Parotid-sparing intensity modulated versus conventional radiotherapy in XXXX (PARSPORT): a phase 3 multicentre randomised controlled trial.

@entity1 @entity135 @entity137 @entity5 @entity2133 @entity957
BACKGROUND: @entity2133 is the most common late side-effect of radiotherapy to the @entity135 . 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 @entity2133 . 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 @entity1 with histologically confirmed @entity957 (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 @entity5 site. Our primary endpoint was the proportion of @entity1 with grade 2 or worse @entity2133 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 @entity1 who had assessments included. Long-term follow-up of @entity1 is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537. FINDINGS: 47 @entity1 were assigned to each treatment arm. Median follow-up was 44  0 months (IQR 30  0-59  7). Six @entity1 from each group died before 12 months and seven @entity1 from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months @entity2133 side-effects were reported in 73 of 82 alive @entity1 ; grade 2 or worse @entity2133 at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56-87] of 34 @entity1 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 @entity1 given conventional radiotherapy vs 35 [74%; 55-89] of 47 given IMRT, p=0  0015). At 24 months, grade 2 or worse @entity2133 was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63-95] of 24 @entity1 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- @entity2133 late @entity137 , locoregional control, or overall survival. INTERPRETATION: Sparing the parotid glands with IMRT significantly reduces the incidence of @entity2133 and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in @entity957 of the @entity135 . FUNDING: Cancer Research UK (CRUK/03/005).
