Microbiota-guided Radiotherapy for Head and Neck Cancer

Phase

N/A

Condition

Head And Neck Cancer

Nasopharyngeal Cancer

Human Papilloma Virus (Hpv)

Treatment

External beam radiotherapy for head and neck cancer

Clinical Study ID

NCT07253402

INT 84/25

Ages > 18
All Genders

Study 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 Criteria

Inclusion

Inclusion Criteria:

Age ≥ 18 years.
ECOG Performance Status ≤ 3.
Histological diagnosis of squamous cell carcinoma, undifferentiated carcinoma,epithelial glandular and non-glandular carcinoma (including adenoid cysticcarcinoma, 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-primarytumors, according to AJCC 7th edition. Patients with stage III-IV tumors of salivarygland or paranasal sinus origin, and patients with stage I-II pharyngeal orlaryngeal tumors, will only be included if prophylactic irradiation of cervicallymph node stations is indicated and/or if the oral and oropharyngeal mucosa as wellas swallowing-related structures are included within the irradiated volume.
Indication for treatment in either definitive or adjuvant settings, with or withoutsystemic therapy (concurrent systemic therapy, with or without prior neoadjuvantchemotherapy, permitted. Adjuvant systemic therapy is allowed for selected advancedstages of pharyngeal carcinoma, according to institutional guidelines).
Formal acceptance of study participation requirements (written informed consent).

Exclusion

Exclusion Criteria:

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 orsurgically treated carcinoma in situ not requiring radiotherapy or systemic therapy.
Absence of formal acceptance of study participation requirements (written informedconsent).
Indication for treatment exclusively in the postoperative setting.

Study Design

External beam radiotherapy for head and neck cancer

October 15, 2025

October 30, 2031

Study Description

The research question addressed by this study is the need to bridge the current gap in understanding the role of the microbiota, as well as potential microbiota-targeted therapies such as antibiotic use, in the treatment of head and neck cancer (HNC). The working hypothesis is that causal relationships can be established between the functional traits of the human oral microbiota and the effectiveness of radiotherapy for HNC, using the statistical framework of causal inference. Identifying this causal knowledge is essential to design and implement microbiota-guided radiotherapy, where the patient's oral microbiota is profiled prior to treatment and evaluated against the risk of developing oral mucositis and/or experiencing unfavorable outcomes. From a microbiota-based perspective, assessing whether different radiotherapy plans may result in tolerable or intolerable side effects would be crucial for developing personalized radiotherapy programs that could enhance tumor control. Furthermore, since this study involves functional metagenomic analysis of the microbiota, it will be possible to infer the mechanisms through which the microbiota modulates radiotherapy and to exploit these insights for the design of new microbiota-based clinical strategies. Such strategies may include administration of specific nutritional supplements, antibiotics, or probiotics to optimise therapy tolerance and improve treatment outcomes.

Study design and setting: MIGRHAN is a single-institution, prospective observational cohort study with an expected total duration of approximately six years. At least 96 consecutive patients with head and neck cancer referred for curative radiotherapy will be enrolled over a 36-month period. Their treatment, toxicity monitoring, and follow-up (3 years) will follow routine clinical practice in accordance with national and international guidelines. Recruitment will take place exclusively at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, with patient enrollment starting in September 2025 and planned completion by October 2031.

Study workflow: Before enrollment, patients will provide written informed consent. Baseline assessments (from -28 days to treatment start) will include demographic data, medical history, dental evaluation, clinical examination, laboratory tests (blood tests, urinalysis, thyroid function, coagulation), radiological imaging (CT scan, multiparametric MRI, whole body FDG-PET/CT or bone scan), and collection of a saliva sample for microbiota profiling. During radiotherapy, weekly clinical evaluations, toxicity assessments following CTCAE v5.0, and patient questionnaires will be conducted, alongside repeated laboratory analyses and collection of dosimetric treatment data (DICOM-RT). At the end of radiotherapy and during follow-up visits (3, 6, and 12 months), patients will undergo repeat clinical evaluations, imaging (MRI, CT, PET/CT or bone scan as indicated), laboratory tests, and additional saliva collections. Long-term follow-up will include survival assessment up to three years post-treatment.

Connect with a study center

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Milan 6951411, Milan 20133
Italy
Active - Recruiting

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