Filippi Luca, Palumbo Barbara, Bagni Oreste, Frantellizzi Viviana, De Vincentis Giuseppe, Schillaci Orazio
Nuclear Medicine Unit, "Santa Maria Goretti" Hospital, Via Antonio Canova, 04100 Latina, Italy.
Section of Nuclear Medicine and Health Physics, Department of Medicine and Surgery, Università Degli Studi di Perugia, Piazza Lucio Severi 1, 06132 Perugia, Italy.
Life (Basel). 2022 Dec 24;13(1):55. doi: 10.3390/life13010055.
The aim of the present review was to assess the impact of DNA damage repair (DDR) mutations on response and outcome of patients (pts) affected by advanced prostate cancer (PCa) submitted to radionuclide therapies with [223Ra]RaCl2 (223Ra-therapy) or prostate specific membrane antigen (PSMA) ligands. A systematic literature search according to PRISMA criteria was made by using two main databases. Only studies published up until to October 2022 in the English language with ≥10 enrolled patients were selected. Seven studies including 326 pts, of whom 201 (61.6%) harboring DDR defects, were selected. The majority of selected papers were retrospective and four out of seven (57.1%) had small sample size (<50 pts). Three out of seven (42.8%) studies reported a more favorable outcome (overall or progression free survival) after therapy with alpha emitters (223Ra-therapy or [225Ac]Ac-PSMA-617) in subjects with DDR defects with respect to those without mutations. In two studies employing alpha or beta emitters ([177Lu]/[225Ac]-PMSA), no significant benefit was registered in pts harboring DDR defects. In all but one paper, no significant difference in response rate was reported among pts with or without DDR mutations. Although preliminary and biased by the retrospective design, preliminary data suggest a trend towards a longer survival in PCa pts harboring DDR defects submitted to radionuclide targeted therapy with alpha emitters.
本综述的目的是评估DNA损伤修复（DDR）突变对晚期前列腺癌（PCa）患者接受[223Ra]RaCl2放射性核素治疗（223Ra治疗）或前列腺特异性膜抗原（PSMA）配体治疗后的反应和预后的影响。通过使用两个主要数据库，根据PRISMA标准进行了系统的文献检索。仅选择截至2022年10月发表的英文研究，且纳入患者≥10例。共选择了7项研究，包括326例患者，其中201例（61.6%）存在DDR缺陷。所选论文大多为回顾性研究，7篇中有4篇（57.1%）样本量较小（<50例患者）。7项研究中有3项（42.8%）报告，与无突变者相比，DDR缺陷患者接受α发射体治疗（223Ra治疗或[225Ac]Ac-PSMA-617）后预后更佳（总生存期或无进展生存期）。在两项使用α或β发射体（[177Lu]/[225Ac]-PMSA）的研究中，DDR缺陷患者未显示出显著获益。除一篇论文外，其他所有论文均未报告DDR突变患者与未突变患者在缓解率上存在显著差异。尽管这些数据为初步数据且受回顾性设计的影响，但初步数据表明，接受α发射体放射性核素靶向治疗的DDR缺陷PCa患者有生存期延长的趋势。
