Pan-Canadian consensus recommendations for GIST management in high- and low-throughput centres across Canada

Abstract

Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.

Keywords: CECT; Canada; DOG1; GIST; GIST management; KIT; PDGFRA; TKIs; advocacy; avapritinib; consensus based; contrast-enhanced CT scan; ctDNA; gastrointestinal; gastrointestinal stromal tumour; imatinib; imatinib resistance; locoregional therapies; mesenchymal; molecular testing; multidisciplinary; mutation; progression; regorafenib; ripretinib; sarcoma; specialized centres; sunitinib; surgery; tertiary centres; tyrosine kinase receptor inhibitors.

Figure 1.

Treatment pathways of GIST patients. ^$At a minimum for c-KIT and PDGFR genes. NGS Preferred. Further molecular testing can be performed as appropriate to look for secondary mutations. *KIT-inhibitor sensitive disease. ^#Clinical trial participation where possible. ^†In some instances, the aim of neoadjuvant imatinib is not purely to accommodate resection but rather the preservation of function or preventing increased morbidity associated with resection per se (e.g. in cases of rectal GIST where sphincter preservation is preferred, or in cases of duodenal GIST that would require pancreaticoduodenectomy). ^@For Imatinib and Ripretinib, consider for double dose in the event of disease progression. GIST, gastrointestinal stromal tumour; NGS, next-generation sequencing; PDGFR, platelet-derived growth factor receptor.