The Lancet Oncology, Early Online Publication, 13 January 2011

Dr Christopher M Nutting FRCR a b , James P Morden MSc b, Kevin J Harrington FRCR a b, Teresa Guerrero Urbano PhD c, Shreerang A Bhide FRCR a, Catharine Clark PhD d, Elizabeth A Miles MPhil e, Aisha B Miah FRCR a, Kate Newbold FRCR a, MaryAnne Tanay MSc a, Fawzi Adab FRCR f, Sarah J Jefferies FRCR g, Christopher Scrase FRCR h, Beng K Yap FRCR i, Roger P A’Hern MSc b, Mark A Sydenham BSc b, Marie Emson BSc b, Emma Hall PhD b, on behalf of the PARSPORT trial management group†

Summary


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. Randomization was by computer-generated permuted blocks and was stratified by centre and tumor 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).