Brain Tumour Research Study in Ireland

IF YOU OR AN ADULT FAMILY MEMBER WERE TREATED FOR A BRAIN TUMOUR AT BEAUMONT HOSPITAL BETWEEN 29 NOVEMBER 1987 AND 7 AUGUST 2018 THIS WEBSITE IS DESIGNED TO PROVIDE INFORMATION ABOUT THE BEAUMONT BRAIN TUMOUR STUDY

IMPORTANT UPDATE TO THE BEAUMONT BRAIN TUMOUR STUDY – AUGUST 2024

Genuity Science (Ireland) Limited (“Genuity Science”) recently announced its withdrawal from the Beaumont Brain Tumour Study.

The brain tumour samples used in the Beaumont Brain Tumour Study, together with the genetic data generated by Genuity Science from these samples, have all been repatriated to Beaumont Hospital (“Beaumont”) and are no longer held by Genuity Science and were not used in any other studies.

Beaumont will continue the Beaumont Brain Tumour Study. When the Beaumont Brain Tumour Study was established in 2016, it was originally focused on the establishment of a Brain Tumour Information System (“BTIS”). Much of the research work in the broader area of brain tumours has already been carried out around the world so going forwards, the Beaumont Brain Tumour Study will now focus on building the BTIS for the important area of meningioma behaviour and prediction.

Please see below for information about the study and about how data will be used in the study.

WHAT IS MENINGIOMA BEHAVIOUR AND PREDICTION?

Unlike other intrinsic tumours of the brain, meningiomas are usually, though not always, located close to the brain surface and as such, the neurosurgeon’s task in removing the meningioma is a little less difficult than with intrinsic tumours of the brain such as gliomas. Nevertheless, meningiomas have an ability to recur. Predicting when recurrence might take place is fraught with uncertainty and frequently defies all of the usual pathology rules associated with tumour behaviour prediction. Meningiomas typically grow slowly so that several years may elapse before a meningioma recurs. Patients with meningioma are usually followed up at clinic visits and by radiologic surveillance in order to detect any early recurrence
Neuropathologists and neurosurgeons at Beaumont Hospital are looking at better ways to predict the behaviour of meningiomas in order to more accurately forecast when, if ever, a meningioma might recur. On occasion, a patient with a meningioma may require post-operative radiotherapy. There is a little uncertainty about which patients having had a meningioma surgically removed might benefit from radiotherapy. All research studies on meningioma recurrence and responsiveness to radiotherapy require many years of patient follow-up.

The original Beaumont Brain Tumour Study concluded patient recruitment in 2018 so that today’s [2024] 6 years of follow up information can be married to the pathologic and genetic data generated from the old, archived specimens. Once the historical clinical and genomic data has been linked by Beaumont Hospital for the BTIS, then the data in the BTIS will be irreversibly de-identified. Together, the neuropathologists, neurosurgeons and radiotherapists will then be able to use the BTIS to see how well or how poorly they predicted the meningioma behaviour. This valuable historical data will then be available to predict meningioma behaviour in all new patients going forwards. Learning from history, the past will have informed the future.

This exciting work will be carried out in the new molecular laboratories at Beaumont Hospital which are equipped with the latest technology and staffed by a team of enthusiastic young scientists.

It is hoped that this work will culminate in the discovery of new predictors of behaviour that will greatly help in the follow-up of patients with meningioma.

