On-line adaptive proton therapy for cervical cancer to reduce the impact on morbidity and the immune system

Principal Investigators: Prof. dr. Remi Nout (Erasmus MC) and dr. Jeremy Schiphof-Godart (Erasmus MC)

PhD students: Sander Kuipers (Erasmus MC), Anouk Corbeau (LUMC)

Funding: HollandPTC – Varian 2019

Description

Proton therapy (PT) can substantially reduce the unwanted exposure of OAR to radiation dose for women with locally advanced cervical cancer. The resulting reductions in morbidity have the potential to importantly improve quality of life and functioning of these women. In addition, the bone marrow-sparing effect of PT may reduce the considerable immune suppressive impact of the current state of the art photon techniques, which may in turn increase the likelihood of safe and effective delivery of additional systemic (immune) therapies. This is especially relevant in patients at high risk of distant metastasis.

To advance the treatment of women with cervical cancer and enable the implementation of PT in the coming years, two main conditions need to be met. Firstly, (model based) indication algorithms for PT need to be developed and validated. Such model based indication algorithms may take into account the expected reduced morbidity, risk status, and expected overall survival. Development and validation in prospective clinical (trial) datasets of model-based indication algorithms is part of this proposal and will serve as an important source of evidence to reach consensus on PT indications on a national level. In addition, the results of the clinical pilot study will provide important realistic estimates of gains that can be achieved using daily adaptive IMPT in this setting. Secondly, the technical aspects of optimal PT delivery need to be optimized and implemented for cervical cancer. The targets and OAR for cervical cancer demonstrate a much bigger range of day-to-day variations in shape, position and density than tumours that are currently being treated with PT, such as head and neck cancer. Techniques for daily adaptive intensity-modulated PT using plan-libraries will be developed and translated into clinical practice as part of the current proposal.