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Therefore, young patients are still treated with conventional techniques rather than with modern IMRT. We challenged this hypothesis in first-of-its-kind experiments using an animal model. Cancer-prone\n                    <jats:italic>Tp53<\/jats:italic>\n                    <jats:sup>+\/C273X<\/jats:sup>\n                    knockout rats received mediastinal irradiation with 3\u2009\u00d7\u20095 or 3\u2009\u00d7\u20098\u2009Gy using volumetric-modulated arc therapy (VMAT, an advanced IMRT) or conventional anterior-posterior\/posterior-anterior (AP\/PA) beams using non-irradiated rats as controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915\/group,\n                    <jats:italic>n<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>total<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u200990). Tumors were assigned to volumes receiving 90\u2013107%, 50\u201390%, 5\u201350%, and &lt;5% of the target dose and characterized by histology and loss-of-heterozygosity (LOH). Irradiated rats predominantly developed lymphomas and sarcomas in areas receiving 50\u2013107% (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200926) rather than 5\u201350% (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097) of the target dose. Latency was significantly shortened only after 3\u2009\u00d7\u20098\u2009Gy vs. controls (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). The frequency (14\/28 vs. 19\/29;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.29) and latency (218 vs. 189 days;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.17) of radiation-associated tumors were similar after VMAT vs. AP\/PA. LOH was strongly associated with sarcoma but not with treatment. The results do not support the hypothesis that IMRT increases the risk of second cancer. Thus the current practice of withholding dose-sparing IMRT from young patients may need to be re-evaluated.\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-51735-3","type":"journal-article","created":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T16:29:48Z","timestamp":1572452988000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Radiation-induced malignancies after intensity-modulated versus conventional mediastinal radiotherapy in a small animal model"],"prefix":"10.1038","volume":"9","author":[{"given":"Kaga","family":"Gomarteli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Fleckenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kirschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3006-1712","authenticated-orcid":false,"given":"Vladimir","family":"Bobu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Brockmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9879-4491","authenticated-orcid":false,"given":"Thomas","family":"Henzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Riffel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan O.","family":"Sch\u00f6nberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlon R.","family":"Veldwijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Kr\u00e4nzlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hoerner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-1576","authenticated-orcid":false,"given":"Gerhard","family":"Glatting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Wenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6554-5907","authenticated-orcid":false,"given":"Carsten","family":"Herskind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A.","family":"Giordano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,29]]},"reference":[{"key":"51735_CR1","unstructured":"Curtis, R. 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