Beyond Dose: Using Pretherapy Biomarkers to Improve Dose Prediction of Outcomes for Radioimmunotherapy of Non-Hodgkin Lymphoma.

Introduction: Non-Hodgkin Lymphoma patients respond differently to therapy according to inherent biological variations. Pretherapy biomarkers may improve dose-response prediction. Materials and Methods: Hybrid single-photon emission computed tomography (SPECT)/computed tomography (CT) three-dimensional imaging at multiple time points plus follow-up positron emission tomography (PET)/CT or CT at 2 and 6 months post therapy were used to fit tumor response to combined biological effect and cell clearance models from which three biological effect response parameters (radiosensitivity, cold effect sensitivity, and proliferation potential) were determined per patient. A correlation of biological effect parameters and pretherapy biomarker data (ki67, p53, and phospho-histone H3) allowed a dose-based equivalent biological effect (EBE) to be calculated for each patient. Results: Significant correlations were found between biological effect parameters and pretherapy biomarkers. Optimum correlations were found by splitting the patient data according to p53 status. Response correlation of progression free survival (PFS) and EBE were significantly improved compared with PFS and absorbed dose alone. Conclusions: It is possible and desirable to use pretherapy biomarkers to enhance the predictive potential of dose calculations for patient-specific treatment planning.