Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial

Abstract

SummaryBackgroundXerostomia 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.MethodsWe 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.Findings47 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.InterpretationSparing 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 fo...

The suitability of common metrics for assessing parotid and larynx autosegmentation accuracy

“…IMRT has been shown to benefit patients in the head and neck, 3 , 4 , 5 with the PARSPORT trial (Institute of Cancer Research, London, UK) demonstrating reduced incidence of xerostomia in patients treated with parotid‐sparing IMRT relative to those treated with conformal radiotherapy (6) . However, in order to realize the benefits afforded by IMRT, accurate delineation of targets and normal structures is essential (7) …”

Dosimetric evaluation of the Acuros XB algorithm for a 4 MV photon beam in head and neck intensity‐modulated radiation therapy

“…Particularly, radiation‐induced xerostomia is one of the most commonly reported long‐term side effects of radiation therapy for head and neck cancers. Intensity‐modulated radiation therapy (IMRT) can spare the major salivary glands and aid saliva flow recovery (6) . Kan et al (7) assessed the dosimetric impact of using AXB instead of AAA for the treatment of nasopharyngeal carcinoma with IMRT using a 6 MV photon beam.…”

Dose variations in tumor volumes and organs at risk during IMRT for head‐and‐neck cancer

“…Highly conformal radiation allows for a high dose to high‐risk areas, whilst sparing adjacent organs at risk (OAR) such as the parotid glands. Clinical studies have shown that IMRT reduces grade‐3 xerostomia in comparison to three‐dimensional conformal radiotherapy (3D CRT) 4 , 5 . For that reason, IMRT has become the standard treatment in many centers.…”