Clinical description and development of a prognostic score for neurofibromatosis type 1 (NF1)-associated GISTs: a...

Gastrointestinal stromal tumors (GISTs) occur in ∼7% of neurofibromatosis type 1 (NF1) patients. Data about their natural history remain scarce and neither risk classifications, prognosis model nor adjuvant treatment have been validated in this population.

This national retrospective study included consecutive operated NF1-GIST cases from 31 reference centers in France, mostly from the NETSARC+ network. Factors associated with relapse were used to build a new prognostic score (RECKGIST). To address potential bias between adjuvant group and follow-up group, a propensity score was used.

A total of 119 patients were included between 2008 and 2023, of whom 61% were women. Median age was 53 years (range 20-78 years). The main primary location was the small bowel (86%) and the stomach (11%). Median size and mitotic count (mit) were 45 mm [95% confidence interval (CI) 45-58 mm] and 2 mit/5 mm² (95% CI 3-9 mit/5 mm²), respectively. The vast majority were KIT/PDGFRA wild type (mutation KIT 2%, PDGFRA 3%). The median follow-up was 6 years. For GISTs <30 mm (n = 35), none relapsed. For GISTS >30 mm (n = 84), 18 developed metastases (21%). There was no difference in relapse according to tumor location (P = 0.45) or tumor rupture (P = 0.11), whereas KIT/PDGFRA-mutated GISTs were at higher risk of relapse [recurrence-free survival (RFS) at 10 years of 30% versus 82.5% for wild type, P = 0.03]. Miettinen and Joensuu classification did not predict relapse accurately. For the RECKGIST score A (size ≤30 mm, n = 34) group, 10-year RFS was 100%; it was 78.5% in the RECKGIST B group (size >30 mm and 0 < mit ≤ 5, n = 60), and 45.5% in the RECKGIST C group (size >30 mm and mit >5, n = 20) (P < 0.0001). After matching, 10-year RFS was similar between adjuvant and surveillance groups (P = 0.34).

For NF1-GISTs <30 mm, prognosis without relapse is excellent. RECKGIST score accurately predicts recurrence and needs to be validated in an external cohort, but it may help treatment decision making. No efficacy of adjuvant treatment was observed.