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OBJECTIVE: This study compares baseline clinical characteristics, physical function testing, and patient-reported outcomes for patients undergoing primary cytoreductive surgery versus neoadjuvant chemotherapy, with the goal of better understanding unique patient needs at diagnosis. METHODS: Patients with suspected advanced stage (IIIC/IV) epithelial ovarian cancer undergoing either primary cytoreductive surgery or neoadjuvant chemotherapy were enrolled in a single-institution, non-randomized prospective behavioral intervention trial of prehabilitation. Baseline clinical characteristics were abstracted. Physical function was evaluated using the Short Physical Performance Battery, Fried Frailty Index, gait speed, and grip strength. Patient-reported outcomes were evaluated using Patient-Reported Outcomes Measurement Information System metrics and the Perceived Stress Scale. RESULTS: There were no significant differences in demographics or clinical characteristics between cohorts at enrollment, with the exception of performance status, clinical stage, and albumin. While gait speed and grip strength were lower amongst neoadjuvant chemotherapy patients, there were no significant differences in physical function using the Short Physical Performance Battery and Fried Frailty Index. Patients in the neoadjuvant chemotherapy cohort reported decreased perception of physical function and increased fatigue on Patient-Reported Outcomes Measurement Information System metrics. A larger proportion of patients in the neoadjuvant cohort reported severe levels of emotional distress and anxiety, as well as greater perceived stress at diagnosis. CONCLUSIONS: Our findings suggest that patients undergoing neoadjuvant chemotherapy for advanced ovarian cancer present with increased psychosocial distress and decreased perception of physical function at diagnosis and may benefit most from early introduction of supportive care.
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BACKGROUND: Machine learning tools such as random forests provide important opportunities for modeling large, complex modern data generated in medicine. Unfortunately, when it comes to understanding why machine learning models are predictive, applied research continues to rely on 'out of bag' (OOB) variable importance metrics (VIMPs) that are known to have considerable shortcomings within the statistics community. After explaining the limitations of OOB VIMPs - including bias towards correlated features and limited interpretability - we describe a modern approach called 'knockoff VIMPs' and explain its advantages. METHODS: We first evaluate current VIMP practices through an in-depth literature review of 50 recent random forest manuscripts. Next, we recommend organized and interpretable strategies for analysis with knockoff VIMPs, including computing them for groups of features and considering multiple model performance metrics. To demonstrate methods, we develop a random forest to predict 5-year incident stroke in the Sleep Heart Health Study and compare results based on OOB and knockoff VIMPs. RESULTS: Nearly all papers in the literature review contained substantial limitations in their use of VIMPs. In our demonstration, using OOB VIMPs for individual variables suggested two highly correlated lung function variables (forced expiratory volume, forced vital capacity) as the best predictors of incident stroke, followed by age and height. Using an organized analytic approach that considered knockoff VIMPs of both groups of features and individual features, the largest contributions to model sensitivity were medications (especially cardiovascular) and measured medical risk factors, while the largest contributions to model specificity were age, diastolic blood pressure, self-reported medical risk factors, polysomnography features, and pack-years of smoking. Thus, we reach very different conclusions about stroke risk factors using OOB VIMPs versus knockoff VIMPs. CONCLUSIONS: The near-ubiquitous reliance on OOB VIMPs may provide misleading results for researchers who use such methods to guide their research. Given the rapid pace of scientific inquiry using machine learning, it is essential to bring modern knockoff VIMPs that are interpretable and unbiased into widespread applied practice to steer researchers using random forest machine learning toward more meaningful results.