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As toxicity outcome data are emerging, we aimed to synthesize the published data for the toxicity outcomes of proton or carbon\u2010ion therapy (together known as particle beam therapy [PBT]) for primary nasopharyngeal carcinoma (NPC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>We searched PubMed and Scopus electronic databases to identify original studies reporting toxicity outcomes following PBT of primary NPC. Quality assessment was performed using NIH's Quality Assessment Tool. Reports were extracted for information on demographics, main results, and clinical and dose factors correlates. Meta\u2010analysis was performed using the random\u2010effects model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twelve studies were selected (six using mixed particle\u2010photon beams, five performed comparisons to photon\u2010based therapy). The pooled event rates for acute grade \u22652 toxicities mucositis, dermatitis, xerostomia weight loss are 46% (95% confidence interval [95% CI]\u201429%\u201364%, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a087%), 47% (95% CI\u201428%\u201367%, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a087%), 16% (95% CI\u20149%\u201329%, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a076%), and 36% (95% CI\u201427%\u201347%, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a045%), respectively. Only one late endpoint (xerostomia grade \u22652) has sufficient data for analysis with pooled event rate of 9% (95% CI\u20143%\u201329%, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a077%), lower than intensity\u2010modulated radiotherapy 27% (95% CI\u201410%\u201354%, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a095%). For most endpoints with significant differences between the PBT and photon\u2010based therapies, PBT resulted in better outcomes. In two studies where dose distribution was studied, doses to the organs at risk were independent risk factors for toxicities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PBT may reduce the risk of acute toxicities for patients treated for primary NPC, likely due to dose reduction to critical structures. The pooled event rate for toxicities derived in this study can be a guide for patient counseling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ajco.13915","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T05:30:30Z","timestamp":1674451830000},"page":"240-250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Toxicity profile of patients treated with proton and carbon\u2010ion therapy for primary nasopharyngeal carcinoma: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2736-6489","authenticated-orcid":false,"given":"Noorazrul","family":"Yahya","sequence":"first","affiliation":[{"name":"Diagnostic Imaging and Radiotherapy, CODTIS, Faculty of Health Sciences National University of Malaysia  Kuala Lumpur Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siti Athiyah","family":"Mohamad 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