Akram Al-Ibraheem, Serin Moghrabi, Mike Machaba Sathekge, Ahmed Saad Abdlkadir
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Methodological quality was assessed using the National Institutes of Health (NIH) Assessment Tool. Stata software was employed to perform pooled xerostomia rates, heterogeneity analysis, meta-regression, and publication bias analysis.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Twenty studies met inclusion criteria, comprising 2949 [<sup>225</sup>Ac]Ac-PSMA cycles administered to 1207 PC patients. For [<sup>225</sup>Ac]Ac-PSMA monotherapy, the pooled rate of any-grade xerostomia was 84% (95%CI: 69–94%). Grade 1–2 xerostomia had a pooled rate 83% (95%CI: 71–93%), while therapy discontinuation due to xerostomia was 5% (95%CI: 0–13%). Grade 3 xerostomia was evident in 13% (95%CI: 7–20%). [<sup>225</sup>Ac]Ac/[<sup>177</sup>Lu]Lu-PSMA tandem therapy resulted in lower pooled rate of 68% for grade 1–2 toxicity (95%CI: 17–100%). Indirect comparison revealed a two-fold decrease in xerostomia risk with tandem protocol compared to monotherapy. Significant heterogeneity was observed, primarily influenced by baseline median prostate-specific antigen values (<i>p</i> = 0.04). Publication bias was present in most xerostomia subgroups, with trim-and-fill analysis adjusting for effect size in specific categories.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Xerostomia is most pronounced in patients undergoing [<sup>225</sup>Ac]Ac-PSMA monotherapy. Tandem approach with [<sup>177</sup>Lu]Lu-PSMA could reduce xerostomia rates and improve compliance. Further large-scale, prospective studies are necessary for generalization and result consolidation.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"82 2 1","pages":""},"PeriodicalIF":7.6000,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluating Xerostomia as a side effect of [255Ac]Ac-PSMA therapy in prostate cancer: a systematic review and meta-analysis\",\"authors\":\"Akram Al-Ibraheem, Serin Moghrabi, Mike Machaba Sathekge, Ahmed Saad Abdlkadir\",\"doi\":\"10.1007/s00259-025-07168-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Purpose</h3><p>This systematic review and meta-analysis evaluates xerostomia occurrence in prostate cancer (PC) patients undergoing [<sup>225</sup>Ac]Ac-prostate-specific membrane antigen ([<sup>225</sup>Ac]Ac-PSMA) therapy.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>Following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines, comprehensive electronic searches were conducted across PubMed, Scopus, and Web of Science. The study included articles addressing xerostomia as a side effect of [<sup>225</sup>Ac]Ac-PSMA therapy in clinical settings, encompassing both tandem and monotherapy strategies. Methodological quality was assessed using the National Institutes of Health (NIH) Assessment Tool. Stata software was employed to perform pooled xerostomia rates, heterogeneity analysis, meta-regression, and publication bias analysis.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>Twenty studies met inclusion criteria, comprising 2949 [<sup>225</sup>Ac]Ac-PSMA cycles administered to 1207 PC patients. For [<sup>225</sup>Ac]Ac-PSMA monotherapy, the pooled rate of any-grade xerostomia was 84% (95%CI: 69–94%). Grade 1–2 xerostomia had a pooled rate 83% (95%CI: 71–93%), while therapy discontinuation due to xerostomia was 5% (95%CI: 0–13%). Grade 3 xerostomia was evident in 13% (95%CI: 7–20%). [<sup>225</sup>Ac]Ac/[<sup>177</sup>Lu]Lu-PSMA tandem therapy resulted in lower pooled rate of 68% for grade 1–2 toxicity (95%CI: 17–100%). Indirect comparison revealed a two-fold decrease in xerostomia risk with tandem protocol compared to monotherapy. Significant heterogeneity was observed, primarily influenced by baseline median prostate-specific antigen values (<i>p</i> = 0.04). Publication bias was present in most xerostomia subgroups, with trim-and-fill analysis adjusting for effect size in specific categories.