REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial.

BACKGROUND: Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others. As regorafenib inhibits these signaling pathways, it was hypothesized that it could be more active as upfront therapy in advanced KP-wtGIST. METHODS: Adult patients with advanced KP-wtGIST after central confirmation by NGS, naïve of systemic treatment for advanced disease, were included in this international phase II trial. Eligible patients received regorafenib 160 mg per day for 21 days every 28 days. The primary endpoint was disease control rate (DCR), according to RECIST 1.1 at 12 weeks by central radiological assessment. RESULTS: From May 2016 to October 2020, 30 patients were identified as KP-wtGIST by Sanger sequencing and 16 were confirmed by central molecular screening with NGS. Finally, 15 were enrolled and received regorafenib. The study was prematurely closed due to the low accrual worsened by COVID outbreak. The DCR at 12 weeks was 86.7% by central assessment. A subset of 60% experienced some tumor shrinkage, with partial responses and stabilization observed in 13% and 87% respectively, by central assessment. SDH-deficient GIST showed better clinical outcome than other KP-wtGIST. CONCLUSIONS: Regorafenib activity in KP-wtGIST compares favorably with other tyrosine kinase inhibitors, especially in the SDH-deficient GIST subset and it should be taken into consideration as upfront therapy of advanced KP-wtGIST. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02638766.

Pancreatoduodenal junction: review of anatomy and pathologic conditions.

INTRODUCTION: The pancreatoduodenal junction is a small anatomic area where pathologic processes involving the distal bile duct, duodenum, pancreatic head, ampulla de Vater, and retroperitoneum converge. Differential diagnosis includes a spectrum of entities that ranges from anatomical variants to malignancies. PURPOSE: The aim of this paper was to review the anatomy and different pathologic conditions, whether tumoral, inflammatory, or congenital in origin, in this specific area that involves the pancreatic head, duodenum, duodenal ampulla, distal pancreatobiliary tract junction, and retroperitoneum. METHODS: Computed tomography (CT) and magnetic resonance (MR) help us to identify specific radiologic signs that allow to divide the pancreatic-duodenal junction abnormalities into three cathegories: (1) normal variants and congenital anomalies (pancreas divisum, santorinicele, annular pancreas,duodenal duplication cyst, choledocal cyst,...); (2) acquired non-tumoral: traumatic, iatrogenic, inflammatory (duodenal hematoma, duodenal iatrogenic perforation, groove pancreatitis, gastroduodenal artery pseudoaneurysm,...); (3) tumoral (pancreatic head adenocarcinoma, periampullary tumors, neuroendocrine pancreatic tumors, duodenal adenocarcinoma,...). The images illustrate morphologic aspects of these entities. RESULTS AND CONCLUSIONS: CT and MR are the most appropiate imaging modalities to evaluate pancreatoduodenal junction. Knowing the imaging features is crucial to reach the right diagnosis and treatment of the different entities that involve this anatomic area.