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

Author:

Incorvaia Lorena1,De Biase Dario23,Nannini Margherita4,Fumagalli Elena5,Vincenzi Bruno6,De Luca Ida1,Brando Chiara1,Perez Alessandro1,Pantaleo Maria A4,Gasperoni Silvia7,D’Ambrosio Lorenzo8,Grignani Giovanni8,Maloberti Thais39,Pedone Erika1,Bazan Russo Tancredi Didier1,Mazzocca Alessandro6,Algeri Laura1,Dimino Alessandra1,Barraco Nadia1,Serino Roberta5,Gristina Valerio1,Galvano Antonio1,Bazan Viviana10,Russo Antonio1,Badalamenti Giuseppe1

Affiliation:

1. Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo , Palermo , Italy

2. Department of Pharmacy and Biotechnology, University of Bologna , Bologna , Italy

3. Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna , Italy

4. Department of Experimental, Diagnostic and Specialized Medicine, S. Orsola-Malpighi Hospital, University of Bologna , Bologna , Italy

5. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy

6. Department of Medical Oncology, Campus Biomedico University of Rome , Rome , Italy

7. Department of Oncology and Robotic Surgery, Translational Oncology Unit, University Hospital Careggi , Firenze , Italy

8. Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS , Candiolo, TO , Italy

9. Department of Medical and Surgical Sciences (DIMEC), University of Bologna , Bologna , Italy

10. Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), Section of Medical Oncology, University of Palermo , Palermo , Italy

Abstract

Abstract 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.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3