{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T09:28:22Z","timestamp":1786613302081,"version":"build-2736575974"},"reference-count":22,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: The implementation of tattoo-free radiotherapy (RT) for breast cancer reflects an effort to mitigate the psychological distress of permanent marks through surface-guided techniques, while simultaneously evaluating its utility in meeting setup precision requirements. Methods: In this prospective trial, patients were positioned for breast cancer RT including regional nodal irradiation exclusively using surface-guided RT (SGRT). Cone-beam computed tomography (CBCT) was acquired at each fraction as the ground truth to analyze translational setup deviations. Results: A total of 457 paired SGRT\u2013CBCT data points in 30 patients were acquired. A residual translational setup deviation of \u22646 mm was achieved in 97.6% of all fractions with a median deviation of 2 mm (range: 0\u201312). Neither age, comorbidities, body mass index, extent of target volumes, choice of breathing technique, nor patient-reported symptoms (pain, dermatitis, anxiety) correlated significantly with setup deviations. The median in-room positioning time was 92 s (range: 20 s\u20136 min and 37 s) and significantly prolonged in patients with an elevated BMI and higher grades of pain and skin dermatitis, and for chest wall irradiation. Manual assessment of the accuracy of regional nodal CTVs in each CBCT relative to the planning CT showed good-to-minor deviations in 99.7% (Level 1\/2), 95.0% (Supra-\/infraclavicular), and 90.8% (Internal mammary), respectively, with major deviations in only 0.3% (Level 1\/2), 5.0% (Supra-\/infraclavicular) and 9.2% (Internal mammary). A forward dose calculation on CBCT geometries (n = 86) revealed high median CTV dose coverage of 100.0% (range: 57.1\u2013107.7%) of the original target dose for all lymph node levels combined. Conclusions: The tattoo-free positioning setup for regional nodal irradiation in breast cancer patients exhibited pronounced robustness, maintaining its accuracy and reliability irrespective of patient-, tumor-, or treatment-specific variables with high clinical efficiency. However, larger cohorts are required to confirm whether these parameters genuinely operate independently of setup accuracy.<\/jats:p>","DOI":"10.3390\/jcm15166253","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:06:16Z","timestamp":1786608376000},"page":"6253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Prospective SPOTLESS Trial: Setup Accuracy of Tattoo-Less Surface-Guided Breast Radiotherapy Including Regional Nodal Irradiation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7087-9581","authenticated-orcid":false,"given":"Eva","family":"Meixner","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Albert","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahar","family":"Cepni","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Neugebauer","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4854-1514","authenticated-orcid":false,"given":"Hin Hoi","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Thater","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6325-4193","authenticated-orcid":false,"given":"Klaus","family":"Herfarth","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Mende","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1731-7090","authenticated-orcid":false,"given":"Fabian","family":"Weykamp","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"},{"name":"German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Ayestaran-Aldaz","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line","family":"Hoeltgen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2389-5404","authenticated-orcid":false,"given":"Nathalie","family":"Arians","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Liermann","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer 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Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0687-1849","authenticated-orcid":false,"given":"Hanna","family":"Waldsperger","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, 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Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2733-4134","authenticated-orcid":false,"given":"Vania","family":"Batista","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0958-3947(96)00156-2","article-title":"Anterior-posterior treatment localization in pelvic radiotherapy: Tattoos or fixed couch-to-isocentre 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