Purpose: In carbon ion radiation therapy (CIRT), the dose-averaged LET (LETd) is one of the important factors in determining clinical outcomes. In order to investigate the local control of adenoid cystic carcinoma (ACC) and the optic neuropathy of optic nerve (ON)s in CIRT, the effects of the LETd were evaluated clinically. We propose novel tumor control probability (TCP) and normal tissue complication probability (NTCP) models with D90-value of RBE-weighted dose and LETd as clinical parameters.
Methods: Total 99 patients with head and neck ACC who received CIRT at the National Institute of Radiological Sciences were investigated. The physical dose and LETd distributions for each patient were recalculated using in-house treatment planning system. For ACC tumor, minimum-value of dose-averaged LET and D90-value of RBE-weighted dose as an indicator of evaluation were estimated. For ONs, maximum-value of LETd and maximum-value of RBE-weighted dose were evaluated.
Results: For each prescribed RBE-weighted dose of 57.6 and 64 Gy (RBE), no statistical significance for local control by RBE-weighted dose was found, but for 64 Gy (RBE), we observed the LETd may be a marginally significant. For ONs, it was obvious that the optic neuropathy had a greater effect from RBE-weighted dose rather than dose-averaged LET. The proposed models could be applied to both TCP and NTCP prediction, and was found that the clinical outcomes from low to high LETd region were predictable.
Conclusion: We analysed clinically the physical dose and LETd distributions for 99 patients with head and neck ACC. Our results indicated that LETd may be a determining factor for local control for ACC tumors. For ON, the RBE-weighted dose was related to optic neuropathy rather than LETd. The proposed approach may be helpful to predict whether LETd will affect clinical outcomes and be useful when constraining not only RBE-weighted dose but also LETd.
Funding Support, Disclosures, and Conflict of Interest: This study was supported by the research grant for JSPS KAKENHI Grant Number JP19K08188.
Heavy Ions, Treatment Verification, LET
TH- External Beam- Particle/high LET therapy: Carbon ion therapy - treatment planning/virtual clinical studies/adaptive therapy