Study of late toxicity biomarkers of locally advanced head and neck cancer patients treated with radiotherapy plus cisplatin or cetuximab points to the relevance of skin macrophages (TOX-TTCC-2015-01).
Biomarkers
Cetuximab
Chemotherapy
Cisplatin
Head and neck cancer
Late toxicity
Macrophages
Radiotherapy
Journal
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
ISSN: 1699-3055
Titre abrégé: Clin Transl Oncol
Pays: Italy
ID NLM: 101247119
Informations de publication
Date de publication:
23 May 2024
23 May 2024
Historique:
received:
12
02
2024
accepted:
14
05
2024
medline:
24
5
2024
pubmed:
24
5
2024
entrez:
23
5
2024
Statut:
aheadofprint
Résumé
Radiotherapy (RT) with concomitant cisplatin (CRT) or cetuximab (ERT) are accepted treatment options for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Long-term adverse events (AEs) have a vast impact on patients' quality of life. This study explored tissue biomarkers which could help predict late toxicity. Single-institution prospective study including patients aged ≥ 18 with histologically confirmed newly diagnosed LA-SCCHN treated with RT and either concomitant cisplatin q3w or weekly cetuximab, according to institutional protocols. All patients underwent pre- and post-treatment skin biopsies of neck regions included in the clinical target volume. Angiogenesis, macrophages, and extracellular matrix (ECM) markers were evaluated by immunohistochemistry (IHC). From April 15, 2016, to December 11, 2017; 31 patients were evaluated [CRT = 12 (38.7%) and ERT = 19 (61.3%)]. 27 patients (87%) had received induction chemotherapy. All patients finished RT as planned. IHC expression of vasculature (CD34) and collagen (Masson's Trichrome) did not differ significantly between and within CRT and ERT arms. Conversely, an increased CD68 and CD163 macrophage infiltration expression was observed after treatment, without significant impact of treatment modality. Patients with higher late toxicity showed lower expression of macrophage markers in pre-treatment samples compared with those with lower late toxicity, with statistically significant differences for CD68. Angiogenesis and ECM biomarkers did not differ significantly between CRT and ERT. Macrophage markers increased after both treatments and deserve further investigation as predictors of late toxicity in LA-SCCHN patients. [Protocol code: TOX-TTCC-2015-01/Spanish registry of clinical studies (REec): 2015-003012-21/Date of registration: 27/01/2016].
Identifiants
pubmed: 38782865
doi: 10.1007/s12094-024-03526-0
pii: 10.1007/s12094-024-03526-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Machiels JP, Leemans CR, Golusinski W, Grau C, Licitra L, Gregoire V. Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS–ESMO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2020;31(11):1462–75.
doi: 10.1016/j.annonc.2020.07.011
pubmed: 33239190
Blanchard P, Baujat B, Holostenco V, Bourredjem A, Baey C, Bourhis J, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiother Oncol J Eur Soc Ther Radiol Oncol. 2011;100(1):33–40.
doi: 10.1016/j.radonc.2011.05.036
Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567–78.
doi: 10.1056/NEJMoa053422
pubmed: 16467544
Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton-Lieuw T, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet Lond Engl. 2019;393(10166):51–60.
doi: 10.1016/S0140-6736(18)32752-1
Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet Lond Engl. 2019;393(10166):40–50.
doi: 10.1016/S0140-6736(18)32779-X
Langendijk JA, Doornaert P, Verdonck-de Leeuw IM, Leemans CR, Aaronson NK, Slotman BJ. Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26(22):3770–6.
doi: 10.1200/JCO.2007.14.6647
Taberna M, Rullan AJ, Hierro C, Navarro V, Vázquez S, Lozano A, et al. Late toxicity after radical treatment for locally advanced head and neck cancer. Oral Oncol. 2015;51(8):795–9.
doi: 10.1016/j.oraloncology.2015.05.002
pubmed: 26051499
Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS, et al. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26(21):3582–9.
doi: 10.1200/JCO.2007.14.8841
Rivelli TG, Mak MP, Martins RE, da Costa e Silva VT, de Castro G. Cisplatin based chemoradiation late toxicities in head and neck squamous cell carcinoma patients. Discov Med. 2015;20(108):57–66.
