Purpose: To evaluate the effect of magnetic resonance (MR) imaging (MRI) geometric distortions on head and neck radiation therapy treatment planning (RTP) for an MRI-only RTP. We also assessed the potential benefits of patient-specific shimming to reduce the magnitude of MR distortions for a 3-T scanner.

Methods and Materials: Using an in-house Matlab algorithm, shimming within entire imaging volumes and user-defined regions of interest were simulated. We deformed 21 patient computed tomography (CT) images with MR distortion fields (gradient nonlinearity and patient-induced susceptibility effects) to create distorted CT (dCT) images using bandwidths of 122 and 488 Hz/mm at 3 T. Field parameters from volumetric modulated arc therapy plans initially optimized on dCT data sets were transferred to CT data to compute a new plan. Both plans were compared to determine the impact of distortions on dose distributions.

Results: Shimming across entire patient volumes decreased the percentage of voxels with distortions of more than 2 mm from 15.4% to 2.0%. Using the user-defined region of interest (ROI) shimming strategy, (here the Planning target volume (PTV) was the chosen ROI volume) led to increased geometric for volumes outside the PTV, as such voxels within the spinal cord with geometric shifts above 2 mm increased from 11.5% to 32.3%. The worst phantom-measured residual system distortions after 3-dimensional gradient nonlinearity correction within a radial distance of 200 mm from the isocenter was 2.17 mm. For all patients, voxels with distortion shifts of more than 2 mm resulting from patient-induced susceptibility effects were 15.4% and 0.0% using bandwidths of 122 Hz/mm and 488 Hz/mm at 3 T. Dose differences between dCT and CT treatment plans in D-50 at the planning target volume were 0.4% +/- 0.6% and 0.3% +/- 0.5% at 122 and 488 Hz/mm, respectively.

Conclusions: The overall effect of MRI geometric distortions on data used for RTP was minimal. Shimming over entire imaging volumes decreased distortions, but user-defined subvolume shimming introduced significant errors in nearby organs and should probably be avoided.

Purpose: We describe a public dataset with MR and CT images of patients performed in the same position with both multiobserver and expert consensus delineations of relevant organs in the male pelvic region. The purpose was to provide means for training and validation of segmentation algorithms and methods to convert MR to CT like data, i.e., so called synthetic CT (sCT).

Acquisition and validation methods: T1- and T2-weighted MR images as well as CT data were collected for 19 patients at three different departments. Five experts delineated nine organs for each patient based on the T2-weighted MR images. An automatic method was used to fuse the delineations. Starting from each fused delineation, a consensus delineation was agreed upon by the five experts for each organ and patient. Segmentation overlap between user delineations with respect to the consensus delineations was measured to describe the spread of the collected data. Finally, an open-source software was used to create deformation vector fields describing the relation between MR and CT images to further increase the usability of the dataset.

Data format and usage notes: The dataset has been made publically available to be used for academic purposes, and can be accessed from . Potential applicationsThe dataset provides a useful source for training and validation of segmentation algorithms as well as methods to convert MR to CT-like data (sCT). To give some examples: The T2-weighted MR images with their consensus delineations can directly be used as a template in an existing atlas-based segmentation engine; the expert delineations are useful to validate the performance of a segmentation algorithm as they provide a way to measure variability among users which can be compared with the result of an automatic segmentation; and the pairwise deformably registered MR and CT images can be a source for an atlas-based sCT algorithm or for validation of sCT algorithm.

PURPOSE: To establish predictive models for late objective aspiration and late patient-reported choking based on dose-volume parameters and baseline patient and treatment characteristics, for patients with head and neck cancer undergoing definitive radiotherapy (RT). The impact of electively treated volume on late aspiration was also investigated.

METHODS AND MATERIAL: This prospective cohort is a subsample of 124 survivors from the ARTSCAN study. Late aspiration was identified with videofluoroscopy, at a minimum of 25months after the start of RT. Patient-reported choking was analysed at 12 and 60months post RT using the EORTC Quality of Life Module for Head and Neck Cancer 35. Univariable and multivariable analyses were performed to describe the association between clinical factors and dose-volume descriptors for organs at risk (OARs) and late dysphagia.

RESULTS: Aspiration was found in 47% of the eligible patients. Mean dose to the middle pharyngeal constrictor (MPC), neck dissection post RT and age at randomisation in ARTSCAN were associated to late aspiration. Mean dose to the superior pharyngeal constrictor (SPC) and swallowing complaints at baseline were associated to patient reported choking at both time-points.

CONCLUSIONS: Three separate risk groups for late aspiration, and two risk groups for late patient-reported choking were identified based on number of risk factors. The size of the electively treated volume could be used as a surrogate for individual OARs predicting late aspiration.

Background In the treatment of head and neck cancers (HNCs), radiotherapy (RT) has the advantage of organ preservation compared to surgery. However, treatment toxicities associated with RT can affect important functions for everyday life, both in the acute and late stage. RT to macroscopic tumour in HNC is commonly combined with elective RT to cervical lymph nodes at risk of microscopic involvement. The resulting risk reduction of the elective treatment based on dose-volume parameters is sparsely evaluated. So is the relationship between the elective treatment and treatment toxicity. The present thesis addresses these aspects.

