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Aims: Determining appropriate PTV margins for SBRT of liver metastases is a non-trivial task, especially with motion management included. The widely used analytical van Herk margin recipe (van Herk et al., 2000) could break down due to (i) a low number of fractions, (ii) non-Gaussian errors, or (iii) non-homogenous dose distributions. We evaluated the validity of the analytical margin recipe in this setting for two very different guidelines for SBRT of liver metastases in three fractions - one with a relatively homogenous dose within the PTV (British) and one allowing much steeper dose gradients within the PTV (Danish)., Materials and Methods: We extracted sagittal motion traces for nineteen consecutive MR-guided and beam-gated treatments (57 fractions) on an MR-linac. We used these motion traces to calculate analytical van Herk GTV-to-PTV margins to account for intrafractional motion according to both British and Danish guidelines. We used the same motion traces to validate the analytical margins with motion-compensated dose accumulation in dose distributions obtained from British and Danish plans with varying PTV margins., Results: Analytical margins for the British guidelines were 2.4 mm superior-inferiorly (SI) and 3.2 mm anterior-posteriorly (AP). For the Danish guidelines, analytical margins were 1.7 mm SI and 2.7 mm AP. Dose accumulation validation showed that a margin of 3 mm SI and 1.5 mm AP would have been sufficient for British plans to ensure 95% of the prescription dose to at least 99% of the GTV in 90% of the treatments (same criterion as used in the analytical calculation) of the patients. No PTV margin was needed to achieve the same with Danish guidelines., Conclusion: GTV dose escalation can reduce the required motion-related PTV margins in SBRT with motion management. The van Herk margin recipe overestimates PTV margins in SBRT with inhomogeneous target dose distributions and becomes less applicable when the inhomogeneity increases., Competing Interests: Conflict of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Isak Wahlstedt, Claus P. Behrens, and Ivan R. Vogelius report financial support provided by ViewRay Inc. and by Danish Comprehensive Cancer Center. Mette van Overeem Felter reports financial support provided by Varian Medical Systems Inc. Isak Wahlstedt, Claus P. Behrens, and Ivan R. Vogelius report institutional research and teaching contracts with Varian Medical Systems, Brainlab, and ViewRay. Tomas Janssen reports institutional research funding from Elekta AB. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective . The apparent diffusion coefficient (ADC) extracted from diffusion-weighted magnetic resonance imaging (DWI) is a potential biomarker in radiotherapy (RT). DWI is often implemented with an echo-planar imaging (EPI) read-out due to speed, but unfortunately low geometric accuracy follows. This study aimed to investigate the influence of geometric distortions on the ADCs extracted from the gross tumor volume (GTV) and on the shape of the GTV in abdominal EPI-DWI. Approach . Twenty-one patients had EPI-DWI scans on a 1.5 T MRI sim before treatment and on a 1.5 T MRI-Linac at one of the first treatment fractions. Off-resonance correction with and without eddy current correction were applied to ADC maps. The clinical GTVs were deformed based on the same (but inverted) corrections to assess the local-regional geometric influence of distortions. Mean surface distance (MSD), Hausdorff distance (HD), and Dice similarity coefficient (DSC) were calculated to compare the original and distorted GTVs, and ADC values were calculated based on a mono-exponential model. Phantom measurements were performed to validate the applied correction method. Main results . The median (range) ADC change within the GTV after full distortion correction was 1.3% (0.02%-6.9%) for MRI-Sim and 1.5% (0.1%-6.4%) for MRI-Linac. The additional effect of the eddy current correction was small in both systems. The median (range) MSD, HD, and DSC comparing the original and off-resonance distorted GTVs for all patients were 0.43 mm (0.11-0.94 mm), 4.00 mm (1.00-7.81 mm) and 0.93 (0.82-0.99), respectively. Significance . Overall effect of distortion correction was small in terms of derived ADC values, indicating that distortion correction is unimportant for prediction of outcomes based on ADC. However, large local geometric changes occurred after off-resonance distortion correction for some patients, suggesting that if the spatial information from ADC maps is to be used for dose painting strategies, corrections should be applied., (Creative Commons Attribution license.)

