Neurofibromatosis 1 (NF1) and gastrointestinal stromal tumors (GISTs): Five-year experience from a regional center in United Kingdom.

Abstract

11035 Background: NF1 is an inherited autosomal dominant condition characterised by multifocal neurofibromas, café au lait spots, Lisch nodules, freckling. GISTs are the most common mesenchymal tumour of the gastrointestinal tract occurring in NF1 patients. We present our 5 year experience of NF1 associated GISTs from a regional centre in United Kingdom. Methods: 15 patients with GISTs associated with NF1 syndrome were identified from the database. Clinical, pathological, molecular and treatment outcomes were analysed. Results: N = 15. Male-3 and female-12. Median age 46 years. 33% were multifocal and 67% unifocal. Primary site Stomach-6.6%, duodenum-33%, small bowel-67%, colon 6.6%. Presenting symptoms: Abdominal pain-47%, anemia/bleed-40% and incidental finding-13%. Tumour size 0.5-23 cm, median 9 cm. Mitotic index 0-15, median 4 mitoses/5mm2. Risk stratification-Low/intermediate risk 60% and high risk 40%. Histology was spindle cell in 87% and mixed in 13%. All GISTs were CD117 and DOG-1 +ve. SDHB expression was preserved in all GISTs. No activation mutations were detected in KIT (exons 9, 11, 13, 17), PDGFRA (exons 12, 14, 18) and BRAF. Treatment: 67% had the primary GIST resected. None had adjuvant imatinib. 6 patients had been treated with tyrosine kinase inhibitors. 1 partial response lasting < 3 months was observed with Imatinib. No durable responses were seen with Imatinib or Sunitinib or Regorafenib. All 5 patients with metastatic disease died within one year of diagnosis. Conclusions: GISTs associated with NF1 syndrome are rare. Median age of diagnosis is a decade earlier than KIT/PDGFRA mutated GISTs. We observed that NF1 associated GISTs occur predominantly in small bowel, are mostly spindle cell histology and have female preponderance. No durable responses were noted with Imatinib or Sunitinib or Regorafenib. There is an urgent need for systematic international collaboration to identify druggable pathways/targets in NF1 GISTs. Any trials should be multicentre/ multinational to expedite recruitment.