{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T23:14:29Z","timestamp":1777763669620,"version":"3.51.4"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>We report long-term results (median follow-up 12 years) of hypofractionated accelerated radiotherapy (HypoAR) in patients treated with breast-conserving surgery. In total, 367 women were treated with HypoAR. Axillary and supraclavicular area (ASA) were treated in patients with involved nodes. In total, 290 patients (scheme A) received 3.5 Gy\/day \u00d710 fractions (breast\/ASA) followed by two 4 Gy fractions with electrons to the affected breast quadrant within 16 days. In total, 77 patients (Scheme B) received 2.7 Gy\/day for 16 consecutive fractions (breast\/ASA) within 22 days, while concurrently, the affected breast quadrant received an electron booster dose of 0.8 Gy for the first 13 fractions. Amifostine was offered to 252\/367 patients. Early radiation toxicity was minimal. Regarding late toxicities, symptomatic breast edema was noted in 2.2%, asymptomatic breast fibrosis in 1.9%, and arm lymphedema in 3.7% of patients. Amifostine reduced early radiation dermatitis (p = 0.001). In total, 2.2% of patients developed contralateral breast and 1.6% other carcinomas. Locoregional recurrence (LR) occurred in 3.1% of patients (0% for in situ carcinomas). Positive margins after surgery, extracapsular node invasion, and HER2-enriched\/triple-negative tumors were linked with significantly worse LR-free survival. The involvement of more than three nodes and luminal type other than A were independent prognostic variables of metastasis and death events. HypoAR delivering a biological dose of 50\u201352 Gy to the breast\/ASA is a safe and effective therapy for patients treated with conservative surgery. The risk of carcinogenesis is low. Positive surgical margins, extracapsular node invasion, and HER2-enriched\/triple-negative phenotypes appear as a cluster of features linked with a higher risk for locoregional relapse.<\/jats:p>","DOI":"10.3390\/curroncol28050300","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T10:24:25Z","timestamp":1631010265000},"page":"3474-3487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Long-Term Results of Postoperative Hypofractionated Accelerated Breast and Lymph Node Radiotherapy (HypoAR) with Hypofractionated Boost"],"prefix":"10.3390","volume":"28","author":[{"given":"Ioannis M.","family":"Koukourakis","sequence":"first","affiliation":[{"name":"1st Department of Radiology, Radiotherapy Unit, Aretaieion University Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianthi","family":"Panteliadou","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy\/Oncology, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axiotis G.","family":"Giakzidis","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy\/Oncology, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Nanos","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy\/Oncology, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Abatzoglou","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy\/Oncology, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Giatromanolaki","sequence":"additional","affiliation":[{"name":"Department of Pathology, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2324-699X","authenticated-orcid":false,"given":"Michael I.","family":"Koukourakis","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy\/Oncology, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100 Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/S1470-2045(12)70042-6","article-title":"Breast conserving therapy versus mastectomy for stage I-II breast cancer: 20 year follow-up of the EORTC 10801 phase 3 randomised trial","volume":"13","author":"Werutsky","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Early Breast Cancer Trialists\u2019 Collaborative Group (EBCTCG), Darby, S., McGale, P., Correa, C., Taylor, C., Arriagada, R., Clarke, M., Cutter, D., Davies, C., and Ewertz, M. (2011). Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet, 378, 1707\u20131716.","DOI":"10.1016\/S0140-6736(11)61629-2"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1093\/jnci\/92.3.269","article-title":"Travel distance to radiation therapy and receipt of radiotherapy following breast-conserving surgery","volume":"92","author":"Athas","year":"2000","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/0167-8140(91)90106-Q","article-title":"Hypofractionation: Lessons from complications","volume":"20","author":"Fletcher","year":"1991","journal-title":"Radiother. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/0360-3016(90)90216-7","article-title":"The use of a specific hypofractionated radiation therapy regimen versus classical fractionation in the treatment of breast cancer: A randomized study of 230 patients","volume":"19","author":"Baillet","year":"1990","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/S0360-3016(98)00438-6","article-title":"Fractionation and protraction for radiotherapy of prostate carcinoma","volume":"43","author":"Brenner","year":"1999","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.radonc.2005.01.005","article-title":"Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: Long-term results of a randomised trial","volume":"75","author":"Yarnold","year":"2005","journal-title":"Radiother. