CYRAD: a translational study assessing immune response to radiotherapy by photons or protons in postoperative head and neck cancer patients through circulating leukocyte subpopulations and cytokine levels.
Cytokines
Immune response
Lymphoid
Lymphopenia
Myeloid
Photons
Protons
Radiotherapy
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
05 Oct 2024
05 Oct 2024
Historique:
received:
21
05
2024
accepted:
27
09
2024
medline:
6
10
2024
pubmed:
6
10
2024
entrez:
5
10
2024
Statut:
epublish
Résumé
Radiotherapy has both immunostimulant and immunosuppressive effects, particularly in radiation-induced lymphopenia. Proton therapy has demonstrated potential in mitigating this lymphopenia, yet the mechanisms by which different types of radiation affect the immune system function are not fully characterized. The Circulating Immunes Cells, Cytokines and Brain Radiotherapy (CYRAD) trial aims to compare the effects of postoperative X-ray and proton radiotherapy on circulating leukocyte subpopulations and cytokine levels in patients with head and neck (CNS and ear nose throat) cancer. CYRAD is a prospective, non-randomized, single-center non interventional study assessing changes in the circulating leukocyte subpopulations and cytokine levels in head and neck cancer patients receiving X-ray or proton radiotherapy following tumor resection. Dosimetry parameters, including dose deposited to organs-at-risk such as the blood and cervical lymph nodes, are computed. Participants undergo 29 to 35 radiotherapy sessions over 40 to 50 days, followed by a 3-month follow-up. Blood samples are collected before starting radiotherapy (baseline), before the 11th (D15) and 30th sessions (D40), and three months after completing radiotherapy. The study will be conducted with 40 patients, in 2 groups of 20 patients per modality of radiotherapy (proton therapy and photon therapy). Statistical analyses will assess the absolute and relative relationship between variations (depletion, recovery) in immune cells, biomarkers, dosimetry parameters and early outcomes. Previous research has primarily focused on radiation-induced lymphopenia, paying less attention to the specific impacts of radiation on different lymphoid and myeloid cell types. Early studies indicate that X-ray and proton irradiation may lead to divergent outcomes in leukocyte subpopulations within the bloodstream. Based on these preliminary findings, this study aims to refine our understanding of how proton therapy can better preserve immune function in postoperative (macroscopic tumor-free) head and neck cancer patients, potentially improving treatment outcomes. Version 2.1 dated from January 18, 2023. The CYRAD trial is registered from October 19, 2021, at the US National Library of Medicine, ClinicalTrials.gov ID NCT05082961.
Sections du résumé
BACKGROUND
BACKGROUND
Radiotherapy has both immunostimulant and immunosuppressive effects, particularly in radiation-induced lymphopenia. Proton therapy has demonstrated potential in mitigating this lymphopenia, yet the mechanisms by which different types of radiation affect the immune system function are not fully characterized. The Circulating Immunes Cells, Cytokines and Brain Radiotherapy (CYRAD) trial aims to compare the effects of postoperative X-ray and proton radiotherapy on circulating leukocyte subpopulations and cytokine levels in patients with head and neck (CNS and ear nose throat) cancer.
METHODS
METHODS
CYRAD is a prospective, non-randomized, single-center non interventional study assessing changes in the circulating leukocyte subpopulations and cytokine levels in head and neck cancer patients receiving X-ray or proton radiotherapy following tumor resection. Dosimetry parameters, including dose deposited to organs-at-risk such as the blood and cervical lymph nodes, are computed. Participants undergo 29 to 35 radiotherapy sessions over 40 to 50 days, followed by a 3-month follow-up. Blood samples are collected before starting radiotherapy (baseline), before the 11th (D15) and 30th sessions (D40), and three months after completing radiotherapy. The study will be conducted with 40 patients, in 2 groups of 20 patients per modality of radiotherapy (proton therapy and photon therapy). Statistical analyses will assess the absolute and relative relationship between variations (depletion, recovery) in immune cells, biomarkers, dosimetry parameters and early outcomes.
DISCUSSION
CONCLUSIONS
Previous research has primarily focused on radiation-induced lymphopenia, paying less attention to the specific impacts of radiation on different lymphoid and myeloid cell types. Early studies indicate that X-ray and proton irradiation may lead to divergent outcomes in leukocyte subpopulations within the bloodstream. Based on these preliminary findings, this study aims to refine our understanding of how proton therapy can better preserve immune function in postoperative (macroscopic tumor-free) head and neck cancer patients, potentially improving treatment outcomes.
