4 Gy 与 24 Gy 放疗治疗惰性淋巴瘤患者（FORT）：一项随机 3 期非劣效性试验。
4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a randomised phase 3 non-inferiority trial.
机构信息
Mount Vernon Cancer Centre, Northwood, Middlesex, UK.
Cancer Research UK and UCL Cancer Trials Centre, London, UK.
出版信息
Lancet Oncol. 2014 Apr;15(4):457-63. doi: 10.1016/S1470-2045(14)70036-1. Epub 2014 Feb 24.
BACKGROUND
Follicular lymphoma has been shown to be highly radiosensitive with responses to doses as low as 4 Gy in two fractions. This trial was designed to explore the dose response for follicular lymphoma comparing 4 Gy in two fractions with 24 Gy in 12 fractions
METHODS
FORT is a prospective randomised, unblinded, phase 3 non-inferiority study comparing radiotherapy given as 4 Gy in two fractions with a standard dose of 24 Gy in 12 fractions. Entry criteria included all patients aged over 18 years, having local radiotherapy for radical or palliative local control, with follicular lymphoma or marginal zone lymphoma, who had received no previous treatment for at least 1 month before. The primary outcome was time to local progression analysed on an intention-to-treat basis. Randomisation was centralised through the Cancer Research UK and University College London Cancer Trials Centre. Radiotherapy target sites were randomised (1:1) with minimisation stratified by histology (follicular lymphoma vs marginal zone lymphoma), treatment intent (palliative or curative) and centre. This trial is registered with ClinicalTrials.gov number, NCT00310167.
FINDINGS
299 sites were randomly assigned to 24 Gy and 315 sites to 4 Gy between April 7, 2006, and June 8, 2011, at 43 centres in the UK. After a median follow-up of 26 months (range 0·39-75·4), 91 local progressions had been recorded (21 in the 24 Gy group and 70 in the 4 Gy group). Time to local progression with 4 Gy was not non-inferior to 24 Gy (hazard ratio 3·42, 95% CI 2·09-5·55, p<0·0001). Eight (3%) of 282 patients in the 24 Gy group and four (1%) of 300 in the 4 Gy group had acute grade 3-4 toxic effects. Four (1%) patients in the 24 Gy group and four (1%) patients in the 4 Gy group had late toxic effects. Mucositis was the most common event in the 24 Gy group (two patients with acute mucositis and two with late mucositis; all grade 3) and was not reported in the 4 Gy group. The most common acute effect was pain at the site of irradiation (two patients in the 4 Gy group, one patient in the 24 Gy group; all grade 3), and the most common late effect was fatigue (two patients in the 4 Gy group, one patient in the 24 Gy group; all grade 3).
INTERPRETATION
24 Gy in 12 fractions is the more effective radiation schedule for indolent lymphoma and should be regarded as the standard of care. However, 4 Gy remains a useful alternative for palliative treatment.
FUNDING
Cancer Research UK.
背景
滤泡性淋巴瘤对剂量非常敏感，在两次分割中低至 4 Gy 即可产生反应。这项试验旨在通过比较 4 Gy 两次分割与 24 Gy 12 次分割，探索滤泡性淋巴瘤的剂量反应。
方法
FORT 是一项前瞻性随机、非盲、III 期非劣效性研究，比较了 4 Gy 两次分割与标准剂量 24 Gy 12 次分割的放疗。纳入标准包括所有年龄大于 18 岁的患者，因根治性或姑息性局部控制而接受局部放疗，患有滤泡性淋巴瘤或边缘区淋巴瘤，在至少 1 个月前未接受过任何治疗。主要结局为意向治疗分析的局部进展时间。通过英国癌症研究中心和伦敦大学学院癌症试验中心进行中央随机化。通过最小化按组织学（滤泡性淋巴瘤与边缘区淋巴瘤）、治疗意图（姑息性或根治性）和中心分层，对放疗靶区进行随机化（1:1）。这项试验在 ClinicalTrials.gov 注册号为 NCT00310167 注册。
结果
2006 年 4 月 7 日至 2011 年 6 月 8 日，在英国的 43 个中心，299 个部位随机分配至 24 Gy 组，315 个部位随机分配至 4 Gy 组。在中位随访 26 个月（范围 0.39-75.4）后，记录了 91 例局部进展（24 Gy 组 21 例，4 Gy 组 70 例）。4 Gy 的局部进展时间不比 24 Gy 差（风险比 3.42，95%CI 2.09-5.55，p<0.0001）。24 Gy 组 282 例患者中有 8 例（3%）和 4 Gy 组 300 例患者中有 4 例（1%）发生急性 3-4 级毒性反应。24 Gy 组有 4 例（1%）和 4 Gy 组有 4 例（1%）患者发生迟发性毒性反应。24 Gy 组最常见的急性毒性反应是 3 级-4 级粘膜炎（2 例）和迟发性粘膜炎（2 例；均为 3 级），而 4 Gy 组未报告。24 Gy 组最常见的急性效应是照射部位疼痛（4 Gy 组 2 例，24 Gy 组 1 例；均为 3 级），最常见的迟发性效应是疲劳（4 Gy 组 2 例，24 Gy 组 1 例；均为 3 级）。
结论
24 Gy 12 次分割是惰性淋巴瘤更有效的放疗方案，应被视为标准治疗。然而，4 Gy 仍然是姑息性治疗的有用选择。
资金来源
英国癌症研究中心。
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