Dynamic changes in TP53 mutated circulating tumor DNA predicts outcome of patients with high-grade ovarian carcinomas.

There is a lack of biomarkers to predict outcome following initial treatment in patients with high-grade ovarian cancer. We hypothesized that monitoring TP53 mutation ( TP53m ) in circulating tumor DNA (ctDNA) could be a tumor-specific biomarker. Patients enrolled in a prospective study (NCT03010124) consented to analysis of biological samples through the disease course. ctDNA was extracted and analyzed to detect the presence of TP53m Next-generation sequencing was performed on tumor tissue to detect TP53m and on whole blood to detect clonal hematopoiesis of indeterminate potential (CHIP).A total of 102 samples were sequentially collected from 26 patients. ctDNA was detected in all patients at diagnosis. The same TP53m was found in ctDNA and tumor tissue in 77% of patients. TP53m in ctDNA was not CHIP related. During neoadjuvant chemotherapy, increasing ctDNA was associated with failure to achieve complete interval cytoreductive surgery in 60% of patients. Rising ctDNA or de novo TP53m seemed to be associated with a trend for worst survival compared with decrease or complete clearance: progression-free survival 10 versus 26.5 months, HR 3.2. Despite macroscopically complete surgery, 30% of patients had detectable ctDNA post-operatively and had worse survival than those with undetectable ctDNA. Monitoring TP53m in ctDNA during chemotherapy or after surgery could help guide the best adjuvant therapy.
Competing Interests: Competing interests: MK: advisory boards/honoraria: GSK, AstraZeneca; travel, accommodations: Pfizer, GSK, Eisai. ND: travel, accommodations: GSK; advisory boards/honoraria: GSK, AstraZeneca, MSD, Clovis Oncology, EISAI. KH: shareholder/stockholder/stock options, full/part-time employment: Inivata. ER: honoraria: AstraZeneca (Inst), Roche (Inst), BMS (Inst), GlaxoSmithKline (Inst), Clovis Oncology (Inst); consulting or advisory role: AstraZeneca; research funding: AstraZeneca (Inst); travel, accommodations, expenses: AstraZeneca, BMS. JBM : honoraria: Jazz Pharmaceuticals, Astellas Pharma; consulting or advisory role: AbbVie, Servier; travel, accommodations, expenses: AbbVie. AL: honoraria (self): Medscape; AZ, Clovis, GSK, Kephren; advisory/consultancy: AZ, Clovis, GSK, Biocad, Ability Pharma, Merck Serono, Tesaro, MSD, Seattle Genetics, Gamamabs, Gritstone; research grant/funding (self): Inivata, Sanofi, AZ, OSE Immuno; travel/accommodation/expenses: AZ, Roche, Clovis, Tesaro. All other authors have declared no conflicts of interest.
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