{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:29:21Z","timestamp":1786422561890,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"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>Radiotherapy (RT)-induced lymphopenia may hinder the anti-tumor immune response. Preoperative RT or chemo-RT (CRT) for locally advanced rectal cancer is a standard therapeutic approach, while immunotherapy has been approved for mismatch repair-deficient rectal tumors. We retrospectively analyzed 98 rectal adenocarcinoma patients undergoing neoadjuvant CRT with VMAT (groups A, B, C) or IMRT (group D) techniques, with four different RT schemes: group A (n = 24): 25 Gy\/5 Gy\/fraction plus a 0.2 Gy\/fraction rectal tumor boost; group B (n = 22): 34 Gy\/3.4 Gy\/fraction, with a 1-week treatment break after the first five RT fractions; group C (n = 20): 46 Gy\/2 Gy\/fraction plus a 0.2 Gy\/fraction rectal tumor boost; group D (n = 32): 45 Gy\/1.8 Gy\/fraction followed by 5.4 Gy\/1.8 Gy\/fraction to the rectal tumor. We examined the effect of the time-corrected normalized total dose (NTD-T) to the BM on lymphopenia. Groups A and B (hypofractionated RT) had significantly higher lymphocyte counts (LCs) after RT than groups C and D (p &lt; 0.03). An inverse association between the LCs after RT and NTD-T was demonstrated (p = 0.01). An NTD-T threshold of 30 Gy delivered to 30% of the BM volume emerged as a potential constraint for RT planning, which could be successfully integrated in the RT plan. Hypofractionated and accelerated RT schemes, and BM-sparing techniques may reduce lymphocytic damage and prove critical for immuno-RT clinical trials.<\/jats:p>","DOI":"10.3390\/curroncol31100429","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T09:16:10Z","timestamp":1727428570000},"page":"5774-5788","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Lymphopenia Induced by Different Neoadjuvant Chemo-Radiotherapy Schedules in Patients with Rectal Cancer: Bone Marrow as an Organ at Risk"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7138-6671","authenticated-orcid":false,"given":"Christos","family":"Nanos","sequence":"first","affiliation":[{"name":"Department of Radiotherapy and Oncology, Medical School, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis M.","family":"Koukourakis","sequence":"additional","affiliation":[{"name":"Radiation Oncology Unit, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Admir","family":"Mulita","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy and Oncology, Medical School, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphaela","family":"Avgousti","sequence":"additional","affiliation":[{"name":"Medical Physics Unit, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2082-7323","authenticated-orcid":false,"given":"Vassilios","family":"Kouloulias","sequence":"additional","affiliation":[{"name":"Department of Clinical Radiation Oncology, Attikon Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Zygogianni","sequence":"additional","affiliation":[{"name":"Radiation Oncology Unit, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2324-699X","authenticated-orcid":false,"given":"Michael I.","family":"Koukourakis","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy and Oncology, Medical School, Democritus University of Thrace, University Hospital of Alexandroupolis, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. 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