Towards range-guidance in proton therapy to detect organ motion-induced dose degradations.

Introduction.Internal organ motion and deformations may cause dose degradations in proton therapy (PT) that are challenging to resolve using conventional image-guidance strategies. This study aimed to investigate the potential ofrange guidanceusing water-equivalent path length (WEPL) calculations to detect dose degradations occurring in PT.Materials and methods. Proton ranges were estimated using WEPL calculations. Field-specific isodose surfaces in the planning CT (pCT), from robustly optimised five-field proton plans (opposing lateral and three posterior/posterior oblique beams) for locally advanced prostate cancer patients, were used as starting points. WEPLs to each point on the field-specific isodoses in the pCT were calculated. The corresponding range for each point was found in the repeat CTs (rCTs). The spatial agreement between the resulting surfaces in the rCTs (hereafter referred to as iso-WEPLs) and the isodoses re-calculated in rCTs was evaluated for different dose levels and Hausdorff thresholds (2-5 mm). Finally, the sensitivity and specificity of detecting target dose degradation (V95% < 95%) using spatial agreement measures between the iso-WEPLs and isodoses in the pCT was evaluated.Results. The spatial agreement between the iso-WEPLs and isodoses in the rCTs depended on the Hausdorff threshold. The agreement was 65%-88% for a 2 mm threshold, 83%-96% for 3 mm, 90%-99% for 4 mm, and 94%-99% for 5 mm, across all fields and isodose levels. Minor differences were observed between the different isodose levels investigated. Target dose degradations were detected with 82%-100% sensitivity and 75%-80% specificity using a 2 mm Hausdorff threshold for the lateral fields.Conclusion. Iso-WEPLs were comparable to isodoses re-calculated in the rCTs. The proposed strategy could detect target dose degradations occurring in the rCTs and could be an alternative to a fully-fledged dose re-calculation to detect anatomical variations severely influencing the proton range.

Anatomically robust proton therapy using multiple planning computed tomography scans for locally advanced prostate cancer.

BACKGROUND: Proton therapy (PT) is sensitive towards anatomical changes that may occur during a treatment course. The aim of this study was to investigate if anatomically robust PT (ARPT) plans incorporating patient-specific target motion improved target coverage while still sparing normal tissues, when applied on locally advanced prostate cancer patients where pelvic irradiation is indicated. MATERIAL AND METHODS: A planning computed tomography (CT) scan used for dose calculation and two additional CTs (acquired on different days) were used to make patient-specific targets for the ARPT plans on the eight included patients. The plans were compared to a conventional robust PT plan and a volumetric modulated arc therapy (VMAT) photon plan, which were derived from the planning CT (pCT). Worst-case robust optimisation was used for all proton plans with a setup uncertainty of 5 mm and a range uncertainty of 3.5%. Target coverage (V95% and D95%) and normal tissue doses (V5-75 Gy) were evaluated on 6-8 rCTs per patient. RESULTS: The ARPT plans improved the prostate target coverage for the most challenging patient compared to conventional robust PT plans (20% point increase for V95% and 31 Gy increase for D95%). Across the whole cohort the estimated mean value for V95% was 97% for the ARPT plans and 95% for the conventional robust PT plans. The ARPT plans had a slight, statistically insignificant increase in normal tissue doses compared to the conventional robust proton plans. Compared to VMAT, the ARPT plans significantly reduced the normal tissue doses in the low-to-intermediate dose range. CONCLUSIONS: While both proton plans reduced the low-to-intermediate normal tissue doses compared to VMAT, ARPT plans improved the target coverage for the most challenging patient without significantly increasing the normal tissue doses compared to conventional robust PT plans.

On-line dose-guidance to account for inter-fractional motion during proton therapy.

BACKGROUND AND PURPOSE: Proton therapy (PT) of extra-cranial tumour sites is challenged by density changes caused by inter-fractional organ motion. In this study we investigate on-line dose-guided PT (DGPT) to account inter-fractional target motion, exemplified by internal motion in the pelvis. MATERIALS AND METHODS: On-line DGPT involved re-calculating dose distributions with the isocenter shifted up to 15 mm from the position corresponding to conventional soft-tissue based image-guided PT (IGPT). The method was applied to patient models with simulated prostate/seminal vesicle target motion of ±3, ±5 and ±10 mm along the three cardinal axes. Treatment plans were created using either two lateral (gantry angles of 90°/270°) or two lateral oblique fields (gantry angles of 35°/325°). Target coverage and normal tissue doses from DGPT were compared to both soft-tissue and bony anatomy based IGPT. RESULTS: DGPT improved the dose distributions relative to soft-tissue based IGPT for 39 of 90 simulation scenarios using lateral fields and for 50 of 90 scenarios using lateral oblique fields. The greatest benefits of DGPT were seen for large motion, e.g. a median target coverage improvement of 13% was found for 10 mm anterior motion with lateral fields. DGPT also improved the dose distribution in comparison to bony anatomy IGPT in all cases. The best strategy was often to move the fields back towards the original target position prior to the simulated target motion. CONCLUSION: DGPT has the potential to better account for large inter-fractional organ motion in the pelvis than IGPT.

Evaluating the influence of organ motion during photon vs. proton therapy for locally advanced prostate cancer using biological models.

BACKGROUND: Proton therapy (PT) may have a normal tissue sparing potential when co-irradiating pelvic lymph nodes in patients with locally advanced prostate cancer, but may also be more sensitive towards organ motion in the pelvis. Building upon a previous study identifying motion-robust proton beam angles for pelvic irradiation, we aimed to evaluate the influence of organ motion for PT using biological models, and to compare this with contemporary photon-based RT. MATERIAL AND METHODS: Eight locally advanced prostate cancer patients with a planning CT (pCT) and 8-9 repeated CT scans (rCTs) were included. Two PT plans were created, one using two lateral opposed beams at gantry angles of 90°/270° and the other using two lateral oblique beams at 35°/325°; these were compared with volumetric modulated arc therapy (VMAT) plans. All plans were optimised on the pCT and subsequently re-calculated on each rCT (following rigid alignment on the prostate). Dose distributions in organs at risk (OARs) were evaluated using mean dose, generalized equivalent uniform doses (gEUDs) and normal tissue complication probabilities (NTCPs), while mean dose and the volume receiving 98% of the dose (V98%) were used for the targets. RESULTS: PT significantly reduced the mean dose to the OARs and a correlation was seen in the pCTs between the prostate PTV overlapping the relevant OAR and OAR NTCPs, as was also the case for the VMAT plans. The best prostate target coverage across the rCTs for the IMPT plans were seen with two lateral opposed beams, although a poor coverage of the lymph node target was apparent based on V98% compared to the VMAT plans. CONCLUSIONS: PT reduced the mean dose to normal tissues in the irradiation of pelvic lymph nodes and a strong association between the volume overlap and NTCPs in the pCTs were found.