scholarly journals Abstract 1103: The effects of neo-adjuvant chemotherapy on myeloid cells in high-grade serous ovarian cancer metastases

Author(s):  
Owen M. Heath ◽  
Eleni Maniati ◽  
Chiara Belato ◽  
Ganga Gopinathan ◽  
Laura Lecker ◽  
...  
Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1186 ◽  
Author(s):  
Marica Garziera ◽  
Erika Cecchin ◽  
Giorgio Giorda ◽  
Roberto Sorio ◽  
Simona Scalone ◽  
...  

Carboplatin/paclitaxel is the reference regimen in the treatment of advanced high-grade serous ovarian cancer (HGSOC) in neo-adjuvant chemotherapy (NACT) before interval debulking surgery (IDS). To identify new genetic markers of platinum-resistance, next-generation sequencing (NGS) analysis of 26 cancer-genes was performed on paired matched pre- and post-NACT tumor and blood samples in a patient with stage IV HGSOC treated with NACT-IDS, showing platinum-refractory/resistance and poor prognosis. Only the TP53 c.375+1G>A somatic mutation was identified in both tumor samples. This variant, associated with aberrant splicing, was in trans configuration with the 72Arg allele of the known germline polymorphism TP53 c.215C>G (p. Pro72Arg). In the post-NACT tumor sample we observed the complete expansion of the TP53 c.375+1G>A driver mutant clone with somatic loss of the treatment-sensitive 72Arg allele. NGS results were confirmed with Sanger method and immunostaining for p53, BRCA1, p16, WT1, and Ki-67 markers were evaluated. This study showed that (i) the splice mutation in TP53 was present as an early driver mutation at diagnosis; (ii) the mutational profile was shared in pre- and post-NACT tumor samples; (iii) the complete expansion of a single dominant mutant clone through loss of heterozygosity (LOH) had occurred, suggesting a possible mechanism of platinum-resistance in HGSOC under the pressure of NACT.


Author(s):  
Aurelie Auguste ◽  
Soizick Mesnage ◽  
Audrey Le Formal ◽  
Elena Cojocaru ◽  
Francoise Drusch ◽  
...  

2019 ◽  
Vol 153 (3) ◽  
pp. 562-567
Author(s):  
J.O.A.M. van Baal ◽  
K.K. Van de Vijver ◽  
M.D. Algera ◽  
M.A. van der Aa ◽  
G.S. Sonke ◽  
...  

2015 ◽  
Author(s):  
Anne Montfort ◽  
Steffen Boehm ◽  
Thomas Dowe ◽  
Joanne Topping ◽  
Michelle Lockley ◽  
...  

2020 ◽  
Vol 30 (4) ◽  
pp. 498-503 ◽  
Author(s):  
Jacek P Grabowski ◽  
Clara Martinez Vila ◽  
Rolf Richter ◽  
Eliane Taube ◽  
Helmut Plett ◽  
...  

ObjectiveLow-grade serous ovarian cancers characterize a unique clinical pattern and lower chemotherapy responsiveness. The expression level of Ki67 is associated with differences in prognosis; however, this has not yet been evaluated in regard to predicting the outcome of therapy.MethodsPatients with low-grade serous ovarian cancers were identified in an institutional database. Receiver-operator characteristics (ROC) curve analysis was performed to find cut-off values of Ki67 to discriminate patients with residual tumor mass after surgery from maximal debulked patients: therapy response and therapy-free interval (TFI).ResultsA total of 68 patients with low-grade serous ovarian cancer were identified. All patients underwent surgery. 61 (89.7%) patients received platinum-based first-line chemotherapy; of these 61 patients, 13 (21.3%) had residual mass (>0 mm) after primary cytoreduction and 11 (18%) received neo-adjuvant chemotherapy. Ki67 ≥3.6% was associated with higher risk of residual mass after surgery (OR 8.1, 95% CI 1.45 to 45.18; p=0.017). Patients with Ki67 <3.6% showed a therapy-free interval of ≥6 months more often (OR 13.9, 95% CI 1.62 to 118.40; p=0.016). In the multivariate analysis of TFI <6 months, including CA125, age at diagnosis, peritoneal carcinomatosis, and ascites, Ki67 <3.6% remained a significant prognostic factor (OR 18.8, 95% CI 1.77 to 199.09; p=0.015). Chemotherapy responsiveness was evaluated in 21 patients who had residual disease and/or received neo-adjuvant chemotherapy. Ki67 ≥4.0% (OR 44.1, 95%CI 2.36-825.17, p = 0.011) was related to a significantly higher response rate (complete and partial response).ConclusionsThis is the first study to show an association between Ki67 expression and chemotherapy response, duration of TFI to platinum-based chemotherapy as well as outcome of surgery in low-grade serous ovarian cancers. Further prospective trials should use Ki-67 as a stratification factor to explore the effect of chemotherapy and endocrine strategies.


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