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In the Danish Head and Neck Cancer Group (DAHANCA) 35 trial, patients are selected for proton treatment based on simulated reductions of Normal Tissue Complication Probability (NTCP) for proton compared to photon treatment at the referring departments. After inclusion in the trial, immobilization, scanning, contouring and planning are repeated at the national proton centre. The new contours could result in reduced expected NTCP gain of the proton plan, resulting in a loss of validity in the selection process. The present study evaluates if contour consistency can be improved by having access to AI (Artificial Intelligence) based contours. The 63 patients in the DAHANCA 35 pilot trial had a CT from the local DAHANCA centre and one from the proton centre. A nationally validated convolutional neural network, based on nnU-Net, was used to contour OARs on both scans for each patient. Using deformable image registration, local AI and oncologist contours were transferred to the proton centre scans for comparison. Consistency was calculated with the Dice Similarity Coefficient (DSC) and Mean Surface Distance (MSD), comparing contours from AI to AI and oncologist to oncologist, respectively. Two NTCP models were applied to calculate NTCP for xerostomia and dysphagia. The AI contours showed significantly better consistency than the contours by oncologists. The median and interquartile range of DSC was 0.85 [0.78 − 0.90] and 0.68 [0.51 − 0.80] for AI and oncologist contours, respectively. The median and interquartile range of MSD was 0.9 mm [0.7 − 1.1] mm and 1.9 mm [1.5 − 2.6] mm for AI and oncologist contours, respectively. There was no significant difference in Δ NTCP. The study showed that OAR contours made by the AI algorithm were more consistent than those made by oncologists. No significant impact on the Δ NTCP calculations could be discerned. [ABSTRACT FROM AUTHOR]

• Application of consensus guidelines results in increased consistency in high-dose CTV1. • A 3-year local control is not influenced by GTV-CTV1 margin. • Half of analysable radiology-verified local recurrences are in primary GTV. • 76 % of radiology-verified local recurrences are inside CTV1 using 5 mm margin consensus. Treatment planning using a five-millimetre geometrical margin from GTV to high-dose CTV (CTV1) has been used in DAHANCA treatment centres since 2013. We aimed to evaluate changes in CTV1 volumes, local control (LC), and recurrence pattern after the implementation of five-millimetre geometrical margins nationally. 1,948 patients with pharyngeal, and laryngeal squamous cell carcinomas completed definitive IMRT-based treatment in 2010–2012 and 2013–2015 in three centres. The patient-specific margin was calculated as median surface distance from primary tumour GTV (GTV-T) to CTV1. Radiologically verified local recurrences were analysed using a centre of mass (COM) of the delineated recurrence volume, measuring the shortest distance between COM to GTV-T and CTV1 boundaries. Median GTV-CTV1 was 0.9 (0.0–0.97) and 0.47 cm (0.4–0.5) for 2010–2012 and 2013–2015, respectively. Median CTV1 changed in three centres from 76, 28, 42 cm3 to 61, 53, 62 cm3 for 2010–2012 and 2013–2015, respectively. Local failures occurred at 247 patients during first three years after radiotherapy. The 3-year LC rate for 2010–2012 and 2013–2015 was 0.84 and 0.87 (p = 0.06). Out of 146 radiology-verified analysable local recurrences, 102 (69.9%) were inside the CTV1. In 74.6% and 91% of cases, the LRs were covered by 95% isodose in 2010–2012 and 2013–2015, respectively. DAHANCA radiotherapy guidelines based on a geometrically generated isotropic CTV1 margin led to less variation in treatment volumes and between centres than previous guidelines. The transition towards consensus GTV-CTV1 margins did not influence local tumour control. The majority of local recurrences were inside CTV1 and covered by the prescription dose. [ABSTRACT FROM AUTHOR]

