Microbiota-guided Radiotherapy for Head and Neck Cancer
MIcrobiota-Guided RAdiotherapy for Head and Neck Cancer. (MIGRHAN)
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
100 participants
Oct 15, 2025
OBSERVATIONAL
Conditions
Summary
Head and neck cancer (HNC) is the sixth most common cancer worldwide. Therapeutic outcomes for HNC remain unsatisfactory and heterogeneous, with 5-year survival rates ranging from 28% to 67% overall. Moreover, HNC patients experience side effects during treatment, including inflammation and ulceration of the oral mucosa caused by radiation or cytotoxic agents (oral mucositis), which represents a limiting factor for both the escalation of radiotherapy dosage and the duration of treatment. Several observational studies have highlighted statistical associations between the oral microbiota and numerous factors related to HNC and its therapeutic course. The working hypothesis of this study is that it is possible to establish causal relationships between the functional traits of the human oral microbiota and the effectiveness of radiotherapy in HNC treatment, directly from the analysis of data collected in observational cohorts, by leveraging the statistical framework of causal inference. The oral microbiota of HNC patients enrolled in the study will be characterised through metagenomic sequencing of saliva samples collected from each patient, at radiotherapy-baseline, at 2 weeks from radiotherapy start and at radiotherapy end. Main Objectives of the Study: * Creation of a dataset of the oral microbiota in HNC patients, including both bacterial and viral components, as well as data linked to treatment effectiveness and side effects. * Estimation of the causal effect of the functional traits of the oral microbiota on the modulation of radiotherapy in HNC. * Development of predictive models for local tumour control and for oral mucositis, based on the oral microbiota of HNC patients. Clinical Relevance: The causal relationships inferred between the functional/metabolic traits of the microbiota and radiotherapy effectiveness will help build interpretable predictive models and reveal strategies to reprogram the microbiota functionality of patients with head and neck cancer. This will increase the likelihood of tumour eradication or control while reducing the risk of radiation-induced side effects.
Eligibility
Inclusion Criteria6
- Age ≥ 18 years.
- ECOG Performance Status ≤ 3.
- Histological diagnosis of squamous cell carcinoma, undifferentiated carcinoma, epithelial glandular and non-glandular carcinoma (including adenoid cystic carcinoma, adenocarcinoma, mucoepidermoid carcinoma, neuroendocrine carcinoma, etc.) originating from the oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, salivary glands, paranasal sinuses, or from an unknown primary site.
- Stage III-IV non-metastatic disease for pharyngeal, laryngeal, or unknown-primary tumors, according to AJCC 7th edition. Patients with stage III-IV tumors of salivary gland or paranasal sinus origin, and patients with stage I-II pharyngeal or laryngeal tumors, will only be included if prophylactic irradiation of cervical lymph node stations is indicated and/or if the oral and oropharyngeal mucosa as well as swallowing-related structures are included within the irradiated volume.
- Indication for treatment in either definitive or adjuvant settings, with or without systemic therapy (concurrent systemic therapy, with or without prior neoadjuvant chemotherapy, permitted. Adjuvant systemic therapy is allowed for selected advanced stages of pharyngeal carcinoma, according to institutional guidelines).
- Formal acceptance of study participation requirements (written informed consent).
Exclusion Criteria4
- Prior radiotherapy to the head-neck region.
- Presence of connective tissue disorders (e.g., lupus erythematosus or scleroderma) or synchronous head and neck malignancies, except for superficial skin cancers or surgically treated carcinoma in situ not requiring radiotherapy or systemic therapy.
- Absence of formal acceptance of study participation requirements (written informed consent).
- Indication for treatment exclusively in the postoperative setting.
Interventions
Patients will receive radiotherapy for head and neck cancer and possible concomitant chemotherapies as foreseen by international guidelines. No modification of standard regimens is considered. Intensity-modulated radiotherapy (IMRT) treatment will be administered using X-ray photons with energies ≥6 MV, with daily setup verification performed through IGRT techniques in accordance with institutional standards. Radiotherapy will be delivered with either conventional fractionation or a moderately accelerated hypofractionated schedule (≤2.2 Gy per fraction), with total prescribed doses of up to 70 Gy (2 Gy-equivalent) in the definitive setting, or 54-66 Gy (2 Gy-equivalent) in the postoperative setting. The selection of irradiation targets and dose constraints for organs at risk (OARs) will follow institutional guidelines. OARs will be delineated in accordance with recent international recommendations \[Brouwer CL, Radiotherapy and Oncology, 2015\].
Locations(1)
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NCT07253402