Accumulated Dose Distributions Research Articles

Improvement of accumulated dose distribution in combined cervical cancer radiotherapy with deep learning-based dose prediction.

Difficulties remain in dose optimization and evaluation of cervical cancer radiotherapy that combines external beam radiotherapy (EBRT) and brachytherapy (BT). This study estimates and improves the accumulated dose distribution of EBRT and BT with deep learning-based dose prediction. A total of 30 patients treated with combined cervical cancer radiotherapy were enrolled in this study. The dose distributions of EBRT and BT plans were accumulated using commercial deformable image registration. A ResNet-101-based deep learning model was trained to predict pixel-wise dose distributions. To test the role of the predicted accumulated dose in clinic, each EBRT plan was designed using conventional method and then redesigned referencing the predicted accumulated dose distribution. Bladder and rectum dosimetric parameters and normal tissue complication probability (NTCP) values were calculated and compared between the conventional and redesigned accumulated doses. The redesigned accumulated doses showed a decrease in mean values of V50, V60, and D2cc for the bladder (-3.02%, -1.71%, and -1.19 Gy, respectively) and rectum (-4.82%, -1.97%, and -4.13 Gy, respectively). The mean NTCP values for the bladder and rectum were also decreased by 0.02‰ and 0.98%, respectively. All values had statistically significant differences (p < 0.01), except for the bladder D2cc (p = 0.112). This study realized accumulated dose prediction for combined cervical cancer radiotherapy without knowing the BT dose. The predicted dose served as a reference for EBRT treatment planning, leading to a superior accumulated dose distribution and lower NTCP values.

Evaluation of the availability of single-position treatment with a rotating gantry and the validity of deformable image registration dose assessment for pancreatic cancer carbon-ion radiotherapy.

This study aimed to evaluate the clinical acceptability of rotational gantry-based single-position carbon-ion radiotherapy (CIRT) to reduce the gastrointestinal (GI) dose in pancreatic cancer. We also evaluated the usefulness of the deformable image registration (DIR)-based dosimetry method for CIRT. Fifteen patients with pancreatic cancer were analyzed. The treatment plans were developed for four beam angles in the supine (SP plan) and prone (PR plan) positions. In the case of using multiple positions, the treatment plan was created with two angles for each of the supine and prone position (SP + PR plan). Dose evaluation for multiple positions was performed in two ways: by directly adding the values of the DVH parameters for each position treatment plan (DVH sum), and by calculating the DVH parameters from the accumulative dose distribution created using DIR (DIR sum). The D2cc and D6cc of the stomach and duodenum were recorded for each treatment plan and dosimetry method and compared. There were no significant differences among any of the treatment planning and dosimetry methods (p>0.05). The DVH parameters for the stomach and duodenum were higher in the PR plan and SP plan, respectively, and DVH sum tended to be between the SP and PR plans. DVH sum and DIR sum, DVH sum tended to be higher for D2cc and DIR sum tended to be higher for D6cc. There were no significant differences in the GI dose, which suggests that treatment with a simple workflow performed in one position should be clinically acceptable. In CIRT, DIR-based dosimetry should be carefully considered because of the potential for increased uncertainty due to the steep dose distributions.

Prospects for online adaptive radiation therapy (ART) for head and neck cancer

BackgroundThe aim of the present study is to examine the impact of kV-CBCT-based online adaptive radiation therapy (ART) on dosimetric parameters in comparison to image-guided-radiotherapy (IGRT) in consecutive patients with tumors in the head and neck region from a prospective registry.MethodsThe study comprises all consecutive patients with tumors in the head and neck area who were treated with kV-CBCT-based online ART or IGRT-modus at the linear-accelerator ETHOS™. As a measure of effectiveness, the equivalent-uniform-dose was calculated for the CTV (EUDCTV) and organs-at-risk (EUDOAR) and normalized to the prescribed dose. As an important determinant for the need of ART the interfractional shifts of anatomic landmarks related to the tongue were analyzed and compared to the intrafractional shifts. The latter determine the performance of the adapted dose distribution on the verification CBCT2 postadaptation.ResultsAltogether 59 consecutive patients with tumors in the head-and-neck-area were treated from 01.12.2021 to 31.01.2023. Ten of all 59 patients (10/59; 16.9%) received at least one phase within a treatment course with ART. Of 46 fractions in the adaptive mode, irradiation was conducted in 65.2% of fractions with the adaptive-plan, the scheduled-plan in the remaining. The dispersion of the distributions of EUDCTV-values from the 46 dose fractions differed significantly between the scheduled and adaptive plans (Ansari-Bradley-Test, p = 0.0158). Thus, the 2.5th percentile of the EUDCTV-values by the adaptive plans amounted 97.1% (95% CI 96.6–99.5%) and by the scheduled plans 78.1% (95% CI 61.8–88.7%). While the EUDCTV for the accumulated dose distributions stayed above 95% at PTV-margins of ≥ 3 mm for all 8 analyzed treatment phases the scheduled plans did for margins ≥ 5 mm. The intrafractional anatomic shifts of all 8 measured anatomic landmarks were smaller than the interfractional with overall median values of 8.5 mm and 5.5 mm (p < 0.0001 for five and p < 0.05 for all parameters, pairwise comparisons, signed-rank-test). The EUDOAR-values for the larynx and the parotid gland were significantly lower for the adaptive compared with the scheduled plans (Wilcoxon-test, p < 0.001).ConclusionsThe mobile tongue and tongue base showed considerable interfractional variations. While PTV-margins of 5 mm were sufficient for IGRT, ART showed the potential of decreasing PTV-margins and spare dose to the organs-at-risk.

