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Scatter plots comparing individual MRI measurements (tumor volume, baseline R2* and percentage of fluctuating volume) against pathology (Hoechst 33342 uptake for perfusion, pimonidazole adduct formation for hypoxia) determined from the cohort of CALR xenografts.

Fluctuating volume percentages detected for HNSCC metastatic lymph node ROIs between two MR sessions 48 hours apart (solid lines - responders, dashed lines - non responders).

Examples of Ktrans and R2* distributions for fluctuating and non-fluctuating parts of human HNSCC (Patient No 5, N2). The non-enhancing part of the tumor (Ktrans = 0) is indicated with an asterisk.

Supplementary Figure Captions

Examples of R2* time series (left column, R2* range 40 s-1) and corresponding power frequency spectra (R2* power range displayed: 0 - 30) for voxels within human HNSCC classified as significantly fluctuating (tumor - top two rows) and without significant fluctuations (tumor - middle two rows, adjacent muscle - bottom row).

T2*-weighted image (TE=4.9 ms) for a stage IV HNSCC patient (Pt No: 5). Marker lines represent image positions used in the assessment of motion correction. B: Time traces of nodal (LN) and primary (P) projections without (S(t)) and with motion correction (S(t)MOCO). Pronounced global motion (i.e. swallowing) is marked with an asterisk. Persistent motion artifacts present in the primary tumor are indicated with an arrow.

Example of coronal T2-weighted image of two simultaneously scanned mice bearing CALR HNSCC xenografts (mice IV and V, tumors are marked with arrows) and a phantom containing 1.5 mM gadoterate meglumine (Dotarem, Guerbet, Villepinte, France) in saline, acquired using the asymmetric high-resolution three element receive coil.

Examples of R2* time series (left column, R2* range 40 s-1) and corresponding power frequency spectra (R2* power range displayed: 0 - 30) for voxels within CALR HNSCC xenografts classified as significantly fluctuating (CALR tumor - top two rows) and without significant fluctuations (CALR tumor - middle two rows, adjacent muscle - bottom row).

Aims With interest in normal tissue sparing and dose-escalated radiotherapy in the treatment of inoperable locally advanced non-small cell lung cancer, this study investigated the impact of motion-managed moderate deep inspiration breath hold (mDIBH) on normal tissue sparing and dose-escalation potential and compared this to planning with a four-dimensional motion-encompassing internal target volume or motion-compensating mid-ventilation approach. Materials and methods Twenty-one patients underwent four-dimensional and mDIBH planning computed tomography scans. Internal and mid-ventilation target volumes were generated on the four-dimensional scan, with mDIBH target volumes generated on the mDIBH scan. Isotoxic target dose-escalation guidelines were used to generate six plans per patient: three with a target dose cap and three without. Target dose-escalation potential, normal tissue complication probability and differences in pre-specified dose-volume metrics were evaluated for the three motion-management techniques. Results The mean total lung volume was significantly greater with mDIBH compared with four-dimensional scans. Lung dose (mean and V21 Gy) and mean heart dose were significantly reduced with mDIBH in comparison with four-dimensional-based approaches, and this translated to a significant reduction in heart and lung normal tissue complication probability with mDIBH. In 20/21 patients, the trial target prescription dose cap of 79.2 Gy was achievable with all motion-management techniques. Conclusion mDIBH aids lung and heart dose sparing in isotoxic dose-escalated radiotherapy compared with four-dimensional planning techniques. Given concerns about lung and cardiac toxicity, particularly in an era of consolidation immunotherapy, reduced normal tissue doses may be advantageous for treatment tolerance and outcome.

