Abstract：
OBJECTIVE: This multicenter randomized phase III trial evaluated whether locoregional control of patients with LAHNSCC could be improved by fluorodeoxyglucose-positron emission tomography (FDG-PET)-guided dose-escalation while minimizing the risk of increasing toxicity using a dose-redistribution and scheduled adaptation strategy.
METHODS: Patients with T3-4-N0-3-M0 LAHNSCC were randomly assigned (1:1) to either receive a dose distribution ranging from 64-84 Gy/35 fractions with adaptation at the 10thfraction (rRT) or conventional 70 Gy/35 fractions (cRT). Both arms received concurrent three-cycle 100 mg/m2cisplatin. Primary endpoints were 2-year locoregional control (LRC) and toxicity. Primary analysis was based on the intention-to-treat principle.
RESULTS: Due to slow accrual, the study was prematurely closed (at 84 %) after randomizing 221 eligible patients between 2012 and 2019 to receive rRT (N = 109) or cRT (N = 112). The 2-year LRC estimate difference of 81 % (95 %CI 74-89 %) vs. 74 % (66-83 %) in the rRT and cRT arm, respectively, was not found statistically significant (HR 0.75, 95 %CI 0.43-1.31,P=.31). Toxicity prevalence and incidence rates were similar between trial arms, with exception for a significant increased grade ≥ 3 pharyngolaryngeal stenoses incidence rate in the rRT arm (0 versus 4 %,P=.05). In post-hoc subgroup analyses, rRT improved LRC for patients with N0-1 disease (HR 0.21, 95 %CI 0.05-0.93) and oropharyngeal cancer (0.31, 0.10-0.95), regardless of HPV.
CONCLUSIONS: Adaptive and dose redistributed radiotherapy enabled dose-escalation with similar toxicity rates compared to conventional radiotherapy. While FDG-PET-guided dose-escalation did overall not lead to significant tumor control or survival improvements, post-hoc results showed improved locoregional control for patients with N0-1 disease or oropharyngeal cancer treated with rRT.
METHODS: Patients with T3-4-N0-3-M0 LAHNSCC were randomly assigned (1:1) to either receive a dose distribution ranging from 64-84 Gy/35 fractions with adaptation at the 10thfraction (rRT) or conventional 70 Gy/35 fractions (cRT). Both arms received concurrent three-cycle 100 mg/m2cisplatin. Primary endpoints were 2-year locoregional control (LRC) and toxicity. Primary analysis was based on the intention-to-treat principle.
RESULTS: Due to slow accrual, the study was prematurely closed (at 84 %) after randomizing 221 eligible patients between 2012 and 2019 to receive rRT (N = 109) or cRT (N = 112). The 2-year LRC estimate difference of 81 % (95 %CI 74-89 %) vs. 74 % (66-83 %) in the rRT and cRT arm, respectively, was not found statistically significant (HR 0.75, 95 %CI 0.43-1.31,P=.31). Toxicity prevalence and incidence rates were similar between trial arms, with exception for a significant increased grade ≥ 3 pharyngolaryngeal stenoses incidence rate in the rRT arm (0 versus 4 %,P=.05). In post-hoc subgroup analyses, rRT improved LRC for patients with N0-1 disease (HR 0.21, 95 %CI 0.05-0.93) and oropharyngeal cancer (0.31, 0.10-0.95), regardless of HPV.
CONCLUSIONS: Adaptive and dose redistributed radiotherapy enabled dose-escalation with similar toxicity rates compared to conventional radiotherapy. While FDG-PET-guided dose-escalation did overall not lead to significant tumor control or survival improvements, post-hoc results showed improved locoregional control for patients with N0-1 disease or oropharyngeal cancer treated with rRT.
摘要：
目的：这项多中心随机III期试验评估了是否可以通过氟脱氧葡萄糖-正电子发射断层扫描（FDG-PET）指导的剂量递增来改善LAHNSCC患者的局部区域控制，同时使用剂量再分配和计划适应策略将毒性增加的风险降至最低。
方法：将T3-4-N0-3-M0LAHNSCC患者随机分配（1：1），接受剂量分布范围为64-84Gy/35分，并适应10分（rRT）或常规70Gy/35分（cRT）。两组同时接受三个周期的100mg/m2顺铂。主要终点是2年局部区域控制（LRC）和毒性。初步分析基于意向治疗原则。
结果：由于应计速度缓慢，该研究在2012年至2019年随机分组221例符合条件的患者接受rRT(N=109)或cRT(N=112)后过早结束(84%).2年LRC估计差异为81%(95CI74-89%)与rRT和cRT臂中的74％（66-83％），分别,无统计学意义(HR0.75，95CI0.43-1.31，P=0.31)。试验组之间的毒性患病率和发病率相似，除了rRT组中≥3级咽喉狭窄的发生率显着增加（0对4％，P=0.05）。在事后分组分析中，rRT改善了N0-1疾病（HR0.21，95CI0.05-0.93）和口咽癌（0.31，0.10-0.95）患者的LRC，不管HPV。
结论：与常规放疗相比，自适应和剂量再分配放疗使剂量增加，毒性率相似。虽然FDG-PET引导的剂量递增总体上并未导致显著的肿瘤控制或生存改善，事后结果显示，对于接受rRT治疗的N0-1疾病或口咽癌患者，局部区域控制得到改善。
方法：将T3-4-N0-3-M0LAHNSCC患者随机分配（1：1），接受剂量分布范围为64-84Gy/35分，并适应10分（rRT）或常规70Gy/35分（cRT）。两组同时接受三个周期的100mg/m2顺铂。主要终点是2年局部区域控制（LRC）和毒性。初步分析基于意向治疗原则。
结果：由于应计速度缓慢，该研究在2012年至2019年随机分组221例符合条件的患者接受rRT(N=109)或cRT(N=112)后过早结束(84%).2年LRC估计差异为81%(95CI74-89%)与rRT和cRT臂中的74％（66-83％），分别,无统计学意义(HR0.75，95CI0.43-1.31，P=0.31)。试验组之间的毒性患病率和发病率相似，除了rRT组中≥3级咽喉狭窄的发生率显着增加（0对4％，P=0.05）。在事后分组分析中，rRT改善了N0-1疾病（HR0.21，95CI0.05-0.93）和口咽癌（0.31，0.10-0.95）患者的LRC，不管HPV。
结论：与常规放疗相比，自适应和剂量再分配放疗使剂量增加，毒性率相似。虽然FDG-PET引导的剂量递增总体上并未导致显著的肿瘤控制或生存改善，事后结果显示，对于接受rRT治疗的N0-1疾病或口咽癌患者，局部区域控制得到改善。