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"START Trialists\u2019 Group, Bentzen, S.M., Agrawal, R.K., Aird, E.G., Barrett, J.M., Barrett-Lee, P.J., Bliss, J.M., Brown, J., Dewar, J.A., and Dobbs, H.J. (2008). The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: A randomised trial. Lancet Oncol., 9, 331\u2013341.","DOI":"10.1016\/S1470-2045(08)70077-9"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1056\/NEJMoa0906260","article-title":"Long-term results of hypofractionated radiation therapy for breast cancer","volume":"362","author":"Whelan","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S0360-3016(01)01759-X","article-title":"Hypofractionated and accelerated radiotherapy with cytoprotection (HypoARC): A short, safe, and effective postoperative regimen for high-risk breast cancer patients","volume":"52","author":"Koukourakis","year":"2002","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.ijrobp.2008.09.016","article-title":"Hypofractionated and accelerated radiotherapy with subcutaneous amifostine cytoprotection as short adjuvant regimen after breast-conserving surgery: Interim report","volume":"74","author":"Koukourakis","year":"2009","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1016\/j.ijrobp.2012.08.017","article-title":"Postmastectomy hypofractionated and accelerated radiation therapy with (and without) subcutaneous amifostine cytoprotection","volume":"85","author":"Koukourakis","year":"2013","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/0360-3016(89)90503-8","article-title":"Dose fractionation and regeneration in radiotherapy for cancer of the oral cavity and oropharynx: Tumor dose-response and repopulation","volume":"16","author":"Maciejewski","year":"1989","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0167-8140(90)90149-Q","article-title":"Time-dose factors in radiotherapy: A review of the human data","volume":"19","author":"Thames","year":"1990","journal-title":"Radiother. Oncol."},{"key":"ref_15","unstructured":"(2021, June 01). Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Available online: https:\/\/www.eortc.be\/services\/doc\/ctc\/CTCAE_v5_Quick_Reference_5x7.pdf."},{"key":"ref_16","unstructured":"(1995). LENT SOMA tables. Radiother. Oncol., 35, 17\u201360."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.ijrobp.2020.09.004","article-title":"Trends in Use of Hypofractionated Whole Breast Radiation in Breast Cancer: An Analysis of the National Cancer Database","volume":"109","author":"Woodward","year":"2021","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3261","DOI":"10.1200\/JCO.19.02750","article-title":"Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer","volume":"38","author":"Brunt","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.ijrobp.2020.03.049","article-title":"Acute Toxicity and Quality of Life of Hypofractionated Radiation Therapy for Breast Cancer","volume":"107","author":"Arsenault","year":"2020","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/S1470-2045(13)70386-3","article-title":"START Trialists\u2019 Group. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials","volume":"14","author":"Haviland","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.clon.2005.11.008","article-title":"Placing the boost in breast-conservation radiotherapy: A review of the role, indications and techniques for breast-boost radiotherapy","volume":"18","author":"Graham","year":"2006","journal-title":"Clin. Oncol. (R. Coll. Radiol.)"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S1470-2045(14)71156-8","article-title":"Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial","volume":"16","author":"Bartelink","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_23","unstructured":"(2021, June 01). Radiotherapy Dose Fractionation. 3rd ed.. Available online: https:\/\/www.rcr.ac.uk\/system\/files\/publication\/field_publication_files\/brfo193_radiotherapy_dose_fractionation_third-edition.pdf."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s10549-015-3666-y","article-title":"The relationship between local recurrence and death in early-stage breast cancer","volume":"155","author":"Sopik","year":"2016","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.radonc.2017.10.033","article-title":"Late normal tissue effects in the arm and shoulder following lymphatic radiotherapy: Results from the UK START (Standardisation of Breast Radiotherapy) trials","volume":"126","author":"Haviland","year":"2018","journal-title":"Radiother. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.soc.2017.08.005","article-title":"Molecular Subtypes and Local-Regional Control of Breast Cancer","volume":"27","author":"Fragomeni","year":"2018","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.ijrobp.2006.12.011","article-title":"Risk of second malignancies after adjuvant radiotherapy for breast cancer: A large-scale, single-institution review","volume":"68","author":"Kirova","year":"2007","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1742-4682-7-4","article-title":"Hypofractionated radiotherapy has the potential for second cancer reduction","volume":"7","author":"Schneider","year":"2010","journal-title":"Theor. Biol. Med. Model."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1259\/bjr\/16386034","article-title":"Radiation damage and radioprotectants: New concepts in the era of molecular medicine","volume":"85","author":"Koukourakis","year":"2012","journal-title":"Br. J. Radiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1016\/S0140-6736(20)30932-6","article-title":"Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial","volume":"395","author":"Haviland","year":"2020","journal-title":"Lancet"}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/28\/5\/300\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:58:18Z","timestamp":1760165898000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/28\/5\/300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,7]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["curroncol28050300"],"URL":"https:\/\/doi.org\/10.3390\/curroncol28050300","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,7]]}}}