Background and Purpose: Daily target re-delineation in online adaptive radiotherapy (oART) introduces uncertainty. The aim of this study was to evaluate artificial intelligence (AI) generated contours and inter-observer target variation among radiotherapy technicians in cone-beam CT (CBCT) guided oART of bladder cancer., Materials and Methods: For each of 10 consecutive patients treated with oART for bladder cancer, one CBCT was randomly selected and retrospectively included. The bladder (CTV-T) was AI-segmented (CTV-T AI ). Seven radiotherapy technicians independently reviewed and edited CTV-T AI , generating CTV-T ADP . Contours were benchmarked against a ground truth contour (CTV-T GT ) delineated blindly from scratch. CTV-T ADP and CTV-T AI were compared to CTV-T GT using volume, dice similarity coefficient, and bidirectional local distance. Dose coverage (D 99% >95 %) of CTV-T GT was evaluated for treatment plans optimized for CTV-T AI and CTV-T ADP with clinical margins. Inter-observer variation among CTV-T ADP was assessed using coefficient of variation and generalized conformity index., Results: CTV-T GT ranged from 48.7 cm 3 to 211.6 cm 3 . The median [range] volume difference was 4.5 [-17.8, 42.4] cm 3 for CTV-T ADP and -15.5 [-54.2, 4.3] cm 3 for CTV-T AI , compared to CTV-T GT . Corresponding dice similarity coefficients were 0.87 [0.71, 0.95] and 0.84 [0.64, 0.95]. CTV-T GT was adequately covered in 68/70 plans optimized on CTV-T ADP and in 6/10 plans optimized on CTV-T AI with clinical margins. The median [range] coefficient of variation was 0.08 [0.05, 0.11] and generalized conformity index was 0.78 [0.71, 0.88] among CTV-T ADP ., Conclusions: Target re-delineation in CBCT-guided oART of bladder cancer demonstrated non-isotropic inter-observer variation. Manual adjustment of AI-generated contours was necessary to cover ground truth targets., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Purpose: The purpose of this study was to evaluate the clinical benefits of nivolumab with/without ipilimumab combined with stereotactic body radiotherapy (SBRT) in patients with pretreated metastatic biliary tract cancer (mBTC)., Patients and Methods: The study was a phase 2 randomized trial with Simon's optimal two-stage design requiring 36 evaluable patients per group after second stage. Sixty-one patients were included from September 2018 to January 2022 and randomized (1:1) to receive SBRT (15 Gy × 1 on day 1 to a primary or metastatic lesion) and nivolumab (3 mg/kg intravenously on day 1 and every 2 weeks) with/without ipilimumab (1 mg/kg intravenously on day 1 and every 6 weeks). Primary endpoint was clinical benefit rate (CBR), defined as the percentage of patients with complete response, partial response, or stable disease. Decision to continue accrual into the second stage depended on the CBR from the first stage., Results: Forty-two patients received SBRT/nivolumab/ipilimumab with a CBR of 31.0% [95% confidence interval (CI), 17.6-47.1]. Five patients (11.9%) achieved partial response with median duration of 4.4 months (range, 1.1-21.5). Nineteen patients received SBRT/nivolumab. This group was closed after the initial stage based on a CBR of 10.5% (95% CI, 1.3-33.1). Adverse events were graded with National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Grade ≥3 treatment-related adverse events occurred in 13 (31%) and 3 (16%) patients in the SBRT/nivolumab/ipilimumab and SBRT/nivolumab groups, respectively. One patient died from immune-related hepatitis in the SBRT/nivolumab/ipilimumab group., Conclusions: Combining SBRT, nivolumab, and ipilimumab is well tolerated, feasible, and shows response in a subgroup of patients with mBTC., (©2024 American Association for Cancer Research.)

