"Dose of the day" based on cone beam computed tomography and deformable image registration for lung cancer radiotherapy.

PURPOSE:Adaptive radiotherapy (ART) has potential to reduce toxicity and facilitate safe dose escalation. Dose calculations with the planning CT deformed to cone beam CT (CBCT) have shown promise for estimating the "dose of the day". The purpose of this study is to investigate the "dose of the day" calculation accuracy based on CBCT and deformable image registration (DIR) for lung cancer radiotherapy. METHODS:A total of 12 lung cancer patients were identified, for which daily CBCT imaging was performed for treatment positioning. A re-planning CT (rCT) was acquired after 20 Gy for all patients. A virtual CT (vCT) was created by deforming initial planning CT (pCT) to the simulated CBCT that was generated from deforming CBCT to rCT acquired on the same day. Treatment beams from the initial plan were copied to the vCT and rCT for dose calculation. Dosimetric agreement between vCT-based and rCT-based accumulated doses was evaluated using the Bland-Altman analysis. RESULTS:Mean differences in dose-volume metrics between vCT and rCT were smaller than 1.5%, and most discrepancies fell within the range of ± 5% for the target volume, lung, esophagus, and heart. For spinal cord Dmax , a large mean difference of -5.55% was observed, which was largely attributed to very limited CBCT image quality (e.g., truncation artifacts). CONCLUSION:This study demonstrated a reasonable agreement in dose-volume metrics between dose accumulation based on vCT and rCT, with the exception for cases with poor CBCT image quality. These findings suggest potential utility of vCT for providing a reasonable estimate of the "dose of the day", and thus facilitating the process of ART for lung cancer

Optimization of Decision Making in Personalized Radiation Therapy using Deformable Image Registration

Cancer has become one of the dominant diseases worldwide, especially in western countries, and radiation therapy is one of the primary treatment options for 50% of all patients diagnosed. Radiation therapy involves the radiation delivery and planning based on radiobiological models derived primarily from clinical trials. Since 2015 improvements in information technologies and data storage allowed new models to be created using the large volumes of treatment data already available and correlate the actually delivered treatment with outcomes. The goals of this thesis are to 1) construct models of patient outcomes after receiving radiation therapy using available treatment and patient parameters and 2) provide a method to determine real accumulated radiation dose including the impact of registration uncertainties. In Chapter 2, a model was developed predicting overall survival for patients with hepatocellular carcinoma or liver metastasis receiving radiation therapy. These models show which patients benefit from curative radiation therapy based on liver function, and the survival benefit of increased radiation dose on survival. In Chapter 3, a method was developed to routinely evaluate deformable image registration (DIR) with computer-generated landmark pairs using the scale-invariant feature transform. The method presented in this chapter created landmark sets for comparing lung 4DCT images and provided the same evaluation of DIR as manual landmark sets. In Chapter 4, an investigation was performed on the impact of DIR error on dose accumulation using landmarked 4DCT images as the ground truth. The study demonstrated the relationship between dose gradient, DIR error and dose accumulation error, and presented a method to determine error bars on the dose accumulation process. In Chapter 5, a method was presented to determine quantitatively when to update a treatment plan during the course of a multi-fraction radiation treatment of head and neck cancer. This method investigated the ability to use only the planned dose with deformable image registration to predict dose changes caused by anatomical deformations. This thesis presents the fundamental elements of a decision support system including patient pre-treatment parameters and the actual delivered dose using DIR while considering registration uncertainties

Toward adaptive radiotherapy for head and neck patients: Uncertainties in dose warping due to the choice of deformable registration algorithm.

The aims of this work were to evaluate the performance of several deformable image registration (DIR) algorithms implemented in our in-house software (NiftyReg) and the uncertainties inherent to using different algorithms for dose warping

On voxel-by-voxel accumulated dose for prostate radiation therapy using deformable image registration.