Adaptation Time as a Determinant of the Dosimetric Effectiveness of Online Adaptive Radiotherapy for Bladder Cancer

Interfraction anatomic deformations decrease the precision of radiotherapy, which can be improved by online adaptive radiation therapy (oART). However, oART takes time, allowing intrafractional deformations. In this study on focal radiotherapy for bladder cancer, we analyzed the time effect of oART on the equivalent uniform dose in the CTV (EUDCTV) per fraction and for the accumulated dose distribution over a treatment series as measure of effectiveness. A time-dependent digital CTV model was built from deformable image registration (DIR) between pre- and post-adaptation imaging. The model was highly dose fraction-specific. Planning target volume (PTV) margins were varied by shrinking the clinical PTV to obtain the margin-specific CTV. The EUDCTV per fraction decreased by—4.4 ± 0.9% of prescribed dose per min in treatment series with a steeper than average time dependency of EUDCTV. The EUDCTV for DIR-based accumulated dose distributions over a treatment series was significantly dependent on adaptation time and PTV margin (p &lt; 0.0001, Chi2 test for each variable). Increasing adaptation times larger than 10 min by five minutes requires a 1.9 ± 0.24 mm additional margin to maintain EUDCTV for a treatment series. Adaptation time is an important determinant of the precision of oART for one half of the bladder cancer patients, and it should be aimed at to be minimized.

Quantifying the Effect of 4-Dimensional Computed Tomography–Based Deformable Dose Accumulation on Representing Radiation Damage for Patients with Locally Advanced Non-Small Cell Lung Cancer Treated with Standard-Fractionated Intensity-Modulated Radiation Therapy

The aim of this study was to investigate the dosimetric and clinical effects of 4-dimensional computed tomography (4DCT)-based longitudinal dose accumulation in patients with locally advanced non-small cell lung cancer treated with standard-fractionated intensity-modulated radiation therapy (IMRT). Sixty-seven patients were retrospectively selected from a randomized clinical trial. Their original IMRT plan, planning and verification 4DCTs, and ∼4-month posttreatment follow-up CTs were imported into a commercial treatment planning system. Two deformable image registration algorithms were implemented for dose accumulation, and their accuracies were assessed. The planned and accumulated doses computed using average-intensity images or phase images were compared. At the organ level, mean lung dose and normal-tissue complication probability (NTCP) for grade ≥2 radiation pneumonitis were compared. At the region level, mean dose in lung subsections and the volumetric overlap between isodose intervals were compared. At the voxel level, the accuracy in estimating the delivered dose was compared by evaluating the fit of a dose versus radiographic image density change (IDC) model. The dose-IDC model fit was also compared for subcohorts based on the magnitude of NTCP difference (|ΔNTCP|) between planned and accumulated doses. Deformable image registration accuracy was quantified, and the uncertainty was considered for the voxel-level analysis. Compared with planned doses, accumulated doses on average resulted in <1-Gy lung dose increase and <2% NTCP increase (up to 8.2 Gy and 18.8% for a patient, respectively). Volumetric overlap of isodose intervals between the planned and accumulated dose distributions ranged from 0.01 to 0.93. Voxel-level dose-IDC models demonstrated a fit improvement from planned dose to accumulated dose (pseudo-R2 increased 0.0023) and a further improvement for patients with ≥2% |ΔNTCP| versus for patients with <2% |ΔNTCP|. With a relatively large cohort, robust image registrations, multilevel metric comparisons, and radiographic image-based evidence, we demonstrated that dose accumulation more accurately represents the delivered dose and can be especially beneficial for patients with greater longitudinal response.