WHAT IS GENOMICS

Genomics is the study of our genes - the DNA contained in the cells of our body that acts as a blueprint for a human being. Each of us has a slightly different DNA sequence that sets out who we are, how we work… and even how we can be repaired. Studying our DNA can help us understand an amazing range of health-related characteristics, including: • understanding disease risk; • predicting our response to medications; • pointing the way to new treatments and cures. The famous double-helix structure of our DNA contains a lot of information; there may only be four building blocks in the structure (A, C, G and T) but every strand of our DNA contains 3.2 billion of these letters. Technological advances mean we can now decode a person’s genome in days, compared to the 13 years it took to complete the first ever genomic map. This has made genomic research a viable and revolutionary new front in the pursuit of improved human health. Tumours have their own unique sets of genes that usually bear little or no relationship to the genes inherited from a parent. We know that the study of all of the genes within a tumour, as well as how those genes are switched on and switched off, can tell us so much more about how a tumour will grow and spread and how it may or it may not respond to treatment or indeed whether the tumour should be exposed to treatments that may injure the patient but have little or no effect on the tumour. How this massive amount of information influences the behaviour of a tumour can only be fully understood if we have access to the genetic techniques that can deliver the order of every letter in the book, so called whole genome sequencing. This massive amount of information, which can only be processed by dedicated software programmes, is only of use if we know how the tumour from which we derived the sequence has already behaved.

HISTORY OF THE BEAUMONT BRAIN TUMOUR STUDY

WHAT IS THE PURPOSE OF THE STUDY AND DATA PROCESSING?

The Beaumont Brain Tumour Study was established in 2016 in collaboration with Genuity Science to marry the genomic information derived from archived brain tumours with subsequent clinical behaviour in order to form a Brain Tumour Information System [BTIS] that can be interrogated and used to better predict behaviour of new tumours in new patients. Since the establishment of the study in 2016, much of the research work in the broader area of brain tumours has already been carried out around the world so going forwards the Beaumont Brain Tumour Study will now focus on building a Brain Tumour Information System for the important area of meningioma behaviour and prediction. Genuity Science withdrew from the study in May 2024 and repatriated all study samples and data to Beaumont. The Beaumont study samples were not used in any other studies.

WHAT IS THE LEGAL BASIS FOR PROCESSING THE STUDY DATA?

The Beaumont Brain Tumour Study originally received a waiver of consent from the Beaumont Research Ethics Committee in July 2016. All sample and data transfers were in compliance with applicable regulations at that time. Beaumont Hospital and Genuity Science paused the study following the introduction of the Health Research Regulations in August 2018. No samples were sent to Genuity Science after August 2018.

The Health Research Regulations, which were introduced as part of the Data Protection Act in 2018, recognise that sometimes, in limited situations, obtaining consent will not be possible and that the public interest of doing the research significantly outweighs the need for explicit consent. The Health Research Regulations established a process to obtain a Consent Declaration in such circumstances. In line with this process, the Beaumont Brain Tumour Study was reviewed independently and received a conditional consent declaration under the Health Research Regulations on November 6th 2019, which remains valid until December 31st 2024. In accordance with the Conditions of the Consent Declaration, a public consultation process was held (ending April 1st 2021, giving a total of 13 months public notification of the study with opportunities to seek further information on the study and its implications of the study for individuals and families, and for individuals, or their families on their behalf, to withdraw from the study*. In November 2023, the HRCDC approved an amendment to the Conditional Consent Declaration to take account of the withdrawal of Genuity Science from the study, the repatriation of the samples and data by Genuity Science to Beaumont hospital, and for the focus of the BTIS on meningioma behaviour and prediction.

*The legal basis under GDPR for use of the data in this study is Article 6(f) “Public Interest” and Article 9.2(j) “Scientific Research”.