Highlights • The MR-Linac provides the tools to deliver online MR-guided Adaptive Radiotherapy • Adapt-to-Shape-Lite is a novel radiotherapy planning workflow on the Elekta Unity MR-Linac • Adapt-to-Shape-Lite generated plans that fulfilled 99.9% of mandatory dose constraints • Adapt-to-Shape-Lite workflow can generate plans in relatively short durations • Therefore, we prefer Adapt-To-Shape-Lite as the primary workflow to treat Head-and-Neck cancers, Introduction The Elekta Unity MR-Linac (MRL) has enabled adaptive radiotherapy (ART) for patients with head and neck cancers (HNC). Adapt-To-Shape-Lite (ATS-Lite) is a novel Adapt-to-Shape strategy that provides ART without requiring daily clinician presence to perform online target and organ at risk (OAR) delineation. In this study we compared the performance of our clinically-delivered ATS-Lite strategy against three Adapt-To-Position (ATP) variants: Adapt Segments (ATP-AS), Optimise Weights (ATP-OW), and Optimise Shapes (ATP-OS). Methods Two patients with HNC received radical-dose radiotherapy on the MRL. For each fraction, an ATS-Lite plan was generated online and delivered and additional plans were generated offline for each ATP variant. To assess the clinical acceptability of a plan for every fraction, twenty clinical goals for targets and OARs were assessed for all four plans. Results 53 fractions were analysed. ATS-Lite passed 99.9% of mandatory dose constraints. ATP-AS and ATP-OW each failed 7.6% of mandatory dose constraints. The Planning Target Volumes for 54 Gy (D95% and D98%) were the most frequently failing dose constraint targets for ATP. ATS-Lite median fraction times for Patient 1 and 2 were 40 mins 9 s (range 28 mins 16 s – 47 mins 20 s) and 32 mins 14 s (range 25 mins 33 s – 44 mins 27 s), respectively. Conclusions Our early data show that the novel ATS-Lite strategy produced plans that fulfilled 99.9% of clinical dose constraints in a time frame that is tolerable for patients and comparable to ATP workflows. Therefore, ATS-Lite, which bridges the gap between ATP and full ATS, will be further utilised and developed within our institute and it is a workflow that should be considered for treating patients with HNC on the MRL.

The implementation of MRI-guided online adaptive radiotherapy has facilitated the extension of therapeutic radiographers' roles to include contouring, thus releasing the clinician from attending daily treatment. Following undergoing a specifically designed training programme, an online interobserver variability study was performed.117 images from six patients treated on a MR Linac were contoured online by either radiographer or clinician and the same images contoured offline by the alternate profession. Dice similarity coefficient (DSC), mean distance to agreement (MDA), Hausdorff distance (HD) and volume metrics were used to analyse contours. Additionally, the online radiographer contours and optimised plans (n=59) were analysed using the offline clinician defined contours. After clinical implementation of radiographer contouring, target volume comparison and dose analysis was performed on 20 contours from five patients.Comparison of the radiographers' and clinicians' contours resulted in a median (range) DSC of 0.92 (0.86 - 0.99), median (range) MDA of 0.98 mm (0.2-1.7) and median (range) HD of 6.3 mm (2.5 -11.5) for all 117 fractions. There was no significant difference in volume size between the two groups. Of the 59 plans created with radiographer online contours and overlaid with clinicians' offline contours, 39 met mandatory dose constraints and 12 were acceptable because 95% of the high dose PTV was covered by 95% dose, or the high dose PTV was within 3% of online plan. A clinician blindly reviewed the eight remaining fractions and, using trial quality assurance metrics, deemed all to be acceptable. Following clinical implementation of radiographer contouring, the median (range) DSC of CTV was 0.93 (0.88 - 1.0), median (range) MDA was 0.8 mm (0.04 - 1.18) and HD was 5.15 mm (2.09 - 8.54) respectively. Of the 20 plans created using radiographer online contours overlaid with clinicians' offline contours, 18 met the dosimetric success criteria, the remaining 2 were deemed acceptable by a clinician.Radiographer and clinician prostate and seminal vesicle contours on MRI for an online adaptive workflow are comparable and produce clinically acceptable plans. Radiographer contouring for prostate treatment on a MR-linac can be effectively introduced with appropriate training and evaluation. A DSC threshold for target structures could be implemented to streamline future training.

