Microbiota-guided Radiotherapy for Head and Neck Cancer

NCT07253402 | Recruiting

• 1 other identifier: INT 84/25
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Head and Neck Cancer

Keywords

Oral microbiota; Radiotherapy; Tumour control; Oral mucositis; Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Locoregional tumour control

  The primary endpoint is local tumor control at 12 months of follow-up, considering both partial and complete responses as defined by the oncological RECIST 1.1 radiological criteria. Tumor volume analysis from MRI imaging between pre-RT and 3 months post-RT will be used to quantify tumor volume reduction (shrinkage) in patients undergoing curative radiotherapy alone. Tumor volume analysis from MRI imaging at 3, 6, and 12 months post-RT will be used to quantify tumor volume recurrence.

  1 year following radiotherapy end

Secondary Outcomes (1)

• Acute toxicity

  <8 weeks from radiotherapy end

Other Outcomes (1)

• Progression-free survival (PFS)

  3 years from radiotherapy end

Interventions

External beam radiotherapy for head and neck cancer RADIATION

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 \[Brouwer CL, Radiotherapy and Oncology, 2015\].

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients undergoing external beam radiotherapy for head and neck cancer at Fondazione IRCCS Istituto Nazionale dei Tumori di Milano.

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Milan, Milan, 20133, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Saliva samples

MeSH Terms

Conditions

Head and Neck Neoplasms; Stomatitis

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Jacopo Iacovacci, PhD

  Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

  PRINCIPAL INVESTIGATOR

• Nicola A Iacovelli, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

  STUDY DIRECTOR

• Loris DeCecco, PhD

  Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

  STUDY DIRECTOR

Central Study Contacts

Jacopo Iacovacci, PhD

CONTACT

+39 02-23902994; jacopo.iacovacci@istitutotumori.mi.it

Tiziana Rancati, MS

CONTACT

tiziana.rancati@istitutotumori.mi.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: November 28, 2025
• Study Start: October 15, 2025
• Primary Completion (Estimated): October 30, 2031
• Study Completion (Estimated): October 30, 2031
• Last Updated: November 28, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)