Three-dimensional dose and LET_D prediction in proton therapy using artificial neural networks

Purpose: Challenges in proton therapy include identifying patients most likely to benefit; ensuring consistent, high-quality plans as its adoption becomes more widespread; and recognizing biological uncertainties that may be related to increased relative biologic effectiveness driven by linear energy transfer (LET). Knowledge-based planning (KBP) is a domain that may help to address all three.

Methods: Artificial neural networks were trained using 117 unique treatment plans and associated dose and dose-weighted LET (LET_D ) distributions. The data set was split into training (n = 82), validation (n = 17), and test (n = 18) sets. Model performance was evaluated on the test set using dose- and LET_D -volume metrics in the clinical target volume (CTV) and nearby organs at risk and Dice similarity coefficients (DSC) comparing predicted and planned isodose lines at 50%, 75%, and 95% of the prescription dose.

Results: Dose-volume metrics significantly differed (α = 0.05) between predicted and planned dose distributions in only one dose-volume metric, D_2% to the CTV. The maximum observed root mean square (RMS) difference between corresponding metrics was 4.3 Gy_RBE (8% of prescription) for D_1cc to optic chiasm. DSC were 0.90, 0.93, and 0.88 for the 50%, 75%, and 95% isodose lines, respectively. LET_D -volume metrics significantly differed in all but one metric, L_0.1cc of the brainstem. The maximum observed difference in RMS differences for LET_D metrics was 1.0 keV/μm for L_0.1cc to brainstem.

Conclusions: We have devised the first three-dimensional dose and LET_D -prediction model for cranial proton radiation therapy has been developed. Dose accuracy compared favorably with that of previously published models in other treatment sites. The agreement in LET_D supports future investigations with biological doses in mind to enable the full potential of KBP in proton therapy.