Background: Chemo-radiotherapy with curative intent for anal cancer has high complete remission rates, but acute treatment-related gastrointestinal (GI) toxicity is significant. Toxicity occurs due to irradiation of surrounding normal tissue. Current radiotherapy requires the addition of large planning margins to the radiation field to ensure target coverage regardless of the considerable organ motion in the pelvic region. This increases the irradiated volume and radiation dose to the surrounding normal tissue and thereby toxicity. Online adaptive radiotherapy uses artificial intelligence to adjust the treatment to the anatomy of the day. This allows for the reduction of planning margins, minimizing the irradiated volume and thereby radiation to the surrounding normal tissue.This study examines if cone beam computed tomography (CBCT)-guided oART with daily automated treatment re-planning can reduce acute gastrointestinal toxicity in patients with anal cancer., Methods/design: The study is a prospective, single-arm, phase II trial conducted at Copenhagen University Hospital, Herlev and Gentofte, Denmark. 205 patients with local only or locally advanced anal cancer, referred for radiotherapy with or without chemotherapy with curative intent, are planned for inclusion. Toxicity and quality of life are reported with Common Terminology Criteria of Adverse Events and patient-reported outcome questionnaires, before, during, and after treatment. The primary endpoint is a reduction in the incidence of acute treatment-related grade ≥ 2 diarrhea from 36 to 25% after daily online adaptive radiotherapy compared to standard radiotherapy. Secondary endpoints include all acute and late toxicity, overall survival, and reduction in treatment interruptions., Results: Accrual began in January 2022 and is expected to finish in January 2026. Primary endpoint results are expected to be available in April 2026., Discussion: This is the first study utilizing online adaptive radiotherapy to treat anal cancer. We hope to determine whether there is a clinical benefit for the patients, with significant reductions in acute GI toxicity without compromising treatment efficacy., Trial Registration: ClinicalTrials.gov Identifier: NCT05438836. Danish Ethical Committee: H-21028093., (© 2024. The Author(s).)

Background and Purpose: The SOFT trial is a prospective, multicenter, phase 2 trial investigating magnetic resonance (MR)-guided stereotactic ablative radiotherapy (SABR) for abdominal, soft tissue metastases in patients with oligometastatic disease (OMD) (clinicaltrials.gov ID NCT04407897). We present the primary endpoint analysis of 1-year treatment-related toxicity (TRAE)., Materials and Methods: Patients with up to five oligometastases from non-hematological cancers were eligible for inclusion. A risk-adapted strategy prioritized fixed organs at risk (OAR) constraints over target coverage. Fractionation schemes were 45-67.5 Gy in 3-8 fractions. The primary endpoint was grade ≥ 4 TRAE within 12 months post-SABR. The association between the risk of gastrointestinal (GI) toxicity and clinical and dosimetric parameters was tested using a normal tissue complication probability model., Results: We included 121 patients with 147 oligometastatic targets, mainly located in the liver (41 %), lymph nodes (35 %), or adrenal glands (14 %). Nearly half of all targets (48 %, n = 71) were within 10 mm of a radiosensitive OAR. No grade 4 or 5 TRAEs, 3.5 % grade 3 TRAEs, and 43.7 % grade 2 TRAEs were reported within the first year of follow-up. We found a significant association between grade ≥ 2 GI toxicity and the parameters GI OAR D 0.1cc, D 1cc, and D 20cc ., Conclusion: In this phase II study of MR-guided SABR of oligometastases in the infra-diaphragmatic region, we found a low incidence of toxicity despite half of the lesions being within 10 