CBCT-based deformable dose accumulation of external beam radiotherapy in cervical cancer

Background: Delivered radiotherapy doses do not exactly match those planned for a course of treatment, largely due to inter-fraction changes in anatomy. In this study, accumulated delivered dose was calculated for a sample of cervical cancer patients, by deformably registering daily cone beam computed tomography (CBCT) images to the planning computed tomography (CT) scan. Planned and accumulated doses were compared for the clinical target volume (CTV), bladder, and rectum. Material and Methods: For 10 patients receiving 45 Gy in 25 fractions of external beam radiotherapy, daily dose distributions were calculated on CBCT. These images were deformed onto the planning CT and the dose was accumulated using Velocity 4.1 (Varian Medical Systems, Palo Alto, USA). The quality of deformable image registration was evaluated visually and by calculating Dice similarity coefficients and mean distance to agreement. Results: V95%>99% was achieved for the primary CTV in 9/10 patients for the planned dose distribution and 7/10 patients for the accumulated dose distribution. Primary CTV coverage by 95% of the prescription dose was reduced in one patient, due to an increase in anterior-posterior separation. Comparison of planned and accumulated dose volume histograms (DVHs) for the bladder and rectum found agreement within 5% at low and intermediate doses, but differences exceeded 20% at higher doses. Direct addition of CBCT DVHs was seen to be a poor estimate for the accumulated DVH at higher doses. Conclusion: Computation of delivered radiotherapy dose that accounts for inter-fraction anatomical changes is important for establishing dose-effect relationships. Updating delivered dose distributions after each fraction would support informed clinical decision making on any potential treatment interventions.

4D dosimetric-blood flow model: impact of prolonged fraction delivery times of IMRT on the dose to the circulating lymphocytes

To investigate the impact of prolonged fraction delivery of modern intensity-modulated radiotherapy (IMRT) on the accumulated dose to the circulating blood during the course of fractionated radiation therapy. We have developed a 4D dosimetric blood flow model (d-BFM) capable of continuously simulating the blood flow through the entire body of the cancer patient and scoring the accumulated dose to blood particles (BPs). We developed a semi-automatic approach that enables us to map the tortuous blood vessels of the surficial brain of individual patients directly from standard magnetic resonance imaging data of the patient. For the rest of the body, we developed a fully-fledged dynamic blood flow transfer model according to the International Commission on Radiological Protection human reference. We proposed a methodology enabling us to design a personalized d-BFM, such it can be tailored for individual patients by adopting intra- and inter-subject variations. The entire circulatory model tracks over 43 million BPs and has a time resolution of = 10−3 s. A dynamic dose delivery model was implemented to emulate the spatial and temporal time-varying pattern of the dose rate during the step-and-shoot mode of IMRT. We evaluated how different configurations of the dose rate delivery, and a time prolongation of fraction delivery may impact the dose received by the circulating blood (CB).Our calculations indicate that prolonging the fraction treatment time from 7 to 18 min will augment the blood volume receiving any dose from 36.1% to 81.5% during one single fraction. The results indicate that increasing the segment number has only a negligible effect on the irradiated blood volume, when the fraction time is kept identical. We developed a novel concept of customized 4D d-BFM that can be tailored to the hemodynamics of individual patients to quantify dose to the CB during fractionated radiotherapy. The prolonged fraction delivery and the variability of the instantaneous dose rate have a significant impact on the accumulated dose distribution during IMRT treatments. This impact should be considered during IMRT treatments design to reduce RT-induced immunosuppressive effects.

Dose mimicking based strategies for online adaptive proton therapy of head and neck cancer

Objective. To compare a not adapted (NA) robust planning strategy with three fully automated online adaptive proton therapy (OAPT) workflows based on the same optimization method: dose mimicking (DM). The added clinical value and limitations of the OAPT methods are investigated for head and neck cancer (HNC) patients. Approach. The three OAPT strategies aimed at compensating for inter-fractional anatomical changes by mimiking different dose distributions on corrected cone beam CT images (corrCBCTs). Order by complexity, the OAPTs were: (1) online adaptive dose restoration (OADR) where the approved clinical dose on the planning-CT (pCT) was mimicked, (2) online adaptation using DM of the deformed clinical dose from the pCT to corrCBCTs (OADEF), and (3) online adaptation applying DM to a predicted dose on corrCBCTs (OAML). Adaptation was only applied in fractions where the target coverage criteria were not met (D98% < 95% of the prescribed dose). For 10 HNC patients, the accumulated dose distributions over the 35 fractions were calculated for NA, OADR, OADEF, and OAML. Main results. Higher target coverage was observed for all OAPT strategies compared to no adaptation. OADEF and OAML outperformed both NA and OADR and were comparable in terms of target coverage to initial clinical plans. However, only OAML provided comparable NTCP values to those from the clinical dose without statistically significant differences. When the NA initial plan was evaluated on corrCBCTs, 51% of fractions needed adaptation. The adaptation rate decreased significantly to 25% when the last adapted plan with OADR was selected for delivery, to 16% with OADEF, and to 21% with OAML. The reduction was even greater when the best plan among previously generated adapted plans (instead of the last one) was selected. Significance. The implemented OAPT strategies provided superior target coverage compared to no adaptation, higher OAR sparing, and fewer required adaptations.

