Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer (HYPRO): final efficacy results from a randomised, multicentre, open-label, phase 3 trial
Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer (HYPRO): final efficacy results from a randomised, multicentre, open-label, phase 3 trial
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DOI：
10.1016/s1470-2045(16)30070-5
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发表时间：
2016-08-01
期刊：
影响因子：
51.1
通讯作者：
Pos, Floris
中科院分区：
文献类型：
--
作者：
Incrocci, Luca;Wortel, Ruud C.;Pos, Floris
研究报道了前列腺癌的低α / β比值，这表明低分割可以增加生物肿瘤剂量，而不会增加泌尿生殖系统和胃肠道毒性。在多中心3期，前列腺癌的低分割放疗（HYPRO）试验中，将低分割放疗与常规分割放疗治疗前列腺癌进行了比较。我们以前报道过急性和晚期泌尿生殖系统和胃肠道毒性；在这里，我们报告了协议定义的5年无复发生存结果。方法：我们在7个荷兰放疗中心进行了一项开放标签、随机化的3期试验。我们招募了中危至高危T1b-T4NX-N0MX-M0局限性前列腺癌患者，前列腺特异性抗原浓度为60 μ g/L或更低，WHO成绩为0-2。我们使用基于网络的应用程序随机分配（1:1）患者接受64.6 Gy的低分割放疗（19次3.4 Gy，每周3次）或78.0 Gy的常规分割放疗（39次2.0 Gy，每周5次）。根据估计前列腺癌的α / β比值为1.5 Gy，低分割术中2.0 Gy的等效总剂量为90.4 Gy，而常规分割术为78.0 Gy。主要终点为无复发生存期。所有分析均在所有符合条件的患者意向治疗基础上进行。HYPRO试验于2010年完成招募，后续工作正在进行中。本试验已在ISRCTN注册，注册号为ISRCTN85138529。在2007年3月19日至2010年12月3日期间，纳入了820例患者，其中804例符合意向治疗分析的评估条件。其中407人接受低分割放疗，397人接受常规分割放疗。804例患者中有537例（67%）接受了雄激素剥夺治疗，中位持续时间为32个月（IQR 10-44）。中位随访60个月（IQR 51-69）。804例患者中有169例（21%）治疗失败，低分割组有80例（20%），常规分割组有89例（22%）。低分割患者的5年无复发生存率为80.5% (95% CI 75.7-84.4)，常规分割患者的5年无复发生存率为77.1%(71.9-81.5)（校正危险比0.86,95% CI 0.63-1.16; log-rank p=0.36）。没有与治疗相关的死亡。解释：在5年无复发生存率方面，低分割放疗并不优于常规放疗。我们的低分割放疗方案不能被视为治疗中危高危前列腺癌患者的新标准。
Background Studies have reported a low alpha/beta ratio for prostate cancer, suggesting that hypofractionation could enhance the biological tumour dose without increasing genitourinary and gastrointestinal toxicity. In the multicentre phase 3, HYpofractionated irradiation for PROstate cancer (HYPRO) trial, hypofractionated radiotherapy was compared with conventionally fractionated radiotherapy for treatment of prostate cancer. We have previously reported acute and late incidence of genitourinary and gastrointestinal toxicity; here we report protocol-defined 5-year relapse-free survival outcomes.Methods We did an open-label, randomised, phase 3 trial at seven Dutch radiotherapy centres. We enrolled patients with intermediate-risk to high-risk T1b-T4NX-N0MX-M0 localised prostate cancer, a prostate-specific antigen concentration of 60 mu g/L or less, and a WHO performance status of 0-2. We used a web-based application to randomly assign (1:1) patients to either hypofractionated radiotherapy of 64.6 Gy (19 fractions of 3.4 Gy, three fractions per week) or conventionally fractionated radiotherapy of 78.0 Gy (39 fractions of 2.0 Gy, five fractions per week). Based on an estimated alpha/beta ratio for prostate cancer of 1.5 Gy, the equivalent total dose in fractions of 2.0 Gy was 90.4 Gy for hypofractionation compared with 78.0 Gy for conventional fractionation. The primary endpoint was relapse-free survival. All analyses were done on an intention-to-treat basis in all eligible patients. The HYPRO trial completed recruitment in 2010 and follow-up is ongoing. This trial is registered with ISRCTN, number ISRCTN85138529.Findings Between March 19, 2007, and Dec 3, 2010, 820 patients were enrolled, of whom 804 were eligible and assessable for intention-to-treat analyses. Of these, 407 were assigned hypofractionated radiotherapy and 397 were allocated conventionally fractionated radiotherapy. 537 (67%) of 804 patients received concomitant androgen deprivation therapy for a median duration of 32 months (IQR 10-44). Median follow-up was 60 months (IQR 51-69). Treatment failure was reported in 169 (21%) of 804 patients, 80 (20%) in the hypofractionation group and 89 (22%) in the conventional fractionation group. 5-year relapse-free survival was 80.5% (95% CI 75.7-84.4) for patients assigned hypofractionation and 77.1% (71.9-81.5) for those allocated conventional fractionation (adjusted hazard radio 0.86, 95% CI 0.63-1.16; log-rank p=0.36). There were no treatment-related deaths.Interpretation Hypofractionated radiotherapy was not superior to conventional radiotherapy with respect to 5-year relapse-free survival. Our hypofractionated radiotherapy regimen cannot be regarded as the new standard of care for patients with intermediate-risk or high-risk prostate cancer.