Nishioka Kentaro, Hashimoto Takayuki, Mori Takashi, Uchinami Yusuke, Kinoshita Rumiko, Katoh Norio, Taguchi Hiroshi, Yasuda Koichi, Ito Yoichi M, Takao Seishin, Tamura Masaya, Matsuura Taeko, Shimizu Shinichi, Shirato Hiroki, Aoyama Hidefumi
Radiation Oncology Division, Global Center for Biomedical Science and Engineering, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
Department of Radiation Oncology, Hokkaido University Hospital, Sapporo, Japan.
Adv Radiat Oncol. 2024 Feb 8;9(5):101464. doi: 10.1016/j.adro.2024.101464. eCollection 2024 May.
In real-time image-gated spot-scanning proton therapy (RGPT), the dose distribution is distorted by gold fiducial markers placed in the prostate. Distortion can be suppressed by using small markers and more than 2 fields, but additional fields may increase the dose to organs at risk. Therefore, we conducted a prospective study to evaluate the safety and short-term clinical outcome of RGPT for prostate cancer.
Based on the previously reported frequency of early adverse events (AE) and the noninferiority margin of 10%, the required number of cases was calculated to be 43 using the one-sample binomial test by the Southwest Oncology Group statistical tools with the one-sided significance level of 2.5% and the power 80%. Patients with localized prostate cancer were enrolled and 3 to 4 pure gold fiducial markers of 1.5-mm diameter were inserted in the prostate. The prescribed dose was 70 Gy(relative biologic effectiveness) in 30 fractions, and treatment was performed with 3 fields from the left, right, and the back, or 4 fields from either side of slightly anterior and posterior oblique fields. The primary endpoint was the frequency of early AE (≥grade 2) and the secondary endpoint was the biochemical relapse-free survival rate and the frequency of late AE.
Forty-five cases were enrolled between 2015 and 2017, and all patients completed the treatment protocol. The median follow-up period was 63.0 months. The frequency of early AE (≥grade 2) was observed in 4 cases (8.9%), therefore the noninferiority was verified. The overall 5-year biochemical relapse-free survival rate was 88.9%. As late AE, grade 2 rectal bleeding was observed in 8 cases (17.8%).
The RGPT for prostate cancer with 1.5-mm markers and 3- or 4- fields was as safe as conventional proton therapy in early AE, and its efficacy was comparable with previous studies.
在实时图像引导的点扫描质子治疗（RGPT）中，置于前列腺内的金基准标记会使剂量分布发生畸变。使用小标记和超过2个射野可抑制畸变，但额外的射野可能会增加危及器官的剂量。因此，我们开展了一项前瞻性研究，以评估RGPT治疗前列腺癌的安全性和短期临床疗效。
根据先前报道的早期不良事件（AE）发生率以及10%的非劣效性界值，使用西南肿瘤协作组统计工具进行单样本二项式检验，单侧显著性水平为2.5%，检验效能为80%，计算得出所需病例数为43例。纳入局限性前列腺癌患者，在前列腺内植入3至4枚直径1.5毫米的纯金基准标记。处方剂量为70 Gy（相对生物效应），分30次给予，治疗采用来自左、右和后方的3个射野，或来自稍前斜和后斜野两侧的4个射野。主要终点是早期AE（≥2级）的发生率，次要终点是生化无复发生存率和晚期AE的发生率。
2015年至2017年共纳入45例患者，所有患者均完成治疗方案。中位随访期为63.0个月。4例患者（8.9%）出现早期AE（≥2级），因此验证了非劣效性。5年总体生化无复发生存率为88.9%。作为晚期AE，8例患者（17.8%）出现2级直肠出血。
对于前列腺癌，采用1.5毫米标记和3或4个射野的RGPT在早期AE方面与传统质子治疗一样安全，其疗效与先前研究相当。