Applying Multi-Metric Deformable Image Registration for Dose Accumulation in Combined Cervical Cancer Radiotherapy

(1) Purpose: Challenges remain in dose accumulation for cervical cancer radiotherapy combined with external beam radiotherapy (EBRT) and brachytherapy (BT) as there are many large and complex organ deformations between different treatments. This study aims to improve deformable image registration (DIR) accuracy with the introduction of multi-metric objectives for dose accumulation of EBRT and BT. (2) Materials and methods: Twenty cervical cancer patients treated with EBRT (45-50 Gy/25 fractions) and high-dose-rate BT (≥20 Gy in 4 fractions) were included for DIR. The multi-metric DIR algorithm included an intensity-based metric, three contour-based metrics, and a penalty term. Nonrigid B-spine transformation was used to transform the planning CT images from EBRT to the first BT, with a six-level resolution registration strategy. To evaluate its performance, the multi-metric DIR was compared with a hybrid DIR provided by commercial software. The DIR accuracy was measured by the Dice similarity coefficient (DSC) and Hausdorff distance (HD) between deformed and reference organ contours. The accumulated maximum dose of 2 cc (D2cc) of the bladder and rectum was calculated and compared to simply addition of D2cc from EBRT and BT (ΔD2cc). (3) Results: The mean DSC of all organ contours for the multi-metric DIR were significantly higher than those for the hybrid DIR (p ≤ 0.011). In total, 70% of patients had DSC > 0.8 using the multi-metric DIR, while 15% of patients had DSC > 0.8 using the commercial hybrid DIR. The mean ΔD2cc of the bladder and rectum for the multi-metric DIR were 3.25 ± 2.29 and 3.54 ± 2.02 GyEQD2, respectively, whereas those for the hybrid DIR were 2.68 ± 2.56 and 2.32 ± 3.25 GyEQD2, respectively. The multi-metric DIR resulted in a much lower proportion of unrealistic D2cc than the hybrid DIR (2.5% vs. 17.5%). (4) Conclusions: Compared with the commercial hybrid DIR, the introduced multi-metric DIR significantly improved the registration accuracy and resulted in a more reasonable accumulated dose distribution.

Dose evaluations of organs at risk and predictions of gastrointestinal toxicity after re-irradiation with stereotactic body radiation therapy for pancreatic cancer by deformable image registration.

Re-irradiation of locally recurrent pancreatic cancer may be an optimal choice as a local ablative therapy. However, dose constraints of organs at risk (OARs) predictive of severe toxicity remain unknown. Therefore, we aim to calculate and identify accumulated dose distributions of OARs correlating with severe adverse effects and determine possible dose constraints regarding re-irradiation. Patients receiving two courses of stereotactic body radiation therapy (SBRT) for the same irradiated regions (the primary tumors) due to local recurrence were included. All doses of the first and second plans were recalculated to an equivalent dose of 2 Gy per fraction (EQD2). Deformable image registration with the workflow "Dose Accumulation-Deformable" of the MIM® System (version: 6.6.8) was performed for dose summations. Dose-volume parameters predictive of grade 2 or more toxicities were identified, and the receiver operating characteristic (ROC) curve was used to determine optimal thresholds of dose constraints. Forty patients were included in the analysis. Only the V 10 of the stomach [hazard ratio (HR): 1.02 (95% CI:1.00-1.04), P = 0.035] and D mean of the intestine [HR: 1.78 (95% CI: 1.00-3.18), P = 0.049] correlated with grade 2 or more gastrointestinal toxicity. Hence, the equation of probability of such toxicity was Additionally, the area under the ROC curve and threshold of dose constraints of V 10 of the stomach and D mean of the intestine were 0.779 and 77.575 cc, 0.769 and 4.22 Gy3 (α/β = 3), respectively. The area under the ROC curve of the equation was 0.821. The V 10 of the stomach and D mean of the intestine may be vital parameters to predict grade 2 or more gastrointestinal toxicity, of which the threshold of dose constraints may be beneficial for the practice of re-irradiation of locally relapsed pancreatic cancer.

Robustness of a multi-isocenter VMAT Total Body Irradiation (TBI) dose distribution against daily patient setup errors