Highlights • VMAT in combination with voluntary deep inspiratory breath hold is a feasible alternative to machine operated techniques. • Voluntary deep inspiration breath hold (vDIBH) can be used in combination with wax bolus. • A novel low cost couch mounted laser offers a reliable method for monitoring vDIBH. • Intrafraction and interfraction reproducibility is equivalent between vDIBH and ABC™ breath hold in combination with VMAT with or without wax bolus., Background Deep-inspiration breath-hold (DIBH) reduces radiation dose to the heart in patients undergoing locoregional breast radiotherapy. In the context of tangential irradiation of the breast/ chest wall, a voluntary breath hold (vDIBH) technique has been shown to be as reproducible as a machine-assisted breath hold technique using the active breathing co-ordinator (ABC™, Elekta, Crawley, UK, ABC_DIBH). This study compares set-up reproducibility for vDIBH versus ABC_DIBH in patients undergoing volumetric-modulated arc radiotherapy (VMAT) for breast cancer, both with and without wax bolus. Method Patients with breast cancer requiring pan regional lymph node VMAT +/− wax bolus in breath-hold were CT scanned in vDIBH and ABC_DIBH. Patients were randomised to receive one technique for fractions 1–7 and the other for fractions 8–15. Daily cone beam computed tomography (CBCT) was performed and registered to planning-CT using bony anatomy. Within-patient comparisons of mean daily chest wall position were made using a paired t-test. Population, systematic (∑) and random errors (α) were estimated. Intrafraction reproducibility was assessed by comparing chest wall position and diaphragm movement between consecutive breath holds on CBCT. Results 16 patients were recruited. All completed treatment with both techniques (9 patients with wax bolus, 7 patients without). CBCT derived ∑ were 2.1–6.4 mm (ABC_DIBH) and 2.1–4.9 mm (vDIBH), α were 1.7–2.6 mm (ABC_DIBH) and 2.2–2.7 mm (vDIBH) and mean daily chest wall displacements (MD) were 0.0–1.5 mm (ABC_DIBH) and -0.1–1.6 vDIBH (all p non-significant). Chest wall and diaphragm position was equivalent between consecutive breath holds in ABC and vDIBH (median difference 1.0 mm and 0.8 mm respectively, non p significant) demonstrating equivalent intrafraction reproducibility. Conclusion This study demonstrates that a simple voluntary breath hold technique is feasible in combination with VMAT (+/− bolus) and is as reproducible as ABC_DIBH with VMAT for the irradiation of the breast and axillary and IMC lymph nodes in breast cancer patients.

Highlights • Deliverable plans for 1 and 2 fraction SBRT can be created for the Unity MR-Linac. • Dose constraints and objectives from HDR and SBRT clinical studies were applied. • In 40% of 1 and 2 fraction plans target doses were compromised to meet OAR goals., The drive towards hypofractionated prostate radiotherapy is motivated by a low alpha/beta ratio for prostate cancer (1 to 3 Gy) compared to surrounding organs at risk, implying an improved therapeutic ratio with increasing dose per fraction. Early evidence from studies of ultrahypofractionated (UHF) prostate HDR brachytherapy has shown good tolerability in terms of normal tissue toxicities and clinical outcomes similar to conventional fractionation schedules. MR-guided stereotactic body radiotherapy (SBRT) with online plan adaptation and real-time tumour imaging may enable UHF doses to be delivered to the prostate safely, without the invasiveness of brachytherapy. The feasibility of UHF prostate treatment planning for the Unity MR-Linac (MRL, Elekta AB, Stockholm) was investigated for target prescriptions and planning constraints derived from the HDR brachytherapy and SBRT literature. Monaco 5.40 (Elekta) was used to generate MRL step-and-shoot IMRT plans for three dose fractionation protocols (5, 2 and 1 fractions), for ten randomly selected previously treated prostate cancer patients. Of the ten plans per UHF scheme, all clinical goals were met in all cases for 5 fractions, and in six cases for both 2 and 1 fraction schemes. PTV D95% was compromised by up to 6.4% and 3.9% of the associated target dose for 2 and 1 fraction plans respectively. There were two cases of PTV D95% compromise greater than a 5% dose decrease for the 2 fraction plans. The study suggests feasibility of the UHF treatment planning approaches if combined with real-time motion mitigation strategies.

