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

Study Purpose

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 (SR) 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. This study therefore has several focuses: 1. Evaluation of the benefit of early remnographic assessment (6 weeks): impact on recurrence-free survival and overall survival. 2. Evaluation of a diagnostic approach to radionecrosis: complementarity of DOPA PET and multimodal MRI. 3. The benefits of longitudinal remnographic monitoring with the development of segmentation and automated follow-up tools

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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.

Exclusion Criteria:

  • - Patients with primary brain tumors.
  • - Patients treated with normofractionated external cerebral radiotherapy.
  • - Age < 18 years.
- Patients under legal protection (guardianship, curatorship, etc.)

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06029140
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University Hospital, Brest
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Vincent Bourbonne, MD, PhD
Principal Investigator Affiliation Radiation Oncology Department, Brest University Hospital
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries France
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Brain Metastases, Adult
Additional Details

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: 1. Evaluation of the benefit of early remnographic assessment (6 weeks): impact on recurrence-free survival and overall survival. 2. Evaluation of a diagnostic approach to radionecrosis: complementarity of DOPA PET and multimodal MRI. 3. The benefits of longitudinal remnographic monitoring with the development of segmentation and automated follow-up tools

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International Sites

Chu Brest, Brest, France

Status

Recruiting

Address

Chu Brest

Brest, , 29609

Site Contact

Vincent Bourbonne, MD, PhD

[email protected]

+33298223398

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