寡转移去势抵抗性前列腺癌的 C-Choline-PET/CT 识别下立体定向消融放疗（SABR）和免疫的 II 期评估。
Phase II Evaluation of Stereotactic Ablative Radiotherapy (SABR) and Immunity in C-Choline-PET/CT-Identified Oligometastatic Castration-Resistant Prostate Cancer.
机构信息
Departments of Urology and Immunology, Mayo Clinic, Rochester, Minnesota.
Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
出版信息
Clin Cancer Res. 2021 Dec 1;27(23):6376-6383. doi: 10.1158/1078-0432.CCR-21-2510. Epub 2021 Sep 30.
PURPOSE
Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking.
PATIENTS AND METHODS
Eighty-nine patients with oligometastatic CRPC were identified by C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR. Prespecified coprimary endpoints were 2-year overall survival (OS) and PSA progression. Secondary endpoints included 2-year SABR-treated local failure and 6-month adverse events. Correlative studies included peripheral blood T-cell subpopulations before and after SABR.
RESULTS
128 lesions in 89 patients were included in this analysis. Median OS was 29.3 months, and 1- and 2-year OS were 96% and 80%, respectively. PSA PFS was 40% at 1 year and 21% at 2 years. Local PFS was 84.4% and 75.3% at 1 and 2 years, respectively, and no grade ≥3 AEs were observed. Baseline high levels of tumor-reactive T cells (T; CD8CD11a) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (T; CCR7CD45RA) were associated with improved PSA PFS. An increase in T at day 14 from baseline was associated with superior OS.
CONCLUSIONS
This is the first comprehensive effector T-cell immunophenotype analysis in a phase II trial before and after SABR in CRPC. Results are favorable and support the incorporation of immune-based markers in the design of future randomized trials in patients with oligometastatic CRPC treated with SABR.
目的
耐药性转移性去势抵抗性前列腺癌（CRPC）的预后较差。立体定向消融放疗（SABR）在临床和临床前研究中诱导抗肿瘤免疫，但缺乏免疫生物标志物。
方法
2016 年 8 月至 2019 年 12 月，通过 C-胆碱-PET（Choline-PET）识别出 89 例寡转移性 CRPC 患者，并接受 SABR 治疗。预设的主要终点是 2 年总生存率（OS）和 PSA 进展。次要终点包括 2 年 SABR 治疗局部失败和 6 个月不良事件。相关研究包括 SABR 前后外周血 T 细胞亚群。
结果
本分析纳入了 89 例患者的 128 个病灶。中位 OS 为 29.3 个月，1 年和 2 年 OS 分别为 96%和 80%。PSA PFS 在 1 年时为 40%，在 2 年时为 21%。局部 PFS 分别为 1 年和 2 年的 84.4%和 75.3%，未观察到≥3 级的不良事件。基线时高水平的肿瘤反应性 T 细胞（T；CD8CD11a）预测局部、PSA 和远处 PFS 较好。基线时高水平的效应记忆 T 细胞（T；CCR7CD45RA）与 PSA PFS 改善相关。与基线相比，第 14 天 T 细胞增加与 OS 较好相关。
结论
这是首例在 CRPC 患者 SABR 前后进行的 II 期试验中对效应 T 细胞免疫表型的全面分析。结果是有利的，并支持在接受 SABR 治疗的寡转移性 CRPC 患者的未来随机试验设计中纳入免疫相关标志物。
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