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Background and Purpose: The impact of weight loss and anatomical change during head and neck (H&N) radiotherapy on spinal cord dosimetry is poorly understood, limiting evidence-based adaptive management strategies., Materials and Methods: 133 H&N patients treated with daily mega-voltage CT image-guidance (MVCT-IG) on TomoTherapy, were selected. Elastix software was used to deform planning scan SC contours to MVCT-IG scans, and accumulate dose. Planned (D P ) and delivered (D A ) spinal cord D 2% (SCD 2% ) were compared. Univariate relationships between neck irradiation strategy (unilateral vs bilateral), T-stage, N-stage, weight loss, and changes in lateral separation (LND) and CT slice surface area (SSA) at C1 and the superior thyroid notch (TN), and ΔSCD 2% [(D A - D P ) D 2% ] were examined., Results: The mean value for (D A - D P ) D 2% was -0.07 Gy (95%CI -0.28 to 0.14, range -5.7 Gy to 3.8 Gy), and the mean absolute difference between D P and D A (independent of difference direction) was 0.9 Gy (95%CI 0.76-1.04 Gy). Neck treatment strategy (p = 0.39) and T-stage (p = 0.56) did not affect ΔSCD 2% . Borderline significance (p = 0.09) was seen for higher N-stage (N2-3) and higher ΔSCD 2% . Mean reductions in anatomical metrics were substantial: weight loss 6.8 kg; C1LND 12.9 mm; C1SSA 12.1 cm 2 ; TNLND 5.3 mm; TNSSA 11.2 cm 2 , but no relationship between weight loss or anatomical change and ΔSCD 2% was observed (all r 2  < 0.1)., Conclusions: Differences between delivered and planned spinal cord D 2% are small in patients treated with daily IG. Even patients experiencing substantial weight loss or anatomical change during treatment do not require adaptive replanning for spinal cord safety., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: L'Hermitte's sign (LS) after chemoradiotherapy for head and neck cancer appears related to higher spinal cord doses. IMRT plans limit spinal cord dose, but the incidence of LS remains high., Methods: One hundred seventeen patients treated with TomoTherapy™ between 2008 and 2015 prospectively completed a side-effect questionnaire (VoxTox Trial Registration: UK CRN ID 13716). Baseline patient and treatment data were collected. Radiotherapy plans were analysed; mean and maximum spinal cord dose and volumes receiving 10, 20, 30 and 40 Gy were recorded. Dose variation across the cord was examined. These data were included in a logistic regression model., Results: Forty two patients (35.9%) reported LS symptoms. Concurrent weekly cisplatin did not increase LS risk (p = 0.70, OR = 1.23 {95% CI 0.51-2.34}). Of 13 diabetic participants (9 taking metformin), only 1 developed LS (p = 0.025, OR = 0.13 {95% CI 0.051-3.27}). A refined binary logistic regression model showed that patients receiving unilateral radiation (p = 0.019, OR = 2.06 {95% CI 0.15-0.84}) were more likely to develop LS. Higher V 40Gy (p = 0.047, OR = 1.06 {95% CI 1.00-1.12}), and younger age (mean age 56.6 vs 59.7, p = 0.060, OR = 0.96 {95% CI 0.92-1.00}) were associated with elevated risk of LS, with borderline significance., Conclusions: In this cohort, concomitant cisplatin did not increase risk, and LS incidence was lower in diabetic patients. Patient age and dose gradients across the spinal cord may be important factors.

To determine delivered dose to the spinal cord, a technique has been developed to propagate manual contours from kilovoltage computed-tomography (kVCT) scans for treatment planning to megavoltage computed-tomography (MVCT) guidance scans. The technique uses the Elastix software to perform intensity-based deformable image registration of each kVCT scan to the associated MVCT scans. The registration transform is then applied to contours of the spinal cord drawn manually on the kVCT scan, to obtain contour positions on the MVCT scans. Different registration strategies have been investigated, with performance evaluated by comparing the resulting auto-contours with manual contours, drawn by oncologists. The comparison metrics include the conformity index (CI), and the distance between centres (DBC). With optimised registration, auto-contours generally agree well with manual contours. Considering all 30 MVCT scans for each of three patients, the median CI is [Formula: see text], and the median DBC is ([Formula: see text]) mm. An intra-observer comparison for the same scans gives a median CI of [Formula: see text] and a DBC of ([Formula: see text]) mm. Good levels of conformity are also obtained when auto-contours are compared with manual contours from one observer for a single MVCT scan for each of 30 patients, and when they are compared with manual contours from six observers for two MVCT scans for each of three patients. Using the auto-contours to estimate organ position at treatment time, a preliminary study of 33 patients who underwent radiotherapy for head-and-neck cancers indicates good agreement between planned and delivered dose to the spinal cord.