Since delivered dose is rarely the same with planned, we calculated the delivered total dose to ten prostate radiotherapy patients treated with rectal balloons using deformable dose accumulation (DDA) and compared it with the planned dose. The patients were treated with TomoTherapy using two rectal balloon designs: five patients had the Radiadyne balloon (balloon A), and five patients had the EZ-EM balloon (balloon B). Prostate and rectal wall contours were outlined on each pre-treatment MVCT for all patients. Delivered fractional doses were calculated using the MVCT taken immediately prior to delivery. Dose grids were accumulated to the last MVCT using DDA tools in Pinnacle3 TM (v9.100, Philips Radiation Oncology Systems, Fitchburg, USA). Delivered total doses were compared with planned doses using prostate and rectal wall DVHs. The rectal NTCP was calculated based on total delivered and planned doses for all patients using the Lyman model. For 8/10 patients, the rectal wall NTCP calculated using the delivered total dose was less than planned, with seven patients showing a decrease of more than 5% in NTCP. For 2/10 patients studied, the rectal wall NTCP calculated using total delivered dose was 2% higher than planned. This study indicates that for patients receiving hypofractionated radiotherapy for prostate cancer with a rectal balloon, total delivered doses to prostate is similar with planned while delivered dose to rectal walls may be significantly different from planned doses. 8/10 patients show significant correlation between rectal balloon anterior-posterior positions and some VD values

Improving Dose-Response Correlations for Locally Advanced NSCLC Patients Treated with IMRT or PSPT

The standard of care for locally advanced non-small cell lung cancer (NSCLC) is concurrent chemo-radiotherapy. Despite recent advancements in radiation delivery methods, the median survival time of NSCLC patients remains below 28 months. Higher tumor dose has been found to increase survival but also a higher rate of radiation pneumonitis (RP) that affects breathing capability. In fear of such toxicity, less-aggressive treatment plans are often clinically preferred, leading to metastasis and recurrence. Therefore, accurate RP prediction is crucial to ensure tumor coverage to improve treatment outcome. Current models have associated RP with increased dose but with limited accuracy as they lack spatial correlation between accurate dose representation and quantitative RP representation. These models represent lung tissue damage with radiation dose distribution planned pre-treatment, which assumes a fixed patient geometry and inevitably renders imprecise dose delivery due to intra-fractional breathing motion and inter-fractional anatomy response. Additionally, current models employ whole-lung dose metrics as the contributing factor to RP as a qualitative, binary outcome but these global dose metrics discard microscopic, voxel-(3D pixel)-level information and prevent spatial correlations with quantitative RP representation. To tackle these limitations, we developed advanced deformable image registration (DIR) techniques that registered corresponding anatomical voxels between images for tracking and accumulating dose throughout treatment. DIR also enabled voxel-level dose-response correlation when CT image density change (IDC) was used to quantify RP. We hypothesized that more accurate estimates of biologically effective dose distributions actually delivered, achieved through (a) dose accumulation using deformable registration of weekly 4DCT images acquired over the course or radiotherapy and (b) the incorporation of variable relative biological effectiveness (RBE), would lead to statistically and clinically significant improvement in the correlation of RP with biologically effective dose distributions. Our work resulted in a robust intra-4DCT and inter-4DCT DIR workflow, with the accuracy meeting AAPM TG-132 recommendations for clinical implementation of DIR. The automated DIR workflow allowed us to develop a fully automated 4DCT-based dose accumulation pipeline in RayStation (RaySearch Laboratories, Stockholm, Sweden). With a sample of 67 IMRT patients, our results showed that the accumulated dose was statistically different than the planned dose across the entire cohort with an average MLD increase of ~1 Gy and clinically different for individual patients where 16% resulted in difference in the score of the normal tissue complication probability (NTCP) using an established, clinically used model, which could qualify the patients for treatment planning re-evaluation. Lastly, we associated dose difference with accuracy difference by establishing and comparing voxel-level dose-IDC correlations and concluded that the accumulated dose better described the localized damage, thereby a closer representation of the delivered dose. Using the same dose-response correlation strategy, we plotted the dose-IDC relationships for both photon patients (N = 51) and proton patients (N = 67), we measured the variable proton RBE values to be 3.07–1.27 from 9–52 Gy proton voxels. With the measured RBE values, we fitted an established variable proton RBE model with pseudo-R2 of 0.98. Therefore, our results led to statistically and clinically significant improvement in the correlation of RP with accumulated and biologically effective dose distributions and demonstrated the potential of incorporating the effect of anatomical change and biological damage in RP prediction models

Dosimetric comparison of autocontouring techniques for online adaptive proton therapy.

anatomical and daily set-up uncertainties impede high precision delivery of proton therapy. With online adaptation, the daily plan is reoptimized on an image taken shortly before the treatment, reducing these uncertainties and, hence, allowing a more accurate delivery. This reoptimization requires target and organs-at-risk (OAR) contours on the daily image, which need to be delineated automatically since manual contouring is too slow. Whereas multiple methods for autocontouring exist, none of them are fully accurate, which affects the daily dose. This work aims to quantify the magnitude of this dosimetric effect for four contouring techniques.

