Multicentre Phase II Trial Evaluating Stereotactic Body Radiotherapy on Ultra-central Lung Tumors on MR-Linac

N/ANot Yet RecruitingNCT07733219

Centre Oscar Lambret59 enrolled

Overview

Phase II multicenter trial evaluating the safety, tolerability, and feasibility of MRI-guided stereotactic radiotherapy using MRI-LINAC in patients with ultracentral lung tumors or lymphadenopathy in the context of controlled oligometastatic disease. The study investigates the potential of this innovative technology, which enables real-time treatment adaptation, with the goal of optimizing the benefit-risk ratio in a population at high risk of radiotherapy-related toxicity

This interventional, prospective, multicenter, non-randomized Phase II study primarily aims to evaluate the safety of MRI-guided stereotactic radiotherapy delivered with an MRI-LINAC, particularly in terms of late toxicity of grade ≥3. Ultracentral lung tumors represent a major therapeutic challenge due to their immediate proximity to critical structures such as the tracheobronchial tree, oesophagus, and pericardium. This location exposes patients to an increased risk of severe complications (haemorrhage, fistula, stenosis, pneumonitis), limiting the doses that can be delivered with conventional radiotherapy and potentially compromising tumor control. The use of an MRI-LINAC enables real-time visualization of anatomical structures and adaptation of the treatment plan at each session (adaptive radiotherapy). This technology also incorporates respiratory motion management systems (gating), allowing for reduced treatment margins and improved sparing of organs at risk. Enrolled patients will receive stereotactic radiotherapy delivered in 8 fractions, with extended clinical, radiological, and functional follow-up. In addition to assessing late toxicity, the study will also evaluate the feasibility of the technique, early adverse events, overall survival, progression-free survival, tumor control, and changes in respiratory function. The overall objective is to demonstrate that MRI-LINAC-guided radiotherapy can reduce toxicity while maintaining satisfactory tumor control in this high-risk population, thereby improving the management of ultracentral lung tumors.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 18 year-old 2. Clinical status: 1. Primary lung tumour T1-T2 N0, confirmed histologically by bronchoscopic examination, or meeting the criteria set out in the Aura 2026 and ASTRO guidelines for the indication of stereotactic radiotherapy (tumor growth of at least 2 mm between two CT scans performed 3 months apart, metabolic hyper-intensity on PET, and no pathological evidence), OR 2. Metachronous oligometastatic disease: isolated mediastinal or non-central pulmonary lymph node recurrence occurring sometimes after initial cancer treatments for an initially localised, locally advanced or oligometastatic cancer that has been treated OR 3. Synchronous oligometastatic disease: all metastatic sites and the primary tumour must be amenable to local debulking treatment following systemic treatment. Systemic treatment (chemotherapy or targeted therapy) must not be administered concurrently with radiotherapy OR 4. Metachronous oligoprogression: isolated metastatic recurrence in the mediastinal or ultra-central lung lymph nodes, with the primary tumour and metastatic sites under control (no change observed on two consecutive imaging scans and a complete metabolic response on PET) and not requiring continued treatment with chemotherapy or targeted therapy to ensure disease control (hormone therapy is, however, permitted) 3. Patient unsuitable for surgery, and treatment with stereotactic RT validated by multidisciplinary tumor board (including the radiation oncologist and medical physician) 4. Ultracentral lesion defined by a GTV less than 1 cm of the PBT (proximal bronchial trachea, including the main bronchi, trachea and intermediate bronchi), oesophagus, or pericardum 5. ECOG performance status ≤2 (for all patients) 6. Patient covered by a health insurance system 7. Patient agreed to take part in the study, and signed an informed consent form 8. Use of a method of contraception (for female patients of childbearing age) Exclusion Criteria: 1. Tumour with intrabronchial or intratracheal invasion identified by fibroscopy, bronchoscopy or localisation MRI 2. Prior RT overlapping the intended treatment field 3. Patients with oligoprogression requiring continued systemic treatment during RT 4. Uncontrolled intercurrent diseases 5. Contraindication to radiotherapy due to a comorbidity such as pulmonary fibrosis or scleroderma 6. Respiratory contraindications (FEV1 \< 20%) 7. Need of oncologic systemic treatment during RT 8. Contraindication to MRI (e.g. severe claustrophobia unmanageable) 9. Pregnancy or breastfeeding patient 10. Patient under guardianship or curatorship

Outcomes

Primary Outcomes

Incidence of late treatment-related toxicity

Treatment-related toxicity is assessed according to NCI-CTCAE v6.0 and defined as grade ≥ 3 adverse events such as: pneumonitis, bronchopulmonary haemorrhage, fibrosis, airway obstruction, fistula, or oesophageal toxicity, or other severe toxicity. Death possibly related to radiotherapy within 36 months is also considered as an event.

Time frame: from 90 days post-radiotherapy to 36 months after end of treatment

Secondary Outcomes

Early and late adverse events (all grades)

Early and late adverse events are assessed according to NCI-CTCAE v6.0. Adverse events that are definitively linked to the underlying disease, the progression of the underlying disease, or systemic treatment are excluded.

Time frame: From radiotherapy simulation up to 36 months post-radiotherapy

Feasibility of MR-guided radiotherapy

Feasibility of MR-guided radiotherapy is evaluated considering occurrence of primary failures (patient who dindn't start treatment) or secondary failures (incomplete treatment, or significant interruption of more than one week).

Time frame: from treatment initiation up to 3 months after completion of radiotherapy

Progression-Free Survival (PFS)

Time from treatment initiation to disease progression (local, regional, or distant) or death from any cause

Time frame: from treatment initiation to progression or death, assessed up to 36 months

Overall Survival (OS)

Time from treatment initiation to death from any cause.

Time frame: from treatment initiation up to 36 months

Local, regional, and distant disease control

Assessed using imaging-based evaluation and cumulative incidence of progression.

Time frame: at 6, 12, 24, and 36 months after treatment

FEV1 lung test

This test evaluates forced expiratory volume in one second

Time frame: at baseline, and at 6, 18, and 30 months post-treatment

Dosimetric parameters related to target coverage (GTV, CTV, PTV)

Gross Tumor Volume (GTV), Clinical Target Volume (CTV), and Planning Target Volume (PTV) are evaluated, and recorded during treatment planning, and at each adaptive fraction to document the benefit of online plan adaptation enabled by the MR-LINAC technology.

Time frame: During treatment planning (less than 30 days after enrollment), and then at each radiotherapy session (8 sessions spaced 2 days apart over a period of 17 days). Radiotherapy should start no later than 30 days after enrollment. .

Radiation dose delivered to CTV and OAR

The radiation dose delivered (Gy) to the clinical target volume (CTV) and healthy nearby tissues (OAR, Organs at Risk) is evaluated, and recorded during treatment planning, and at each adaptive fraction, to document the benefit of online plan adaptation enabled by the MR-LINAC technology.

Lung diffusion test (DLCO)

The DLCO test measures how effectively the lungs transfer oxygen from inhaled air to the blood