P-264 The molecular-metabolic interplay in metastatic gastrointestinal stromal tumors (GISTs): The predictive role of body mass index

Abstract

KIT exon 11 Pathogenic Variants (PVs) are the most frequent mutations in Gastrointestinal Stromal Tumors (GISTs). These patients represent a heterogeneous subgroup in terms of biological and clinical behavior: despite most GISTs with KIT exon 11 mutations are highly sensitive to front-line imatinib, the Progression Free Survival (PFS) may vary greatly. We investigated the predictive role of Body Mass Index (BMI), Neutrophil–Lymphocyte Ratio (NLR), and type and codon location of KIT exon 11 mutations in metastatic GIST patients treated with first-line imatinib 400 mg/die. Clinico-pathological characteristics, mutational status, BMI and NLR, were analyzed from a GIST System database prospectively collected. The primary outcome investigated was the Time to Treatment Failure (TTF). We classified the patients in 2 groups: i) KIT Exon 11 deletion or insertion/deletion in codons 557 and/or 558 (named “D-557/8”); ii) other than D-557/8 mutations (named “No-D-557/8”). The NLR was recorded from the routinely performed blood cell count as the absolute count of neutrophils divided by the absolute count of lymphocytes from peripheral blood samples collected at baseline. Sixty (60) KIT exon 11 mutated patients were included in the study: 25 (31.3%) showed exon 11 deletion or delins involving 557 and/or 558 codons (D-557/8 group), and 35 patients (43.7%) had a deletion in codons other than 557/558 or other PV types (duplication, insertion or SNV)(No-D-557/8 group). A total of 41 events (progression or death) were observed (68.3%): 18 events in the D-557/8 group of 25 patients (72%); 23 events in the No-D-557/8 group of 35 patients (65.7%). Overall median TTF was 37 months (95% confidence interval [CI]: 26.8-47.1). Median TTF was 24 months (95% CI: 21.3, 26.7) for the D-557/8 Group, and 49 months (95% CI: 39.4, 58.6) for the No-D-557/8 Group (p 25 (median TTF: 57.4 months (range 32-92) vs 24.2 months (range 3-45); p=0.001). In the KIT exon 11 mutated patients, who are the most common molecular-based subgroup of advanced GIST patients, our results reveal the important impact of BMI on TTF. These data support the functional cross-talk between metabolic and molecular features also in GISTs, paradigmatic model of oncogene addiction, and represent the rationale to better investigate whether factors of metabolic interest, such as BMI, could have a further impact on response to treatment.