<h3>Objectives</h3> A VMAT technique using a rotatable tabletop for TBI in supine position is newly applied at UMC Utrecht. We aimed to assess the dose distribution robustness against daily isocenter shifts. <h3>Methods</h3> The tabletop enables rotation from head-first (HF) to feet-first (FF) supine position while the patient remains immobilized in an individualized whole-body vacuum matrass and a thermoplastic facemask. The treatment plan was optimized on the HF and FF CT-scans, co-registered on the overlapping anatomical region (20 cm longitudinal). Depending on patient-length, 4 to 6 isocenters with overlapping arcs (4 cm longitudinal) were used. Prescription dose (PD) was 12Gy in 6 fractions with mean dose constraints for lungs/kidneys <10Gy and lenses <8Gy. Daily patient-position verification procedure (PV) comprised: pelvic HF-iso3 (CBCT + online corrected); thoracic HF-iso2 (CBCT only, no correction); knee region FF-iso (CBCT + online corrected). Brain HF-iso1 and FF-iso4 or -iso5 (patient length dependent) not imaged. HF (FF) radiation delivery followed HF (FF)-PV. After each fraction, the dose distribution of the first 3 treated patients (length range 110-195 cm) was recalculated applying the registered isocenter corrections/shifts. Then, the 6-fraction rigidly accumulated dose distribution was compared to the original. <h3>Results</h3> The maximum shift for HF-iso2 was 0.4 cm lateral, 0.8 cm longitudinal and 0.9 vertical and for the knee region FF-iso 0.7 cm lateral, 0.4 cm longitudinal and 0.5 cm vertical over all patients/fractions. Over all patients, the differences in PTV volume receiving 80%, 90% and 120% PD between accumulated and original dose distribution were <1%, while a +3% V110% PD maximum difference was found. The maximum mean dose difference for lenses, lungs and kidneys between accumulated and original dose distributions was +1.0 Gy, +0.2 Gy and +0.6 Gy, respectively. <h3>Conclusion</h3> The dose distribution of the described VMAT technique for TBI, is proven to be robust against daily observed isocenter shifts.

Evaluating the accumulated dose distribution of organs at risk in combined radiotherapy for cervical carcinoma based on deformable image registration

ObjectiveTo evaluate the feasibility and value of deformable image registration (DIR) in calculating the cumulative doses of organs at risk (OARs) in the combined radiotherapy of cervical cancer. Patients and methodsThirty cervical cancer patients treated with external beam radiotherapy (EBRT) combined with intracavitary brachytherapy (ICBT) were reviewed. The simulation CT images of EBRT and ICBT were imported into Varian Velocity 4.1 for the DIR-based dose accumulation. Cumulative dose-volume parameters of D2cc for rectum and bladder were compared between the direct addition (DA) and DIR methods. The quantitative parameters were measured to evaluate the accuracy of DIR. ResultsThe three-dimensional cumulative dose distribution of the tumor and OARs were graphically well illustrated by composite isodose lines. In combined EBRT and ICBT, the mean cumulative bladder D2cc calculated by DIR and DA was 86.13 Gy and 86.27 Gy, respectively. The mean cumulative rectal D2cc calculated by DIR and DA was 72.97 Gy and 73.90 Gy, respectively. No significant differences were noted between these two methods (p > 0.05). As to the parameters used to evaluate the DIR accuracy, the mean DSC, Jacobian, MDA (mm) and Hausdorff distance (mm) were 0.79, 1.0, 3.84, and 22.01 respectively for the bladder and 0.53, 1.2, 7.31, and 29.58 respectively for the rectum. In this study, the DSC seemed to be slightly lower compared with previous studies. ConclusionDose accumulation based on DIR might be an alternative method to illustrate and evaluate the cumulative doses of the OARs in combined radiotherapy for cervical cancer. However, DIR should be used with caution before overcoming the relevant limitations.

Accumulated Dose Prediction for Assisting Radiation Treatment in Cervical Cancer

<h3>Purpose/Objective(s)</h3> For cervical cancer treated with combined external beam radiotherapy (EBRT) and brachytherapy (BT), ideally, the treatment optimization and evaluation should take the accumulated dose distribution into account. However, in current clinical practice different treatment parts are linked to different planning images and optimized independently, resulting in multiple dose distributions. In this study, we used a combination of deformable image registration (DIR) and deep learning techniques to predict the accumulated dose for assisting treatment planning and dose estimation. <h3>Materials/Methods</h3> The dose distributions of both EBRT and BT plans from 32 cervical cancer patients were used for this study. Firstly, the BT images were registered to the EBRT images using DIR to obtain the accumulated dose distributions. Then, a deep learning model based on a 101-layers ResNet was trained to predict pixel-wise dose distributions. The input data was combined anatomic maps including the CT images, structure maps and distance maps. The output data was the corresponding accumulated dose maps. We used 5-fold cross-validation to test the performance of the prediction model. The evaluation parameters included the voxel-based mean absolute error (MAE) and dice similarity coefficient (DSC) of isodose volumes for the prescription dose (PD) of EBRT (45/50 Gy) and the summed PD of EBRT and BT (76.25/82 Gy_EQD2). Finally, we randomly selected 10 patients to validate the effect of the dose prediction on treatment planning. For each patient, two EBRT plans were separately designed by a single physicist in the cases of unknowing and knowing the predicted accumulated dose distribution. The resulting two EBRT doses were separately accumulated with BT dose for comparison. <h3>Results</h3> In the comparison between the predicted and original dose distributions, the mean MAE of the whole body, normal tissue, bladder and rectum were 3.73±1.58, 3.27±1.06, 6.55±3.10 and 8.05±4.95 Gy, respectively. The mean DSC of the isodose volumes for 45/50 Gy and 76.25/82 Gy_EQD2 were 0.89±0.02 and 0.69±0.09, respectively. Compared to the planning without knowing the predicted dose, the planning with knowing the predicted dose resulted in a lower D2cc (-1.2±0.80 Gy, p=0.04), V40 (-3.23±2.19%, p=0.002), V50 (-2.19±%1.34, p=0.001) and V60 (-0.79±0.82%, p=0.02) of the rectum. For the bladder, the V40 of were decreased by 1.48±0.58% (p<0.001) but other dosimetric parameters had no significant difference. <h3>Conclusion</h3> The accumulated dose prediction could help to estimate and further decrease the doses to organs at risk. The predicted dose is recommended to be used as a reference during treatment planning in order to pursue a superior accumulated dose distribution for the combined cervical cancer treatment.

