The impact of organ motion and the appliance of mitigation strategies on the effectiveness of hypoxia-guided proton therapy for non-small cell lung cancer

•We investigated the impact of organ motion on the effectiveness of hypoxia-guided proton therapy in lung cancer patients.•Large motion amplitude, especially together with increased dose escalation, was associated with a reduction of target coverage and dose homogeneity.•TCP benefits from dose escalation outweigh motion-induced TCP losses.•Large NTCP benefits for lungs, heart and oesophagus were found for escalated proton plans, even compared to photon plans.•Respiratory gating in combination with rescanning is the recommended strategy should motion mitigation be necessary.