Dosimetric benefit of 4D robustly optimized proton plans for NSCLC patients with intrafractional motion above 5 mm

Background: We analyse the benefit of 4D robust plan optimization (RO) for proton therapy treatments of NSCLC patients with pronounced breathing-induced anatomical variations.

Methods: Eight NSCLC patients with relevant maximal intrafractional motion of the primary (CTVp; 5.6-24.5mm) and/or nodal CTV (CTVn; 5.8-17.3mm) on the planning 4DCT (pCT) were included. We optimized three robust normo-fractionated plans with a criterion of 5mm setup and 3.5%+2mm range uncertainty: RO on the AverageCT with iGTVp density override (3DRO); RO on the AverageCT and three 4DCT phases (4DRO3); and RO on the AverageCT and all eight 4DCT phases (4DRO8). Setup and range error scenarios were analysed on the pCT. To assess robustness against intra- and inter-fractional changes, 4D doses were calculated on the pCT and up to two control 4DCTs (cCTs) assuming equal weights between breathing phases. Interplay effects were simulated on the pCT from patient breathing signals and machine logfiles of plan deliveries with and without 5 layered rescans. Fractionation effects were emulated by accumulating four interplay scenarios with different starting times.

Results: All nominal plans fulfilled target coverage (D98%>95%) and OAR sparing; CTVp/CTVn coverage failed setup and range robustness in 12%/35% (3DRO), 14%/18% (4DRO3) and 13%/20% (4DRO8) of the scenarios (Fig1a), respectively. 4D dose target coverage on the pCT was >94% for all plans; interfractional changes in the cCTs reduced the CTVp coverage by about 2pp (Fig1b). Interplay analyses (Fig1c) revealed a mean CTVp/CTVn coverage loss by 3.4pp/2.4pp, 3.0pp/2.3pp, and 2.9pp/3.2pp in single scenarios of 3DRO, 4DRO3 and 4DRO8 plans, respectively. D98% values were improved on average by 1.0pp with rescanning, but were even worsened in some scenarios. Irrespective of rescanning, the simulated fractionation fullfilled the target coverage in all cases.

Conclusion: 3DRO and 4DRO showed similar robustness against different motion effects. 4DRO provides benefits for some patients, but 3DRO demands less workload.