Linear energy transfer-inclusive models of brainstem necrosis following proton therapy of paediatric ependymoma

Radiation-induced brainstem necrosis after proton therapy is a severe toxicity with potential association to uncertainties in the proton relative biological effectiveness (RBE). This work aimed to construct models describing the association between brainstem necrosis and LET in the brainstem.. First author Andreas Handeland is PhD student at UiB and Haukeland University Hospital and associate member of the Bioproton project.

A matched case-control cohort (n = 28, 1:3 case-control ratio) of symptomatic brainstem necrosis was selected from 954 paediatric ependymoma brain tumour patients treated with passively scattered proton therapy.

A 1 keV/µm increase in L_10% to the brainstem volume receiving dose over 54 Gy(RBE) led to an increased brainstem necrosis risk [95% confidence interval] of 2.5 [0.0, 7.8] percentage points. The corresponding logistic regression model had area under the receiver operating characteristic curve (AUC) of 0.76, increasing to 0.84 with the anterior pons substructure as a second parameter. 19 [7, 350] patients with toxicity were required to associate the L_10% (D > 54 Gy(RBE)) and brainstem necrosis with 80% statistical power.

The established models of brainstem necrosis illustrate a potential impact of high LET regions in patients receiving high doses to the brainstem, and thereby support LET mitigation during clinical treatment planning.