International Journal of Radiation Biology ( IF 2.6 ) Pub Date : 2020-11-03 , DOI: 10.1080/09553002.2020.1838655 Viviana Frantellizzi 1 , Fabio Monari 2 , Manlio Mascia 3 , Renato Costa 4 , Giuseppe Rubini 5 , Angela Spanu 6 , Alessio Farcomeni 7 , Elisa Lodi Rizzini 8 , Luca Cindolo 9 , Maria Licari 4 , Valentina Lavelli 5 , Susanna Nuvoli 6 , Maria Ricci 10 , Valeria Dionisi 2 , Anna Giulia Nappi 5 , Giuseppe De Vincentis 10
Abstract
Purpose
Radium-223 has demonstrated efficacy in improving overall survival (OS) and in delaying symptomatic skeletal-related events (SREs). Bone Health Agents (BHA), i.e. RANK ligand inhibitor (Denosumab) and bisphosphonate such as zoledronic acid, are indicated to prevent SREs without a clear survival benefit. SREs on patient health have a high impact and it is, therefore, important to consider the role of new therapies with BHA to better understand the involvement of combination therapy. The primary aim of this multicentric study is to assess OS in mCRPC patients treated with Radium-223 in combination with BHA.
Materials and methods
430 consecutive patients treated with Radium-223 alone or in combination with BHA, affected by mCRPC, from January 2015 to July 2019 in six Italian Nuclear Medicine Units, were included. Furthermore, data were collected at baseline, after every Radium-223 administration, and during follow-up, at 3 and 6 months and 1 year after the 6th cycle. Clinical data have been evaluated before starting treatment with Radium-223 and at the end of treatment and/or at progression. Patients who received target bone therapy with BHA before Radium-223 treatment together with patients who did not receive this therapy at all (NO BHA GROUP), were compared to patients treated with concomitant Radium-223 and BHA (BHA GROUP).
Results
In univariate models (p < .05) several clinical aspects have an impact on OS: concomitant BHA (p = .018), BMI (p .001), ECOG PS (p = .000), Baseline Hb (p = .000), Baseline PSA (p = .000), Baseline tALP (p = .000), Baseline LDH (p = .000), and Baseline neutrophils (p = .009). Baseline Hb, Baseline tALP, and Baseline LDH have been confirmed as statistically significant parameters in multivariate models. Indeed, concomitant BHA has not a significant impact on OS (p = .244) in multivariate models.
Conclusions
At univariate analysis, our data showed that NO BHA GROUP and BHA GROUP differ in OS by 7 months (95%CI: (1–16.4), p = .02). This is not confirmed at multivariate analysis where after adjusting for other baseline factors, BHA is not significant anymore. This is clearly explained as bias by indication: patients with the same levels of tALP, Hb, and LDH receiving or not receiving BHA are expected to have a similar survival. Our results support and confirm the role of Radium-223 therapy on OS and, furthermore, appear to confirm that BHA treatment has not a survival benefit.
中文翻译:
一项全国性多中心研究:接受Radium-223联合骨健康药物治疗的mCPRC患者的总体生存率
摘要
目的。Radium-223已显示出改善总体生存(OS)和延迟症状性骨骼相关事件(SRE)的功效。骨健康剂(BHA),即RANK配体抑制剂(Denosumab)和双膦酸盐(如唑来膦酸)被表明可以预防SRE,而没有明显的生存获益。SRE对患者健康有很大影响,因此,重要的是考虑新的BHA疗法的作用,以更好地了解联合疗法的介入。这项多中心研究的主要目的是评估接受Radium-223联合BHA治疗的mCRPC患者的OS。
材料和方法。纳入2015年1月至2019年7月在六个意大利核医学科接受430例连续mCRPC影响的单独或联合Radium-223治疗的患者。此外,在第6个周期后的3、6个月和1年时,在每次Radium-223给药后以及随访期间的基线收集数据。在开始使用Radium-223治疗之前和治疗结束时和/或进展过程中已经评估了临床数据。将接受Radium-223治疗之前接受BHA靶骨治疗的患者以及完全没有接受这种治疗的患者(NO BHA GROUP)与接受Radium-223和BHA伴随治疗的患者(BHA GROUP)进行比较。
结果。在单变量模型中(p <0.05),一些临床方面会影响OS:伴随的BHA(p 0.018),BMI(p 0.001),ECOG PS(p 0.000),基线Hb(p 0.000),基线PSA(p 0.000) ,基线tALP(p 0.000),基线LDH(p 0.000),基线中性粒细胞(p 0.009)。在多变量模型中,已确认基线Hb,基线tALP和基线LDH是具有统计学意义的参数。实际上,在多变量模型中,伴随的BHA对OS的影响不大(p = 0.244)。
结论。在单变量分析中,我们的数据显示NO BHA GROUP和BHA GROUP在OS上的差异为7个月(95%CI:(1 16.4),p = 0.02)。这在多变量分析中并未得到证实,在对其他基线因素进行调整之后,BHA不再显着。明确地将其解释为适应症的偏倚:接受或不接受BHA的tALP,Hb和LDH含量相同的患者的生存期相似。我们的结果支持并证实了Radium-223治疗对OS的作用,此外,似乎证实了BHA治疗没有生存益处。