mm of a radiosensitive OAR. GI OAR D 0.1cc, D 1cc, and D 20cc were associated with grade ≥ 2 GI toxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MF has received research grant from Varian Medical Systems and support from The Danish National Research Centre for Radiotherapy and the Danish Cancer Society. CPB reports institutional research contracts with Brainlab, Varian Medical Systems, Siemens, and ViewRay and teaching contracts with Varian Medical Systems. Research funding from Danish Comprehensive Cancer Center National Thematic Center on radiotherapy (DCCC-RT). UB reports institutional research contracts with Elekta. IVR reports institutional research contracts with Brainlab, Varian Medical Systems, and ViewRay and teaching contracts with Varian Medical Systems. GP has received research grants from Varian Medical Systems, The Danish National Research Centre for Radiotherapy, and the Danish Cancer Society, Herlev & Gentofte Hospitals Internal Research Council, Villadsens Family Foundation. Conference participance from MSD, Daiichi Sankyo, and Pfizer, Pierre Fabre and honoraria for consultancies and lectures from Astra Zeneca. PP has received research grant from Viewray; not relevant to this article; Stock ownership of Nuvaira (COPD device company). MJ have received research support from The Danish National Research Centre for Radiotherapy and the Danish Cancer Society. MP have received honoraria for lectures from Astra Zeneca, BMS, MSD, Pfizer, Roche, Amgen. TS have received honoraria for lectures and travel expenses from Elekta and declares travel assistance from ELEKTA and is member of the MR-L consortium. SB have received research support from The Danish National Research Centre for Radiotherapy. PG reports institutional research contracts with Viewray. PK, ESH, and KJ has nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The combination of magnetic resonance (MR) imaging and linear accelerators (linacs) into MR-Linacs enables continuous MR imaging and advanced gated treatments of patients. Previously, a dose-rate transient (∼8% reduced dose rate during the initial 0.5 s of each beam) was identified for a Viewray MRIdian MR-Linac (Klavsen et al 2022 Radiation Measurement 106759). Here, the dose-rate transient is studied in more detail at four linacs of the same type at different hospitals. The implications of dose-rate transients were examined for gated treatments. The dose-rate transients were investigated using dose-per pulse measurements with organic plastic scintillators in three experiments: (i) A gated treatment with the scintillator placed in a moving target in a dynamic phantom, (ii) a gated treatment with the same dynamic conditions but with the scintillator placed in a stationary target, and (iii) measurements in a water-equivalent material to examine beam quality deviations at a dose-per-pulse basis. Gated treatments (i) compared with non-gated treatments with a static target in the same setup showed a broadening of accumulated dose profiles due to motion (dose smearing). The linac with the largest dose-rate transient had a reduced accumulated dose of up to (3.1 ± 0.65) % in the center of the PTV due to the combined dose smearing and dose-rate transient effect. Dose-rate transients were found to vary between different machines. Two MR-Linacs showed initial dose-rate transients that could not be identified from conventional linearity tests. The source of the transients includes an initial change in photon fluence rate and an initial change in x-ray beam quality. For gated treatments, this caused a reduction of more than 1% dose delivered at the central part of the beam for the studied, cyclic-motion treatment plan. Quality assurance of this effect should be considered when gated treatment with the Viewray MRIdian is implemented clinically., (Creative Commons Attribution license.)