Approach: plans reoptimized on automatic contours are compared with plans reoptimized on manual contours. The methods include rigid and deformable registration (DIR), deep-learning based segmentation and patient-specific segmentation.

Results: it was found that independently of the contouring method, the dosimetric influence of using automatic OAR contours is small ( 5% prescribed dose in most cases), indicating that manual verification of that contour remains necessary. However, when compared to non-adaptive therapy, the dose differences caused by automatically contouring the target were small and target coverage was improved, especially for DIR.

Significance: the results show that manual adjustment of OARs is rarely necessary and that several autocontouring techniques are directly usable. Contrarily, manual adjustment of the target is important. This allows prioritizing tasks during time-critical online adaptive proton therapy and therefore supports its further clinical implementation

Online dosimetric evaluation of larynx SBRT: A pilot study to assess the necessity of adaptive replanning

PURPOSE: We have initiated a multi-institutional phase I trial of 5-fraction stereotactic body radiotherapy (SBRT) for Stage III-IVa laryngeal cancer. We conducted this pilot dosimetric study to confirm potential utility of online adaptive replanning to preserve treatment quality. METHODS: We evaluated ten cases: five patients enrolled onto the current trial and five patients enrolled onto a separate phase I SBRT trial for early-stage glottic larynx cancer. Baseline SBRT treatment plans were generated per protocol. Daily cone-beam CT (CBCT) or diagnostic CT images were acquired prior to each treatment fraction. Simulation CT images and target volumes were deformably registered to daily volumetric images, the original SBRT plan was copied to the deformed images and contours, delivered dose distributions were re-calculated on the deformed CT images. All of these were performed on a commercial treatment planning system. In-house software was developed to propagate the delivered dose distribution back to reference CT images using the deformation information exported from the treatment planning system. Dosimetric differences were evaluated via dose-volume histograms. RESULTS: We could evaluate dose within 10 minutes in all cases. Prescribed coverage to gross tumor volume (GTV) and clinical target volume (CTV) was uniformly preserved; however, intended prescription dose coverage of planning treatment volume (PTV) was lost in 53% of daily treatments (mean: 93.9%, range: 83.9-97.9%). Maximum bystander point dose limits to arytenoids, parotids, and spinal cord remained respected in all cases, although variances in carotid artery doses were observed in a minority of cases. CONCLUSIONS: Although GTV and CTV SBRT dose coverage is preserved with in-room three-dimensional image guidance, PTV coverage can vary significantly from intended plans and dose to critical structures may exceed tolerances. Online adaptive treatment re-planning is potentially necessary and clinically applicable to fully preserve treatment quality. Confirmatory trial accrual and analysis remains ongoing

Dosimetric influence of deformable image registration uncertainties on propagated structures for online daily adaptive proton therapy of lung cancer patients

Purpose: A major burden of introducing an online daily adaptive proton therapy (DAPT) workflow is the time and resources needed to correct the daily propagated contours. In this study, we evaluated the dosimetric impact of neglecting the online correction of the propagated contours in a DAPT workflow.Material and methods: For five NSCLC patients with nine repeated deep-inspiration breath-hold CTs, proton therapy plans were optimised on the planning CT to deliver 60 Gy-RBE in 30 fractions. All repeated CTs were registered with six different clinically used deformable image registration (DIR) algorithms to the corresponding planning CT. Structures were propagated rigidly and with each DIR algorithm and reference structures were contoured on each repeated CT. DAPT plans were optimised with the uncorrected, propagated structures (propagated DAPT doses) and on the reference structures (ideal DAPT doses), nonadapted doses were recalculated on all repeated CTs.Results: Due to anatomical changes occurring during the therapy, the clinical target volume (CTV) coverage of the non-adapted doses reduces on average by 9.7% (V95) compared to an ideal DAPT doses. For the propagated DAPT doses, the CTV coverage was always restored (average differences in the CTV V95 &lt; 1% compared to the ideal DAPT doses). Hotspots were always reduced with any DAPT approach.Conclusion: For the patients presented here, a benefit of online DAPT was shown, even if the daily optimisation is based on propagated structures with some residual uncertainties. However, a careful (offline) structure review is necessary and corrections can be included in an offline adaption.(c) 2021 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 159 (2021) 136-143 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).</p