Design of multi-ion therapy for head and neck cancers using carbon-, oxygen-, and neon-ion beams: potential efficacy against tumor hypoxia

<i>Objective</i>. In order to initiate multi-ion therapy for head and neck cancers, it is necessary to predetermine the target dose-averaged linear energy transfer (LET_d) prescription to the gross tumor volume (GTV). This study investigated LET_doptimized treatment plans with carbon-, oxygen-, and neon-ion beams and demonstrated their potential efficacy against tumor hypoxia.<i>Approach</i>. Sixteen head and neck cancer patients with GTV sizes ranging from 5.5 to 143.1 cm³were selected for this retrospective planning study. Carbon, oxygen, and neon ions were used alone or in combination with two ion species. The treatment plans were optimized to increase LET_dwithin the GTV and to make the LET_ddistribution uniform while maintaining the relative biological effectiveness weighted dose distributions of conventional intensity modulated carbon-ion therapy (IMIT). The effective dose improvement rate against IMIT was then estimated by changing oxygen partial pressure within the GTV to 0 mmHg because a substantial number of anoxic cancer cells is predicted to exist in a hypoxic tumor microenvironment.<i>Main results</i>. The target LET_dof 90 keV<i>μ</i>m^-1was prescribable without deteriorating the dose distributions when: for example, carbon- and oxygen-ion beams were used for small tumors (around 20 cm³); oxygen-ion beams alone were used for medium tumors (around 50 cm³); and carbon- and neon-ion beams were used for large tumors (around 100 cm³). The uniformity of the LET_ddistributions within the GTV was about 10%. With the LET_dprescription, the improvement rate of the effective dose covering 98% (i.e.D98%) of the GTV against anoxic cancer cells was about 30%.<i>Significance</i>. For the application to the first multi-ion therapy program, the target LET_dprescription to the GTV was determined to be 90 keV<i>μ</i>m^-1. If tumor hypoxia contributes to the cause of recurrence, the proposed treatment may offer better local tumor control without compromising normal tissue sparing.