RESUMEN
Objective@#Our aim was to reach a consensus on the management of the most controversial issues of advanced ovarian cancer. @*Methods@#Nominal group and Delphi techniques were used. A steering committee of 5 experts analyzed current management of advanced ovarian cancer, identified controversies, critically analyzed the evidence, and formulated guiding statements for clinicians. Subsequently, a panel of 15 experts was selected to test agreement with the statements through two Delphi rounds. Items were scored on a 4-point Likert scale from 1 (totally disagree) to 4 (totally agree). In the first and second rounds, consensus was considered if ≥70% of answers pertained to category 1 or category 4. @*Results@#Overall, 112 statements were incorporated in the following areas: 1) biomarkers and hereditary ovarian cancer; 2) first-line treatment; 3) recurrent disease when platinum might be the best option; and 4) post-poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors setting. In the first Delphi round, 37 statements reached consensus and did thus not pass to the second round. After the second round, another 18 statements reached consensus. Forty-six of the consensus were with the agreement and 9 with the disagreement. @*Conclusion@#Through the methodology used, a consensus was reached in approximately half of the statements. The results of this work may be useful in addressing the most controversial issues on the management of advanced ovarian cancer.
RESUMEN
OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. METHODS: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and < or = median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. RESULTS: Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells. CONCLUSION: Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.