Multi-modality functional image guided dose escalation in the presence of uncertainties

Background and purpose: In order to increase local tumour control by radiotherapy without increasing toxicity, it appears promising to harness functional imaging (FI) to guide dose to sub-volumes of the target with a high tumour load and perhaps de-escalate dose to low risk volumes, in order to maximise the efficiency of the deposited radiation dose. Methods and materials: A number of problems have to be solved to make focal dose escalation (FDE) efficient and safe: (1) how to combine ambiguous information from multiple imaging modalities; (2) how to take into account uncertainties of FI based tissue classification; (3) how to account for geometric uncertainties in treatment delivery; (4) how to add complementary FI modalities to an existing scheme. A generic optimisation concept addresses these points and is explicitly designed for clinical efficacy and for lowering the implementation threshold to FI-guided FDE. It combines classic tumour control probability modelling with a multi-variate logistic regression model of FI accuracy and an uncomplicated robust optimisation method. Results: Its key elements are (1) that dose is deposited optimally when it achieves equivalent expected effect everywhere in the target volume and (2) that one needs to cap the certainty about the absence of tumour anywhere in the target region. For illustration, an example of a PET/MR-guided FDE in prostate cancer is given. Conclusions: FDE can be safeguarded against FI uncertainties, at the price of a limit on the sensible dose escalation