1974P - Improved risk stratification with a prognostic nomogram incorporating the KIT-Variant Allele Frequency (VAF)

and the 557/558 deletions: results from a multi-institutional study in a cohort of intermediate-risk GIST patients
Lorena Incorvaia ,
Dario De
1 Andrea Biase ,
Margherita
2 Gottardo ,
Chiara 1 Elena Bruno Nannini ,
Ida De
3 Brando ,
Tancredi Didier3 Fumagalli ,
4 Vincenzi ,
5 Luca ,
1

Bazan Russo1, Maria A. Pantaleo3, Silvia Gasperoni6, Lorenzo D’Ambrosio7, Giovanni Grignani7, Laura Algeri1, Alessandra Dimino1, Valerio Gristina1, Antonio
Galvano , Viviana Bazan , Antonio Russo , and Giuseppe Badalamenti .
1 10 1 1
1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, Italy; 2 Anatomic Pathology and Molecular Diagnostic Unit-University of Bologna Medical Center, Bologna, Italy; Department of Pharmacy and Biotechnology
(FaBit), University of Bologna, Bologna, Italy; 3 Department of Experimental, Diagnostic and Specialized Medicine, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; 4 Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 5
Department of Medical Oncology, Campus Biomedico University of Rome, Rome, Italy; 6 Translational Oncology Unit, University Hospital Careggi, Firenze, Italy; 7 Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, TO, Italy; 8 Department of Biomedicine,
Neuroscience and Advanced Diagnostics (BIND), Section of Medical Oncology, University of Palermo, 90127 Palermo, Italy

BACKGROUND RESULTS

In the intermediate-risk (I-R) GIST patients, the choice of adjuvant imatinib is
challenging. Historically, patient risk stratification is based on tumor size, mitotic index,
tumor location, and tumor rupture. Innovative measures from NGS, such as the KIT-
Variant Allele Frequency (VAF), may act as surrogate of tumor burden, and thus might
negatively correlate with prognosis of localized GIST patients, along with specific
tumor genotyping.
Overall, data from 240 GIST patients treated between 2015 and 2022 at 6 Oncologic
Centers in the EURACAN Network were collected. The cohort of I-R patients with tumors
harboring KIT mutations, without adjuvant imatinib, included 66 patients. Diameter of
primary tumor >5 cm (p=0.005), mitosis >5/mmq (p<0.001), no-gastric site of origin
(p=0.01), KIT Exon 11 deletions or delins involving codons 557 and/or 558 (p<0.001), and
nVAF > 50% (p=0.006), were significantly associated with Relapse-Free Survival (RFS).
At the median follow-up of 24 months, RFS rate of I-R cohort was 74.4% in the high-nVAF
group vs 100% in the low-nVAF group. When RFS between the 2 groups was compared,
I-R patients with high-nVAF showed poorer RFS than low-nVAF group. Nomogram
analysis including KIT-PVs–nVAF, and the presence/absence of 557/558 del/delins,
predicted 2-year RFS.
A Relapse-Free Survival (RFS) B Relapse-Free Survival (RFS)

Intermediate-Risk Intermediate-Risk
VAF nVAF

Survival Probability
Survival Probability
+ censored
+ censored
p=0.01 p=0.01

VAF ≤ 45 (%) Months nVAF ≤ 50 (%) Months

VAF > 45 (%) nVAF > 50 (%)

METHODS CONCLUSIONS

We used real-world data from a multicenter, hospital-based, retrospective/prospective Prognostication in the intermediate-risk subgroup is still challenging for optimal patient
cohort study to develop a prognostic nomogram integrating VAF levels and type/gene selection for adjuvant imatinib. In this sub-population the use of a nomogram
location of KIT mutations. The receiver operating characteristic (ROC) analysis was incorporating nVAF and type/gene location of KIT mutations, might represent a more
used to classify “low” vs “high” VAF values, further normalized on neoplastic cellularity accurate tool in the clinical decision-making process.
(nVAF). The optimal cut-off was 50% (AUC 0.84; p-value < 0.02). Cox Dr. Lorena Incorvaia lorena.incorvaia@unipa.it
regression/nomogram models were developed in SPSS and R, respectively. Prof. Giuseppe Badalamenti giuseppe.badalamenti@unipa.it
Contacts Prof. Antonio Russo antonio.russo@usa.net