Purpose: To quantify estimates of risk in young patients ( Methods and Materials: In 14 patients’ CT datasets from the HeartSpare Plus dosimetry study(1) the CB was further subdivided into quadrants. Three radiotherapy techniques for breast and pan nodal radiotherapy were analysed: Wide Tangents in voluntary Breath Hold (WT-vBH), Volumetric-Modulated Arc Radiotherapy in vBH (VMAT-vBH) and PBT in Free Breathing. (PBT-FB). Mean dose to the whole CB, and contralateral UIQ for each patient across three techniques was calculated. The statistical significance of differences between the mean doses to UIQ across the three techniques were analysed using Friedman’s test followed by Wilcoxon signed rank comparison. Based on estimates of CB cancer risks from the WECARE study (2) and assuming the patients were under 40 years of age, the dose to UIQ was converted to Rate Ratios (RR), both overall and with >5 years follow up. Results: The mean dose and range to CB UIQ (Gy) for WT-vBH was 4.7 (0.5-11.0), VMAT-vBH was 3.9 (0.5-6.8) and PBT-FB 0.5 (0.1-1.7) p value 5 years this translates into a Rate Ratio (RR) with 95% confidence interval (CI) of 6.9 (1.5-19.9) for WT-vBH, 6.3 (1.4 – 18.0) for VMAT-vBH and 1.2 (0.5-3.0) for PBT-FB. WT-vBHVMAT-vBHPBT-FBDose to whole CB (Gy) mean (and range)1.6 (0.3-3.2)1.5 (0.3-3.5)0.2 (0.1-0.8)Dose to UIQ CB (Gy) mean (and range)4.7 (0.5-11.0)3.9 (0.5 – 6.8)0.5 (0.1 –1.7)RR (with 95% CI) of UIQ CB cancer In woman 5 years6.9 (1.5 -19.9)6.3 (1.4-18.0)1.2 (0.5 –3.0) Conclusion: Women Refernces 1. Ranger A, Dunlop A, Hutchinson K, et al. A Dosimetric Comparison of Breast Radiotherapy Techniques to Treat Locoregional Lymph Nodes Including the Internal Mammary Chain. Clin. Oncol. 2018;30:346–353. 2. Stovall M, Smith SA, Langholz BM, et al. Dose to the Contralateral Breast From Radiotherapy and Risk of Second Primary Breast Cancer in the WECARE Study. Int. J. Radiat. Oncol. Biol. Phys. 2008;72:1021–1030. Citation Format: Sarah Settatree, Douglas Brand, Alison Ranger, Alex Dunlop, Anna Kirby. Dosimetric comparison of breast and pan nodal radiotherapy techniques to estimate the risk of developing a second primary cancer in the upper inner quadrant of the contralateral breast [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-25.

Exposure of the heart to radiation increases the risk of ischaemic heart disease, proportionate to the mean heart dose (MHD). Radiotherapy techniques including proton beam therapy (PBT) can reduce MHD. The aims of this study were to quantify the MHD reduction achievable by PBT compared with volumetric modulated arc therapy in breath hold (VMAT-BH) in patients with pectus excavatum (PEx), to identify an anatomical metric from a computed tomography scan that might indicate which patients will achieve the greatest MHD reductions from PBT.Sixteen patients with PEx (Haller Index ≥2.7) were identified from radiotherapy planning computed tomography images. Left breast/chest wall, axilla (I-IV) and internal mammary node (IMN) volumes were delineated. VMAT and PBT plans were prepared, all satisfying target coverage constraints. Signed-rank comparisons of techniques were undertaken for the mean dose to the heart, ipsilateral lung and contralateral breast. Spearman's rho correlations were calculated for anatomical metrics against MHD reduction achieved by PBT.The mean MHD for VMAT-BH plans was 4.1 Gy compared with 0.7 Gy for PBT plans. PBT reduced MHD by an average of 3.4 Gy (range 2.8-4.4 Gy) compared with VMAT-BH (P0.001). PBT significantly reduced the mean dose to the ipsilateral lung (4.7 Gy, P0.001) and contralateral breast (2.7 Gy, P0.001). The distance (mm) at the most inferomedial extent of IMN volume (IMN to heart distance) negatively correlated with MHD reduction achieved by PBT (Spearman's rho -0.88 (95% confidence interval -0.96 to -0.67, P0.001)).For patients with PEx requiring left-sided breast and IMN radiotherapy, a clinically significant MHD reduction is achievable using PBT, compared with the optimal photon technique (VMAT-BH). This is a patient group in whom PBT could have the greatest benefit.