PROTOCOL VERSION
METHODS
Version 2.1 dated from January 18, 2023.
TRIAL REGISTRATION
BACKGROUND
The CYRAD trial is registered from October 19, 2021, at the US National Library of Medicine, ClinicalTrials.gov ID NCT05082961.
Identifiants
pubmed: 39369231
doi: 10.1186/s12885-024-13002-1
pii: 10.1186/s12885-024-13002-1
doi:
Substances chimiques
Cytokines
0
Banques de données
ClinicalTrials.gov
['NCT05082961']
Types de publication
Journal Article
Clinical Trial Protocol
Langues
eng
Sous-ensembles de citation
IM
Pagination
1230Subventions
Organisme : ligue contre le cancer, France
ID : 2021-A01862-39
Organisme : ligue contre le cancer, France
ID : 2021-A01862-39
Informations de copyright
© 2024. The Author(s).
Références
Delaney G, Jacob S, Featherstone C, Barton M. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer. 2005;104:1129–37.
doi: 10.1002/cncr.21324
pubmed: 16080176
de Andrade Carvalho H, Villar RC. Radiotherapy and immune response: the systemic effects of a local treatment. Clinics. 2018;73:e557s.
doi: 10.6061/clinics/2018/e557s
pmcid: 6257057
Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, et al. Immunologic correlates of the Abscopal Effect in a patient with Melanoma. N Engl J Med. 2012;366:925–31.
doi: 10.1056/NEJMoa1112824
pubmed: 22397654
pmcid: 3345206
Janopaul-Naylor JR, Shen Y, Qian DC, Buchwald ZS. The Abscopal Effect: a review of pre-clinical and clinical advances. IJMS. 2021;22:11061.
doi: 10.3390/ijms222011061
pubmed: 34681719
pmcid: 8537037
Rowell NP. The abscopal effect and its implications for radiotherapy-immunotherapy combinations. Transl Cancer Res. 2023;12:8–12.
doi: 10.21037/tcr-22-2354
pubmed: 36760386
pmcid: 9906065
Farese AM, Hankey KG, Cohen MV, MacVittie TJ. Lymphoid and myeloid recovery in Rhesus macaques following total body X-Irradiation. Health Phys. 2015;109:414–26.
doi: 10.1097/HP.0000000000000348
pubmed: 26425902
pmcid: 4593069
Macintyre AN, French MJ, Sanders BR, Riebe KJ, Shterev ID, Wiehe K, et al. Long-term recovery of the adaptive Immune System in Rhesus macaques after total body irradiation. Adv Radiation Oncol. 2021;6:100677.
doi: 10.1016/j.adro.2021.100677
Pham T-N, Coupey J, Toutain J, Candeias SM, Simonin G, Rousseau M et al. Early effects of different brain radiotherapy modalities on circulating leucocyte subpopulations in rodents. Int J Radiat Biol. 2024;:1–12.
Pham T-N, Coupey J, Candeias SM, Ivanova V, Valable S, Thariat J. Beyond lymphopenia, unraveling radiation-induced leucocyte subpopulation kinetics and mechanisms through modeling approaches. J Exp Clin Cancer Res. 2023;42:50.
doi: 10.1186/s13046-023-02621-4
pubmed: 36814272
pmcid: 9945629
Ghosh S, Huang J, Inkman M, Zhang J, Thotala S, Tikhonova E, et al. Radiation-induced circulating myeloid-derived suppressor cells induce systemic lymphopenia after chemoradiotherapy in patients with glioblastoma. Sci Transl Med. 2023;15:eabn6758.
doi: 10.1126/scitranslmed.abn6758
pubmed: 36696484
pmcid: 10501302
Mole RH. Whole body irradiation—radiobiology or medicine? Br J Radiol. 1953;26:234–41.
doi: 10.1259/0007-1285-26-305-234
pubmed: 13042090
Ellsworth SG. Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumors. Adv Radiation Oncol. 2018;3:512–9.
doi: 10.1016/j.adro.2018.08.014
Goitein M, Cox JD. Should Randomized clinical trials be required for Proton Radiotherapy? JCO. 2008;26:175–6.