Background: Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia., Methods: We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1-4, N0-3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537., Findings: 47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0-59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56-87] of 34 patients given conventional radiotherapy vs 15 [38%; 23-55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (18 [41%; 99% CI 23-61] of 44 patients given conventional radiotherapy vs 35 [74%; 55-89] of 47 given IMRT, p=0·0015). At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63-95] of 24 patients given conventional radiotherapy vs nine [29%; 14-48] of 31 given IMRT; p<0·0001). At 12 and 24 months, significant benefits were seen in recovery of saliva secretion with IMRT compared with conventional radiotherapy, as were clinically significant improvements in dry-mouth-specific and global quality of life scores. At 24 months, no significant differences were seen between randomised groups in non-xerostomia late toxicities, locoregional control, or overall survival., Interpretation: Sparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamous-cell carcinoma of the head and neck., Funding: Cancer Research UK (CRUK/03/005)., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aims: To quantify the changes in contours of the target and organs at risk and the differences between planned and delivered doses to the target and organs at risk during the course of radiotherapy in head and neck cancer patients treated with intensity-modulated radiotherapy on the TomoTherapy HiArt™ system., Materials and Methods: Five patients with squamous cell carcinoma of the head and neck treated with radical chemoradiotherapy using the TomoTherapy HiArt system were included in the study. The target volumes were treated to three different dose levels depending on the level of clinical risk for harbouring disease. Patient positions were assessed daily with megavoltage computed tomography (MVCT) and positional correction made before each treatment when necessary. MVCTs were superimposed on to the planning kilovoltage computed tomography images for each patient and target volumes and organ at risk volumes were re-outlined on MVCT images. Doses to clinical target volumes and organs at risk were recalculated to show the actual delivered doses., Results: There was shrinkage in the volume of the parotid glands during treatment in all cases. The mean volume reduction in the ipsilateral parotid gland was more marked at 30.2%, compared with the contralateral parotid glands. However, the mean percentage dose per fraction increase was higher in the contralateral parotid glands at 24%, compared with the ipsilateral parotids. The calculated doses were higher than the planned doses in all CTV-54, CTV-60 and CTV-68, but the mean dose differences were modest, in the range 1.3-2.4%., Conclusions: We have shown that there were considerable changes in the volume and dose to the parotids during treatment. The changes in volume and dose to the clinical target volume were more modest in comparison. Adaptive radiotherapy planning can be helpful in improving the dose to the parotid glands. However, its role in the optimisation of the dosage to the clinical target volume is less likely to result in a significant clinical benefit., (Copyright © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: Radiotherapy is an important treatment option for paraganglioma in the head and neck region. It seems to be highly effective and avoids important surgical morbidity, which can impair quality of life. The aim of this study was to evaluate the outcomes of radiotherapy for paraganglioma of the head and neck region in order to inform our future practice., Materials and Methods: The cohort of patients for the present study comprised 21 patients who received radiotherapy between 1998 and 2008. Follow-up ranged from 6 to 132 months, median 55 months. The mean age was 48.7 years, range 20-78 years. The female:male ratio was 2 : 1. Two patients had confirmed familial tumour syndromes. The gross tumour volume in 20 cases ranged from 1.3 to 74 cm(3), mean 23.2 cm(3), median 14.7 cm(3). Five patients were treated with intensity-modulated radiotherapy. The median dose was 50 Gy in 30 fractions., Results: The crude 5-year local control rate was 95% (20/21), although the 5-year actuarial local control rate was 87%. The one patient who relapsed, at 45 months after radiotherapy, had a comparatively small tumour of 10.8 cm(3). A relationship between tumour volume and local control seems unlikely. It was possible to obtain details of side-effects from electronic records for 11 patients. Grade 3 headache, which resolved, was the most serious acute side-effect. One patient had three teeth extracted due to exacerbation of dental caries, and one had deterioration of hearing thought to be due to a combination of tumour and radiotherapy. There were two serious complications in patients who had embolisation, which we no longer use., Conclusions: Our results show a high level of efficacy for fractionated external beam radiotherapy, with minimal toxicity, in keeping with other series. This should encourage the use of radiotherapy as primary treatment for paragangliomas of the head and neck region., (Copyright 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: To assess the effectiveness of different on-treatment correction strategies on set-up accuracy in patients with head and neck cancer (HNC) treated on a TomoTherapy HiArt system. To assess the adequacy of clinical target volume (CTV) to planning target volume (PTV) treatment planning margins when treating with intensity-modulated radiotherapy without daily image guidance., Materials and Methods: The set-up accuracy measured by daily online volumetric imaging was retrospectively reviewed for the first 15 patients with HNC treated on the TomoTherapy unit at Addenbrooke's Hospital. For each fraction, megavoltage computed tomography was carried out, any discrepancy from the planning scan was noted, and corrected, before treatment. These data were used to evaluate imaging correction protocols using three different action levels. The first three fractions were imaged and used to correct for systematic error, using a 5 mm action level (5 mmAL), a 3 mm action level (3 mmAL), and no action level (NAL). All imaging strategies were applied, to assess the number of fractions that would potentially have exceeded a 5 and 3 mm margin. Systematic and random errors were calculated for the population, assuming the NAL protocol had been applied, and minimum CTV-PTV margins, required to allow for errors attributable only to set-up, were calculated using van Herk's formula., Results: In total, 490 fractions were analysed. Using a 5 mmAL imaging protocol, potentially 198/490 fractions (40%) were outside a 5 mm CTV-PTV margin and 400/490 (82%) were outside a 3 mm margin. Using a 3 mmAL imaging protocol, potentially 67/490 fractions (14%) were outside a 5 mm CTV-PTV margin and 253/490 (52%) were outside a 3 mm margin. A small systematic error was identified in the system; once corrected this would improve these results. Using the NAL imaging protocol, potentially 31/490 fractions (6%) were outside a 5 mm CTV-PTV margin and 143/490 fractions (29%) were outside a 3 mm margin. Estimated minimum CTV-PTV margins to account only for set-up errors, with three-fraction image-guided radiotherapy and a NAL protocol, were 2.8, 3.1 and 4.1 mm in the mediolateral, superior-inferior and anterior-posterior directions, respectively., Conclusion: Reducing the action level at which the systematic error is corrected improves the probability of treatment delivery accuracy. Using the NAL correction protocol reduces the number of fractions that have set-up displacements outside a 5 mm CTV-PTV margin. Although a 5 mm margin is probably sufficient for standard HNC radiotherapy, change to a 3 mm margin is not favoured at our centre without access to daily image-guided radiotherapy.