Leveraging hybrid biomarkers in clinical endpoint prediction

Saad, Maliazurina; Lee, Ik Hyun

BACKGROUND: Clinical endpoint prediction remains challenging for health providers. Although predictors such as age, gender, and disease staging are of considerable predictive value, the accuracy often ranges between 60 and 80%. An accurate prognosis assessment is required for making effective clinical decisions. METHODS: We proposed an extended prognostic model based on clinical covariates with adjustment for additional variables that were radio-graphically induced, termed imaging biomarkers. Eight imaging biomarkers were introduced and investigated in a cohort of 68 non-small cell lung cancer subjects with tumor internal characteristic. The subjects comprised of 40 males and 28 females with mean age at 68.7 years. The imaging biomarkers used to quantify the solid component and non-solid component of a tumor. The extended model comprises of additional frameworks that correlate these markers to the survival ends through uni- and multi-variable analysis to determine the most informative predictors, before combining them with existing clinical predictors. Performance was compared between traditional and extended approaches using Receiver Operating Characteristic (ROC) curves, Area under the ROC curves (AUC), Kaplan-Meier (KM) curves, Cox Proportional Hazard, and log-rank tests (p-value). RESULTS: The proposed hybrid model exhibited an impressive boosting pattern over the traditional approach of prognostic modelling in the survival prediction (AUC ranging from 77 to 97%). Four developed imaging markers were found to be significant in distinguishing between subjects having more and less dense components: (P = 0.002–0.006). The correlation to survival analysis revealed that patients with denser composition of tumor (solid dominant) lived 1.6–2.2 years longer (mean survival) and 0.5–2.0 years longer (median survival), than those with less dense composition (non-solid dominant). CONCLUSION: The present study provides crucial evidence that there is an added value for incorporating additional image-based predictors while predicting clinical endpoints. Though the hypotheses were confirmed in a customized case study, we believe the proposed model is easily adapted to various clinical cases, such as predictions of complications, treatment response, and disease evolution.