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Purpose: Due to the electron return effect (ERE) during magnetic resonance imaging guided radiotherapy (MRIgRT), rectal gas during pelvic treatments can result in hot spots of over‐dosage in the rectal wall. Determining the clinical impact of this effect on rectal toxicity requires estimation of the amount and mobility (and stability) of rectal gas during treatment. We therefore investigated the amount of rectal gas and local inter‐ and intra‐fractional changes of rectal gas in pelvic cancer patients. Methods: To estimate the volume of gas present at treatment planning, the rectal gas contents in the planning computed tomography (CT) scans of 124 bladder, 70 cervical and 2180 prostate cancer patients were calculated. To estimate inter‐ and intra‐fractional variations in rectal gas, 174 and 131 T2‐w MRIs for six cervical and eleven bladder cancer patients were used. These scans were acquired during four scan‐sessions (~20–25 min each) at various time‐points. Additionally, 258 T2‐w MRIs of the first five prostate cancer patients treated using MRIgRT at our center, acquired during each fraction, were analyzed. Rectums were delineated on all scans. The area of gas within the rectum delineations was identified on each MRI slice using thresholding techniques. The area of gas on each slice of the rectum was used to calculate the inter‐ and intra‐fractional group mean, systematic and random variations along the length of the rectum. The cumulative dose perturbation as a result of the gas was estimated. Two approaches were explored: accounting or not accounting for the gas at the start of the scan‐session. Results: Intra‐fractional variations in rectal gas are small compared to the absolute volume of rectal gas detected for all patient groups. That is, rectal gas is likely to remain stable for periods of 20–25 min. Larger volumes of gas and larger variations in gas volume were observed in bladder cancer patients compared with cervical and prostate cancer patients. For all patients, local cumulative dose perturbations per beam over an entire treatment in the order of 60 % were estimated when gas had not been accounted for in the daily adaption. The calculated dose perturbation over the whole treatment was dramatically reduced in all patients when accounting for the gas in the daily set‐up image. Conclusion: Rectal gas in pelvic cancer patients is likely to remain stable over the course of an MRIgRT fraction, and also likely to reappear in the same location in multiple fractions, and can therefore result in clinically relevant over‐dosage in the rectal wall. The over‐dosage is reduced when accounting for gas in the daily adaption. [ABSTRACT FROM AUTHOR]

Purpose: Contouring variation is one of the largest systematic uncertainties in radiotherapy, yet its effect on clinical outcome has never been analyzed quantitatively. We propose a novel, robust methodology to locally quantify target contour variation in a large patient cohort and find where this variation correlates with treatment outcome. We demonstrate its use on biochemical recurrence for prostate cancer patients., Method: We propose to compare each patient's target contours to a consistent and unbiased reference. This reference was created by auto-contouring each patient's target using an externally trained deep learning algorithm. Local contour deviation measured from the reference to the manual contour was projected to a common frame of reference, creating contour deviation maps for each patient. By stacking the contour deviation maps, time to event was modeled pixel-wise using a multivariate Cox proportional hazards model (CPHM). Hazard ratio (HR) maps for each covariate were created, and regions of significance found using cluster-based permutation testing on the z-statistics. This methodology was applied to clinical target volume (CTV) contours, containing only the prostate gland, from 232 intermediate- and high-risk prostate cancer patients. The reference contours were created using ADMIRE® v3.4 (Elekta AB, Sweden). Local contour deviations were computed in a spherical coordinate frame, where differences between reference and clinical contours were projected in a 2D map corresponding to sampling across the coronal and transverse angles every 3°. Time to biochemical recurrence was modeled using the pixel-wise CPHM analysis accounting for contour deviation, patient age, Gleason score, and treated CTV volume., Results: We successfully applied the proposed methodology to a large patient cohort containing data from 232 patients. In this patient cohort, our analysis highlighted regions where the contour variation was related to biochemical recurrence, producing expected and unexpected results: (a) the interface between prostate-bladder and prostate-seminal vesicle interfaces where increase in the manual contour relative to the reference was related to a reduction of risk of biochemical recurrence by 4-8% per mm and (b) the prostate's right, anterior and posterior regions where an increase in the manual contour relative to the reference contours was related to an increase in risk of biochemical recurrence by 8-24% per mm., Conclusion: We proposed and successfully applied a novel methodology to explore the correlation between contour variation and treatment outcome. We analyzed the effect of contour deviation of the prostate CTV on biochemical recurrence for a cohort of more than 200 prostate cancer patients while taking basic clinical variables into account. Applying this methodology to a larger dataset including additional clinically important covariates and externally