of oncogenes KIT and PDGFRA. The global aim was to improve the EUS-diagnostics and study a biopsy approach (EUS-FNB) to obtain a reliable diagnosis of SPLs and SELs. In GISTs, the aim was to evaluate pretreatment samples for tumor risk assessment and the guidance of down-sizing imatinib therapy. Methods: In two prospective, single-center studies (2012–2015), SPLs (n=68,Paper I) and SELs (n=70,Paper II) were sampled with EUS-FNA and EUS-FNB. A reference cohort (2006–2011) was used for comparison. The EUS-FNB-tissue of all GISTs (n=44) was subjected to Ki-67-indexing and DNA-sequencing of KIT and PDGFRA (Paper III). In a last study (Paper IV), pretreatment sequencing of GISTs (n=59) was performed. Results: Paper I: In SPLs, EUS-FNB and EUS-FNA had a comparable diagnostic accuracy (69% vs 78%, p=0.31). The combination EUS-FNA+FNB was superior to EUS-FNA alone in pancreatic non-adenocarcinoma neoplasms (89% vs 69%, p=0.02). Paper II: In SELs, EUS-FNB had a higher diagnostic accuracy compared with EUS-FNA (83% vs 49%, p<0.001) leading to the reduced need for additional diagnostic procedures (14% vs 53%, p<0.001). Paper III: The EUS-FNB-tissue was diagnostic for GIST in 98%, accurate for Ki-67-indexing in 92%, and adequate for successful sequencing in 98% of the cases. In patients treated with down-sizing imatinib [KIT exon 11 (n=9); PDGFRA exon 12 (n=1)], the Ki-67-index was significantly higher in pretreatment FNB-tissue compared with resection specimens: Ki-67DIFF = 2.3 (95% CI: 0.67-5.37, p=0.005). Paper IV: Pretreatment sequencing, compared with no sequencing, lead to a higher rate of accurate down-sizing therapy (97% vs 70 %, p<0.001) and to the increased preoperative tumor size reduction on CT scan (32% vs 22%, p=0.036). Conclusions: The performance of endosonography-guided fine-needle biopsy sampling has a significant diagnostic and clinical value in subepithelial lesions; especially in gastrointestinal stromal tumors. The acquired tissue is also accurate for the early tumor proliferation rate assessment and genetic profiling of GISTs. The suggested work-up approach facilitates the guidance and evaluation of down-sizing tyrosine kinase inhibitor therapy.
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