Dose intensified hypofractionated intensity-modulated radiotherapy with synchronous cetuximab for intermediate stage head and neck squamous cell carcinoma.

BACKGROUND: For stage II and III head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy alone, loco-regional recurrence is the main cause of treatment failure. Strategies to improve loco-regional control should not be at the expense of increased late normal tissue toxicity. We investigated dose-intensified hypofractionated intensity-modulated radiotherapy (IMRT) with synchronous cetuximab. MATERIAL AND METHODS: In a phase I/II trial, 27 patients with stage III or high risk stage II HNSCC were recruited. They received three dose level simultaneous integrated boost IMRT, 62.5 Gy in 25 daily fractions to planning target volume one over five weeks with synchronous cetuximab. The primary endpoint was acute toxicity. Secondary endpoints included: late toxicity and quality of life; loco-regional control, cause-specific and overall survival. RESULTS: Radiotherapy was completed by 26/27 patients; for one (4%) the final fraction was omitted due to skin toxicity. All cycles of cetuximab were received by 23/27 patients. Grade 3 acute toxicities included: pain (81%), oral mucositis (78%) and dysphagia (41%). There were few grade 3 physician-recorded late toxicities, including: pain (11%), problems with teeth (8%) and weight loss (4%). At 12 months, only one (4%) patient required a feeding tube, inserted prior to treatment due to dysphagia. The maximal/peak rates of patient-reported late toxicities included: severe pain (11%), any dry mouth (89%) and swallowing dysfunction that required a soft/liquid diet (23%). At 12 months, all quality of life and most symptoms mean scores had resolved to baseline or were only a little worse; dry mouth, sticky saliva and dentition scores remained very much worse. At a median follow-up of 47 months, there were five (18.5%) loco-regional recurrences and the overall cause-specific survival was 79% (95% CI 53-92). CONCLUSIONS: This regimen is safe with acceptable acute toxicity, low rates of late toxicity and impact on quality of life at 12 months following treatment. Further evaluation is recommended.

Use of a novel atlas for muscles of mastication to reduce inter observer variability in head and neck radiotherapy contouring.

PURPOSE/OBJECTIVE(S): Trismus is caused by injury to the masticatory muscles resulting from cancer or its treatment. Contouring these muscles to reduce dose and radiation related trismus can be problematic due to interobserver variability. This study aimed to evaluate the reduction in interobserver variability achievable with a new contouring atlas. MATERIALS/METHODS: The atlas included: medial and lateral pterygoids (MP, LP), masseter (M) and temporalis (T) muscles, and the temporo-mandibular joint (TMJ). Seven clinicians delineated five paired structures on CT scans from 5 patients without the atlas. After ≥5 weeks, contouring was repeated using the atlas. Using contours generated by the clinicians on the same 5 CT scans as reference, dice similarity coefficient (DSC), mean distance-to-agreement (DTA) and centre of mass (COM) difference were compared with and without the atlas. Comparison was also performed split by training grade. Mean and standard deviation (SD) values were measured. RESULTS: The atlas reduced interobserver variability for all structures. Mean DTA significantly improved for MP (p = 0.01), M (p < 0.01), T (p < 0.01) and TMJ (p < 0.01). Mean DTA improved using the atlas for the trainees across all muscles, with the largest reduction in variability observed for the T (4.3 ±â€¯7.1 v 1.2 ±â€¯0.4 mm, p = 0.06) and TMJ (2.1 ±â€¯0.7 v 0.8 ±â€¯0.3 mm, p < 0.01). Distance between the COM and interobserver variability reduced in all directions for MP and T. CONCLUSION: A new atlas for contouring masticatory muscles during radiotherapy planning for head and neck cancer reduces interobserver variability and could be used as an educational tool.