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Implementation of Comprehensive Genomic Profiling in Ovarian Cancer Patients: A Retrospective Analysis
Shira Peleg Hasson1,2, Dov Hershkovitz3, Lyri Adar1
1Oncology Department, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel.
Abstract:
Comprehensive genomic profiling (CGP) allows for the detection of driver alterations at high resolution, but the limited number of approved targeted therapies and their high costs have contributed to its limited clinical utilization. We retrospectively compared data of 946 women with ovarian cancer (11.4% were referred to CGP, and 88.6% served as control) to examine whether CGP provides a prognosis benefit. Patient baseline parameters were similar between the groups. Cox regression analysis adjusted for age, disease stage at diagnosis, and recurrence status showed statistically significantly longer median overall survival (mOS) in the CGP group versus the control (73.4 versus 54.5 months, p < 0.001). Fifty-four patients (52.9%) had actionable mutations with potential treatments; twenty-six (48.2%) were treated with matched targeted therapy, showing a trend for longer mOS than the eighty-six women in the CGP group who were not given a suggested treatment (105.5 versus 63.6 months, p = 0.066). None of the genomic alterations predicted metastasis location. CCNE1 amplification and KRAS mutations were associated with shorter mOS. Patients with tumor mutation burden ≥4 mutations/megabase had longer mOS. High loss of heterozygosity was associated with longer mOS (99.0 versus 48.2 months, p = 0.004). CGP testing may provide both prognostic and predictive insights for treatment of patients with ovarian cancer. Prospective studies of larger cohorts are warranted.
Insights
Comprehensive genomic profiling (CGP) in ovarian cancer patients significantly improved overall survival. CGP identified actionable mutations and prognostic biomarkers, offering valuable insights for treatment decisions.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Comprehensive genomic profiling (CGP) offers high-resolution detection of driver alterations in cancer.
- Limited availability of targeted therapies and high costs hinder CGP's clinical adoption.
Purpose of the Study:
- To retrospectively evaluate the prognostic benefit of CGP in ovarian cancer patients.
- To identify genomic alterations associated with overall survival and treatment response.
Main Methods:
- Retrospective comparison of 946 ovarian cancer patients: 11.4% underwent CGP, 88.6% served as controls.
- Cox regression analysis adjusted for clinical factors to assess overall survival.
- Analysis of actionable mutations, tumor mutation burden, and loss of heterozygosity.
Main Results:
- CGP group showed significantly longer median overall survival (73.4 vs. 54.5 months, p < 0.001).
- Patients with actionable mutations receiving targeted therapy trended towards longer mOS (105.5 vs. 63.6 months).
- CCNE1 amplification and KRAS mutations correlated with shorter mOS; high tumor mutation burden and loss of heterozygosity correlated with longer mOS.
Conclusions:
- CGP provides significant prognostic benefits and identifies predictive biomarkers for ovarian cancer treatment.
- Further prospective studies are needed to validate these findings in larger cohorts.
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