Genomic Complexity as a Biomarker to De-Escalate Adjuvant Imatinib Treatment in High-Risk Gastrointestinal Stromal Tumor.

Autor:	Boye K; Department of Oncology, Oslo University Hospital, Oslo, Norway., Gorunova L; Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway., Gunawan B; Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany., Hompland I; Department of Oncology, Oslo University Hospital, Oslo, Norway., Sander B; Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany.; Institute of Pathology, Hannover Medical School, Hannover, Germany., Panagopoulos I; Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway., Langer C; Clinic for General, Visceral, Thoracic and Minimally Invasive Surgery, Evangelical Hospital Göttingen-Weende, Göttingen, Germany., Golas M; Human Genetics, Faculty of Medicine, University of Augsburg, Augsburg, Germany.; Comprehensive Cancer Center Augsburg, University Medical Center Augsburg, Augsburg, Germany., Heim S; Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Füzesi L; Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany.; Pathology, Faculty of Medicine, University of Augsburg, Augsburg, Germany., Hølmebakk T; Department of Abdominal and Pediatric Surgery, Oslo University Hospital, Oslo, Norway., Micci F; Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2023 Feb; Vol. 7, pp. e2200351.
DOI:	10.1200/PO.22.00351
Abstrakt:	Purpose: Adjuvant imatinib treatment is recommended for patients with localized gastrointestinal stromal tumor (GIST) at high risk of recurrence. Almost half of high-risk patients are cured by surgery alone, indicating a need for improved selection of patients for adjuvant therapy. The aim of this study was to investigate if genomic tumor complexity could be used as a prognostic biomarker. Methods: The discovery cohort consisted of patients who underwent resection of primary GIST at Oslo University Hospital between 1998 and 2020. Karyotypes were categorized as simple if they had ≤ 5 chromosomal changes and complex if there were > 5 chromosomal aberrations. Validation was performed in an independent patient cohort where chromosomal imbalances were mapped using comparative genomic hybridization. Results: Chromosomal aberrations were detected in 206 tumors, of which 76 had a complex karyotype. The most frequently observed changes were losses at 14q, 22q, 1p, and 15q. The 5-year recurrence-free survival (RFS) in patients classified as very low, low, or intermediate risk was 99%. High-risk patients with a simple tumor karyotype had an estimated 5-year RFS of 94%, and patients with a complex karyotype had an estimated 5-year RFS of 51%. A complex karyotype was associated with poor RFS in patients with and without adjuvant imatinib treatment and in multivariable analysis adjusted for tumor site, size, mitotic count, and rupture. The prognostic impact of genomic complexity was confirmed in the validation cohort. In both cohorts, the 5-year disease-specific survival was > 90% for high-risk patients with genomically simple tumors. Conclusion: Genomic tumor complexity is an independent prognostic biomarker in localized, high-risk GIST. Recurrences were infrequent for tumors with simple karyotypes. De-escalation of adjuvant imatinib treatment should be explored in patients with cytogenetically simple GISTs.
Databáze:	MEDLINE
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