KIT/PDGFRA Variant Allele Frequency as Prognostic Factor in Gastrointestinal Stromal Tumors (GISTs): Results From a Multi-Institutional Cohort Study.

Autor:	Incorvaia L; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., De Biase D; Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.; Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Nannini M; Department of Experimental, Diagnostic and Specialized Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy., Fumagalli E; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Vincenzi B; Department of Medical Oncology, Campus Biomedico University of Rome, Rome, Italy., De Luca I; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Brando C; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Perez A; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Pantaleo MA; Department of Experimental, Diagnostic and Specialized Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy., Gasperoni S; Department of Oncology and Robotic Surgery, Translational Oncology Unit, University Hospital Careggi, Firenze, Italy., D'Ambrosio L; Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, TO, Italy., Grignani G; Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, TO, Italy., Maloberti T; Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy., Pedone E; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Bazan Russo TD; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Mazzocca A; Department of Medical Oncology, Campus Biomedico University of Rome, Rome, Italy., Algeri L; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Dimino A; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Barraco N; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Serino R; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Gristina V; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Galvano A; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Bazan V; Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), Section of Medical Oncology, University of Palermo, Palermo, Italy., Russo A; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Badalamenti G; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
Jazyk:	angličtina
Zdroj:	The oncologist [Oncologist] 2024 Jan 05; Vol. 29 (1), pp. e141-e151.
DOI:	10.1093/oncolo/oyad206
Abstrakt:	Background: The patient selection for optimal adjuvant therapy in gastrointestinal stromal tumors (GISTs) is provided by nomogram based on tumor size, mitotic index, tumor location, and tumor rupture. Although mutational status is not currently used to risk assessment, tumor genotype showed a prognostic influence on natural history and tumor relapse. Innovative measures, such as KIT/PDGFRA-mutant-specific variant allele frequency (VAF) levels detection from next-generation sequencing (NGS), may act as a surrogate of tumor burden and correlate with prognosis and overall survival of patients with GIST, helping the choice for adjuvant treatment. Patients and Methods: This was a multicenter, hospital-based, retrospective/prospective cohort study to investigate the prognostic role of KIT or PDGFRA-VAF of GIST in patients with radically resected localized disease. In the current manuscript, we present the results from the retrospective phase of the study. Results: Two-hundred (200) patients with GIST between 2015 and 2022 afferent to 6 Italian Oncologic Centers in the EURACAN Network were included in the study. The receiver operating characteristic (ROC) curves analysis was used to classify "low" vs. "high" VAF values, further normalized on neoplastic cellularity (nVAF). When RFS between the low and high nVAF groups were compared, patients with GIST with KIT/PDGFRA nVAF > 50% showed less favorable RFS than patients in the group of nVAF ≤ 50% (2-year RFS, 72.6% vs. 93%, respectively; P = .003). The multivariable Cox regression model confirmed these results. In the homogeneous sub-population of intermediate-risk, patients with KIT-mutated GIST, the presence of nVAF >50% was statistically associated with higher disease recurrence. Conclusion: In our study, we demonstrated that higher nVAF levels were independent predictors of GIST prognosis and survival in localized GIST patients with tumors harboring KIT or PDGFRA mutations. In the cohort of intermediate-risk patients, nVAF could be helpful to improve prognostication and the use of adjuvant imatinib. (© The Author(s) 2023. Published by Oxford University Press.)
Databáze:	MEDLINE
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