Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial.
Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial.
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DOI：
10.1016/s1470-2045(10)70290-4
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发表时间：
2011-02
期刊：
影响因子：
51.1
通讯作者：
Hall, Emma
中科院分区：
文献类型：
--
作者：
Nutting, Christopher M.;Morden, James P.;Harrington, Kevin J.;Urbano, Teresa Guerrero;Bhide, Shreerang A.;Clark, Catharine;Miles, Elizabeth A.;Miah, Aisha B.;Newbold, Kate;Tanay, MaryAnne;Adab, Fawzi;Jefferies, Sarah J.;Scrase, Christopher;Yap, Beng K.;A'Hern, Roger P.;Sydenham, Mark A.;Emson, Marie;Hall, Emma
口腔干燥是头颈部放射治疗最常见的晚期副作用。与常规放疗相比，调强放疗（IMRT）可减少腮腺受照剂量。我们评估了保留腮腺的调强放射治疗降低严重口干症发生率的假设。我们在2003年1月21日至2007年12月7日进行了一项随机对照试验，比较了传统放疗（对照）和保留腮腺的IMRT。我们将6个英国放射治疗中心的经组织学证实的咽部鳞状细胞癌患者（T1-4，N 0 -3，M0）随机分配到两种放射治疗技术之间（1：1比例）。处方剂量为60或65戈伊，每日30次，周一至周五给药。治疗未设盲。通过计算机生成的排列区组进行随机化，并按中心和肿瘤部位分层。我们的主要终点是12个月时发生2级或更严重口干症的患者比例，通过正常组织晚期效应（LENT索马）量表进行评估。分析是在意向治疗的基础上进行的，包括所有接受评估的患者。患者的长期随访正在进行中。本研究已在国际标准随机对照试验注册中心注册，编号ISRCTN 48243537。每组47例患者，中位随访时间为44.0个月（IQR 30.0 - 59.7）。每组6例患者在12个月前死亡，7例常规放疗患者和2例IMRT组患者在12个月时未进行评估。在12个月时，82名存活患者中有73名报告了口干症副作用; IMRT组在12个月时的2级或更严重口干症明显低于常规放疗组（34例接受常规放疗的患者中有25例[74%; 95%CI 56-87]，39例接受IMRT的患者中有15例[38%; 23-55]，p= 0.0027）。两组间唯一记录的2级或更严重的急性不良事件是疲劳，IMRT组更常见（44例接受常规放疗的患者中有18例[41%; 99%CI 23-61]，47例接受IMRT的患者中有35例[74%; 55-89]，p= 0.0015）。24个月时，调强放疗组2级或更严重的口干症发生率明显低于常规放疗组（24例常规放疗患者中有20例[83%; 95%CI 63-95]，31例调强放疗患者中有9例[29%; 14-48]; p<0.0001）。在12个月和24个月时，与常规放疗相比，IMRT在恢复唾液分泌方面有显着的益处，口干特异性和整体生活质量评分也有临床显着改善。24个月时，随机分组之间在非口干症晚期毒性、局部控制或总生存率方面没有观察到显着差异。保留腮腺与调强放射治疗显着降低口干症的发病率，并导致唾液分泌的恢复和相关的生活质量的改善，因此强烈支持调强放射治疗的作用，鳞状细胞癌的头部和颈部。英国癌症研究（CRUK/03/005）。
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. 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. 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. 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. Cancer Research UK (CRUK/03/005).