TY - JOUR
T1 - Dynamic changes in TP53 mutated circulating tumor DNA predicts outcome of patients with high-grade ovarian carcinomas
AU - Kfoury, Maria
AU - Bonnet, Clément
AU - Delanoy, Nicolas
AU - Howarth, Karen
AU - Marzac, Christophe
AU - Rouleau, Etienne
AU - Micol, Jean Baptiste
AU - Leary, Alexandra
N1 - Publisher Copyright:
© IGCS and ESGO 2024.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - 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.
AB - 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.
KW - Ovarian Cancer
UR - http://www.scopus.com/inward/record.url?scp=85205454758&partnerID=8YFLogxK
U2 - 10.1136/ijgc-2024-005581
DO - 10.1136/ijgc-2024-005581
M3 - Article
C2 - 39313297
AN - SCOPUS:85205454758
SN - 1048-891X
JO - International Journal of Gynecological Cancer
JF - International Journal of Gynecological Cancer
M1 - ijgc-2024-005581
ER -