Objective: This study investigates the impact of a restricted craniocaudal (CC) field length of Methods: 110 HNC patients who underwent radical primary or adjuvant radiotherapy were retrospectively analysed. We assessed the proportion of treatment fields with a CC length of Results: 95% of HNC patients had a CC field length Conclusion: The majority of patients with HNC at the Royal Marsden Hospital have anthropometric features compatible with their being treated on the MR-Linac using a single isocentre technique. The absolute CC field size may vary according to primary tumour site, patient factors and neck position. A hyo-sternal neck length cut-off of 14.6 cm in the neutral neck position can be used as a surrogate marker for suitability of treatment on MR-Linac. Advances in knowledge: This paper highlights the potential impact of a restricted CC field in HNC patient selection for the MR-Linac treatment. This is the first report to suggest the use of neck length as a surrogate marker for suitability of treatment on the MR-Linac.

Highlights • MR-guided radiotherapy for prostate cancer can be delivered using a high filed MR-linac. • Comparison of estimated delivered dose between MR-guided adapted radiotherapy and conventional C-arm techniques. • MR-guided adaptive radiotherapy demonstrates improved target coverage for a subset of prostate cancer patients., Introduction MR-guided adapted radiotherapy (MRgART) using a high field MR-linac has recently become available. We report the estimated delivered fractional dose of the first five prostate cancer patients treated at our centre using MRgART and compare this to C-Arm linac daily Image Guided Radiotherapy (IGRT). Methods Patients were treated using adapted treatment plans shaped to their daily anatomy. The treatments were recalculated on an MR image acquired immediately prior to treatment delivery in order to estimate the delivered fractional dose. C-arm linac non-adapted VMAT treatment plans were recalculated on the same MR images to estimate the fractional dose that would have been delivered using conventional radiotherapy techniques using a daily IGRT protocol. Results 95% and 93% of mandatory target coverage objectives and organ at risk dose constraints were achieved by MRgART and C-arm linac delivered dose estimates, respectively. Both delivery techniques were estimated to have achieved 98% of mandatory Organ At Risk (OAR) dose constraints whereas for the target clinical goals, 86% and 80% were achieved by MRgART and C-arm linac delivered dose estimates. Conclusions Prostate MRgART can be delivered using the a high field MR-linac. Radiotherapy performed on a C-arm linac offers a good solution for prostate cancer patients who present with favourable anatomy at the time of reference imaging and demonstrate stable anatomy throughout the course of their treatment. For patients with critical OARs abutting target volumes on their reference image we have demonstrated the potential for a target dose coverage improvement for MRgART compared to C-arm linac treatment.

Purpose: To determine the 3-dimensional (3D) intrafractional motion of head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Dynamic contrast-enhanced magnetic resonance images from 56 patients with HNSCC in the treatment position were analyzed. Dynamic contrast-enhanced magnetic resonance imaging consisted of 3D images acquired every 2.9 seconds for 4 minutes 50 seconds. Intrafractional tumor motion was studied in the 3 minutes 43 seconds of images obtained after initial contrast enhancement. To assess tumor motion, rigid registration (translations only) was performed using a region of interest (ROI) mask around the tumor. The results were compared with bulk body motion from registration to all voxels. Motion was split into systematic motion and random motion. Correlations between the tumor site and random motion were tested. The within-subject coefficient of variation was determined from 8 patients with repeated baseline measures. Random motion was also assessed at the end of the first week (38 patients) and second week (25 patients) of radiation therapy to investigate trends of motion. Results: Tumors showed irregular occasional rapid motion (eg, swallowing or coughing), periodic intermediate motion (respiration), and slower systematic drifts throughout treatment. For 95% of the patients, displacements due to systematic and random motion were

Purpose: To investigate the effects of different time-resolved angiography with stochastic trajectories (TWIST) k-space undersampling schemes on calculated pharmacokinetic dynamic contrast-enhanced (DCE) vascular parameters. Methods: A digital perfusion phantom was employed to simulate effects of TWIST on characteristics of signal changes in DCE. Furthermore, DCE-MRI was acquired without undersampling in a group of patients with head and neck squamous cell carcinoma and used to simulate a range of TWIST schemes. Errors were calculated as differences between reference and TWIST-simulated DCE parameters. Parametrical error maps were used to display the averaged results from all tumors. Results: For a relatively wide range of undersampling schemes, errors in pharmacokinetic parameters due to TWIST were under 10% for the volume transfer constant, K-trans, and total extracellular extravascular space volume, V-e. TWIST induced errors in the total blood plasma volume, V-p, were the largest observed, and these were inversely dependent on the area of the fully sampled k-space. The magnitudes of errors were not correlated with K-trans, V-p and weakly correlated with V-e. Conclusions: The authors demonstrated methods to validate and optimize k-space view-sharing techniques for pharmacokinetic DCE studies using a range of clinically relevant spatial and temporal patient derived data. The authors found a range of undersampling patterns for which the TWIST sequence can be reliably used in pharmacokinetic DCE-MRI. The parameter maps created in the study can help to make a decision between temporal and spatial resolution demands and the quality of enhancement curve characterization. (C) 2016 Author(s).