WHY CAN’T CONSENT BE OBTAINED FOR USE OF ARCHIVED TISSUE IN RESEARCH

The samples that will be used in this research have been collected by Beaumont Hospital pathology department over more than a 30 year period. Trying to obtain consent but not knowing whether a patient is alive or deceased is extraordinarily challenging, with great potential for causing patient and family distress, as has been shown with previous re-consent attempts in Ireland. Given that many of these archived tissue samples were collected over thirty years ago, an unknown number of patients are deceased. In addition, given the long period of time, many patients will have changed address, and we have no way of identifying what their new address could be. Previous research into patients’ disposition to the use of archived diagnostic tissues confirms a philanthropic attitude on behalf of the donors of such tissues (Richter et al., Patient Views on research use of clinical data without consent: Legal, but also acceptable? EJHG 2019; 27, 841–847), provided of course that the research is carried out to further disease knowledge in the public interest and which has been approved by a Research Ethics Committee, as has this study. Much tissue-based investigative laboratory work consists of audits to ensure that pathologists are practicing to an acceptable level of expertise. Fundamental research, where pathology researchers use archived surplus tissues to make improvements or to uncover new disease pathways is the pillar that underpins standards in healthcare. The Health Research Regulations, which were introduced as part of the Data Protection Act in 2018, recognise that sometimes, in limited situations, obtaining consent will not be possible and that the public interest of doing the research significantly outweighs the need for explicit consent. The Health Research Regulations established a process to obtain a Consent Declaration in such circumstances. In line with this process, the Beaumont Brain Tumour Study was reviewed independently and a Consent Declaration was granted in November 2019.

WHO IS ORGANISING AND FUNDING THIS STUDY?

Following the withdrawal of Genuity Science from the Beaumont Brain Tumour Study in May 2024, Beaumont Hospital is solely organising and funding this study. It is recognised with gratitude that Beaumont’s exciting molecular diagnostic work on Brain Tumours could not have been initiated or developed without the support, direction and research collaborations fostered by Genuity Science over many years. Genuity Science repatriated all study samples and data to Beaumont Hospital in May 2024 and will not have any further association with the organising or funding of the Beaumont Brain Tumour Study.

WHO IS THE DATA CONTROLLER?

Following the withdrawal of Genuity Science from the Beaumont Brain Tumour Study in May 2024, Beaumont Hospital is now the sole data controller, responsible for the management and control of all data relating to the Beaumont Brain Tumour Study.

WHAT IS MEANT BY SURPLUS TISSUE AND HOW WILL IT BE USED?

A surgeon will always try to remove as much abnormal tissue as is safe to do. Only a small fraction of the removed diseased tissue is needed to make a pathology diagnosis. Well-characterised human tissue specimens are a pillar of human disease research, not just in cancer and dementia research, but in many other areas such as renal disease. Recent technological advances have made it much easier to extract and sequence DNA and RNA from tissues that have been prepared for clinical review by a pathologist. Surplus tissues have enormous research value, especially for clinical and translational research, since they can be linked to information on diagnosis, treatment response, and disease outcome contained within pathology and hospital databases. Never have pathology researchers had access to such incredibly powerful investigative tools, which combined with information on a cancer’s behaviour including response to treatments and survival can yield vital information as to why some patients have done well, while other patients with a virtually identical cancer have not fared so well. Pathology departments will always ensure that adequate diagnostic material remains in the tissue block for future testing and for independent consultation, or when required for medico-legal issues.

WHAT DATA IS USED AND COLLECTED AS PART OF THIS STUDY?

The creation of the BTIS requires that de-identified genomic and epi-genomic data (generated by sequencing the brain tumour sample and importantly by studying sites of gene silencing and activation) be combined with de-identified health information from the patient’s medical notes, such as gender, age and information relating to the brain tumour (location, size, behaviour etc). Beaumont Hospital has in place a comprehensive suite of measures to protect the personal data of its current and former patients. For the purposes of this study, Beaumont provided de-identified brain tumour samples to Genuity Science to generate genomic data. In May 2024, Genuity Science repatriated all study samples and data to Beaumont Hospital. The Beaumont Molecular Laboratory will carry out additional work called methylation profiling on the returned and archived meningioma samples.

AM I IDENTIFIABLE FROM THE PERSONAL DATA USED IN THIS STUDY? WHAT PERSONAL DATA OF MINE WILL BE USED IN THIS STUDY?

