Concurrent chemoradiation is considered the golden standard in the treatment of locally advanced OPC. However, given the very high survival rates in favorable HPV-positive OPC and the high rates of acute and late treatment-related side effects, de-escalation strategies have to be considered. In this chapter, the potential benefit of a number of de-escalation strategies is described, including of replacement of concurrent chemotherapy by cetuximab, radiation dose de-escalation based on response to induction chemotherapy, radiotherapy alone without systemic treatment, and limiting elective nodal target volumes for radiation. In addition to de-escalation, modern radiation technologies like protons will offer increasing opportunities to decrease the dose to normal tissues in order to prevent radiation-induced toxicities. Initial analysis showed that radiation dose de-escalation based on response to induction chemotherapy in combination with intensity-modulated proton therapy (IMPT) has the highest potential to decrease acute and late toxicities.
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