Optic nerve constraints for carbon ion RT at CNAO – Reporting and relating outcome to European and Japanese RBE

Background and purpose: Until now, carbon ion RT (CIRT) dose constraints for the optic nerve (ON) have only been validated and reported in the NIRS RBE-weighted dose (D_NIRS). The aim of this work is to improve CNAO's RBE-weighted dose (D_LEM) constraints by analyzing institutional toxicity data and by relating it to D_NIRS. Material and methods: A total of 65 ONs from 38 patients treated with CIRT to the head and neck region in the period 2013–14 were analyzed. The absorbed dose (D_Abs) of the treatment plans was reproduced and subsequently both D_LEM and D_NIRS were applied, thus relating CNAO clinical toxicity to D_NIRS. Results: Median FU was 47 (26–67) months. Visual acuity was preserved for the 56 ONs in which the old constraints were respected. Three ONs developed visual decline at D_LEM|1% ≥71 Gy(RBE)/D_LEM|20% ≥68 Gy(RBE), corresponding to D_NIRS|1% ≥68 Gy(RBE)/D_NIRS|20% ≥62 Gy(RBE). Dose recalculation revealed that NIRS constraints of D_NIRS|1% ≤40 Gy(RBE)/D_NIRS|20% ≤28 Gy(RBE) corresponded to D_LEM|1% ≤50 Gy(RBE)/D_LEM|20% ≤40 Gy(RBE). Reoptimization of treatment plans with these new D_LEM constraints showed that the dose distribution still complied with NIRS constraints when evaluated in D_NIRS. However, due to uncertainties in the method, and to comply with the EQD2-based constraints used at GSI/HIT, a more moderate constraint relaxation to D_LEM|1% ≤45 Gy(RBE)/D_LEM|20% ≤37 Gy(RBE) has been implemented in CNAO clinical routine since October 2018. Conclusion: New D_LEM constraints for the ON were derived by analyzing CNAO toxicity data and by linking our results to the experience of NIRS and GSI/HIT. This work demonstrates the value of recalculating and reporting results in both D_LEM and D_NIRS.