Purpose

DESTROY—4 (DOSE-ESCALATION STUDY OF STEREOTACTIC BODY RADIATION THERAPY) was a Phase I trial aimed to evaluate the safety and the feasibility of escalating doses of stereotactic body radiation therapy (SBRT) on MRI-defined Dominant Intraprostatic Lesion (DIL) in low- and intermediate-risk pCa patients using a simultaneous integrated boost-volumetric arc therapy (SIB-VMAT) technique.

Methods

Eligible patients included those with low- and intermediate-risk prostate carcinoma (NCCN risk classes) and an International Prostatic Symptoms Score (IPSS) ≤ 15. No restriction about DIL and prostate volumes was set. Pretreatment preparation required an enema and the placement of intraprostatic gold fiducials. SBRT was delivered in five consecutive daily fractions. For the first three patients, the DIL radiation dose was set at 8 Gy per fraction up to a total dose of 40 Gy (PTV1) and was gradually increased in succeeding cohorts to total doses of 42.5 Gy, 45.0 Gy, 47.5 Gy, and finally, 50.0 Gy, while keeping the prescription of 35 Gy/7 Gy per fraction for the entire prostate gland. Dose-limiting toxicity (DLT) was defined as grade 3 or worse gastrointestinal (GI) or genitourinary (GU) toxicity occurring within 90 days of follow-up (Common Terminology Criteria of Adverse Events scale 4.0). Patients completed quality-of-life questionnaires at defined intervals.

Results

Twenty-four patients with a median age of 75 (range, 58–89) years were enrolled. The median follow-up was 26.3 months (8.9–84 months). 66.7% of patients were classified as intermediate-risk groups, while the others were low-risk groups, according to the NCCN guidelines. Enrolled patients were treated as follows: 8 patients (40 Gy), 5 patients (42.5 Gy), 4 patients (45 Gy), 4 patients (47.5 Gy), and 3 patients (50 Gy). No severe acute toxicities were observed. G1 and G2 acute GU toxicities occurred in 4 (16%) and 3 patients (12.5%), respectively. Two patients (8.3%) and 3 patients (12.5%) experienced G1 and G2 GI toxicities, respectively. Since no DLTs were observed, 50 Gy in five fractions was considered the MTD. The median nadir PSA was 0.20 ng/mL. A slight improvement in QoL values was registered after the treatment.

Conclusion

This trial confirms the feasibility and safety of a total SIB-VMAT dose of 35 Gy on the whole gland and 50 Gy on DIL in 5 fractions daily administered in a well-selected low- and intermediate-risk prostate carcinoma population. A phase II study is ongoing to confirm the tolerability of the schedule and assess the efficacy.

中文翻译：

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针对局限性前列腺癌的显性前列腺内病变 (DIL) 进行立体定向全身放射治疗（SIB-VMAT 技术）：剂量递增试验 (DESTROY-4)。

目的

DESTROY—4（立体定向身体放射治疗的剂量递增研究）是一项 I 期试验，旨在评估 MRI 定义的主导放射治疗（SBRT）递增剂量的安全性和可行性使用同时集成升压容积弧治疗 (SIB-VMAT) 技术治疗低风险和中风险 PCA 患者的前列腺内病变 (DIL)。

方法

符合条件的患者包括患有低风险和中风险前列腺癌（NCCN 风险等级）且国际前列腺症状评分 (IPSS) ≤ 15 的患者。对 DIL 和前列腺体积没有设置限制。预处理准备需要灌肠和放置前列腺内金基准。SBRT 每天连续五次进行。对于前三名患者，DIL 辐射剂量设置为每次 8 Gy，直至总剂量 40 Gy (PTV1)，并在后续队列中逐渐增加至总剂量 42.5 Gy、45.0 Gy、47.5 Gy，最后, 50.0 Gy，同时保持整个前列腺每次分次 35 Gy/7 Gy 的处方。剂量限制毒性 (DLT) 定义为随访 90 天内发生的 3 级或更严重的胃肠道 (GI) 或泌尿生殖系统 (GU) 毒性（不良事件通用术语标准量表 4.0）。患者按照规定的时间间隔完成生活质量调查问卷。

结果

入组的 24 名患者中位年龄为 75 岁（范围为 58-89 岁）。中位随访时间为 26.3 个月（8.9-84 个月）。根据NCCN指南，66.7%的患者被归类为中危组，其余患者为低危组。入组患者接受的治疗如下：8 名患者（40 Gy）、5 名患者（42.5 Gy）、4 名患者（45 Gy）、4 名患者（47.5 Gy）和 3 名患者（50 Gy）。没有观察到严重的急性毒性。G1 和 G2 急性 GU 毒性分别发生在 4 名（16%）和 3 名患者（12.5%）中。2 名患者 (8.3%) 和 3 名患者 (12.5%) 分别经历了 G1 和 G2 胃肠道毒性。由于未观察到 DLT，因此将 5 个部分中的 50 Gy 视为 MTD。PSA 最低值中位数为 0.20 ng/mL。治疗后，生活质量值略有改善。

结论

该试验证实了在精心挑选的低风险和中风险前列腺癌人群中每天分 5 次施用的全腺 35 Gy 总 SIB-VMAT 剂量和 DIL 50 Gy 总剂量的可行性和安全性。一项 II 期研究正在进行中，以确认该方案的耐受性并评估疗效。