Evaluation of Repeated Lung Stereotactic Body Radiotherapy Using a Radiotherapy Dose Accumulation Routine

<h3>Purpose/Objective(s)</h3> Repeated lung SBRT has been used for recurrent or metachronous non-small-cell lung cancer. Comprehensive evaluation of cumulative dose is essential for safe reirradiation to minimize the risk of pneumonitis and esophageal toxicity. We evaluated an in-house script named RADAR (Radiotherapy Dose Accumulation Routine) designed to provide accurate dose assessment that accounts for registration uncertainties, and improve the efficiency of clinical workflow. <h3>Materials/Methods</h3> In this pilot study, we analyzed a cohort of 20 patients who underwent 2-5 courses of repeated lung SBRT. Lung volume changed 8±8% between courses. Planning CT images from earlier treatment courses were registered onto the final course in two steps: first, a rigid registration based on alignment of spine and rib cage, then a deformable image registration (DIR) using a ‘demons' algorithm in a planning system. The resulting deformable vector fields were used by RADAR to transform voxels for automated dose accumulation. User can choose to output either physical dose or equivalent dose in 2Gy fractions (EQD2, α/β=3) with a discount factor (Paradis, ARO 2019). RADAR provides three approaches for dose accumulation: 1) direct sum that outputs voxel level dose summation; 2) unrestricted search that incorporates DIR uncertainty by conservatively assigning the maximum dose within a search radius (3mm) to the voxel of interest for dose accumulation; 3) restricted search, which performs the same dose accumulation as in 2) but imposes structure label matching in the search radius, therefore including only voxels within the same structure. Accumulated dose distribution was written back to the planning system for evaluation. We extracted mean lung dose (MLD) and esophagus D5cc (EsoD5cc) with respect to various accumulation approaches for comparison. <h3>Results</h3> MLD and EsoD5cc were significantly higher when accounting for DIR uncertainties (<i>p</i><0.001 two-tailed t-test). MLD has less uncertainty than EsoD5cc due to its averaging nature. For radiotherapy with >2 courses, RADAR considerably shortened the processing time by auto-accumulating dose from multiple courses simultaneously, as opposed to the cumbersome manual approach of creating plan sums iteratively. Typical time for dose accumulation and evaluation using RADAR is < 10 mins. <h3>Conclusion</h3> RADAR is a convenient and efficient tool to calculate and evaluate cumulative dose for lung reirradiation cases. It identifies higher OAR doses due to dose accumulation uncertainties, for example coming from the registration. Our study provides initial data to establish clinical guidance for design and optimization of repeated lung SBRT.

Dose and robustness comparison of nominal, daily and accumulated doses for photon and proton treatment of sinonasal cancer

IntroductionThe aim was to evaluate and compare the dosimetric effect and robustness towards day-to-day anatomical and setup variations in the delivered dose for photon and proton treatments of sinonasal cancer (SNC) patients. Materials and MethodsPhoton (VMAT) and proton (IMPT) plans were optimized retrospectively for 24 SNC patients. Synthetic CTs (synCT) were obtained by deforming the planning CT (pCT) to the anatomy of every daily cone-beam CT. Both VMAT and IMPT plans were recalculated on the synCTs. The recalculated daily dose was accumulated over the whole treatment on the pCT. Target coverage and dose to organs and risk (OARs) were evaluated for all patients for the nominal, daily and accumulated dose distribution. ResultsIn general, dose to OARs farther away from the target, including brain, chiasm and contralateral optic nerve, was lower for proton plans than photon plans. Whereas, OARs in proximity of the target received a lower dose for photon plans.For proton plans, the target coverage (volume of CTV receiving 95% of prescribed dose), V95%, fell below 99% for 9/24 patients in one or more fractions. For photon plans, 4/24 patients had one or more fractions where V95% fell below 99%. For accumulated doses, V95% was below 99% only in two cases, but above 98% for all patients. ConclusionPhoton and proton treatment have different strengths regarding OAR sparing. The robustness was high for both treatment modalities. Patient selection for either proton or photon radiation therapy of SNC patients should be based on a case-by-case comparison.

An adaptive planning strategy in carbon ion therapy of pancreatic cancer involving beam angle selection.