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 D 95% 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Online adaptive radiotherapy (oART) potentially spares OARs as PTV margins are reduced. This study evaluates dosimetric benefits, compared to standard non-adaptive radiotherapy (non-ART), target propagation methods, and first clinical treatments of CBCT-guided oART of anal cancer., Materials and Methods: Treatment plans with standard non-ART and reduced oART PTV margins were retrospectively generated for 23 consecutive patients with anal cancer. For five patients randomly selected among the 23 patients, weekly CBCT-guided oART sessions were simulated, where the targets were either deformed or rigidly propagated. Preferred target propagation method and dose to OARs were evaluated. Ten consecutive patients with anal cancer were treated with CBCT-guided oART. Target propagation methods and oART procedure time were evaluated., Results: For the retrospective treatment plans, oART resulted in median reductions in bowel bag V 45 Gy of 11.4 % and bladder V 35 Gy of 16.1%. Corresponding values for the simulated sessions were 7.5% and 27.1%. In the simulated sessions, 35% of all targets were deformed while 65% were rigidly propagated. Manual editing and rigid propagation were necessary to obtain acceptable target coverage. In the clinical treatments, the primary and some elective targets were rigidly propagated, while other targets were deformed. The median oART procedure time, measured from CBCT acquisition to completion of plan review and QA, was 23 min., Conclusions: Simulated oART reduced the dose to OARs, indicating potential reduction in toxicity. Rigid propagation of targets was necessary to reduce the need for manual edit. Clinical treatments demonstrated that oART of anal cancer is feasible but time-consuming., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Online adaptive radiotherapy (oART) potentially reduces the dose to organs at risk (OARs) as the planning target volume (PTV) margins are reduced compared to a non-adaptive approach (non-ART). This study evaluates the feasibility and dosimetric impact of cone-beam computed tomography (CBCT)-guided oART of urinary bladder cancer for the first patients treated, using patient-specific margins., Materials and Methods: Sixteen consecutive patients with muscle-invasive bladder cancer received two or more (median = 23) fractions as oART, and remaining fractions as non-ART. The non-ART fractions were delivered with standard population-based margins, while reduced patient-specific margins based on intra-fractional variations extracted from 2-4 fractions were applied to the primary PTV (PTV-T) during the oART fractions. Target volume and coverage, and dose to OARs were compared between non-ART and oART plans, and the oART procedure time was recorded., Results: In total, 297/512 fractions were delivered as oART with full re-optimization to the anatomy of the day. The median (interquartile range, IQR) oART procedure time, measured from the end of CBCT generation to completion of plan review, and quality assurance was 13.9 (11.9;16.6) min. The median (IQR) volume reduction in PTV-T volume was 33.9 (24.2;45.0)%, comparing oART and non-ART plans, resulting in median (IQR) reductions in bowel bag V 45 Gy of 18.8 (12.7;27.9)% and rectum V 50 Gy of 70.7 (35.9;94.8)%. By re-optimizing the plan to the daily anatomy, full target coverage was achieved at all oART fractions., Conclusions: oART resulted in large reductions in treatment volumes and doses to OARs, compared to non-ART, while ensuring target coverage. This indicates potential reductions in gastrointestinal toxicity., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

YKL-40 (also named chitinase 3 like-1 protein [CHI3L1]) is a secreted chitinase-like protein which is upregulated in cancers and suggested to have pro-tumorigenic activity. YKL-40 lacks enzymatic function, but it can bind carbohydrates such as chitin. Chitooligosaccharides (COS) derived from deacetylation and hydrolysis of chitin might be used for the blockade of YKL-40 function. Here, public single-cell RNA sequencing datasets were used to elucidate the cellular source of YKL-40 gene expression in human tumors. Fibroblasts and myeloid cells were the primary sources of YKL-40. Screening of YKL-40 gene expression in syngeneic mouse cancer models showed the highest expression in the Lewis lung carcinoma (LL2) model. LL2 was used to investigate COS monotherapy and combinations with immune checkpoint inhibitors (anti-PD-L1 and anti-CTLA-4) (ICIs) and radiotherapy (8 Gy × 3) (RT). COS tended to reduce plasma YKL-40 levels, but it did not affect tumor growth. LL2 showed minimal responses to ICIs, or to RT alone. Interestingly, ICIs combined with COS led to delayed tumor growth. RT also enhanced the efficacy of ICIs; however, the addition of COS did not further delay the tumor growth. COS may exert their anti-tumorigenic effects through the inhibition of YKL-40, but additional functions of COS should be investigated.

