Long-term Results of the Phase II Dose and Volume De-escalation Trial for Locoregionally Advanced Nasopharyngeal Carcinoma

Objective: Patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) were assigned to dose and volume de-escalated intensity-modulated radiation therapy (IMRT) based on response to induction chemotherapy (IC) to limit treatment related toxicity while preserving efficacy.
Methods and materials: A single-arm de-escalated phase II trial was performed in this study. Patients with LANPC received two cycles of IC with docetaxel 60 mg/m² d1, cisplatin 25 mg/m2/day d1-3 and 5-fluorouracil 500 mg/m2/day d1-5 q21d, followed by IMRT. The gross tumor volume of the primary intracavity nasopharyngeal tumor and involved lymph nodes were delineated based on the post-IC tumor extension. Part of the prescribed doses were reduced from 70.4 Gy to 66 Gy for T3-4 diseases. The primary end point was 5-year progression-free survival (PFS) in stage III and IVA-B NPC compared with historical controls of 50% and 35%.
Results: Between January 2010 and November 2013, 48 and 83 eligible patients with stage III and IVA-B NPC were accrued to this trial. With a median follow-up of 92 months, the 5-year and 8-year estimated PFS were 89.6% and 76.0%, 63.9% and 58.0% for patients with stage III and IVA-B disease, which were all improved in comparison with historical controls. Grade 3 acute mucositis were developed in 27.5% patients. Cranial neuropathy and asymptomatic temporal lobe necrosis were found in 2.3% and 1.5% patients.
Conclusion: Dose and volume de-escalated IMRT was associated with high PFS and mild late neurological toxicities for IC responders. Further exploration of de-escalation strategies in appropriate patients is needed.

研究目标：对于局部晚期鼻咽癌（LANPC）患者，基于对诱导化疗（IC）的反应，将其分配至剂量和体积递减的调强放射治疗（IMRT），以限制治疗相关毒性同时保持治疗效果。研究方法与材料：本研究进行了一项单臂递减的II期临床试验。局部晚期鼻咽癌患者接受了2个周期的诱导化疗，包括60 mg/m²的紫杉醇（d1）、25 mg/m²/日的顺铂（d1-3）和500 mg/m²/日的5-氟尿嘧啶（d1-5），每21天一次，随后进行调强放射治疗。根据诱导化疗后的肿瘤扩展情况，确定了原发性腔内鼻咽肿瘤和受累淋巴结的总体肿瘤体积。对于T3-4疾病，部分推荐剂量从70.4 Gy降至66 Gy。主要终点是与历史对照的50%和35%相比，III期和IVA-B期鼻咽癌患者的5年无进展生存率（PFS）。研究结果：在2010年1月至2013年11月期间，共有48例和83例符合资格的III期和IVA-B期鼻咽癌患者被纳入本研究。中位随访时间为92个月，III期和IVA-B期患者的5年和8年估计PFS分别为89.6%和76.0%，63.9%和58.0%，均优于历史对照。27.5%的患者出现了3级急性黏膜炎。2.3%的患者出现颅神经病变，1.5%的患者出现无症状的颞叶坏死。研究结论：对于诱导化疗反应者，剂量和体积递减的调强放射治疗与高PFS和轻微的晚期神经毒性相关。在适当的患者中进一步探索递减策略是必要的。