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)

• Antonio Rullan ^[1] ; Juan A. Marín Jiménez ^[1] ; Alicia Lozano ^[2] ; Oriol Bermejo ^[3] ; Lorena Arribas ^[4] ; Nuria Ruiz ^[5] ; Isabel Linares ^[2] ; Miren Taberna ^[1] ; Xavi Pérez ^[6] ; María Plana ^[1] ; Marc Oliva ^[1] ; Ricard Mesía ^[7]
  1. [1] Department of Medical Oncology, Catalan Institute of Oncology (ICO), L’Hospitalet de Llobregat, Barcelona, Spain
  2. [2] Department of Radiation Oncology, Catalan Institute of Oncology (ICO), L’Hospitalet de Llobregat, Barcelona, Spain
  3. [3] Departament of Plastic and Reconstructive Surgery, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
  4. [4] Clinical Nutrition Unit, Catalan Institute of Oncology (ICO), L’Hospitalet de Llobregat, Barcelona, Spain
  5. [5] Department of Pathology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
  6. [6] Clinical Investigation Unit (UIC), Catalan Institute of Oncology (ICO) L’Hospitalet, Barcelona, Spain
  7. [7] Department of Medical Oncology, Catalan Institute of Oncology (ICO), B-ARGO Group, IGTP, Badalona, Barcelona, Spain

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 26, Nº. 12, 2024, págs. 3003-3012
• Idioma: inglés
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• Resumen

  • Purpose 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.

    Methods/patients 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).

    Results 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.

    Conclusions 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].