Histone deacetylase inhibitor use as a radiosensitizer in solid organ malignancies: a systematic review protocol

Objective: The objective of this review is to evaluate the efficacy and adverse effects of histone deacetylase inhibitors (HDACi) in combination with radiotherapy for the treatment of solid organ malignancies. Introduction: Histone deacetylase inhibitors are a diverse class of drugs that have shown promise as novel anti-cancer therapeutics via epigenetic modification and radiosensitization of neoplastic cells. The aim of HDACi in combination with radiotherapy is to reduce radiation dosage requirements, improve radiotherapy efficacy, and reduce treatment side effects. Inclusion criteria: This review will consider studies utilizing HDACi in conjunction with radiotherapy in adult patients with solid organ malignancy. Sources to be included in this review include experimental and quasi-experimental study designs, analytical studies, and descriptive observational studies. Methods: A systematic review of effectiveness will be conducted in accordance with JBI methodology. A detailed search will be conducted via MEDLINE (Ovid), Embase (Ovid), and Scopus. A search of the Cochrane Central Register of Controlled Trials, the International Clinical Trials Registry Platform, and ClinicalTrials.gov will also be performed for relevant trials. Inclusion and exclusion criteria will be utilized to select studies, and papers selected for retrieval will be assessed for methodological validity using the JBI critical appraisal instruments. Evidence will be extracted from eligible studies and summarized using quantitative methods, where possible, including meta-analysis and assessment of heterogeneity. Where statistical pooling is not possible, the findings will be presented in diagrammatic or tabular form accompanied by a narrative summary. Systematic review registration number: PROSPERO CRD42021293005

Automated summary

This review aims to evaluate the effectiveness and adverse effects of histone deacetylase inhibitors (HDACi) in combination with radiotherapy for the treatment of solid organ malignancies. Studies utilizing HDACi in adult patients with solid organ malignancy will be considered. A systematic review and meta-analysis will be conducted, and methodological validity will be assessed using JBI methodology.