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
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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