Adjuvant radiotherapy versus observation alone for patients at risk of lymph-node field relapse after therapeutic lymphadenectomy for melanoma: a randomised trial
Adjuvant radiotherapy versus observation alone for patients at risk of lymph-node field relapse after therapeutic lymphadenectomy for melanoma: a randomised trial
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DOI：
10.1016/s1470-2045(12)70138-9
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发表时间：
2012-06-01
期刊：
影响因子：
51.1
通讯作者：
Thompson, John F.
中科院分区：
文献类型：
--
作者：
Burmeister, Bryan H.;Henderson, Michael A.;Thompson, John F.
背景：对于有进一步淋巴结转移和远处复发高风险的黑色素瘤患者，治疗性淋巴结切除术后放射治疗的使用是有争议的。在这种情况下，放射治疗的决定是基于回顾性、非随机研究。我们做了这个随机试验，以评估淋巴结领域控制的患者谁经历了治疗性淋巴结切除术转移性黑色素瘤在regional lymph nodes.Methods这个随机对照试验包括16家医院在澳大利亚，新西兰，荷兰和巴西的患者辅助放疗的效果。为了符合这项试验的条件，患者必须处于淋巴结区域复发的高风险中，根据受累淋巴结的数量、淋巴结扩散和受累淋巴结的最大尺寸进行判断。淋巴结切除术后，通过计算机集中进行随机化，并通过电话以1：1的比例将患者分配至接受48戈伊的辅助放疗（分20次）或观察，将机构、淋巴结野、受累淋巴结数量、最大淋巴结直径和淋巴结扩散程度作为最小化因素。参与者、给予治疗的人和评估结果的人对治疗分配不设盲。主要终点是淋巴结野复发（作为首次复发），对所有合格患者进行分析。该研究在ClinicalTrials.gov上注册，编号为NCT 00287196。结果123例患者被随机分配到辅助放疗组和127到观察组之间的2002年3月20日，2007年9月21日。2例患者撤回知情同意书，31例患者根据独立数据监测委员会的决定存在重大资格违规，导致217例患者符合主要分析的条件（辅助放疗组109例，观察组108例）。中位随访时间为40个月（IQR 27-55）。与观察组相比，辅助放疗组的淋巴结区域复发风险显著降低（放疗组复发20例，观察组复发34例，HR 0.56，95% CI 0.32-0.98; p=0.041），但无复发生存率无差异（70 vs 73起事件，HR 0.91，95% CI 0.65-1.26; p=0.56）或总生存期（59 vs 47例死亡，HR 1.37，95% CI 0.94-2.01; p=0.12）。最常见的3级和4级不良事件是血清肿（放疗组9例，观察组11例），放射性皮炎放疗组19例，和伤口感染（放疗组3例，观察组7例）。解释辅助放疗可改善淋巴结转移高危患者的淋巴结野控制。转移性黑色素瘤治疗性淋巴结切除术后的淋巴结区域复发。淋巴结切除术后复发风险高的患者应讨论辅助放疗。
Background The use of radiotherapy after therapeutic lymphadenectomy for patients with melanoma at high risk of further lymph-node field and distant recurrence is controversial. Decisions for radiotherapy in this setting are made on the basis of retrospective, non-randomised studies. We did this randomised trial to assess the effect of adjuvant radiotherapy on lymph-node field control in patients who had undergone therapeutic lymphadenectomy for metastatic melanoma in regional lymph nodes.Methods This randomised controlled trial included patients from 16 hospitals in Australia, New Zealand, the Netherlands, and Brazil. To be eligible for this trial, patients had to be at high risk of lymph-node field relapse, judged on the basis of number of nodes involved, extranodal spread, and maximum size of involved nodes. After lymphadenectomy, randomisation was done centrally by computer and patients assigned by telephone in a ratio of 1: 1 to receive adjuvant radiotherapy of 48 Gy in 20 fractions or observation, with institution, lymph-node field, number of involved nodes, maximum node diameter, and extent of extranodal spread as minimisation factors. Participants, those giving treatment, and those assessing outcomes were not masked to treatment allocation. The primary endpoint was lymph-node field relapse (as a first relapse), analysed for all eligible patients. The study is registered at ClinicalTrials.gov, number NCT00287196. The trial is now closed and follow-up discontinued.Findings 123 patients were randomly allocated to the adjuvant radiotherapy group and 127 to the observation group between March 20, 2002, and Sept 21, 2007. Two patients withdrew consent and 31 had a major eligibility infringement as decided by the independent data monitoring committee, resulting in 217 eligible for the primary analysis (109 in the adjuvant radiotherapy group and 108 in the observation group). Median follow-up was 40 months (IQR 27-55). Risk of lymph-node field relapse was significantly reduced in the adjuvant radiotherapy group compared with the observation group (20 relapses in the radiotherapy group vs 34 in the observation group, hazard ratio [HR] 0.56, 95% CI 0.32-0.98; p=0.041), but no differences were noted for relapse-free survival (70 vs 73 events, HR 0.91, 95% CI 0.65-1.26; p=0.56) or overall survival (59 vs 47 deaths, HR 1.37, 95% CI 0.94-2.01; p=0.12). The most common grade 3 and 4 adverse events were seroma (nine in the radiotherapy group vs 11 in the observation group), radiation dermatitis (19 in the radiotherapy group), and wound infection (three in the radiotherapy group vs seven in the observation group).Interpretation Adjuvant radiotherapy improves lymph-node field control in patients at high risk of lymph-node field relapse after therapeutic lymphadenectomy for metastatic melanoma. Adjuvant radiotherapy should be discussed with patients at high risk of relapse after lymphadenectomy.