Stereotactic Radiotherapy Management of Brain Metastases: the Value of a Longitudinal Multimodal Approach (POSTPONE)

Sponsor

University Hospital, Brest (Other)

Overall Status

Recruiting

CT.gov ID

NCT06029140

Collaborator

(none)

700

Enrollment

Location

Anticipated Duration (Months)

63.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study therefore has several focuses:

Evaluation of the benefit of early remnographic assessment (6 weeks): impact on recurrence-free survival and overall survival.
Evaluation of a diagnostic approach to radionecrosis: complementarity of DOPA PET and multimodal MRI.
The benefits of longitudinal remnographic monitoring with the development of segmentation and automated follow-up tools

Condition or Disease	Intervention/Treatment	Phase
Brain Metastases, Adult

Detailed Description

The management of brain metastases has evolved́ rapidly in recent years. It is estimated that 20% to 40% of cancer patients will develop brain metastases (BM) during the course of their disease. Whole-brain radiotherapy has long been the first-line treatment for brain metastases. However, large-scale international clinical trials conducted over the past decade have established stereotactic radiotherapy (SRT) as the treatment of choice for the management of brain metastases (BM). However, even though the method of radiation delivery has evolved considerably, the problem of monitoring and managing brain metastases remains unresolved. Indeed, BM patients constitute a growing population due to the increased efficacy of systemic treatments, making the occurrence of BM higher. Management of the disease is not only aimed at alleviating symptoms and, initially, improving survival, but must also take into account patients' quality of life. Patients with a poor prognosis should not be over-treated, while those with a more favorable prognosis should not be under-treated.

With this in mind, a number of tools were rapidly developed to grade the prognosis of patients with BM. Recursive partitioning analysis (RPA) and Graded Prognostic Assessment (GPA) are the main ones. They are based on prognostic factors that include age, Karnofsky index, primary tumor control, presence of extracerebral localization, histological type and presence of genetic mutations for each primary. Finally, we must also take into account the growing involvement of systemic treatments in the control of brain disease when the blood-brain barrier (BBB) is crossed.

Several studies have shown that patients with symptomatic cerebral recurrences have poorer survival and generate higher costs for the healthcare system than asymptomatic patients whose recurrences have been detected by routine surveillance imaging. The importance of frequent surveillance imaging is therefore essential. National Comprehensive Cancer Network (NCCN) recommendations include MRI every 2-3 months for the first year, then every 4-6 months indefinitely. The recommendations of the Association des Neuro-Oncologues d'Expression Française (ANOCEF) recommend brain MRI at least every 3 months for the first year (9), RECORAD recommends MRI surveillance every 3 months for the first 2 years, then every 6 months (10), and Cancer Care Ontario Organization (CCO) recommends a 1st follow-up MRI 2 to 3 months after the end of treatment, followed by MRI surveillance every 2 to 3 months for 1 year, and MRI surveillance every 3 to 4 months for 2 to 3 years. Given the heterogeneity of follow-up modalities, and the absence of any recommendation for surveillance MRI imaging earlier than 3 months after treatment, the Brest University Hospital decided to carry out an early remnographic reassessment of patients treated with intracerebral stereotactic radiotherapy 6 weeks after the end of treatment, and then every 3 months for a minimum of 2 years.

After SRT for brain metastases, the median time to development of a radiation-induced adverse event or radionecrosis is 7 to 11 months. Similarly, the risk of local tumor recurrence after SR is < 5% after 18 months. In terms of complications, improvements in systemic therapy mean that patients are living longer and are at greater risk of tumour recurrence later than previously (defined as > 18 months after SRT). Radionecrosis may therefore occur in up to 50% of patients several months to several years after irradiation, depending on several factors, including dose fractionation patterns and the volume of normal brain receiving high-dose irradiation.

Radionecrosis can produce symptoms difficult to distinguish from those of local progression and, if left untreated, can lead to significant morbidity and mortality. Correct differential diagnosis between radionecrosis and local progression is extremely important, as the two situations must be managed differently. Surgery or re-irradiation is generally proposed as salvage therapy in patients with local progression, whereas radionecrosis is most often treated with corticosteroids.

Differential diagnosis between radiation-induced changes and brain tumor recurrence is a challenge in the treatment of brain metastases. The RANO (Response Assessment in Neuro-Oncology) group has recognized that an approach based on a single imaging modality is insufficient to establish a correct diagnosis. It recommends the use of advanced imaging techniques, such as MRI with diffusion sequence and perfusion map, spectroscopy and PET.

Several radiopharmaceuticals, including the amino acid tracers O-(2-[18F]fluoroethyl)-L-tyrosine (FET) and 3,4-dihydroxy-6-[18F]-fluoro- l-phenylalanine (F-DOPA), have proved useful in distinguishing radionecrosis from local progression in patients with brain metastases.

Several observations can therefore be made:

Heterogeneity of practices concerning remnographic surveillance, particularly at an early stage.
Heterogeneity in practices concerning suspicion of radionecrosis

This study therefore has several focuses:

Evaluation of the benefit of early remnographic assessment (6 weeks): impact on recurrence-free survival and overall survival.
Evaluation of a diagnostic approach to radionecrosis: complementarity of DOPA PET and multimodal MRI.
The benefits of longitudinal remnographic monitoring with the development of segmentation and automated follow-up tools

Study Design

Study Type:

Observational

Anticipated Enrollment :

700 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

Stereotactic Radiotherapy Management of Brain Metastases: the Value of a Longitudinal Multimodal Approach

Actual Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Outcome Measures

Primary Outcome Measures

Risk factors of radionecrosis [Through study completion, an average of 1 year]
The main objective is to identify risk factors for cerebral radionecrosis after stereotactic radiotherapy in patients treated for brain metastases.

Secondary Outcome Measures

Risk factors of local relapse [Through study completion, an average of 1 year]
Clinical, dosimetric and radiological factors influencing local control
Post-SRT follow-up [Through study completion, an average of 1 year]
Practical analysis of the benefits of performing MRI 6 weeks after the end of stereotactic radiotherapy treatment, and determining precise criteria to better target patients who would benefit most from it.

Other Outcome Measures

Automatic segmentation of brain metastasis [Through study completion, an average of 1 year]
Development of a deep-learning algorithm for the automatic segmentation on MRI, CT and CT scanners
Automatic follow-up [Through study completion, an average of 1 year]
Development of a deep-learning algorithm for the automatic longitudinal follow-up

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years
Patients with solid cancer with brain metastases treated by hypofractionated external stereotactic radiotherapy at the CHRU de Brest between 01/01/2014 and 31/12/2022
Patient affiliated to a social security scheme