Integrated Clinical and Genomic Models to Predict Optimal Cytoreduction in High-Grade Serous Ovarian Cancer

SIMPLE SUMMARY: Approximately 30% of patients with advanced, high-grade serous ovarian cancer who undergo surgery will have a suboptimal result, resulting in decreased overall survival. Improving the ability to predict a successful surgery would improve survival. We aimed to use tumor genomics to create prediction models, which would predict an optimal or complete cytoreduction prior to entering the operating room. We created two sets of models, one for optimal and one for complete cytoreduction. We then validated those models using the TCGA database as well as statistical learning. We developed 21 models for optimal cytoreduction and 37 models for complete cytoreduction, which have the potential to improve our ability to predict these surgical results in patients with ovarian cancer before taking them to the operating room. Improving our pre-operative decision-making will result in more patients having the desired surgical results and, therefore, improved survival. ABSTRACT: Advanced high-grade serous (HGSC) ovarian cancer is treated with either primary surgery followed by chemotherapy or neoadjuvant chemotherapy followed by interval surgery. The decision to proceed with surgery primarily or after chemotherapy is based on a surgeon’s clinical assessment and prediction of an optimal outcome. Optimal and complete cytoreductive surgery are correlated with improved overall survival. This clinical assessment results in an optimal surgery approximately 70% of the time. We hypothesize that this prediction can be improved by using biological tumor data to predict optimal cytoreduction. With access to a large biobank of ovarian cancer tumors, we obtained genomic data on 83 patients encompassing gene expression, exon expression, long non-coding RNA, micro RNA, single nucleotide variants, copy number variation, DNA methylation, and fusion transcripts. We then used statistical learning methods (lasso regression) to integrate these data with pre-operative clinical information to create predictive models to discriminate which patient would have an optimal or complete cytoreductive outcome. These models were then validated within The Cancer Genome Atlas (TCGA) HGSC database and using machine learning methods (TensorFlow). Of the 124 models created and validated for optimal cytoreduction, 21 performed at least equal to, if not better than, our historical clinical rate of optimal debulking in advanced-stage HGSC as a control. Of the 89 models created to predict complete cytoreduction, 37 have the potential to outperform clinical decision-making. Prospective validation of these models could result in improving our ability to objectively predict which patients will undergo optimal cytoreduction and, therefore, improve our ovarian cancer outcomes.