BACKGROUND: The dosimetric effect of setup uncertainty and tissue deformations in left-sided whole-breast irradiation with complementary surface-guided radiotherapy (SGRT) and cone-beam computed tomography (CBCT) setup was evaluated.
METHODS: Treatment courses of 40.05 Gy prescribed dose in 15 fractions were simulated for 29 patients by calculating the dose on deformed CT images, that were based on daily CBCT images, and deforming and accumulating the dose onto the planning CT image. Variability in clinical target volume (CTV) position and shape was assessed as the 95% Hausdorff distance (HD95) between the planning CTV and deformed CTV structures. DVH metrics were evaluated between the planned and simulated cumulative dose distributions using two treatment techniques: tangential volumetric modulated arc therapy (tVMAT) and conventional 3D-conformal radiotherapy (3D-CRT).
RESULTS: Based on the HD95 values, the variations in CTV shape and position were enclosed by the 5 mm CTV-PTV margin in 85% of treatment fractions using complementary CBCT and SGRT setup. A residual error of 8.6 mm was observed between the initial SGRT setup and CBCT setup. The median CTV V95% coverage was 98.1% (range 93.1-99.8%) with tVMAT and 98.2% (range 84.5-99.7%) with 3D-CRT techniques with CBCT setup. With the initial SGRT-only setup, the corresponding coverages were 96.3% (range 92.6-99.4%) and 96.6% (range 84.2-99.4%), respectively. However, a considerable bias in vertical residual error between initial SGRT setup and CBCT setup was observed. Clinically relevant changes between the planned and cumulative doses to organs-at-risk (OARs) were not observed.
CONCLUSIONS: The CTV-to-PTV margin should not be reduced below 5 mm even with daily CBCT setup. Both tVMAT and 3D-CRT techniques were robust in terms of dose coverage to the target and OARs. Based on the shifts between setup methods, CBCT setup is recommended as a complementary method with SGRT.

This study quantifies setup uncertainty in brain tumor patients who received image-guided proton therapy. Patients analyzed include 165 children, adolescents, and young adults (median age at radiotherapy: 9 years (range: 10 months to 24 years); 80 anesthetized and 85 awake) enrolled in a single-institution prospective study from 2020 to 2023. Cone-beam computed tomography (CBCT) was performed daily to calculate and correct manual setup errors, once per course after setup correction to measure residual errors, and weekly after treatments to assess intrafractional motion. Orthogonal radiographs were acquired consecutively with CBCT for paired comparisons of 40 patients. Translational and rotational errors were converted from 6 degrees of freedom to a scalar by a statistical approach that considers the distance from the target to the isocenter. The 95th percentile of setup uncertainty was reduced by daily CBCT from 10 mm (manual positioning) to 1-1.5 mm (after correction) and increased to 2 mm by the end of fractional treatment. A larger variation existed between the roll corrections reported by radiographs vs. CBCT than for pitch and yaw, while there was no statistically significant difference in translational variation. A quantile mixed regression model showed that the 95th percentile of intrafractional motion was 0.40 mm lower for anesthetized patients (p=0.0016). Considering additional uncertainty in radiation-imaging isocentricity, the commonly used total plan robustness of 3 mm against positional uncertainty would be appropriate for our study cohort.

OBJECTIVE: In this work, we implemented a method to obtain a nonuniform clinical target volume (CTV) to planning target volume (PTV) margin caused by both rotational and translational uncertainties and evaluated it in the treatment planning system (TPS).
METHODS: Based on a previously published statistical model, the relationship between a target margin and the distance d (from isocenter to target point), setup uncertainties, and significance level was established. For a single CTV, it can be thought as a combination of many small volume elements or target points. The margin of each point could be obtained using the suggested statistical model. The whole nonuniform CTV-PTV margin was determined by the union of all possible margins of the CTV boundary points. This method was implemented in the Pinnacle3 treatment planning system and compared with uniform margin algorithm. Ten vertebral metastases targets and multiple brain metastases targets were chosen for evaluation.
RESULTS: The combined CTV-PTV margin as a function of d for various initial translational margin and rotational uncertainties was calculated. The combined margin increases as d, rotational uncertainties and translational margin increase. For the same rotational uncertainty, a smaller initial translational margin requires a larger rotational margin to compensate for the rotational error. Compared with the uniform margin algorithm, the advantage of this method is that it could minimize the PTVs volume for given CTVs to obtain same significance level. Using vertebral metastases targets and multiple brain metastases targets, a series of volume difference was obtained for various translational margins and rotational uncertainties. The volume difference of PTV could be more than 17% when translational margin is 2 mm and rotational uncertainty is 1.4°.
CONCLUSIONS: Nonuniform margin algorithm could avoid excessive compensation for the CTV boundary points near isocenter. This method could be used for clinical margin determination and might be useful for the protection of risk organs.