A strategy aimed at improving the outcome of RT is accelerated fractionation (AF). AF strives to shorten total treatment time to minimise proliferation of the tumour tissue during the RT period. We have investigated the impact of AF on both disease control and toxicity.

Methods In the ARTSCAN study, 750 patients with localised HNC were randomised between AF (68 Gy in 4.5 weeks) and conventional fractionation (CF) (68 Gy in 7 weeks). The elective treatment volume was prescribed 46 Gy with CF in both treatment arms. The thesis is based on four individual papers, investigating the issues above in the whole study population or in sub-populations.

Results No difference in disease control or late toxicity between CF and AF was observed at five years. However, there was an increased acute toxicity with AF. Weight loss was associated with treatment volume, independent of tumour stage. The elective treatment volume was found to be an independent risk factor for late aspiration, as well as mean dose to the pharyngeal constrictor muscles, neck dissection, and age at randomisation. There was a significant risk reduction for node relapses in volumes treated to an elective dose. Only a relapse in volumes treated to >60 Gy affected the survival.

Conclusion The present thesis questions the benefit of AF in definitive RT as well as extensive elective treatment of the cervical nodes.

Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry.

Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries.

Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number.

Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion. 

Background and purpose: Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer.

Material and methods: 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, NO glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1 + 2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment.

Results: The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline.

Conclusion: In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase.

Background and purpose: This report contains the mature five-year data from the Swedish ARTSCAN trial including information on the influence of p16 positivity (p16+) for oropharyngeal cancers. Material and methods: Patients with previously untreated squamous cell carcinoma without distant metastases of the oral cavity, oropharynx, larynx (except T1-2, NO glottic cancers) and hypopharynx were included. Patients were randomised between accelerated fractionation (AF) (1.1 Gy + 2 Gy per day, 5 days/week for 4.5 weeks, total dose 68 Gy) and conventional fractionation (CF) (2 Gy per day, 5 days/week for 7 weeks, total dose 68 Gy). Human papillomavirus (HPV)-associated p16-expression was assessed retrospectively in tumour tissues from patients with oropharyngeal carcinoma. Results: There was no significant difference in loco-regional control (LRC) between AF and CF (log-rank test p = 0.75). LRC at 5 years was 65.5% for AF and 64.9% for CF. Overall survival (OS) was similar in both arms (p = 0.99). The estimated cancer specific survival (CSS) at 5 years was 62.2% (AF) and 63.3% (CF) (p = 0.99). 206 specimens were analysed for p16 with 153 specimens (74%) identified as p16+. P16 status did not discriminate for response to AF vs. CF with regard to LRC, OS or CSS. Patients with p16+ tumours had a statistically significant better overall prognosis compared with p16 tumours. Conclusion: This update confirms the results of the 2-year report. We failed to identify a positive effect resulting from AF with regards to LRC, OS and CSS. The addition of information on the HPV-associated p16 overexpression did not explain this lack of effect.

Background: Elective treatment of lymph nodes in oropharyngeal cancer (OPC) has impact on both regional recurrences (RR) and risk of late side effects. This study was performed to quantify the dose-dependent impact on RR and overall survival (OS) in a prospectively collected cohort of OPC from the ARTSCAN study with emphasis on elective treatment. Methods: ARTSCAN is a previously published prospective, randomized, multicentre study of altered radiotherapy (RT) fractionation in head and neck cancer. In ARTSCAN the elective treatment volume for node positive OPC varied significantly between centres due to local treatment principles. All patients with OPC in complete response after primary treatment were eligible for the present case-control study. Cases were patients with RR during five years follow-up. Patients with no recurrence were eligible as controls. Four controls per case were matched according to T-and N-stage. Mean (D-mean) and median (D-50%) dose for the lymph node level (LNL) of RR in the cases and the corresponding LNL in the controls were analysed with conditional logistic regression. OS was estimated with the Kaplan-Meier method and evaluated by multivariate Cox regression analysis. Results: There was a dose-dependent risk reduction for D-50% in the interval that represented elective treatment (40-50 Gy) (OR = 0.18, p < 0.05) and a trend in the same dose interval for D-mean (OR = 0.19, p = 0.07). OS rates at five years were 0.39 (0.24-0.65) for cases and 0.70 (0.62-0.81) for controls (p < 0.001). The Kaplan-Meier and the Cox regression analysis for cases categorised by delivered dose showed an inverse relationship between dose and survival. The cases with RR in a LNL outside planning target volume (PTV) (D-mean < 40 Gy) had an OS rate comparable to that of all patients, and those with RR in a LNL in PTVelective (D-mean 40-60 Gy) or PTVtumour (D-mean > 60 Gy) did significantly worse (p < 0.05). The same inverse relationship was also shown for a small subset of patient with known HPV-status, defined by over expression of p16 (p < 0.05). Conclusions: There was a significant risk reduction for RR of elective treatment. However the OS for patients with RR outside target volumes was not affected, with similar results for patients with HPV-positive OPC. This could be an argument for a prospective randomized study on limited elective target volumes in OPC.