O'Sullivan Brian, Hui Huang Shao, Keane Thomas, Xu Wei, Su Jie, Waldron John, Gullane Patrick, Liu Fei-Fei, Warde Padraig, Payne David, Tong Li, Cummings Bernard
Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Department of Otolaryngology-Head and Neck Surgery, Princess Margaret Cancer Centre, University of Toronto, Canada.
Clin Transl Radiat Oncol. 2020 Jan 28;21:69-76. doi: 10.1016/j.ctro.2020.01.003. eCollection 2020 Mar.
PURPOSE/OBJECTIVES: To examine the therapeutic ratio and mortality profile over time in a radiotherapy randomized trial in stage III-IV larynx/pharynx cancer with long-term follow-up.
MATERIALS/METHODS: From 1988 to 1995, 331 cases were randomized to either hyperfractionated (HF) (58 Gy/40 fractions, twice daily) or conventional (CF) (51 Gy/20 fractions, once daily) radiotherapy. Overall survival (OS), locoregional (LRC), distant control (DC), ≥Grade 3 late toxicity (LT), and relative mortality risk profile over time were compared between both arms.
Median follow-up was 13.6 years. HF had a 10% improved OS at 5-years (40% vs 30%, p = 0.04), but the benefit diminished to 3% at 10-years (21% vs 18%). A trend towards higher LRC with HF remained (5-year: 49% vs 40%; 10-year: 49% vs 39%, p = 0.05). DC rates were unchanged (5-year: 87% vs 85%; 10-year: 87 vs 84%, p = 0.56). LT rates were similar (HF vs CF: 5-year: 9% vs 12%; 10-year: 11% vs 14%, p = 0.27). Multivariable analysis confirmed that HF reduced mortality risk by 31% [HR 0.69 (0.55-0.88), p < 0.01] and locoregional failure risk by 35% [HR 0.65 (0.48-0.89), p < 0.01]. Index cancer mortality (5-year: 46% vs 51%; 10-year: 49% vs 55%) was lower in the HF arm. Competing mortality (mostly smoking-related) was also numerically lower with HF at 5-years (14% vs 19%) but became similar at 10-years (30% vs 28%).
This trial confirms that HF with augmented total dose has a durable 10% effect size on LRC with comparable LT. OS benefit is evident at 5-years (10%) but relative mortality risk profile changes in longer follow-up.
目的/目标：在一项针对III-IV期喉/咽癌的放疗随机试验中，进行长期随访，以研究治疗比和随时间变化的死亡率情况。
材料/方法：1988年至1995年，331例患者被随机分为超分割放疗组（HF）（58 Gy/40次，每日两次）或常规放疗组（CF）（51 Gy/20次，每日一次）。比较两组的总生存率（OS）、局部区域控制率（LRC）、远处控制率（DC）、≥3级晚期毒性反应（LT）以及随时间变化的相对死亡风险情况。
中位随访时间为13.6年。超分割放疗组在5年时总生存率提高了10%（40%对30%，p = 0.04），但在10年时获益降至3%（21%对18%）。超分割放疗组局部区域控制率仍有升高趋势（5年：49%对40%；10年：49%对39%，p = 0.05）。远处控制率无变化（5年：87%对85%；10年：87对84%，p = 0.56）。晚期毒性反应率相似（超分割放疗组对常规放疗组：5年：9%对12%；10年：11%对14%，p = 0.27）。多变量分析证实，超分割放疗使死亡风险降低31%[风险比（HR）0.69（0.55 - 0.88），p < 0.01]，局部区域失败风险降低35%[HR 0.65（0.48 - 0.89），p < 0.01]。超分割放疗组的指数癌症死亡率较低（5年：46%对51%；10年：49%对55%）。5年时超分割放疗组的竞争性死亡率（大多与吸烟相关）在数值上也较低（14%对19%），但在10年时变得相似（30%对28%）。
该试验证实，增加总剂量的超分割放疗对局部区域控制有持久的10%的效应大小，且晚期毒性反应相当。5年时总生存率获益明显（10%），但在更长随访期内相对死亡风险情况发生变化。
