目的:介绍在不同颅外部位的原发性或转移性肿瘤患者中使用体积调制电弧疗法(VMAT)进行立体定向放射外科(SRS)的I期试验的最终结果。
方法:DESTROY-2试验,计划作为一项针对寡转移(1-5个病灶)癌症患者的前瞻性剂量递增研究依赖于利用高精度技术进行的单次高剂量放射.主要研究终点是SRS-VMAT的最大耐受剂量(MTD)的定义。该研究的次要目标是安全性评估,功效,和长期结果。纳入符合纳入标准的在我们放疗单元连续观察的所有患者。每位入选的受试者都被纳入不同的I期研究组,取决于肿瘤部位和疾病阶段(肺,肝脏,骨头,其他),并依次分配到特定的剂量水平。
结果:对164例连续患者(男/女:97/67,中位年龄:68岁;范围:29-92)的两组27个病灶进行了治疗。主要原发肿瘤为:前列腺癌(60例),结直肠癌(47例患者),乳腺癌(39例)。所有研究组均达到了最大计划剂量水平,并且未超过MTD。34Gy,32Gy,24Gy,和24Gy被确定为治疗肺的单次剂量,肝脏,骨头,和其他颅外病变,分别。规定的BED2Gyα/β:10至计划目标体积的范围为26.4Gy至149.6Gy。27名患者(16.5%)出现1-2级急性毒性,只有1名患者出现3级急性毒性,那是肺的.在后期毒性方面,我们只记录了5个毒性>G2:一个G3胃肠道毒性,三种G3骨毒性,和G3喉部毒性。199个病变的总体反应:107个完全反应(53.8%),50部分反应(25.1%),和31稳定的疾病(15.6%),导致94.5%的总反应率。仅在11例(5.5%)中记录了进展。各臂的总有效率为88.6%至96.4%。整个两年的地方控制,无远处转移生存率,无病生存,总生存率为81.7%,33.0%,25.4%,分别为78.7%。
结论:结论:计划剂量为34Gy,32Gy,24Gy,和24Gy作为单部分成功用于治疗肺,肝脏,骨头,和其他颅外病变,分别,在一项前瞻性SRS剂量递增试验中.没有记录剂量限制性毒性,报告了最小的急性和晚期毒性。目前,正在接受靶向药物或与免疫疗法联合治疗的寡进患者中研究SRS的新适应症。DESTROY-2试验代表,在我们看来,未来现代放射外科试验的可靠起点。
OBJECTIVE: To present the final results of a phase I
trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumors in different extracranial sites.
METHODS: The DESTROY-2
trial, planned as a prospective dose escalation
study in oligometastatic (one to five lesions) cancer patients relied on the delivery of a single high dose of radiation utilizing high-precision technology. The primary
study endpoint was the definition of the maximum tolerated dose (MTD) of SRS-VMAT. The secondary objectives of the study were the evaluation of safety, efficacy, and long-term outcomes. All patients consecutively observed at our radiotherapy unit matching the inclusion criteria were enrolled. Each enrolled subject was included in a different phase I study arm, depending on the tumor site and the disease stage (lung, liver, bone, other), and sequentially assigned to a particular dose level.
RESULTS: Two hundred twenty seven lesions in 164 consecutive patients (male/female: 97/67, median age: 68 years; range: 29-92) were treated. The main primary tumors were: prostate cancer (60 patients), colorectal cancer (47 patients), and breast cancer (39 patients). The maximum planned dose level was achieved in all study arms, and the MTD was not exceeded. 34 Gy, 32 Gy, 24 Gy, and 24 Gy were established as the single-fraction doses for treating lung, liver, bone, and other extracranial lesions, respectively. The prescribed BED 2Gyα/β:10 to the planning target volume ranged from 26.4 Gy to 149.6 Gy. Twenty-seven patients (16.5%) experienced grade 1-2 and only one grade 3 acute toxicity, which was a pulmonary one. In terms of late toxicity, we registered only 5 toxicity>G2: a G3 gastro-intestinal one, three G3 bone toxicity, and a G3 laryngeal toxicity. The overall response was available for 199 lesions: 107 complete response (53.8%), 50 partial response (25.1%), and 31 stable disease (15.6%), leading to an overall response rate of 94.5%. Progression was registered only in 11 cases (5.5%). The overall response rate in each arm ranged from 88.6% to 96.4%. The overall two-year local control, distant metastasis free survival, disease free survival, and overall survival were 81.7%, 33.0%, 25.4%, and 78.7% respectively.
CONCLUSIONS: In conclusion, the planned doses of 34 Gy, 32 Gy, 24 Gy, and 24 Gy were successfully administered as single-fractions for the treatment of lung, liver, bone, and other extracranial lesions, respectively, in a prospective SRS dose-escalation
trial. No dose-limiting toxicities were registered, and minimal acute and late toxicity were reported. New indications for SRS are currently being studied in oligoprogressive patients receiving targeted drugs or in combination with immunotherapy. The DESTROY-2
trial represents, in our opinion, a credible starting point for future modern radiosurgery trials.