Applicability and usage of dose mapping/accumulation in radiotherapy.

Dose mapping/accumulation (DMA) is a topic in radiotherapy (RT) for years, but has not yet found its widespread way into clinical RT routine. During the ESTRO Physics workshop 2021 on "commissioning and quality assurance of deformable image registration (DIR) for current and future RT applications", we built a working group on DMA from which we present the results of our discussions in this article. Our aim in this manuscript is to shed light on the current situation of DMA in RT and to highlight the issues that hinder consciously integrating it into clinical RT routine. As a first outcome of our discussions, we present a scheme where representative RT use cases are positioned, considering expected anatomical variations and the impact of dose mapping uncertainties on patient safety, which we have named the DMA landscape (DMAL). This tool is useful for future reference when DMA applications get closer to clinical day-to-day use. Secondly, we discussed current challenges, lightly touching on first-order effects (related to the impact of DIR uncertainties in dose mapping), and focusing in detail on second-order effects often dismissed in the current literature (as resampling and interpolation, quality assurance considerations, and radiobiological issues). Finally, we developed recommendations, and guidelines for vendors and users. Our main point include: Strive for context-driven DIR (by considering their impact on clinical decisions/judgements) rather than perfect DIR; be conscious of the limitations of the implemented DIR algorithm; and consider when dose mapping (with properly quantified uncertainties) is a better alternative than no mapping.

Interfractional dose accumulation for MR-guided liver SBRT: Variation among algorithms is highly patient- and fraction-dependent.

BACKGROUND AND PURPOSE: Daily plan adaptations could take the dose delivered in previous fractions into account. Due to high dose delivered per fraction, low number of fractions, steep dose gradients, and large interfractional organ deformations, this might be particularly important for liver SBRT. This study investigates inter-algorithm variation of interfractional dose accumulation for MR-guided liver SBRT. MATERIALS AND METHODS: We assessed 27 consecutive MR-guided liver SBRT treatments of 67.5 Gy in three (n = 15) or 50 Gy in five fractions (n = 12), both prescribed to the GTV. We calculated fraction doses on daily patient anatomy, warped these doses to the simulation MRI using seven different algorithms, and accumulated the warped doses. Thus, we obtained differences in planned doses and warped or accumulated doses for each algorithm. This enabled us to calculate the inter-algorithm variations in warped doses per fraction and in accumulated doses per treatment course. RESULTS: The four intensity-based algorithms were more consistent with planned PTV dose than affine or contour-based algorithms. The mean (range) variation of the dose difference for PTV D95% due to dose warping by these intensity-based algorithms was 10.4 percentage points (0.3 to 43.7) between fractions and 8.6 (0.3 to 24.9) between accumulated treatment doses. As seen by these ranges, the variation was very dependent on the patient and the fraction being analyzed. Nevertheless, no correlations between patient or plan characteristics on the one hand and inter-algorithm dose warping variation on the other hand was found. CONCLUSION: Inter-algorithm dose accumulation variation is highly patient- and fraction-dependent for MR-guided liver SBRT. We advise against trusting a single algorithm for dose accumulation in liver SBRT.

Gating has a negligible impact on dose delivered in MRI-guided online adaptive radiotherapy of prostate cancer.

