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Purpose: To investigate the impact of four-dimensional robust optimization (4DRO) on dose delivered to lung cancer patients in pencil beam scanning proton therapy., Methods and Materials: 2 strategies were compared for 20 lung cancer patients, using a different number of breathing phases of the reconstructed 4D computed tomography (CT) included in the plan optimization problem. In the restricted approach combined with gating, only 3 phases close to reference end-exhale were considered instead of the whole breathing cycle. The prescribed dose was 60 Gy(RBE) in 10 fractions. Target coverage (D98%) and dose to healthy tissues were evaluated using Wilcoxon signed-rank test. To assess the robustness against interfractional anatomical and respiratory variations, the optimized plans were recalculated on re-evaluation 4DCTs. To compare the sensitivity of both strategies to interplay effects, we implemented an end-to-end test with a home-made heterogeneous moving phantom and ionization chambers measurements. Robustly optimized plans with prescription doses of 6 Gy(RBE) were delivered in different dynamic conditions., Results: Both 4D robustly optimized plans reached the same target coverage (p = 0.56), while a statistically significant decrease of the homolateral lung dose was observed using the restricted approach (p < 0.0001). Plan recalculations within 15 days from the treatment simulation showed the same robustness of target D98% against interfractional variations (p = 0.48), with an average decrease of approximately 3 Gy(RBE). Phantom measurements confirmed the delivery accuracy of the restricted approach (mean dose deviations <5%). Higher deviations were found for ungated full 4DRO and larger motion amplitude., Conclusion: The restricted approach combined with gating improved normal tissue sparing and was shown to be more robust to single fraction deliveries and large motion amplitude., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: To compare RECIST 1.1 with volume modifications in patients with sacral chordoma not suitable for surgery treated with carbon ions radiotherapy (CIRT) alone. To evaluate patients pain before and after CIRT. To detect if baseline Apparent Diffusion Coefficient values (ADC) from Diffusion Weighted sequences could predict response to treatment., Material and Methods: Patients included had one cycle of CIRT and underwent MRI before and after treatment. For each MRI, lesion maximum diameter and volume were obtained, and ADC values were analyzed within the whole lesion volume. Patients pain was evaluated with Numerical Rating Scale (NRS), considering the upper tumor level at baseline MRIs., Results: 39 patients were studied (mean follow-up 18 months). Considering RECIST 1.1 there was not a significant reduction in tumor diameters (p = 0.19), instead there was a significant reduction in tumor volume (p < 0.001), with a significant reduction in pain (p = 0.021) if the tumors were above vertebrae S2-S3 at baseline MRIs. The assessment of baseline ADC maps demonstrated higher median values and more negative skewness values in progressive disease (PD) patients versus both partial response (PR) and stable disease (SD)., Conclusions: Lesion volume measurement is more accurate than maximum diameter to better stratify the response of sacral chordoma treated with CIRT. Preliminary results suggest that baseline ADC values could be predictive of response to CIRT., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: In carbon ion radiotherapy (CIRT), the use of different relative biological effectiveness (RBE) models in the RBE-weighted dose (DRBE) calculation can lead to deviations in the physical dose (Dphy) delivered to the patient. Our aim is to reduce target Dphy deviations by converting prescription dose values., Material and Methods: Planning data of patients treated at the National Institute of Radiological Sciences (NIRS) were collected, with prescribed doses per fraction ranging from 3.6Gy (RBE) to 4.6Gy (RBE), according to the Japanese semi-empirical model. The Dphy was Monte Carlo (MC) re-calculated simulating the NIRS beamline. The local effect model (LEM)&#95;I was then applied to estimate DRBE. Target median DRBE ratios between MC+LEM&#95;I and NIRS plans determined correction factors for the conversion of prescription doses. Plans were re-optimized in a LEM&#95;I-based commercial system, prescribing the NIRS uncorrected and corrected DRBE., Results: The MC+LEM&#95;I target median DRBE was respectively 15% and 5% higher than the NIRS reference, for the lowest and highest dose levels. Uncorrected DRBE prescription resulted in significantly lower target Dphy in re-optimized plans, with respect to NIRS plans., Conclusions: Prescription dose conversion factors could minimize target physical dose variations due to the use of different radiobiological models in the calculation of CIRT RBE-weighted dose., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)