Highlights • Novel dose reconstruction workflow based on log files and online MR imaging. • Intrafractional motion and dose changes were clinically meaningless in most fractions. • Rarely, large shifts caused the delivered dose to deviate from the treatment plan. • Blueprint for dose reconstruction on MR-linacs for other cancer sites., Background and purpose Anatomical changes during external beam radiotherapy prevent the accurate delivery of the intended dose distribution. Resolving the delivered dose, which is currently unknown, is crucial to link radiotherapy doses to clinical outcomes and ultimately improve the standard of care. Material and methods In this study, we present a dose reconstruction workflow based on data routinely acquired during MR-guided radiotherapy. It employs 3D MR images, 2D cine MR images and treatment machine log files to calculate the delivered dose taking intrafractional motion into account. The developed pipeline was used to measure anatomical changes and assess their dosimetric impact in 89 prostate radiotherapy fractions delivered with a 1.5 T MR-linac at our institute. Results Over the course of radiation delivery, the CTV shifted 0.6 mm ± 2.1 mm posteriorly and 1.3 mm ± 1.5 mm inferiorly. When extrapolating the dose changes in each case to 20 fractions, the mean clinical target volume D98% and clinical target volume D50% dose-volume metrics decreased by 1.1 Gy ± 1.6 Gy and 0.1 Gy ± 0.2 Gy, respectively. Bladder D3% did not change (0.0 Gy ± 1.2 Gy), while rectum D3% decreased by 1.0 Gy ± 2.0 Gy. Although anatomical changes and their dosimetric impact were small in the majority of cases, large intrafractional motion caused the delivered dose to substantially deviate from the intended plan in some fractions. Conclusions The presented end-to-end workflow is able to reliably, non-invasively and automatically reconstruct the delivered prostate radiotherapy dose by processing MR-linac treatment log files and online MR images. In the future, we envision this workflow to be adapted to other cancer sites and ultimately to enter widespread clinical use.

242 Background: The Unity MR-Linac combines a 7-MV Linac with 1.5T magnetic resonance (MR) imaging capability and it enables adaptive radiotherapy, whereby the target and organs at risk are recontoured and a plan is optimised daily. During treatment a session MR image is taken first, on which the target and organs-at-risk are contoured, and a plan created. A verification image is taken prior to dose delivery to identify intra-fractional changes. If present, the daily treatment plan is shifted to reflect the anatomy. A post-treatment image is acquired at the end of treatment. This study evaluates the dosimetric changes to the rectum caused by intra-fractional changes during treatment delivery for prostate stereotactic body radiotherapy (SBRT) calculated on the verification and post-treatment images. Methods: The first five patients treated on the MR-Linac with 5-fraction SBRT to the prostate are included in this study. For each patient, the rectum was contoured on the verification and post-treatment MR images for each of the five fractions. The dose delivered to the rectum with the original treatment plan was then calculated on each image and the V36Gy rectal dose constraint was noted. Results: Out of the 25 fractions, a post treatment image was not performed in one fraction; 24 fractions were therefore analysed in total. The rectal V36Gy dose constraint exceeded the mandatory target of 2cc on 50% of the verification images and 46% of the post-treatment images. In 6 fractions the rectal V36Gy was greater than 2cc on both the verification and post-treatment images suggesting this rectal constraint was exceeded throughout treatment. In 17% of patients, the volume of rectum receiving 36Gy increased at each timepoint an image was taken during the treatment workflow. Conclusions: The rectal V36Gy dose constraint is susceptible to minor changes in rectal filling, which may often lead to higher than the accepted dose constraint. Thus, a single planning CT scan is unlikely to be representative of dose delivered. Adaptive radiotherapy can reduce this uncertainty somewhat, but intra-fraction dose re-optimisation would be required to ensure the rectal V36Gy remains acceptable at all times.