The creation of the BTIS requires that genomic data (generated by sequencing the brain tumour sample) be combined with de-identified information from the patient’s medical notes, such as gender, age and information relating to the brain tumour (location, size, behaviour etc). Health information will be stripped of any personally identifying data points (name, date of birth, address, contact number etc), therefore it will never be possible for any future researchers to link back any findings to individual patients. The research files will be maintained in a secure location in Beaumont under the control of the IT Department with access restricted to approved researchers only. A patient’s clinical, radiology and pathology files will not be impacted in any way.

HOW WILL MY DATA BE ACCESSED AND USED?

The data for this study will be stored securely by Beaumont Hospital. This exciting research work will be carried out in the new molecular laboratories at Beaumont Hospital which are equipped with the latest technology and staffed by a team of enthusiastic young scientists.
When the relevant authorities have formulated public policy in relation to publication and sharing of genomic data for research, the genomic data from this study will be made publicly available on a recognised genomic data repository in a de-identified and appropriately controlled way and in compliance with all relevant legislation. The results of the research study will be published in peer reviewed journals and on this website.

HOW LONG WILL MY DATA BE KEPT AND USED FOR?

Your de-identified data will be retained indefinitely by Beaumont Hospital and used for the benefit of future patients at Beaumont Hospital. Continual analysis is necessary as medical and technological changes and advances emerge over time and the data collected may gain new significance. In May 2024, Genuity Science repatriated all samples and data to Beaumont Hospital.

WHAT ARE THE POSSIBLE BENEFITS OF PARTICIPATING?

Participating in this study will not benefit you directly. As all data used in the research will be de-identified, you will not receive any results or feedback from this study. However, information obtained from the study may help us to better understand brain tumours and to improve diagnosis and treatments of patients in the future.

WHAT ARE THE POSSIBLE RISKS OF TAKING PART?

As explained in the section “What data is collected and used as part of this study?”, the tumour samples and health data in this study will be de-identified, any risk of re-identification of a participant from the data is minimised.

WHAT IS THE DEADLINE FOR OPTING-OUT OF THE STUDY?

The deadline for opting-out from this study closed on 1st April 2021.

WHO HAS THIS STUDY BEEN REVIEWED BY?

The study has been reviewed and approved by Beaumont Research Ethics Committee. This study has also received a conditional consent declaration from an independent Appeals Panel in accordance with the Health Research Consent Declaration process established by the Health Research Regulations 2018.

WILL THE DATA BE SHARED OUTSIDE THE EUROPEAN ECONOMIC AREA (EAA)?

In accordance with the Conditions attached to the HRCDC Declaration, when the relevant authorities have formulated public policy in relation to publication and sharing of genomic data for research, the BTIS will be made publicly available on a recognised genomic data repository in a de-identified and appropriately controlled way and in compliance with all relevant legislation.

WHAT DO YOU DO IF YOU HAVE A QUERY OR COMPLAINT ABOUT THE STUDY OR HOW WE USE YOUR DATA?

Should you have any questions about the study, please contact Dr. Michael Farrell at michaelfarrell@beaumont.ie.

If you have any questions or concerns relating to Beaumont Hospital’s use of personal data in this study, please contact the Data Protection Officer at Beaumont Hospital using the email address: dpo@beaumont.ie or via the post: FAO The Data Protection Officer, Beaumont Hospital, Beaumont, Dublin 9, D09V2N0 Ireland.

You also have the right to contact Ireland’s data protection authority, the Data Protection Commission (DPC), if you have any concerns about Beaumont’s use of personal data in this study.

ADDITIONAL INFORMATION ABOUT MENINGIOMA: DIAGNOSIS AND TREATMENT.

Meningioma is a primary tumour of the central nervous system which includes brain and spinal cord. Meningiomas are the most common type of primary brain tumour with over 250 patients undergoing surgery each year in Ireland for meningioma removal. The great majority of meningiomas are “benign” and if completely removed, are unlikely to recur. Some meningiomas will recur because they may be located in areas of the brain or spinal cord that are very challenging for the neurosurgeon. Others may recur because of their intrinsic behaviour which is not truly benign. In fact neurosurgeons and brain pathologists tend to avoid using the term “benign” because there is always the possibility of meningioma regrowth.