</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusion</h3><p>Xerostomia is most pronounced in patients undergoing [<sup>225</sup>Ac]Ac-PSMA monotherapy. Tandem approach with [<sup>177</sup>Lu]Lu-PSMA could reduce xerostomia rates and improve compliance. 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引用次数: 0
摘要
目的：本系统综述和荟萃分析评估前列腺癌（PC）患者接受[225Ac] ac -前列腺特异性膜抗原（[225Ac]Ac-PSMA）治疗后口干的发生率。方法根据系统评价和元分析方案的首选报告项目（PRISMA-P）指南，在PubMed、Scopus和Web of Science上进行全面的电子检索。该研究纳入了一些文章，讨论了[225Ac]Ac-PSMA治疗在临床环境中的副作用，包括串联和单药治疗策略。采用美国国立卫生研究院（NIH）评估工具评估方法学质量。采用Stata软件进行口干率汇总、异质性分析、meta回归和发表偏倚分析。结果20项研究符合纳入标准，包括2949个[225Ac]Ac-PSMA周期，给药1207例PC患者。对于[225Ac]Ac-PSMA单药治疗，任何级别口干的总发生率为84% （95%CI: 69-94%）。1-2级口干的总发生率为83% (95%CI: 71-93%)，而因口干而停止治疗的发生率为5% （95%CI: 0-13%）。3级口干发生率为13% （95%CI: 7-20%）。[225Ac]Ac/[177Lu]Lu-PSMA串联治疗导致1-2级毒性的总发生率较低，为68% （95%CI: 17-100%）。间接比较显示，与单药治疗相比，串联方案的口干风险降低了两倍。观察到显著的异质性，主要受基线前列腺特异性抗原中位数值的影响（p = 0.04）。在大多数口干症亚组中存在发表偏倚，在特定类别中采用补齐分析调整效应大小。结论口腔干燥在[225Ac]Ac-PSMA单药治疗中最为明显。[177Lu]Lu-PSMA串联治疗可降低口干率并提高依从性。进一步的大规模、前瞻性研究对推广和结果巩固是必要的。
Evaluating Xerostomia as a side effect of [255Ac]Ac-PSMA therapy in prostate cancer: a systematic review and meta-analysis
Purpose
This systematic review and meta-analysis evaluates xerostomia occurrence in prostate cancer (PC) patients undergoing [225Ac]Ac-prostate-specific membrane antigen ([225Ac]Ac-PSMA) therapy.
Methods
Following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines, comprehensive electronic searches were conducted across PubMed, Scopus, and Web of Science. The study included articles addressing xerostomia as a side effect of [225Ac]Ac-PSMA therapy in clinical settings, encompassing both tandem and monotherapy strategies. Methodological quality was assessed using the National Institutes of Health (NIH) Assessment Tool. Stata software was employed to perform pooled xerostomia rates, heterogeneity analysis, meta-regression, and publication bias analysis.
Results
Twenty studies met inclusion criteria, comprising 2949 [225Ac]Ac-PSMA cycles administered to 1207 PC patients. For [225Ac]Ac-PSMA monotherapy, the pooled rate of any-grade xerostomia was 84% (95%CI: 69–94%). Grade 1–2 xerostomia had a pooled rate 83% (95%CI: 71–93%), while therapy discontinuation due to xerostomia was 5% (95%CI: 0–13%). Grade 3 xerostomia was evident in 13% (95%CI: 7–20%). [225Ac]Ac/[177Lu]Lu-PSMA tandem therapy resulted in lower pooled rate of 68% for grade 1–2 toxicity (95%CI: 17–100%). Indirect comparison revealed a two-fold decrease in xerostomia risk with tandem protocol compared to monotherapy. Significant heterogeneity was observed, primarily influenced by baseline median prostate-specific antigen values (p = 0.04). Publication bias was present in most xerostomia subgroups, with trim-and-fill analysis adjusting for effect size in specific categories.
Conclusion
Xerostomia is most pronounced in patients undergoing [225Ac]Ac-PSMA monotherapy. Tandem approach with [177Lu]Lu-PSMA could reduce xerostomia rates and improve compliance. Further large-scale, prospective studies are necessary for generalization and result consolidation.
期刊介绍：
The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.
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