Clinical implications of plasma circulating tumor DNA in gynecologic cancer patients
Autor: | Richard B. Lanman, Lindsey M. Charo, Ryosuke Okamura, Mina Nikanjam, Razelle Kurzrock, Michael T. McHale, David Piccioni, Ramez N. Eskander, Shumei Kato, Sandip Pravin Patel |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Oncology Cancer Research Multivariate analysis Time Factors Biopsy next‐generation sequencing medicine.disease_cause 0302 clinical medicine Gene Frequency Gynecologic cancer Medicine Research Articles RC254-282 Cancer Aged 80 and over circulating tumor DNA Hazard ratio Neoplasms. Tumors. Oncology. Including cancer and carcinogens General Medicine Middle Aged Prognosis Ovarian Cancer 030220 oncology & carcinogenesis mutation allele frequency Molecular Medicine Female gynecologic cancer KRAS Research Article Adult medicine.medical_specialty Genital Neoplasms Female Concordance Oncology and Carcinogenesis matched therapy 03 medical and health sciences Rare Diseases Clinical Research Internal medicine Genetics Humans Oncology & Carcinogenesis Liquid biopsy Allele frequency Aged liquid biopsy business.industry Human Genome medicine.disease Survival Analysis 030104 developmental biology Multivariate Analysis Mutation next-generation sequencing business |
Zdroj: | Molecular Oncology, vol 15, iss 1 Molecular Oncology, Vol 15, Iss 1, Pp 67-79 (2021) Molecular Oncology Molecular oncology, vol 15, iss 1 |
Popis: | In gynecologic cancer patients, therapy matched to ctDNA alterations (N = 33 patients) was independently associated with improved overall survival (hazard ratio: 0.34, P = 0.007) compared to unmatched therapy (N = 28 patients) in multivariate analysis. Tissue and ctDNA genomic results showed high concordance unaffected by temporal or spatial factors. ctDNA may be an important tool to individualize cancer therapy in patients with gynecologic cancer. Molecular characterization of cancers is important in dictating prognostic factors and directing therapy. Next‐generation sequencing of plasma circulating tumor DNA (ctDNA) offers less invasive, more convenient collection, and a more real‐time representation of a tumor and its molecular heterogeneity than tissue. However, little is known about the clinical implications of ctDNA assessment in gynecologic cancer. We describe the molecular landscape identified on ctDNA, ctDNA concordance with tissue‐based analysis, and factors associated with overall survival (OS) in gynecologic cancer patients with ctDNA analysis. We reviewed clinicopathologic and genomic information for 105 consecutive gynecologic cancer patients with ctDNA analysis, including 78 with tissue‐based sequencing, enrolled in the Profile‐Related Evidence Determining Individualized Cancer Therapy (NCT02478931) trial at the University of California San Diego Moores Cancer Center starting July 2014. Tumors included ovarian (47.6%), uterine (35.2%), cervical (12.4%), vulvovaginal (2.9%), and unknown gynecologic primary (1.9%). Most ovarian and uterine cancers (86%) were high grade. 34% (N = 17) of ovarian cancers had BRCA alterations, and 22% (N = 11) were platinum sensitive. Patients received median 2 (range 0–13) lines of therapy prior to ctDNA collection. Most (75.2%) had at least one characterized alteration on ctDNA analysis, and the majority had unique genomic profiles on ctDNA. Most common alterations were TP53 (N = 59, 56.2% of patients), PIK3CA (N = 26, 24.8%), KRAS (N = 14, 13.3%), BRAF (N = 10, 9.5%), ERBB2 (N = 8, 7.6%), and MYC (N = 8, 7.6%). Higher ctDNA maximum mutation allele frequency was associated with worse OS [hazard ratio (HR): 1.91, P = 0.03], while therapy matched to ctDNA alterations (N = 33 patients) was independently associated with improved OS (HR: 0.34, P = 0.007) compared to unmatched therapy (N = 28 patients) in multivariate analysis. Tissue and ctDNA genomic results showed high concordance unaffected by temporal or spatial factors. This study provides evidence for the utility of ctDNA in determining outcome and individualizing cancer therapy in patients with gynecologic cancer. |
Databáze: | OpenAIRE |
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