Online adaptive dose restoration in intensity modulated proton therapy of lung cancer to account for inter-fractional density changes

Abstract

Background and purpose: In proton therapy, inter-fractional density changes can severely compromise the effective delivery of the planned dose. Such dose distortion effects can be accounted for by treatment plan adaptation, that requires considerable automation for widespread implementation in clinics. In this study, the clinical benefit of an automatic online adaptive strategy called dose restoration (DR) was investigated. Our objective was to assess to what extent DR could replace the need for a comprehensive offline adaptive strategy.

Materials and methods: The fully automatic and robust DR workflow was evaluated in a cohort of 14 lung IMPT patients that had a planning-CT and two repeated 4D-CTs (rCT1,rCT2). Initial plans were generated using 4D-robust optimization (including breathing-motion, setup and range errors). DR relied on isodose contours generated from the initial dose and associated patient specific weighted objectives to mimic this initial dose in repeated-CTs. These isodose contours, with their corresponding objectives, were used during re-optimization to compensate proton range distortions disregarding re-contouring. Robustness evaluations were performed for the initial, not-adapted and restored (adapted) plans.

Results: The resulting DVH-bands showed overall improvement in DVH metrics and robustness levels for restored plans, with respect to not-adapted plans. According to CTV coverage criteria (D95%>95%Dprescription) in not-adapted plans, 35% (5/14) of the cases needed offline adaptation. After DR, Median(D95%) was increased by 1.1 [IQR,0.4] Gy and only one patient out of 14 (7%) still needed offline adaptation because of important anatomical changes.

Conclusions: DR has the potential to improve CTV coverage and reduce offline adaptation rate.

Keywords: Adaptive proton therapy; Adaptive radiation therapy; Automated adaptation; Proton therapy; Range uncertainties.

Fig. 1

Example of the proposed adaptive workflow, which combines offline and online-adaptive strategies including dose restoration to perform optimal IMPT proton treatment. Three different stages are presented in this workflow: planning, adaptation and delivery day. If online adaptation strategy is chosen, the adaptation stage is performed on the delivery day. (*): IBO-plan is the key that automatizes dose restoration re-optimization.

Fig. 2

D95%(CTV) (dose received at 95% of the CTV volume) and homogeneity index values from nominal scenario are represented using boxplots. The nominal scenario stand for doses without any simulated uncertainty, which means without robust assessment. Each boxplot contains the 14 patient’s information for a certain plan (not adapted/restored) evaluated on different images: planning CT and two repeated-CTs. Blue and orange boxes correspond to RS_map contours (rigidly mapped) and RS_real contours respectively.The clinical limit is achieved if dose received at D95%(CTV) is higher than 95%(Dp(66 Gy)) = 62.7 Gy . Abbreviations: Dp = Prescribed dose, HI = Homogeneity index, pCT = planning CT , rCT1 = first repeated CT , rCT2 = second repeated CT. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Differences respect to the reference dose in nominal and worst-case metrics reported from DVH-bands were represented using boxplots. The median calculated among fourteen patients is shown by the horizontal line within boxes. Results were evaluated for both repeated-CTs(rCT1,rCT2) in two contours sets : mapped contours (RS_map) a),b) and real contours (RS_real) c),d). Abbreviations: nom = nominal, wc = worst case, MD = mean dose, D2 = D2% dose received at 2% of the volume; PRV SC = Spinal Cord.

Fig. 4

Patient 9. DVH-bands resulting from the robustness tests are presented together with their corresponding nominal dose distributions. The continuous line represents the nominal scenario while the band collects the information from the evaluated uncertainty scenarios. The dashed lines represent the clinical limits (D95%> 95%Dprescribed). The pair of results (dose distribution/DVH-bands) are shown for the initial IBO plan (in the planning CT), the not adapted and the restored plans (in the first repeated-CT). Abbreviations: pCT = planning-CT, rCT1 = first repeated-CT, rCT2 = second repeated-CT; CTV(T + LN) = CTV(tumor and nodes); PRV SC = Spinal Cord; Dp = Prescribed dose. (PRINTED IN COLOUR).

Fig. 5

Absolute dose error respect to the reference dose in small volumes DE(vol = 2%) represented in boxplots for 4 different regions corresponding to prescription, high, medium and low dose levels. Abbreviations: rCT1 = first repeated-CT, rCT2 = second repeated-CT.