Higher levels of normalized variant allele frequency (nVAF) are independent predictors of prognosis and survival in patients with localized gastrointestinal stromal tumors (GISTs) harboring KIT or PDGFRA mutations, according to a new study published in The Oncologist.

The authors of the study also reported that nVAF could help improve prognostication and the use of adjuvant imatinib in a cohort of intermediate-risk patients.

In order to investigate the prognostic role of KIT or PDGFRA-VAF in patients with GIST who had radically resected localized disease, a team of researchers led by Giuseppe Badalamenti, MD, from the department of surgical, oncological and oral sciences, section of medical oncology, University of Palermo, Italy, conducted a hospital-based, retrospective/prospective cohort study in 200 patients from 2015 to 2022 at 6 different oncologic centers in Italy.

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Here, the researchers present results from the retrospective phase of the study.

Using the receiver operating characteristic (ROC) curves analysis, the researchers classified patients as having “low” or “high” VAF values, further normalized on neoplastic cellularity (nVAF). 

Read more about the prognosis of GIST

When they compared patients with low vs high nVAF, the researchers found that patients with a KIT/PDGFRA mutation and nVAF higher than 50% had worse recurrence-free survival, compared to patients with nVAF equal to or less than 50%. More precisely, the 2-year recurrence-free survival of patients with nVAF higher than 50% was 72.6%, while that of patients with nVAF equal to 50% or less was 93%. 

“The multivariable Cox regression model confirmed these results,” the researchers wrote. 

When they analyzed a homogeneous subpopulation of intermediate-risk patients with a KIT mutation, the researchers found that nVAF higher than 50% was statistically associated with higher disease recurrence.

Imatinib is recommended as an adjuvant treatment in patients who have a high risk of GIST recurrence. However, the choice of adjuvant imatinib is challenging in patients with an intermediate risk of GIST recurrence.

Reference

Incorvaia L, De Biase D, Nannini M, et al. KIT/PDGFRA variant allele frequency as prognostic factor in gastrointestinal stromal tumors (GISTs): Results from a multi-institutional cohort study. Oncologist. Published online July 18, 2023. doi:10.1093/oncolo/oyad206

Gastroenterologists Gleevec Imatinib Oncologists