Microbiota-guided Radiotherapy for Head and Neck Cancer

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

Interventions

RADIATION

External beam radiotherapy for head and neck cancer

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

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  lead OTHER

Principal Investigators

• Jacopo Iacovacci, PhD · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

• Nicola A Iacovelli, MD · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

• Loris DeCecco, PhD · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-10-15

Primary Completion

2031-10-30

Completion

2031-10-30

Countries

• Italy

Study Locations