Meyer F, Fortin A, Wang CS, Liu G, Bairati I. Predictors of severe acute and late toxicities in patients with localized head-and-neck cancer treated with radiation therapy. Int J Radiat Oncol Biol Phys. 2012;82(4):1454–62.
doi: 10.1016/j.ijrobp.2011.04.022
pubmed: 21640495
Ghadjar, P., Simcock, M., Zimmermann, F., Betz, M., Bodis, S., Bernier, J., et al. Predictors of severe late radiotherapy-related toxicity after hyperfractionated radiotherapy with or without concomitant cisplatin in locally advanced head and neck cancer. Secondary retrospective analysis of a randomized phase III trial (SAKK 10/94). Radiother Oncol J Eur Soc Ther Radiol Oncol [Internet]. 2012 Aug [cited 2023 Apr 16];104(2). Available from: https://pubmed.ncbi.nlm.nih.gov/22726581/
Fanetti G, Polesel J, Fratta E, Muraro E, Lupato V, Alfieri S, et al. Prognostic nutritional index predicts toxicity in head and neck cancer patients treated with definitive radiotherapy in association with chemotherapy. Nutrients. 2021;13(4):1277.
doi: 10.3390/nu13041277
pubmed: 33924581
pmcid: 8070136
Bordón E, Henríquez-Hernández LA, Lara PC, Ruíz A, Pinar B, Rodríguez-Gallego C, et al. Prediction of clinical toxicity in locally advanced head and neck cancer patients by radio-induced apoptosis in peripheral blood lymphocytes (PBLs). Radiat Oncol Lond Engl. 2010;5:4.
doi: 10.1186/1748-717X-5-4
Sumner W, Ray X, Sutton L, Rebibo D, Marincola F, Sanghvi P, et al. Gene alterations as predictors of radiation-induced toxicity in head and neck squamous cell carcinoma. J Transl Med. 2021;19(1):212.
doi: 10.1186/s12967-021-02876-5
pubmed: 34001187
pmcid: 8130372
Isaksson LJ, Pepa M, Zaffaroni M, Marvaso G, Alterio D, Volpe S, et al. Machine learning-based models for prediction of toxicity outcomes in radiotherapy. Front Oncol. 2020. https://doi.org/10.3389/fonc.2020.00790 .
doi: 10.3389/fonc.2020.00790
pubmed: 32850390
pmcid: 7403202
Bang C, Bernard G, Le WT, Lalonde A, Kadoury S, Bahig H. Artificial intelligence to predict outcomes of head and neck radiotherapy. Clin Transl Radiat Oncol [Internet]. 2023 Mar 1 [cited 2023 Apr 16];39. Available from: https://www.ctro.science/article/S2405-6308(23)00015-0/fulltext
Grupo de trabajo ICO-ICSPraxis para tumores de cabeza y cuello. ICO-ICSPraxis para el tratamiento médico y con irradiación del cáncer de orofaringe, cavidad oral, hipofaringe, laringe, nasofaringe y carcinoma escamoso cervical de origen desconocido. Barcelona 2014. Institut Català d’Oncologia.
Ottery FD. Definition of standardized nutritional assessment and interventional pathways in oncology. Nutrition. 1996;12(1, Supplement):S15–9.
Bankhead P, Loughrey MB, Fernández JA, Dombrowski Y, McArt DG, Dunne PD, et al. QuPath: open source software for digital pathology image analysis. Sci Rep. 2017;7(1):16878.
doi: 10.1038/s41598-017-17204-5
pubmed: 29203879
pmcid: 5715110
Yarnold J, Brotons MCV. Pathogenetic mechanisms in radiation fibrosis. Radiother Oncol. 2010;97(1):149–61.
doi: 10.1016/j.radonc.2010.09.002
pubmed: 20888056
Autio P, Saarto T, Tenhunen M, Elomaa I, Risteli J, Lahtinen T. Demonstration of increased collagen synthesis in irradiated human skin in vivo. Br J Cancer. 1998;77(12):2331–5.
doi: 10.1038/bjc.1998.387
pubmed: 9649154
pmcid: 2150405
Borrelli MR, Shen AH, Lee GK, Momeni A, Longaker MT, Wan DC. Radiation-induced skin fibrosis: pathogenesis, current treatment options, and emerging therapeutics. Ann Plast Surg. 2019;83(4S Suppl 1):S59–S64.