In carbon-ion radiotherapy for pancreatic cancer, altered dose distributions due to changes in the gastrointestinal gas volume and anatomy during irradiation are an unresolved therapeutic issue. We developed and investigated an adaptive strategy involving beam angle selection to improve dose distributions in pancreatic cancer. In the adaptive strategy, multiple beams were prepared with angles similar to those of the conventional strategy, and the beam that best reproduces the dose distribution of the treatment plan was used. The dose distributions of the adaptive strategy were compared with those of the conventional strategy for five patients. Patients underwent computed tomography (CT) before every irradiation. The adaptive strategy was evaluated using the same irradiation schedule as that of the conventional method and an adjusted method based on anatomical changes per fraction. Dose distributions on the pre-treatment CT and accumulated dose distributions on the treatment planning CT were evaluated using the volume receiving ≥95% of the prescription dose (V95) from the clinical target volume (CTV) between strategies. There were significant differences in the CTV V95 values for the pre-treatment CT between all strategies. The median (range) CTV V95 for the conventional strategy was 92.7% (87.1-96.1%), for the proposed adaptive strategy without adjusted schedules was 96.9% (95.1-97.8%), and for the proposed strategy with adjusted schedules was 97.8% (96.5-99.2%). The adaptive strategy can improve target coverage for the pre-treatment CT and accumulated dose distributions for the treatment planning CT without increasing the dose to critical organs.

A comprehensive Monte Carlo study of CT dose metrics proposed by the AAPM Reports 111 and 200.

A Monte Carlo (MC) modeling of single axial and helical CT scan modes has been developed to compute single and accumulated dose distributions. The radiation emission characteristics of an MDCT scanner has been modeled and used to evaluate the dose deposition in infinitely long head and body PMMA phantoms. The simulated accumulated dose distributions determined the approach to equilibrium function, H(L). From these curves, dose-related information was calculated for different head and body clinical protocols. The PENELOPE/penEasy package has been used to model the single axial and helical procedures and the radiation transport of photons and electrons in the phantoms. The bowtie filters, heel effect, focal-spot angle, and fan-beam geometry were incorporated. Head and body protocols with different pitch values were modeled for x-ray spectra corresponding to 80, 100, 120, and 140kV. The analytical formulation for the single dose distributions and experimental measurements of single and accumulated dose distributions were employed to validate the MC results. The experimental dose distributions were measured with OSLDs and a thimble ion chamber inserted into PMMA phantoms. Also, the experimental values of the along the center and peripheral axes of the CTDI phantom served to calibrate the simulated single and accumulated dose distributions. The match of the simulated dose distributions with the reference data supports the correct modeling of the heel effect and the radiation transport in the phantom material reflected in the tails of the dose distributions. The validation of the x-ray source model was done comparing the CTDI ratios between simulated, measured and CTDosimetry data. The average difference of these ratios for head and body protocols between the simulated and measured data was in the range of 13-17% and between simulated and CTDosimetry data varied 10-13%. The distributions of simulated doses and those measured with the thimble ion chamber are compatible within 3%. In this study, it was demonstrated that the efficiencies of the measurements in head phantoms with nT=20mm and 120kV are 80.6% and 87.8% at central and peripheral axes, respectively. In the body phantoms with =40mm and 120kV, the efficiencies are 56.5% and 86.2% at central and peripheral axes, respectively. In general terms, the clinical parameters such as pitch, beam intensity, and voltage affect the Deq values with the increase of the pitch decreasing the Deq and the beam intensity and the voltage increasing its value. The H(L) function does not change with the pitch values, but depends on the phantom axis (central or peripheral). The computation of the pitch-equilibrium dose product, , evidenced the limitations of the method to determine the dose delivered by a CT scanner. Therefore, quantities derived from the propagate this limitation. The developed MC model shows excellent compatibility with both measurements and literature quantities defined by AAPM Reports 111 and 200. These results demonstrate the robustness and versatility of the proposed modeling method.

Intra-fractional per-beam adaptive workflow to mitigate the need for a rotating gantry during MRI-guided proton therapy

The integration of real-time magnetic resonance imaging (MRI) guidance and proton therapy would potentially improve the proton dose steering capability by reducing daily uncertainties due to anatomical variations. The use of a fixed beamline coupled with an axial patient couch rotation would greatly simplify the proton delivery with MRI guidance. Nonetheless, it is mandatory to assure that the plan quality is not deteriorated by the anatomical deformations due to patient rotation. In this work, an in-house tool allowing for intra-fractional per-beam adaptation of intensity-modulated proton plans (BeamAdapt) was implemented through features available in RayStation. A set of three MRIs was acquired for two healthy volunteers (V 1, V 2): (1) no rotation/static, (2) rotation to the right and (3) left. V 1 was rotated by 15°, to simulate a clinical pediatric abdominal case and V 2 by 45°, to simulate an extreme patient rotation case. For each volunteer, a total of four intensity-modulated pencil beam scanning plans were optimized on the static MRI using virtual abdominal targets and two-three posterior-oblique beams. Beam angles were defined according to the angulations on the rotated MRIs. With BeamAdapt, each original plan was initially converted into separate plans with one beam per plan. In an iterative order, individual beam doses were non-rigidly deformed to the rotated anatomies and re-optimized accounting for the consequent deformations and the beam doses delivered so far. For evaluation, the final accumulated dose distribution was propagated back to the static MRI. Planned and adapted dose distributions were compared by computing relative differences between dose-volume histogram metrics. Absolute target dose differences were on average below 1% and organs-at-risk mean dose differences were below 3%. With BeamAdapt, not only intra-fractional per-beam proton plan adaptation coupled with axial patient rotation is possible but also the need for a rotating gantry during MRI guidance might be mitigated.

