Abstract Background Nowadays there is an increasing in the numbers of cases of head and neck squamous cell carcinoma (HNSCC) all over the world. Which affect upper aerodigestive tract including the nasopharynx, paranasal sinuses, oral cavity, oropharynx, hypopharynx and larynx. Objective To compare the using of radiotherapy (RT) with cisplatin versus cetuximab with RT in the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The comparison between these two treatment regimens will be done in terms of overall survival rate and toxicity. Patients and Methods We performed this systematic review and meta-analysis in accordance to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) statement. PRISMA and MOOSE are reporting checklists for Authors, Editors, and Reviewers of Meta-analyses of interventional and observational studies. According to International committee of medical journal association (ICJME), reviewers must report their findings according to each of the items listed in those checklists. Results cetuximab with RT is associated with lower overall survival compared to cisplatin with RT in management of locally advanced head and neck squamous cell carcinoma, also patient treated with cetuximab were associated with higher rates of mortality compared to those treated with cisplatin Data Sources Medline databases (PubMed, Medscape, ScienceDirect. EMF-Portal) and all materials available in the Internet till 2020. Conclusion According to our study in the comparison between cisplatin with RT versus cetuximab with RT, cetuximab with RT is associated with lower overall survival compared to cisplatin with RT in management of locally advanced head and neck squamous cell carcinoma, also patient treated with cetuximab were associated with higher rates of mortality compared to those treated with cisplatin
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