Liver tumor motion and reconstructed doses in a clinical trial of respiratory gated proton therapy for hepatocellular carcinoma.

Abstract

PurposePencil beam scanning proton therapy of hepatocellular carcinoma (HCC) may reduce the risk of radiation-induced liver disease compared to photon radiotherapy, but tumor motion and anatomical changes can distort the dose. This was investigated through daily reconstruction of the delivered dose in a clinical trial of gated HCC proton therapy.Methods and materialsSixteen patients with HCC included in a prospective phase II trial received 58-67.5 Gy (RBE) of proton therapy in 15 fractions with treatment planning in the exhale phase of a 4DCT and exhale gated treatment guided by an external gating block. CBCT-guided setup was based on 2-3 implanted fiducial markers. At 3-8 fractions per patient, the 3D tumor motion during pre-treatment and post-treatment CBCT acquisition was measured via the positions of the fiducial markers as a surrogate for the moving tumor. The tumor motion during treatment was estimated from the gating block motion using an external-internal motion correlation model constructed from the CBCTs. The delivered CTV dose was estimated by modelling tumor motion as proton spot position shifts and energy shifts in the treatment planning system. Effects of interfractional anatomical changes were assessed by dose recalculation on weekly control 4DCTs.ResultsThe mean (±SD) root-mean-square tumor position error during spot delivery was 1.1±0.8mm (left-right), 2.9±1.2mm (cranio-caudal) and 1.6±0.7mm (anterior-posterior). Motion increased the CTV homogeneity index, defined as 100%⋅(D2%-D98%)/D50%, by 4.1±2.6 percentage points for individual fractions and 1.5±2.1 percentage points when accumulated over all analyzed fractions. Control 4DCTs demonstrated minimal CTV dose variations.ConclusionsIntrafractional motion affected single fraction tumor doses due to interplay effects that tended to smear out after more than three fractions. The tumor dose was robust to interfractional anatomical changes.