Toesca Diego A S, Hartsell William F, DeWees Todd A, Chang John H, Laughlin Brady S, Voss Molly M, Dodoo Christopher A, Mohammed Nasiruddin, Keole Sameer R, McGee Lisa A, Gondi Vinai, Sweeney Patrick J, Dorn Paige, Sinesi Christopher C, Doh Lucius S, Rich Tyvin, Vargas Carlos E
Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona.
Proton Collaborative Group, Warrenville, Illinois; Radiation Oncology Consultants, Elk Grove Village, Illinois.
Int J Radiat Oncol Biol Phys. 2024 Dec 1;120(5):1377-1385. doi: 10.1016/j.ijrobp.2024.05.014. Epub 2024 Jul 6.
We aimed to determine if ultrahypofractionated proton therapy delivered via stereotactic body proton therapy (SBPT) is noninferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer.
This study was a multicenter, randomized, controlled, noninferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score grouping 1, Prostate-specific antigen <10 ng/mL, and clinical stage T1-T2a N0 M0 according to 7th edition of the American Joint Committee on Cancer tumor-node-metastasis cancer staging system. Eligible participants were randomly assigned initially at a 1:1 ratio and later at a 2:1 ratio to SBPT (38 Gy in 5 fractions) or CFPT (79.2 Gy in 44 fractions). The primary endpoint was freedom from failure (FFF) at 2 years from the date of randomization. Noninferiority for FFF was determined based on 1-sided confidence intervals. Toxicities were compared at different time points using Fisher's exact test. Health-related quality-of-life (HRQoL) was analyzed at different time points using a mixed-effects linear model. This trial is registered with ClinicalTrials.gov, NCT01230866, and is closed to accrual.
Between December 10, 2010, and September 29, 2020, 144 patients were enrolled and 135 were randomly assigned (90 to the SBPT group and 45 to the CFPT group). The median follow-up was 5 years (IQR, 3.9-5.2). The 2-year FFF was 100% for both groups, with the 1-sided 5-year risk difference in FFF between groups reported as 2.63% (90% CI, -1.70% to 6.96%), favoring the SBRT arm, thus fulfilling the prespecified criteria for noninferiority of SBPT compared with CFPT. Rates of gastrointestinal and genitourinary G2 and G3 toxicities did not differ significantly between groups. Further, HRQoL metrics did not differ significantly between groups over the study's median follow-up.
SBPT is noninferior to CFPT regarding FFF, with similar long-term genitourinary and gastrointestinal toxicity rates and minimal impact in patient-reported HRQoL over time.
我们旨在确定通过立体定向体部质子治疗（SBPT）进行的超分割质子治疗在早期前列腺癌患者中是否不劣于常规分割质子治疗（CFPT）。
本研究是一项多中心、随机、对照、非劣效性3期试验，纳入了根据美国癌症联合委员会第7版肿瘤-淋巴结-转移癌症分期系统，经组织学证实为低风险前列腺腺癌的患者，其定义为Gleason评分分组1、前列腺特异性抗原<10 ng/mL以及临床分期T1-T2a N0 M0。符合条件的参与者最初以1:1的比例随机分配，后来以2:1的比例随机分配至SBPT组（5次分割，共38 Gy）或CFPT组（44次分割，共79.2 Gy）。主要终点是随机分组日期起2年的无失败生存率（FFF）。基于单侧置信区间确定FFF的非劣效性。使用Fisher精确检验比较不同时间点的毒性。使用混合效应线性模型分析不同时间点的健康相关生活质量（HRQoL）。本试验已在ClinicalTrials.gov注册，注册号为NCT01230866，现已停止入组。
在2010年12月10日至2020年9月29日期间，共纳入144例患者，135例被随机分组（90例至SBPT组，45例至CFPT组）。中位随访时间为5年（四分位间距，3.9 - 5.2年）。两组的2年FFF均为100%，两组间5年FFF的单侧风险差异报告为2.63%（90%置信区间，-1.70%至6.96%），支持立体定向体部放疗组，因此满足SBPT与CFPT相比非劣效性的预设标准。两组间胃肠道和泌尿生殖系统G2和G3毒性发生率无显著差异。此外，在研究的中位随访期内，两组间HRQoL指标无显著差异。
在FFF方面，SBPT不劣于CFPT，具有相似的长期泌尿生殖系统和胃肠道毒性发生率，且随着时间推移对患者报告的HRQoL影响最小。