Dosimetric Uncertainties Resulting From Interfractional Anatomic Variations for Patients Receiving Pancreas Stereotactic Body Radiation Therapy and Cone Beam Computed Tomography Image Guidance

PurposeTo estimate the effects of interfractional anatomic changes on dose to organs at risk (OARs) and tumors, as measured with cone beam computed tomography (CBCT) image guidance for pancreatic stereotactic body radiation therapy. Methods and MaterialsWe evaluated 11 patients with pancreatic cancer whom were treated with stereotactic body radiation therapy (33-40 Gy in 5 fractions) using daily CT-on-rails (CTOR) image guidance immediately before treatment with breath-hold motion management. CBCT alignment was simulated in the treatment planning software by aligning the original planning CT to each fractional CTOR image set via fiducial markers. CTOR data sets were used to calculate fractional doses after alignment by applying the rigid shift of the planning CT and CTOR image sets to the planning treatment isocenter and recalculating the fractional dose. Accumulated dose to the gross tumor volume (GTV), tumor vessel interface, duodenum, small bowel, and stomach were calculated by summing the 5 fractional absolute dose-volume histograms into a single dose-volume histogram for comparison with the original planned dose. ResultsFour patients had a GTV D100% of at least 1.5 Gy less than the fractional planned value in several fractions; 4 patients had fractional underestimation of duodenum dose by 1.0 Gy per fraction. The D1.0 cm3 <35 Gy constraint was violated for at least 1 OAR in 3 patients, with either the duodenum (n = 2) or small bowel (n = 1) D1.0 cm3 being higher on the accumulated dose distribution (P = .01). D100% was significantly lower according to accumulated dose GTV (P = .01) and tumor vessel interface (P = .02), with 4 and 2 patients having accumulated D100% ≥4 Gy lower than the planned value for the GTV and tumor vessel interface, respectively. ConclusionsFor some patients, CBCT image guidance based on fiducial alignment may cause large dosimetric uncertainties for OARs and target structures, according to accumulated dose.

How does CBCT reconstruction algorithm impact on deformably mapped targets and accumulated dose distributions?

PurposeWe performed quantitative analysis of differences in deformable image registration (DIR) and deformable dose accumulation (DDA) computed on CBCT datasets reconstructed using the standard (Feldkamp‐Davis‐Kress: FDK_CBCT) and a novel iterative (iterative_CBCT) CBCT reconstruction algorithms.MethodsBoth FDK_CBCT and iterative_CBCT images were reconstructed for 323 fractions of treatment for 10 prostate cancer patients. Planning CT images were deformably registered to each CBCT image data set. After daily dose distributions were computed, they were mapped to planning CT to obtain deformed doses. Dosimetric and image registration results based CBCT images reconstructed by two algorithms were compared at three levels: (A) voxel doses over entire dose calculation volume, (B) clinical constraint results on targets and sensitive structures, and (C) contours propagated to CBCT images using DIR results based on three algorithms (SmartAdapt, Velocity, and Elastix) were compared with manually delineated contours as ground truth.Results(A) Average daily dose differences and average normalized DDA differences between FDK_CBCT and iterative_CBCT were ≤1 cGy. Maximum daily point dose differences increased from 0.22 ± 0.06 Gy (before the deformable dose mapping operation) to 1.33 ± 0.38 Gy after the deformable dose mapping. Maximum differences of normalized DDA per fraction were up to 0.80 Gy (0.42 ± 0.19 Gy). (B) Differences in target minimum doses were up to 8.31 Gy (−0.62 ± 4.60 Gy) and differences in critical structure doses were 0.70 ± 1.49 Gy. (C) For mapped prostate contours based on iterative_CBCT (relative to standard FDK_CBCT), dice similarity coefficient increased by 0.10 ± 0.09 (p < 0.0001), mass center distances decreased by 2.5 ± 3.0 mm (p < 0.00005), and Hausdorff distances decreased by 3.3 ± 4.4 mm (p < 0.00015).ConclusionsThe new iterative CBCT reconstruction algorithm leads to different mapped volumes of interest, deformed and cumulative doses than results based on conventional FDK_CBCT.