BACKGROUND AND PURPOSE: MR-guided radiotherapy (MRgRT) allows real-time beam-gating to compensate for intra-fractional target position variations. This study investigates the dosimetric impact of beam-gating and the impact of PTV margin on prostate coverage for prostate cancer patients treated with online-adaptive MRgRT. MATERIALS AND METHODS: 20 consecutive prostate cancer patients were treated with online-adaptive MRgRT SBRT with 36.25 Gy in 5 fractions (PTV D95% ≥ 95% (N = 5) and PTV D95% ≥ 100% (N = 15)). Sagittal 2D cine MRIs were used for gating on the prostate with a 3 mm expansion as the gating window. We computed motion-compensated dose distributions for (i) all prostate positions during treatment (simulating non-gated treatments) and (ii) for prostate positions within the gating window (gated treatments). To evaluate the impact of PTV margin on prostate coverage, we simulated coverage with smaller margins than clinically applied both for gated and non-gated treatments. Motion-compensated fraction doses were accumulated and dose metrics were compared. RESULTS: We found a negligible dosimetric impact of beam-gating on prostate coverage (median of 0.00 Gy for both D95% and Dmean). For 18/20 patients, prostate coverage (D95% ≥ 100%) would have been ensured with a prostate-to-PTV margin of 3 mm, even without gating. The same was true for all but one fraction. CONCLUSION: Beam-gating has negligible dosimetric impact in online-adaptive MRgRT of prostate cancer. Accounting for motion, the clinically used prostate-to-PTV margin could potentially be reduced from 5 mm to 3 mm for 18/20 patients.

Automation of DVH Constraint Checks and Physics Quality Control Review Improves Patient Safety in Radiotherapy.

This study investigates whether patient safety can be enhanced by the implementation of an automated electronic checklist (PlanCheck) for physics quality control review (QCR) of radiotherapy photon plans. PlanCheck evaluates both technical aspects and DVH constraints. Three hundred and thirty-one consecutively approved radiotherapy plans previously reviewed with manual QCR were retrospectively checked with PlanCheck. Four hundred and thirty-three (3.4%) of the 12783 automated technical checks executed in the 331 plans yielded an error. All errors were scored using the severity rating from the American Association of Physicists in Medicine TG-100 report. Nineteen of these errors (4%) either could have affected or affected target dose (severity 5+) implicating a maximum dose difference to the target or a critical organ at risk of 0.5% to 10% and 3 errors could have resulted in stereotactic brain treatments being delivered to the wrong location (severity 10). Forty-seven breast cancer plans were retrospectively subjected to automated DVH check, 10 undocumented dose constraint violations were found. PlanCheck has been shown to reduce errors in manually reviewed radiotherapy plans and thus to enhance patient safety.

Analysis of early respiratory-related mortality after radiation therapy of non-small-cell lung cancer: feasibility of automatic data extraction for dose-response studies.

Purpose: To examine the feasibility of automatic data extraction from clinical radiation therapy (RT) databases at four hospitals to investigate the impact of mean lung dose (MLD) and age on the risk of early respiratory-related death and early overall death for patients treated with RT for non-small-cell lung cancer (NSCLC).Material and methods: We included adult patients with NSCLC receiving curatively intended RT between 2002 and 2017 at four hospitals. A script was developed to automatically extract RT-related data. The cause of death for patients deceased within 180 days of the start of RT was retrospectively assessed. Using logistic regression, the risks of respiratory-related death and of overall death within 90 and 180 days were investigated using MLD and age as variables.Results: Altogether, 1785 patients were included in the analysis of early overall mortality and 1655 of early respiratory-related mortality. The respiratory-related mortalities within 90 and 180 days were 0.9% (15/1655) and 3.6% (60/1655). The overall mortalities within 90 and 180 days were 2.5% (45/1785) and 10.6% (190/1785). Higher MLD and older age were associated with an increased risk of respiratory-related death within 180 days and overall death within 90 and 180 days (all p<.05). For example, the risk of respiratory-related death within 180 days and their 95% confidence interval for patients aged 65 and 75 years with MLDs of 20 Gy was according to our logistic model 3.8% (2.6-5.0%) and 7.7% (5.5-10%), respectively.Conclusions: Automatic data extraction was successfully used to pool data from four hospitals. MLD and age were associated with the risk of respiratory-related death within 180 days of the start of RT and with overall death within 90 and 180 days. A model quantifying the risk of respiratory-related death within 180 days was formulated.

Dose response of three-dimensional silicone-based radiochromic dosimeters for photon irradiation in the presence of a magnetic field.

