Ryg Una, Seierstad Therese, Nilsen Line Brennhaug, Hellebust Taran Paulsen, Djupvik Linda Holth, Gustafson Hilde, Hydal Jørgen, Kishan Amar U, Hole Knut Håkon, Lilleby Wolfgang
Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
Department of Medical Physics, Oslo University Hospital, Oslo, Norway.
Front Oncol. 2022 Apr 5;12:861127. doi: 10.3389/fonc.2022.861127. eCollection 2022.
Up to half of patients with localized prostate cancer experience biochemical relapse within 10 years after definitive radiotherapy. The aim of this prospective study was to investigate the toxicity, dose to the organs at risk (OARs), and efficacy of dose-intensified focal salvage radiotherapy.
Thirty-three patients (median age 68.8 years) with histologically confirmed relapse after primary definitive radiotherapy were enrolled between 2012 and 2019. No patients had metastases at imaging or in bone marrow aspiration. Twenty-three patients were treated with high dose-rate brachytherapy to the recurrent tumor, defined at multiparametric MRI, with 3 fractions of 10 Gy with two weeks interval, and 10 patients by stereotactic body radiotherapy with 35 Gy to the local recurrence and 25 Gy to the whole prostate in 5 fractions. We used the RTOG-scoring system to grade genitourinary (GU) and gastrointestinal toxicity (GI) at three months (acute), and at 12, 24, and 36 months (late). Dose-volume histogram parameters to the local recurrence and the OARs were obtained and 2 Gy equivalent (EQD2) total dose was calculated using the linear-quadratic model with α/β = 3 Gy. Efficacy was assessed by the progression-free interval and overall survival.
Median follow-up time was 81 months (range 21-115). The cumulative moderate to severe GI and GU toxicities were 3.0% (1/33) and 15.2% (5/33). Six patients had grade 1 acute GI toxicity, none had grade 2 or 3. One patient had grade 3 acute GU toxicity, two had grade 2, and fourteen had grade 1. One patient had late GI toxicity grade 2 and eight had grade 1. Four patients had late GU toxicity grade 2 and eight had grade 1. No patients had grade 3 late toxicity. The mean total D90 to the recurrent tumor was 77.7 ± 17.0 Gy. The mean total rectum D2cc was 17.0 ± 7.9 Gy and the mean total urethra D0.1cc was 29.1 ± 8.2 Gy. Twenty-eight patients had re-irradiation without androgen deprivation therapy (ADT). Nine of these are still relapse-free and 10 had a recurrence-free interval longer than 2 years.
The toxicity of salvage radiotherapy was mild to moderate. One-third of the patients achieved long-term stable disease without ADT and one-third had a recurrence-free interval longer than 2 years. Some patients progressed rapidly and probably did not benefit from re-irradiation.
高达一半的局限性前列腺癌患者在根治性放疗后10年内会出现生化复发。这项前瞻性研究的目的是调查剂量强化局部挽救性放疗的毒性、对危及器官（OARs）的剂量以及疗效。
2012年至2019年间纳入了33例（中位年龄68.8岁）经组织学证实为初次根治性放疗后复发的患者。影像学检查或骨髓穿刺均未发现转移患者。23例患者接受了针对多参数MRI定义的复发性肿瘤的高剂量率近距离放疗，分3次给予10 Gy，间隔两周，10例患者接受立体定向体部放疗，局部复发灶给予35 Gy，全前列腺给予25 Gy，分5次。我们使用RTOG评分系统在3个月（急性）、12个月、24个月和36个月（晚期）对泌尿生殖系统（GU）和胃肠道毒性（GI）进行分级。获取局部复发灶和OARs的剂量体积直方图参数，并使用α/β = 3 Gy的线性二次模型计算2 Gy等效剂量（EQD2）总剂量。通过无进展生存期和总生存期评估疗效。
中位随访时间为81个月（范围21 - 115个月）。累积的中度至重度GI和GU毒性分别为3.0%（1/33）和15.2%（5/33）。6例患者有1级急性GI毒性，无2级或3级。1例患者有3级急性GU毒性，2例有2级，14例有1级。1例患者有2级晚期GI毒性，8例有1级。4例患者有2级晚期GU毒性，8例有1级。无患者有3级晚期毒性。复发性肿瘤的平均总D90为77.7 ± 17.0 Gy。直肠平均总D2cc为17.0 ± 7.9 Gy，尿道平均总D0.1cc为29.1 ± 8.2 Gy。28例患者在未接受雄激素剥夺治疗（ADT）的情况下接受了再放疗。其中9例仍无复发，10例的无复发生存期超过2年。
挽救性放疗的毒性为轻度至中度。三分之一的患者在未接受ADT的情况下实现了长期疾病稳定，三分之一的患者无复发生存期超过2年。一些患者进展迅速，可能未从再放疗中获益。