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 D 95%  ≥ 95% (N = 5) and PTV D 95%  ≥ 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 D 95% and D mean ). For 18/20 patients, prostate coverage (D 95%  ≥ 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., Competing Interests: Conflict of interest statement Isak Wahlstedt’s Ph.D. studies are partly funded by Danish Comprehensive Cancer Center and ViewRay. Nicolaus Andratschke reports research grants, speaker honorary, and travel grants from Brainlab and ViewRay. Claus P. Behrens reports research contracts with Brainlab, Varian, and ViewRay outside of the submitted work. Ivan R Vogelius reports institutional research and teaching contracts with Brainlab, Varian, and ViewRay. Stefanie Ehrbar, Hubert S. Gabryś, Helena Garcia Schüler, Matthias Guckenberger, Abraham George Smith, Stephanie Tanadini-Lang, José D. Tascón-Vidarte, and Janita E. van Timmeren report no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The Ethos system has enabled online adaptive radiotherapy (oART) by implementing an automated treatment planning system (aTPS) for both intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy (VMAT) plan creation. The purpose of this study is to evaluate the quality of aTPS plans in the pelvic region., Material and Methods: Sixty patients with anal (n = 20), rectal (n = 20) or prostate (n = 20) cancer were retrospectively re-planned with the aTPS. Three IMRT (7-, 9- and 12-field) and two VMAT (2 and 3 arc) automatically generated plans (APs) were created per patient. The duration of the automated plan generation was registered. The best IMRT-AP and VMAT-AP for each patient were selected based on target coverage and dose to organs at risk (OARs). The AP quality was analyzed and compared to corresponding clinically accepted and manually generated VMAT plans (MPs) using several clinically relevant dose metrics. Calculation-based pre-treatment plan quality assurance (QA) was performed for all plans., Results: The median total duration to generate the five APs with the aTPS was 55 min, 39 min and 35 min for anal, prostate and rectal plans, respectively. The target coverage and the OAR sparing were equivalent for IMRT-APs and VMAT-MPs, while VMAT-Aps.demonstrated lower target dose homogeneity and higher dose to some OARs. Both conformity and homogeneity index were equivalent (rectal) or better (anal and prostate) for IMRT-APs compared to VMAT-MPs. All plans passed the patient-specific QA tolerance limit., Conclusions: The aTPS generates plans comparable to MPs within a short time-frame which is highly relevant for oART treatments., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background and Purpose: Diffusion-Weighted Magnetic Resonance imaging (DWI) quantifies water mobility through the Apparent Diffusion Coefficient (ADC), a promising radiotherapy response biomarker. ADC measurements depend on manual delineation of a region of interest, a time-consuming and observer-dependent process. Here, the aim was to introduce and test the performance of a new, semi-automatic delineation tool (SADT) for ADC calculation within the viable region of the tumour., Materials and Methods: Thirty patients with rectal cancer were scanned with DWI before radiotherapy (RT) (baseline) and two weeks into RT (week 2). The SADT was based on intensities in b=1100 s mm -2 DWI and derived ADC maps. ADC values measured using the SADT and manual delineations were compared using Bland-Altman- and correlation analyses. Delineations were repeated to assess intra-observer variation, and repeatability was estimated using repeated DWI scans., Results: ADC measured using the SADT and manual delineation showed strong and moderate correlation at baseline and week 2, respectively, with the SADT measuring systematically smaller values. Intra-observer ADC variation was slightly smaller for the SADT compared to manual delineation both at baseline, [-0.00; 0.03] vs. [-0.02; 0.04] 10 -3  mm 2  s -1 , and week 2, [-0.01; 0.00] vs. [-0.04; 0.07] 10 -3  mm 2  s -1 (68.3% limits of agreement). The ADC change between baseline and week 2 was larger than the ADC uncertainty ( ± 0.04 · 10 -3  mm 2  s -1 ) in all cases except one., Conclusion: The presented SADT showed performance comparable to manual expert delineation, and with sufficient consistency to allow extraction of potential biological information from the viable tumour., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology.)