e18540 Background: RAD is a significant treatment-related functional morbidity in OPC and is associated with irradiation of the pharyngeal constrictor muscle (PCM). This study investigated whether a novel PCM-sparing Do-VMAT technique reduced the risk of RAD, compared to S-VMAT. Methods: Twenty OPC patients who previously underwent radiotherapy (RT) to bilateral neck were selected for this retrospective study. For each patient, S-VMAT and Do-VMAT plans were created. In both arms, the mucosal and nodal tumour received 65 Gy while the remaining oropharynx and at-risk nodal levels received 54 Gy; delivered in 30 fractions over 6 weeks. For Do-VMAT, a mandatory mean dose constraint of < 50 Gy to the volume of the combined superior (SPCM) and middle PCM (MPCM) together with an optimal dose constraint of < 20 Gy to the volume of inferior PCM (IPCM), lying outside the high-dose clinical target volume, were additionally defined and optimised to minimise PCM dose. Normal tissue complication probabilities for physician-scored RAD at 6 months (RAD6M) were determined as per the model by Christianen et al in which the 2 variables were mean dose to SPCM and supraglottic larynx (SGL). Statistical analysis was performed using paired t tests. Results: All plans had adequate target volume coverage, and dose to critical organs were within acceptable parameters. Dose to the parotid and submandibular glands were similar between the 2 RT techniques. The mean integral dose was 110.8 Gy-litre (standard deviation 17.1) with S-VMAT and 103.4 Gy-litre (15.4) with Do-VMAT, p < 0.001. With Do-VMAT, the average of the mean dose to PCM, SPCM, MPCM, IPCM, and SGL were 9.3 Gy (1.4), 4.7 Gy (1.7), 7.4 Gy (3.6), 22.7 Gy (4.1), and 2.6 Gy (2.3) respectively lower than S-VMAT (p < 0.001 for all). The mean predicted risk for RAD6M was 31.0 % (4.4) with S-VMAT, and 23.9 % (3.8) with Do-VMAT, p < 0.001. The absolute reduction in estimated toxicity risk with Do-VMAT was > 5 %, the minimally clinically important difference, in every patient. Conclusions: Do-VMAT demonstrated clinically relevant reductions in the predicted risk of RAD, compared to S-VMAT, by reducing dose to the PCM in OPC. The clinical benefits of Do-VMAT is being prospectively evaluated in DARS (CRUK/14/014), a randomised phase III study.

Aims: Irradiation of the internal mammary chain (IMC) is increasing following recently published data, but the need for formal delineation of lymph node volumes is slowing implementation in some healthcare settings. A field-placement algorithm for irradiating locoregional lymph nodes including the IMC could reduce the resource impact of introducing irradiation of the IMC. This study describes the development and evaluation of such an algorithm. Materials and methods: An algorithm was developed in which six points representing lymph node clinical target volume borders (based on European Society for Radiotherapy and Oncology consensus nodal contouring guidelines) were placed on computed tomography-defined anatomical landmarks and used to place tangential and nodal fields. Single-centre testing in 20 cases assessed the success of the algorithm in covering planning target volumes (PTVs) and adequately sparing organs at risk. Plans derived using the points algorithm were also compared with plans generated following formal delineation of nodal PTVs, using the Wilcoxon signed rank test. Timing data for point placement were collected. Multicentre testing using the same methods was then carried out to establish whether the technique was transferable to other centres. Results: Single-centre testing showed that 95% of cases met the nodal PTV coverage dose constraints (binomial probability confidence interval 75.1-99.9%) with no statistically significant reduction in mean heart dose or ipsilateral lung V-17Gy associated with formal nodal delineation. In multicentre testing, 69% of cases met nodal PTV dose constraints and there was a statistically significant difference in IMC PTV coverage using the points algorithm when compared with formally delineated nodal volumes (P < 0.01). However, there was no difference in axillary level 1-4 PTV coverage (P = 0.11) with all cases meeting target volume constraints. Conclusions: The optimal strategy for breast and locoregional lymph node radiotherapy is target volume delineation. However, use of this novel points-based field-placement algorithm results in dosimetrically acceptable plans without the need for formal lymph node contouring in a single-centre setting and for the breast and level 1-4 axilla in a multicentre setting. Further quality assurance measures are needed to enable implementation of the algorithm for irradiation of the IMC in a multicentre setting. (C) 2018 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.