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Preclinical data suggest that stereotactic body radiotherapy (SBRT) could work synergistically with CPIs by acting as an in situ cancer vaccine, thus potentially increasing response rates and prolonging disease control. Though SBRT administered concurrently with CPIs has been shown to be safe, evidence of its efficacy from large randomized trials is still lacking. The aim of this multicenter randomized phase II trial is to assess whether SBRT administered concurrently with CPIs could prolong progression-free survival as compared to standard of care in patients with advanced solid tumors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods\/design<\/jats:title>\n                <jats:p>Ninety-eight patients with locally advanced or metastatic disease will be randomized in a 1:1 fashion to receive CPI treatment combined with SBRT (Arm A) or CPI monotherapy (Arm B). Randomization will be stratified according to tumor histology (melanoma, renal, urothelial, head and neck squamous cell or non-small cell lung carcinoma) and disease burden (\u2264 or\u2009&gt;\u20093 cancer lesions). The recommended SBRT dose is 24Gy in 3 fractions, which will be administered to a maximum of 3 lesions and is to be completed prior to the second or third CPI cycle (depending on CPI treatment schedule). The study\u2019s primary endpoint is progression-free survival as per iRECIST. Secondary endpoints include overall survival, objective response, local control, quality of life and toxicity. Translational analyses will be performed using blood, fecal and tissue samples. <jats:italic>Discussion:<\/jats:italic> The CHEERS trial will provide further insights into the clinical and immunological impact of SBRT when combined with CPIs in patients with advanced solid tumors. Furthermore, study results will inform the design of future immuno-radiotherapy trials. <\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">Clinicaltrials.gov<\/jats:ext-link> identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03511391\">NCT03511391<\/jats:ext-link>. Registered 17 April 2018.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12885-021-08088-w","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T12:03:55Z","timestamp":1620389035000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Checkpoint inhibition in combination with an immunoboost of external beam radiotherapy in solid tumors (CHEERS): study protocol for a phase 2, open-label, randomized controlled trial"],"prefix":"10.1186","volume":"21","author":[{"given":"Mathieu","family":"Spaas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"Sundahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Hulstaert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vibeke","family":"Kruse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Rottey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daan","family":"De Maeseneer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veerle","family":"Surmont","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annabel","family":"Meireson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lieve","family":"Brochez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dries","family":"Reynders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Els","family":"Goetghebeur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robbe","family":"Van den Begin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Van Gestel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Renard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piet","family":"Dirix","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter","family":"Mestdagh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piet","family":"Ost","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"issue":"4","key":"8088_CR1","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1200\/JCO.2016.71.8023","volume":"36","author":"J Larkin","year":"2018","unstructured":"Larkin J, Minor D, D'Angelo S, Neyns B, Smylie M, Miller WH Jr, et al. 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All patients will give their written informed consent before inclusion. This will be obtained from each participant by the radiation oncologist.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MS has received travel grants from Astellas, unrelated to this research project. NS has received travel grants from Merck Sharpe & Dohme, Astellas, Bayer and Bristol-Myers Squibb, all unrelated to this research project. VK has served on advisory boards for and received travel grants from Bristol-Myers Squibb and Merck Sharpe & Dohme, unrelated to this research project. SR has received honoraria from Bristol-Myers Squibb, Merck and Roche, as well as grant funding from Merck and Roche, all unrelated to this research project. DVG has received consultancy fees from Sanofi, Merck, Takeda, Novartis. PD has received honoraria from Bayer, Ferring Pharmaceuticals, Ipsen, Janssen, Astellas, as well as grant funding from Janssen, all unrelated to this research project. PO has received research funding from Merck and Varian, has consulted for Ferring Pharmaceuticals, Bayer AG and Janssen, and has received travel grants from Ipsen and Ferring Pharmaceuticals, all unrelated to this research project. The other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"514"}}