Employing the therapeutic operating characteristic (TOC) graph for individualised dose prescription

Background: In current practice, patients scheduled for radiotherapy are treated according to 'rigid' protocols with predefined dose prescriptions that do not consider risk-taking preferences of individuals. The therapeutic operating characteristic (TOC) graph is applied as a decision-aid to assess the trade-off between treatment benefit and morbidity to facilitate dose prescription customisation. Methods: Historical dose-response data from prostate cancer patient cohorts treated with 3D-conformal radiotherapy is used to construct TOC graphs. Next, intensity-modulated (IMRT) plans are generated by optimisation based on dosimetric criteria and dose-response relationships. TOC graphs are constructed for dose-scaling of the optimised IMRT plan and individualised dose prescription. The area under the TOC curve (AUC) is estimated to measure the therapeutic power of these plans. Results: On a continuous scale, the TOC graph directly visualises treatment benefit and morbidity risk of physicians' or patients' choices for dose (de-) escalation. The trade-off between these probabilities facilitates the selection of an individualised dose prescription. TOC graphs show broader therapeutic window and higher AUCs with increasing target dose heterogeneity. Conclusions: The TOC graph gives patients and physicians access to a decision-aid and read-out of the trade-off between treatment benefit and morbidity risks for individualised dose prescription customisation over a continuous range of dose levels.