Ionizing Radiation Protein Biomarkers in Normal Tissue and Their Correlation to Radiosensitivity: Protocol for a Systematic Review.

Radiosensitivity is a significantly enhanced reaction of cells, tissues, organs or organisms to ionizing radiation (IR). During radiotherapy, surrounding normal tissue radiosensitivity often limits the radiation dose that can be applied to the tumour, resulting in suboptimal tumour control or adverse effects on the life quality of survivors. Predicting radiosensitivity is a component of personalized medicine, which will help medical professionals allocate radiation therapy decisions for effective tumour treatment. So far, there are no reviews of the current literature that explore the relationship between proteomic changes after IR exposure and normal tissue radiosensitivity systematically. The main objective of this protocol is to specify the search and evaluation strategy for a forthcoming systematic review (SR) dealing with the effects of in vivo and in vitro IR exposure on the proteome of human normal tissue with focus on radiosensitivity. The SR framework has been developed following the guidelines established in the National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT) Handbook for Conducting a Literature-Based Health Assessment, which provides a standardised methodology to implement the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to environmental health assessments. The protocol will be registered in PROSPERO, an open source protocol registration system, to guarantee transparency. Only experimental studies, in vivo and in vitro, investigating effects of ionizing radiation on the proteome of human normal tissue correlated with radio sensitivity will be included. Eligible studies will include English peer reviewed articles with publication dates from 2011-2020 which are sources of primary data. The search strings will be applied to the scientific literature databases PubMed and Web of Science. The reference lists of included studies will also be manually searched. Data will be extracted according to a pre-defined modality and compiled in a narrative report following guidelines presented as a "Synthesis without Meta-analyses" method. The risk of bias will be assessed based on the NTP/OHAT risk of bias rating tool for human and animal studies (OHAT 2019). : A comprehensive assessment of the quality of evidence for both in vivo and in vitro studies will be followed, by assigning a confidence rating to the literature. This is followed by translation into a rating on the level of evidence (high, moderate, low, or inadequate) regarding the research question. Registration: PROSPERO Submission ID 220064.