Abstract 1535P
Background
The exon 11 mutations are the most frequent KIT mutations, but represent a heterogeneous subgroup in terms of biological and clinical behavior. The exact pathogenic variant (PV) type and codon location, and other biological factors, could affect the Recurrence-Free Survival and the development of an organ-selective pattern of tumor metastasis to relapse.
Methods
116 GIST patients completely resected were included in the study between January 2005 and September 2020. The association between Exon 11 PV type with RFS was evaluated. In relapsed patients, metastatic sites were described, Neutrophil–Lymphocyte Ratio (NLR) was calculated, and plasma PD-1, PD-L1, BTN3A1, and BTN2A1 levels have been measured using homemade ELISA assays not yet commercially available.
Results
Deletions (del) of the codons 557/558 showed more aggressive tumor behavior and a higher risk of recurrence compared to other exon 11 del, or duplication/insertion/SNV (7-year RFS: 48.6% vs 73.1% vs 87.9%; p<0.001). In the 557/558 population, 77.8% of relapsed GIST harbored del simultaneously involving 557 and 558 codons (mainly KIT p.W557_K558del); when 557 and 558 deletions were analyzed separately, only 22.2% showed a tumor relapse, miming the prognostic behavior of tumor carrying del outside 557/558 position. In contrast to previous findings, in relapsed patients with 557/558 del, the peritoneum is the most frequent metastatic site (72.2%). Using thresholds by ROC analysis and multivariate analysis, we found that the patients with a tumor harboring del outside 557/558 and prevalent peritoneal metastasis, had NLR significantly lower compared to the relapsed patients with other exon 11 PVs (median 2.3 vs 3.1 G/L; p=0.029), and lower baseline levels of plasma PD-1 (>7.9 ng/mL), PD-L1 (<0.65 ng/mL), and BTN3A1 (<7.4 ng/mL).
Conclusions
The result supporting the functional cross-talk between the inflammatory response, the immune microenvironment and tumor progression, also in GIST, paradigmatic model of oncogene addiction, and represent the rationale to better investigate whether other factors of clinical or biological interest could have a further impact on tumor recurrence.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.