The magnetic field in magnetic resonance imaging guided radiotherapy (MRgRT) delivery systems influences charged-particle trajectories and hence the three-dimensional (3D) radiation dose distributions. This study investigated the dose-response as well as dose-rate and fractionation dependencies of silicone-based 3D radiochromic dosimeters for photon irradiation in a magnetic field using a 0.35 T MRgRT system. We found a linear dose response up to 22.6 Gy and no significant dose-rate dependency as a function of depth. A difference in optical response was observed for dosimeters irradiated in a single compared to multiple fractions. The dosimeter showed clinical potential for verification of MRgRT delivery.

Evaluation of setup and intrafraction motion for surface guided whole-breast cancer radiotherapy.

Surface Guided Radiotherapy (SGRT) is a relatively new technique for positioning patients and for monitoring patient movement during treatment. SGRT is completely non-invasive since it uses visible light for determining the position of the patient surface. A reduction in daily imaging for patient setup is possible if the accuracy of SGRT is comparable to imaging. It allows for monitoring of intrafraction motion and the radiation beam can be held beyond a certain threshold resulting in a more accurate irradiation. The purpose of this study was to investigate setup uncertainty and the intrafraction motion in non-gated whole breast cancer radiotherapy treatment using an integrated implementation of AlignRT (OSMS) system as SGRT. In initial setup, SGRT was compared to three-point setup using tattoos on the patient and orthogonal kV imaging. For the investigation of intrafraction motion, OSMS monitored the patient with six degrees of freedom during treatment. Using three-point setup resulted in a setup root-mean-square error from the isocenter of 5.4 mm. This was improved to 4.2 mm using OSMS. For the translational directions, OSMS showed improvements in the lateral direction (P = 0.0009, Wilcoxon rank-sum), but for the longitudinal direction and rotation it was not possible to show improvements (P = 0.96 and P = 0.46, respectively). The vertical direction proved more accurate for three-point setup than OSMS (P = 0.000004). Intrafraction motion was very limited with a translational median of 1.1 mm from the isocenter. While OSMS showed marked improvements over laser and tattoo setup, the system did not prove accurate enough to replace the daily orthogonal kV images aligned to bony anatomy.

Temperature and temporal dependence of the optical response for a radiochromic dosimeter.

PURPOSE: Both temporal and thermal dependencies of the dose response have been observed in radiochromic dosimeters. As these dependencies may be influenced by the dose level, the present study investigates the temperature dependence during irradiation and the temporal change of the optical response following irradiation of radiochromic dosimeters at a range of doses. METHODS: Cuvette samples of the PRESAGE™ radiochromic dosimeter were irradiated within a dose range of 0-10 Gy at irradiation temperatures within 5-35 °C and postirradiation storage within 6-30 °C. The optical response due to irradiation was measured using a standard spectrophotometer and the data were analyzed in terms of thermal and temporal change. RESULTS: The initial dose response was linear over the applied dose range independent of irradiation temperature. However, the optical response to a specific dose increased exponentially with irradiation temperature corresponding to an activation energy of 0.114 ± 0.007 eV. The temporal change in dose response after irradiation consisted of an offset, an auto-oxidation rate with activation energy 0.84 ± 0.03 eV, and an initial exponential increase in optical response (1.6 ± 0.2 eV) followed by an exponential decrease in optical response (0.98 ± 0.08 eV). These contributions depended on both storage temperature and the dose given, leading to a nonlinear dose response with time at low storage temperatures and a high auto-oxidation rate at high storage temperatures. CONCLUSIONS: Thermal equilibration is important to the radiochromic dosimeter investigated due to an exponential change in dose response with irradiation temperature and a considerable postirradiation temporal change in response. For the dosimeter version investigated in this study, a compromise in storage temperature has to be made between increasing the nonlinearity of the dose response with time and inducing a high auto-oxidation rate.