1761P - Clinical description and development of a prognosis score for neurofibromatosis type 1 (NF1) associated GISTs in the RECKGIST cohort: A retrospective study from the French NETSARC+ network

Background

GISTs occur in 7% of NF1 patients. Data about their natural history remain scarce and Miettinen or Joensuu classification have not been validated in this population.

Methods

This retrospective study included consecutive NF1 patients with operated localized GIST in NF1 patients, from 2008-2023 in 25 NETSARC+ centers. Factors to predict relapse identified in uni/multivariate analysis (Kaplan-Meier curves compared with LogRank test) were used to build a prognosis score.

Results

119 patients were included, median follow up was 6 years, 61% were women, age at diagnosis was 53 (20-78). The primary location was the small bowel in 86% (duodenum in 25%), the stomach in 11% and unknown in 3%. Median size of the largest GIST and mitotic count (mit) were 45 mm (CI95: 45-58) and 2/5 mm² (CI95: 3-9). The vast majority were KIT/PDGFRa wildtype, the others harboring a KIT (2%) or a PDGFRa (3%) mutation. 43% patients had initial complication (21% pain, 17% bleeding, 5% occlusion). 63 had upfront surgery, 56 patients had active surveillance, median time to surgery was 8.3 months and tumor growth rate (TGR) was 0.59 (range -8.5% – +62%/month). Below 30 mm (n=35), no GIST relapsed after surgery. Above 30 mm (n=84), 18 developed metastasis and hazard ratio for GIST between 0-5 mit (75%) versus >6 mit was 4.18 (CI95: 1.54-11.37, p=0.005). There was no difference for relapse according to location (small bowel vs gastric, p=0.45) or tumor rupture (p=0.11), while KIT/PDGFRa mutated GISTs were at higher risk (10 years (10y) relapse free survival (RFS): 30% vs 82.5%, p=0.03). Miettinen (10y-RFS: Null 100%, Very Low 67%, Low 94%, Intermediate 77%, High 66%) and Joensuu (10y-RFS: Very Low 100%, Low 92%, Intermediate 100%, High 69%) classification did not predict relapse accurately. For RECKGIST score A (size ≤ 30 mm, n=34) group, 10y-RFS was 100%, it was 78.5% in the RECKGIST B (size > 30 mm and 0 < mit ≤ 5, n=63) group and 45.5% in the RECKGIST C (size > 30 mm and mit > 5, n=18) group (p<0.0001).

Conclusions

For NF1-GISTs > 30 mm, relapse rate is 21%. Other clinical data will be presented at the congress. RECKGIST score needs to be validated in an external cohort.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

CHU Amiens Picardie.

Funding

Has not received any funding.

Disclosure

M. Brahmi: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Amgen, PharmaMar, Deciphera. B. Verret: Financial Interests, Institutional, Invited Speaker: Lilly, Pfizer, Pierre Fabre, Seagen, Daiichi Sankyo, Gilead, Novartis, MSD, AstraZeneca; Financial Interests, Institutional, Advisory Board: Lilly, Daiichi Sankyo, Gilead, Novartis, Owkins, AstraZeneca, MSD, Boehringer Ingelheim. N. Penel: Financial Interests, Institutional, Research Grant, Research grant for clinical trials in sarcoma filed: Bayer HealthCare. M. Muller: Financial Interests, Institutional, Invited Speaker: Servier. S. Watson: Financial Interests, Personal, Invited Speaker: Deciphera, AstraZeneca; Financial Interests, Personal, Advisory Board: Deciphera, Boehringer Ingelheim. T. Lecomte: Financial Interests, Personal, Advisory Board: Sanofi, Merck Serono, Servier, Amgen, Ipsen, Pierre Fabre, AstraZeneca, Deciphera, Bayer. O. Bouche: Financial Interests, Personal, Advisory Board: Amgen, Merck, Apmonia Therapeutics, Deciphera, Astellas, Takeda; Financial Interests, Personal, Invited Speaker: Servier, Pierre Fabre, Bayer. All other authors have declared no conflicts of interest.