validating it can more robustly identify regions where contour variation directly relates to treatment outcome. For example, in the prostate case we use to demonstrate our novel methodology, external validation will help confirm or reject the counter-intuitive results (larger contours resulting in higher risk). Ultimately, the results of this methodology could inform contouring protocols based on actual patient outcomes., (© 2021 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Due to differences in attenuation and the electron return effect (ERE), the presence of gas can increase the risk of toxicity in organs at risk (OAR) during magnetic resonance-guided radiotherapy (MRgRT). Current adaptive MRgRT workflows using density overrides negate gas from the dose calculation, meaning that the effects of ERE around gas are not taken into account. In order to achieve an accurate adaptive MRgRT treatment, we should be able to quickly evaluate whether gas present during treatment causes dose constraint violation during an MRgRT fraction. We propose an analytic method for predicting dose perturbations caused by air cavities in OARs during MRgRT., Method: Ten virtual water phantoms were created: nine containing a centrally located spherical air cavity and a reference phantom without an air cavity. Monte Carlo dose calculations were produced to irradiate the phantoms with a single 7 MV photon beam under the influence of a 1.5 T transverse magnetic field (Monaco 5.19.02 Treatment Panning System (TPS) (Elekta AB, Stockholm, Sweden)). Dose distributions of the phantoms with and without air cavities were compared. We used a spherical coordinate system originating in the center of the cavity to sample the dose distributions and calculate the dose perturbation as a result of the presence of each air cavity, ∆D%(θ,Φ) calc . . Dose effects due to ERE and differences in attenuation due to density changes were considered separately. Least squared analysis was used to fit the calculated dose perturbations to mathematical functions. Effects due to ERE were fit to a modulated sinusoidal function and those due to attenuation differences were fit to a 2D Gaussian function. We used the fits to derive a single equation describing dose perturbations around spherical air cavities as a function of angles, θ, Φ, distance from cavity surface, d, and cavity radius, r. We measured the fitting error by calculating the residual error (RE); the difference between the calculated and fitted dose perturbation., Results: Both ERE and differences in attenuation contribute toward the total dose effects of air cavities in MRgRT. Whereas ERE dominates close to the surface of the cavities, attenuation effects dominate at distances >0.5 cm from the cavities. We showed that dose effects around a spherical air cavity (≤1 cm from the surface) due to ERE fit a modulated sinusoidal function with mean (RE) ≤-1.4E-5% and root mean square error (rms) (RE) ≤4.1%. Effects due to attenuation differences fit a Gaussian function with mean (RE) ≤0.7% and rms (RE) ≤1.8%. Our general equation, which we verified using multiple sizes of spherical and cylindrical air cavity, fits Monte Carlo simulated data with mean (RE) ≤±0.9% and rms (RE) ≤6.9%., Conclusion: We show that local dose perturbations around unplanned spherical air cavities during MRgRT can be well characterized analytically. We present an equation that can be incorporated into the clinical workflow to allow for fast evaluation of dose effects of unplanned gas. We also envision this method contributing to the clinical implementation of real time adaptive radiotherapy (ART) for MRgRT using MRI planning., (© 2020 American Association of Physicists in Medicine.)

Purpose: It has been proposed that beam modulation and opposing beam configurations can cancel effects of the Electron Return Effect (ERE) during MR-guided radiotherapy (MRgRT). However, this may not always be the case for unplanned gas cavities outside of the target in the pelvic region. We evaluate dosimetric effects, including effects in the rectal wall, due to unplanned spherical air cavities during MRgRT., Methods: Nine virtual cuboid water phantoms containing spherical air cavities (0.5-7.5 cm diameter) and a reference phantom without air were created. Monte Carlo dose calculations of 7 MV photons under the influence of a 1.5 T transverse magnetic field were produced using Monaco 5.19.02 Treatment Planning System (TPS) (Elekta AB, Stockholm, Sweden). Cavities in the path of a single and multiple beam plans were considered. Dose distributions of phantoms with and without air cavities were compared (ΔD % ) using a spherical coordinate system originating in the center of the cavity. Effects in the rectal wall were quantified by comparing dose volume histogram (DVH) parameters for solid and gaseous filling from simulated rectal wall structures., Results: Max(ΔD % ) of ~70% and 20% were observed around large cavities in the path of a single and multiple beam plans, respectively. Approximately 45 cm 3 of phantom surrounding the largest cavity in a single beam received dose changes of >10%. D mean in the rectal wall was unchanged when comparing gaseous and solid filling in the path of a single beam; however, D 1cc and D max increased by up to ~45% and ~63%, respectively., Conclusions: Unplanned gas cavities in the path of a single beam during pelvic MRgRT with a 1.5 T transverse magnetic field cause dose changes which may impact toxicity in the rectal wall, depending on local dose and fractionation. Effects are reduced but not eliminated with a five-beam plan., (© 2019 American Association of Physicists in Medicine.)