Department of Otolaryngology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou Key Laboratory of Otorhinolaryngology, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.
Department of Otolaryngology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou Key Laboratory of Otorhinolaryngology, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
Lancet Oncol. 2021 Mar;22(3):381-390. doi: 10.1016/S1470-2045(20)30673-2. Epub 2021 Feb 15.
The role of surgery compared with reirradiation in the primary treatment of patients with resectable, locally recurrent nasopharyngeal carcinoma (NPC) who have previously received radiotherapy is a matter of debate. In this trial, we compared the efficacy and safety outcomes of salvage endoscopic surgery versus intensity-modulated radiotherapy (IMRT) in patients with resectable locally recurrent NPC.
This multicentre, open-label, randomised, controlled, phase 3 trial was done in three hospitals in southern China. We included patients aged 18-70 years with a Karnofsky Performance Status score of at least 70 who were histopathologically diagnosed with undifferentiated or differentiated, non-keratinising, locally recurrent NPC with tumours confined to the nasopharyngeal cavity, the post-naris or nasal septum, the superficial parapharyngeal space, or the base wall of the sphenoid sinus. Eligible patients were randomly assigned (1:1) to receive either endoscopic nasopharyngectomy (ENPG group) or IMRT (IMRT group). Randomisation was done manually using a computer-generated random number code and patients were stratified by treatment centre. Treatment group assignment was not masked. The primary endpoint was overall survival, compared between the groups at 3 years. Efficacy analyses were done by intention to treat. Safety analysis was done in patients who received treatment according to the treatment they actually received. This trial was prospectively registered at the Chinese Clinical Trial Registry, ChiCTR-TRC-11001573, and is currently in follow-up.
Between Sept 30, 2011, and Jan 16, 2017, 200 eligible patients were randomly assigned to receive either ENPG (n=100) or IMRT (n=100). At a median follow-up of 56·0 months (IQR 42·0-69·0), 74 patients had died (29 [29%] of 100 patients in the ENPG group and 45 [45%] of 100 patients in the IMRT group). The 3-year overall survival was 85·8% (95% CI 78·9-92·7) in the ENPG group and 68·0% (58·6-77·4) in the IMRT group (hazard ratio 0·47, 95% CI 0·29-0·76; p=0·0015). The most common grade 3 or worse radiation-related late adverse event was pharyngeal mucositis (in five [5%] of 99 patients who underwent ENPG and 26 [26%] of 101 patients who underwent IMRT). Five [5%] of the 99 patients who underwent ENPG and 20 [20%] of the 101 patients who underwent IMRT died due to late toxic effects specific to radiotherapy; attribution to previous radiotherapy or trial radiotherapy is unclear due to the long-term nature of radiation-related toxicity.
Endoscopic surgery significantly improved overall survival compared with IMRT in patients with resectable locally recurrent NPC. These results suggest that ENPG could be considered as the standard treatment option for this patient population, although long-term follow-up is needed to further determine the efficacy and toxicity of this strategy.
Sun Yat-sen University Clinical Research 5010 Program.
对于先前接受过放疗的可切除局部复发性鼻咽癌（NPC）患者，手术与再放疗在初次治疗中的作用一直存在争议。在这项试验中，我们比较了可切除局部复发性 NPC 患者中挽救性内镜手术与调强放疗（IMRT）的疗效和安全性结局。
这是一项在中国南方三家医院进行的多中心、开放性标签、随机、对照、III 期试验。我们纳入了年龄在 18-70 岁之间、卡氏行为状态评分至少为 70 分、经组织病理学诊断为未分化或分化型、非角化性、局部复发性 NPC 的患者，肿瘤局限于鼻咽腔、后鼻孔或鼻中隔、浅表咽旁间隙或蝶窦底壁。符合条件的患者被随机分配（1:1）接受内镜鼻咽切除术（ENPG 组）或 IMRT（IMRT 组）。采用计算机生成的随机数码进行手动随机分组，按治疗中心进行分层。治疗组分配未设盲。主要终点为 3 年总生存率，两组之间的比较。疗效分析采用意向治疗。根据实际接受的治疗对接受治疗的患者进行安全性分析。该试验在中国临床试验注册中心（ChiCTR-TRC-11001573）进行了前瞻性注册，目前正在随访中。
2011 年 9 月 30 日至 2017 年 1 月 16 日，纳入了 200 名符合条件的患者，随机分为接受 ENPG（n=100）或 IMRT（n=100）组。中位随访时间为 56.0 个月（IQR 42.0-69.0），74 名患者死亡（ENPG 组 29 [29%]例和 IMRT 组 45 [45%]例）。ENPG 组 3 年总生存率为 85.8%（95%CI 78.9-92.7），IMRT 组为 68.0%（58.6-77.4）（风险比 0.47，95%CI 0.29-0.76；p=0.0015）。最常见的 3 级或更严重的放射性迟发性不良反应是咽粘膜炎（ENPG 组 99 例中有 5 例[5%]，IMRT 组 101 例中有 26 例[26%]）。ENPG 组 99 例中有 5 例[5%]和 IMRT 组 101 例中有 20 例[20%]因与放疗相关的特定晚期毒性而死亡；由于放射性毒性的长期性质，无法明确归因于先前的放疗或试验放疗。
与 IMRT 相比，内镜手术显著提高了可切除局部复发性 NPC 患者的总生存率。这些结果表明，ENPG 可被视为该患者人群的标准治疗选择，尽管需要长期随访以进一步确定该策略的疗效和毒性。
中山大学临床研究 5010 计划。