Neuropathologists try to predict meningioma behaviour by grading the tumour.

The removed meningioma is sent to the pathologist who examines pieces of the through the microscope, noting all of the microscopic features. The pathologist sends the microscopic finding to the neurosurgeon. Every aspect of the patient and the meningioma are discussed at a multidisciplinary team meeting where a final decision is made about the frequency of follow-up and frequency of surveillance brain scans to make sure that the tumour is not going to return. With regular surveillance, any suggestion that tumour is about to recur, is picked up early. The patient’s case is then re-discussed and a plan of action possibly including more surgery, or perhaps radiotherapy or even just continued surveillance, is prepared.

Is it possible to state that the meningioma will never recur?

At this stage of our knowledge, we can simply say that recurrence in low grade meningiomas is very unlikely, and that the frequency of postoperative surveillance frequency may gradually be reduced as confidence builds that the meningioma is gone for good.

However, and this is the purpose of the proposed study – if we had better biological markers of meningioma behaviour we could make a more informed decision about the need for follow-up and about the frequency of surveillance brain scanning. Additionally we might also be able to better discover those rogue meningiomas that recur when least expected. Being better informed will help us to make more confident decisions with our patients and also provide our patients with more certainty.

How do we predict a meningiomas behaviour?

Currently, the specialist brain pathologist will classify each meningioma into one of 3 grades based on their microscopic characteristics.

Grade 1 meningiomas are the most common meningiomas. They are low grade tumours which grow very slowly.

Grade 2 or atypical meningiomas have a higher chance of coming back after they have been removed. Some of the Grade 2 meningioma subtypes such as chordoid and clear cell types are easy to recognise but for the majority, the pathologist has to rely on findings which are subtle and difficult to interpret especially in terms of their individual likelihood of causing the meningioma to return.

Grade 3 or anaplastic meningiomas are malignant, grow rapidly and will almost certainly return in a few years. They are easy to recognise especially the papillary and rhabdoid types. Invariably the patients will require radiotherapy to the tumour bed after the tumour has been removed.

It seems that behaviour of the Grade 2 meningiomas is most difficult to predict.

This is so. It may take several years before the meningioma’s behaviour is revealed. Fortunately we are able go back to our files and retrieve old meningioma samples which remain after the pathologist has completed the original microscopic interpretation. Using new molecular techniques [such as methylation profiling] which have been developed in Beaumont’s Molecular laboratory it will be possible to determine if the newly generated molecular findings were better able to predict the behaviour of a patient’s meningloma over the many years of follow-up. In reality it is almost certain that a combination of the pathologist’s traditional histology findings coupled with new molecular findings will give the best prediction of behaviour. Right now we just don’t know the answer. Other teams working in this area have studied patients with a relatively short follow-up but we will have the advantage of long follow up in our study.

We will be able to help new patients with meningioma by studying the patients from the past.

Only meningioma samples from the past which were made available to us a part of the original opt-out process described elsewhere on this website will be used. We will always make sure to leave enough tissue behind in the files so that any further techniques or tests that come along in the years ahead may also be tested on the archival samples.

Will I be told if there is any new information about my tumour?

It will not be possible to go back to individual patients, as the researchers will break the links between individual patients and their related clinical data in the study files, though not, of course in the hospital records. Secondly, when we publish our findings, others may disagree with our interpretations. Furthermore several years will elapse while we test our new findings in a cohort of new patients who must be followed up for several years to see if our findings are favourably impacting on their care.

Will you share the results with others?.

Irrespective of whether or not the study uncovers better predictors of meningioma behaviour, we will publish our findings on this web-site and will also submit the findings for consideration by international reviewed journals with a view to publication. Finally when the appropriate legislation is in place we may be able to share the genetic and epi-genetic data with other researchers.

Dr. Michael Farrell
Neuropathologist