doi: 10.1200/JCO.2007.14.4329
Hall EJ. Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int J Radiation Oncology*Biology*Physics. 2006;65:1–7.
doi: 10.1016/j.ijrobp.2006.01.027
Hammi A, Paganetti H, Grassberger C. 4D blood flow model for dose calculation to circulating blood and lymphocytes. Phys Med Biol. 2020;65:055008.
doi: 10.1088/1361-6560/ab6c41
pubmed: 32119649
pmcid: 8268045
Mohan R, Liu AY, Brown PD, Mahajan A, Dinh J, Chung C, et al. Proton therapy reduces the likelihood of high-grade radiation-induced lymphopenia in glioblastoma patients: phase II randomized study of protons vs photons. Neurooncology. 2021;23:284–94.
Ebrahimi S, Lim G, Liu A, Lin SH, Ellsworth SG, Grassberger C, et al. Radiation-Induced Lymphopenia risks of Photon Versus Proton Therapy for Esophageal Cancer patients. Int J Part Therapy. 2021;8:17–27.
doi: 10.14338/IJPT-20-00086
Fang P, Shiraishi Y, Verma V, Jiang W, Song J, Hobbs BP, et al. Lymphocyte-sparing effect of Proton Therapy in patients with esophageal Cancer treated with definitive chemoradiation. Int J Part Therapy. 2017;4:23–32.
doi: 10.14338/IJPT-17-00033.1
Kim N, Myoung Noh J, Lee W, Park B, Park H, Young Park J, et al. Proton Beam therapy reduces the risk of severe radiation-induced lymphopenia during chemoradiotherapy for locally advanced non-small cell lung cancer: a comparative analysis of proton versus photon therapy. Radiother Oncol. 2021;156:166–73.
doi: 10.1016/j.radonc.2020.12.019
pubmed: 33359267
Paganetti H. Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer. Phys Med Biol. 2014;59:R419–72.
doi: 10.1088/0031-9155/59/22/R419
pubmed: 25361443
Durante M, Loeffler JS. Charged particles in radiation oncology. Nat Rev Clin Oncol. 2010;7:37–43.
doi: 10.1038/nrclinonc.2009.183
pubmed: 19949433
Carabe-Fernandez A, Dale RG, Jones B. The incorporation of the concept of minimum RBE (RBE
doi: 10.1080/09553000601087176
pubmed: 17357437
Bodensteiner D. RayStation: external beam treatment planning system. Med Dosim. 2018;43:168–76.
doi: 10.1016/j.meddos.2018.02.013
pubmed: 29650302
Venkatesulu B, Giridhar P, Pujari L, Chou B, Lee JH, Block AM, et al. Lymphocyte sparing normal tissue effects in the clinic (LymphoTEC): a systematic review of dose constraint considerations to mitigate radiation-related lymphopenia in the era of immunotherapy. Radiother Oncol. 2022;177:81–94.
doi: 10.1016/j.radonc.2022.10.019
pubmed: 36334694
Chen F, Jin J-Y, Hui TSK, Jing H, Zhang H, Nong Y, et al. Radiation Induced Lymphopenia is Associated with the effective dose to the circulating Immune cells in breast Cancer. Front Oncol. 2022;12:768956.
doi: 10.3389/fonc.2022.768956
pubmed: 35600350
pmcid: 9118537
Xu C, Jin J-Y, Zhang M, Liu A, Wang J, Mohan R, et al. The impact of the effective dose to immune cells on lymphopenia and survival of esophageal cancer after chemoradiotherapy. Radiother Oncol. 2020;146:180–6.
doi: 10.1016/j.radonc.2020.02.015
pubmed: 32182504
pmcid: 7506523
Coupey J, Pham TN, Toutain J, Ivanova V, HUE E, Helaine C, et al. Investigating the effects of protons versus x-rays on radiation-induced lymphopenia after brain irradiation. bioRxiv. 2024. https://doi.org/10.1101/2024.03.02.583088 .
doi: 10.1101/2024.03.02.583088
Mohan R. A review of proton therapy – current status and future directions. Precision Radiation Oncol. 2022;6:164–76.
doi: 10.1002/pro6.1149
Gordon KB, Smyk DI, Gulidov IA. Proton Therapy in Head and Neck Cancer Treatment: state of the Problem and Development prospects (review). Sovrem Tehnol Med. 2021;13:70.
doi: 10.17691/stm2021.13.4.08