Neoplasms

Symptoms and General Pathology

All Conditions

Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

The study will be organised on three time-periods based on the time of the 1st CNS event:

Part A - Pre-diagnosis period: before diagnosis of the 1st CNS event Part B - At 1st CNS diagnosis period Part C - Post diagnosis period: after the 1st CNS event

At baseline

Part A:

* TNBC/ HER2+ BC: once a year
* NSCLC/SCLC: every 4 months
* Melanoma: every 6 months

Part B:

o As close as possible to the diagnosis of CNS metastases and no later than 6 weeks after diagnosis

Part C:

o Every 3 months (+/- 1 month)

Samples collection: Plasma

Part B: Mandatory CSF sampling at CNS diagnosis when clinically possible unless medically contra-indicated - As close as possible to the diagnosis of CNS metastases and no later than 6 weeks after diagnosis Part C: Additional CSF sampling in case CSF sampling is performed for routine clinical practice

Samples collection: CSF

Part B: Highly recommended non-CNS metastatic tumour tissue collection (1FFPE and 1 FT) at CNS metastases diagnosis (Part B) (NB: Bone lesions are excluded) - As close as possible to the diagnosis of CNS metastases and no later than 6 weeks after diagnosis

Samples collection: Non-CNS Metastatic Tumour Tissue

Part A:

* Brain MRI at inclusion is allowed within 45 days before enrolment
* Brain MRI pre-CNS diagnosis (Part A) : HER2 BC/TNBC: once a year; NSCLC/SCLC: every 4 months; Melanoma: every 6 months (+/- 1 month)

Part B:

o As close as possible to the diagnosis of CNS metastases and no later than 6 weeks after diagnosis

Part C:

o Brain MRI post-CNS diagnosis (Part C): every 3 months (+/- 1 month window)

Brain MRI

At baseline

Part A:

* TNBC/ HER2+ BC: once a year
* NSCLC/SCLC: every 4 months
* Melanoma: every 6 months

Part B:

o As close as possible to the diagnosis of CNS metastases and no later than 6 weeks after diagnosis for cohorts 1-5.

Samples collection: Serum

Nuria Kotecki

Diane Delaroche

Sylvie Bartholomeus

Andrea Gombos

Véronique Goblet

Florence Lefranc, MD

Nathalie Blondeel

François Duhoux

Veronique Petre

Jean-Luc Canon

Lore Vansteelant

Hannelore Denys

Malika Tahiri

Lore Decoster

Inge Wauters

Paul Clement, MD

Anna-Maria Barbuto

Stéphane Holbrechts

Dominique Crasson

Vincent Vanhaudenarde

Solene Charpentier

Claire Cheymol, MD

Anthony Lombardi

Anthony Goncalves, MD

Joseph Gligorov, MD

Imen Hafsi

Edith Borcoman, MD

Delphine Bridelance

Florian Clatot, MD

Sherine Anajar

Philippe Barthelemy, MD

Marina Basmaison

Eleonora De Maio Desposito, MD

Chouaib Mediouni

Caroline Duhem, MD

Nuria Kotecki, MD

Despite some encouraging data, systemic treatment of CNS metastases from solid tumors remains experimental.

Better knowledge on the evolving epidemiology and biology of BM are key elements for the development of new treatment strategies and identification of promising therapeutic targets for new compounds. Further biological findings may help to better understand the heterogeneity between the primary tumor and the CNS metastases and to identify new targets for therapy thus improving patients' outcome.

In this context, the Oncodistinct network and the Jules Bordet institute propose to build a multidisciplinary Brain Metastases Clinical Research Platform called BrainStorm. The BrainStorm program will focus on patients with newly diagnosed non-CNS metastatic solid tumors with high risk of developing CNS metastases and will allow building a large clinico pathological database for CNS metastases including ctDNA analyzes from CSF samples. Substudies will be proposed at each time-period with the final objective to develop innovative treatment approaches and strategies.

A Brain Metastases Research Platform to Tackle the Challenge of CNS Metastases in Solid Tumours

A Brain Metastases Research Platform to Tackle the Challenge of CNS Metastases in Solid Tumours - BrainStorm Program

To collect data regarding the biology of CNS metastases by investigating on :

* Time to the first CNS event
* Time to the second CNS event
* Time to whole brain radiotherapy (WBR)
* Time from the date of diagnosis of the first CNS event and the time of death by any cause

Levels of neuron specific enolase in blood

Deep targeted next-generation sequencing (NGS) on DNA samples from primary or non CNS metastases as well as germline DNA samples and CNS metastases if surgery. A set of 1-3 point mutations (single nucleotide variants) will be selected for each subject based on the above analyses for the identification and quantification of plasma ctDNA and CSF-ctDNA using deep targeted NGS. Subsequently targeted gene sequencing will be performed on DNA samples from CSF and plasma in case of at least 5% tumour mutant allele frequency (MAF) and CNS metastases in case of surgery.

To collect data regarding the epidemiology of CNS metastases from solid tumours and identify risk factors for CNS metastases development, including:

* Time to the first CNS event
* Time to the second CNS after first treatment and subsequent CNS events

To collect data regarding the epidemiology of CNS metastases from solid tumours and identify risk factors for CNS metastases development, including::

- Time to whole brain radiotherapy

To collect data regarding the epidemiology of CNS metastases from solid tumours and identify risk factors for CNS metastases development, including:

- Overall survival

To collect data regarding the biology of CNS metastases by investigating on:

- Presence of CSF-ctDNA at diagnosis of CNS metastases

To collect data regarding the biology of CNS metastases by investigating on:

- Presence of plasma ctDNA at diagnosis of CNS metastases

* quantification of plasma ctDNA and CSF-ctDNA using deep targeted NGS
* deep targeted next-generation sequencing (NGS) on DNA samples from primary or non-CNS metastases as well as germline DNA samples and CNS metastases if surgery

- A set of 1-3 point mutations (single nucleotide variants) will be selected for each subject based on the above analyses for the identification and quantification of plasma ctDNA and CSF-ctDNA using deep targeted NGS

Spots Global Cancer Trial Database for samples collection: plasma