Most ovarian cancers are diagnosed when the disease is already in an advanced stage, i.e. stage III and IV. Physicians surgically remove as much of the tumor as possible, before administering platinum-based chemotherapy. However, the tools to predict how an ovarian cancer patient responds to platinum-based chemotherapy still remain inadequate.
Josephine Kang, M.D., Ph.D., of the Department of Radiation Oncology at the Dana Farber Cancer Institute, and her team wanted to establish whether a DNA repair pathway-focused score could help to predict outcomes for ovarian cancer patients who are treated with platinum-based chemotherapy.
The Cancer Genome Atlas database (TCGA) provided gene expression data of patients with advanced stage ovarian cancer, and the team developed a molecular score by examining the genes involved in platinum-induced DNA damage repair pathways. The patients were categorized into either low or high score categories, and the team assessed the score's prognostic value for overall survival, recurrence free survival, and progression-free survival.
They discovered that compared with low scoring patients, those with high scores had a statistically important improved overall survival and that their score was positively related to response rate, recurrence-free survival, and progression-free survival. The findings also demonstrated that the patients' scores outperformed other known clinical factors in predicting overall survival in the TCGA dataset and also in two additional validation sets.
The researchers conclude:
"Developing the ability to predict OS and outcomes to chemotherapy using prognostic markers such as the score is critical, particular in ovarian cancer, because there are presently no other good clinical measures to predict response to standard platinum-based chemotherapy."
The researchers acknowledge their study's limitations, including the fact that the score has so far not been tested prospectively in a clinical trial, even though they believe it to be ready for testing. They write:
"With additional prospective validation in clinical trials, we hope that the score can become a powerful tool that is useful in stratifying advanced-stage ovarian cancer patients toward optimal treatments incorporating new treatment regimens vs. current standard of care."
Elizabeth M. Swisher, M.D., of the Department of Obstetrics and Gynecology at the University of Washington supports the view in a linked editorial that the score was validated inadequately and is not ready for clinical application. She points out that even though the study is an important effort, the "premature application of inadequately validated biomarkers may adversely impact the successful implementation of individualized therapies."