In head and neck cancer, distant metastases may be present at diagnosis (M1) or occur after treatment (DM). It is unknown whether M1 and DM follow the same clinical development and share prognosis, as population-based studies regarding outcomes are scarce. Therefore, we investigated the incidence, location of metastases and overall survival of patients with M1 and DM. Patients diagnosed with squamous cell carcinoma of the pharynx and larynx in Denmark 2008–2017 were identified in the Danish Head and Neck Cancer Group (DAHANCA) database. We identified 7300 patients, of whom 197 (3%) had M1 and 498 (8%) developed DM during follow-up. The 5-year cumulative incidence of DM was 8%. 1- and 2-year overall survival for DM (27% and 13%) vs. M1 (28% and 9%) were equally poor. There was no significant difference in location of metastases for M1 and DM and the most frequently involved organs were lungs, bone, lymph nodes and liver, in descending order. In oropharyngeal squamous cell carcinomas, the location of metastases did not differ by p16-status. For p16-positive patients, 21% of DM occurred later than three years of follow-up compared to 7% of p16-negative patients. Incidence, location of metastases and prognosis of primary metastatic (M1) or post-treatment metastatic (DM) disease in pharyngeal and laryngeal squamous cell carcinoma are similar in this register-based study [ABSTRACT FROM AUTHOR]

Deformable image registration (DIR) and contour propagation are used in daily online adaptation for hybrid MRI linac (MRL) treatments. The accuracy of the propagated contours may vary depending on the chosen workflow (WF), affecting the amount of required manual corrections. This study investigated the impact of three different WFs of contour propagations produced by a clinical treatment planning system for a high-field MRL on head and neck cancer patients. Seventeen patients referred for curative radiotherapy for oropharyngeal cancer underwent standard CT-based dose planning and MR scans in the treatment position for planning (pMR), and at the 10th (MR10), 20th (MR20) and 30th (MR30) fraction (±2). The primary tumour, a metastatic lymph node and 8 organs at risk were manually delineated on each set of T2 weighted images. Delineations were repeated one month later on the pMR by the same observer to determine the intra-observer variation (IOV). Three WFs were used to deform images in the treatment planning system for the high-field MRL: In WF1, only the planning image and contours were used as a reference for DIR and propagation to MR10,20,30. The most recently acquired image set prior to the daily images was deformed and uncorrected (WF2) versus manually corrected (WF3) structures propagated to the session image. Dice similarity coefficient (DSC), mean surface distance (MSD) and Hausdorff distance (HD) were calculated for each structure in each model. Population median DSC, MSD and HD for WF1 and WF3 were similar and slightly better than for WF2. WF3 provided higher accuracy than WF1 for structures that are likely to shrink. All DIR workflows were less accurate than the IOV. WF1 and WF3 provide higher accuracy in structure propagation than WF2. Manual revision and correction of propagated structures are required for all evaluated workflows. [ABSTRACT FROM AUTHOR]

• Head and neck cancer patients at risk of distant metastases (DM) are difficult to identify. • We investigated the influence of initial tumor volume (cm3) on the risk of DM. • Gross tumor volumes (GTV) were extracted from treatment planning systems. • We found that GTV is an independent factor strongly associated with the risk of DM. • This may improve the selection of patients for intervention trials. Distant metastases (DM) in head and neck squamous cell carcinomas (HNSCC) are in most circumstances non-curable. The TNM staging system is insufficient to predict the risk of DM. This study investigates if the DM risk can be predicted using a multivariate model including pre-treatment total tumor volume for both p16-positive oropharyngeal squamous cell carcinoma (OPSCC) and all other sites (other HNSCC). The study includes patients with localized pharyngeal and laryngeal squamous cell carcinomas treated with primary radiotherapy from 2008-2017 from three head and neck cancer centers. Patients were identified in the Danish Head and Neck Cancer (DAHANCA) database. Total (nodal and primary) tumor volume (Gross Tumor Volume, GTV) was extracted from local treatment planning systems. The GTV was grouped by volume (cm3) in four intervals and included in a multivariate Cox proportional hazard regression controlled for pre-selected clinical values incl. stage. The study includes 2,865 patients, of which 321 (11 %) had DM post-treatment. The risk of DM was assessed in a multivariate model based on 2,751 patients (p16-positive OPSCC: 1,032; and other HNSCC: 1,719). There was a significant association between GTV and the risk of DM, and in tumor volumes ≥ 50 cm3 hazard ratios of 7.6 (2.5–23.4) for p16-positive OPSCC and 4.1 (2.3–7.2) in other HNSCC were observed. Tumor volume is an independent risk factor for DM. The addition of total tumor volume to a predictive model is important to identify subgroups of HNSCC patients at high risk of DM. [ABSTRACT FROM AUTHOR]