For patients where it is thought that surgery will benefit, a surgeon often removes as much tumour as possible, whilst limiting the risk of causing damage, such as weakness, speech, or cognitive difficulties. However, which technology a surgeon should use during surgery to remove the tumour safely is unclear. This can affect how soon the cancer returns, what effects of surgery or symptoms a patient develops, and how a patient feels.
High frequency sound waves that create an image, called Ultrasound (US), is one of the tools a surgeon can use during the operation to find the tumour and see how much is removed. Another technology, Diffusion Tensor Imaging (DTI), allows important nerve pathways involved in certain functions, for example, speech/language, vision and movement, to be avoided in surgery.
This trial aims to see if GB surgery with these extra technologies (tools) added to the standard ones, increases a patient’s good functioning quality of life, so-called Deterioration Free Survival (DFS).
For patients with a brain tumour called Glioblastoma (GB) prolonging survival whilst ensuring quality of life are key, but remain challenging. GB is incurable and the most frequent and aggressive form of brain cancer, with an extremely poor prognosis both in quality and length of life. Patients experience a decline in Health-Related Quality of Life (HRQoL), and caregivers report high levels of distress and carer burden. The main treatments for GB are surgery, radiotherapy, and chemotherapy, used in various combinations. For patients where it is thought that surgery will benefit, a surgeon often removes as much as possible, whilst limiting the risk of causing problems, such as, weakness, speech or cognitive difficulties. However, it is unclear as to which techniques a surgeon should use to remove the tumour safely. This influences when the cancer returns, what symptoms the patient has, and how a patient feels. Ultrasound (US) (high frequency sound waves that create an image) is one of the tools a surgeon can use during the operation to find the tumour and assess how much is being removed during the operation. Another technique, Diffusion Tensor Imaging (DTI) allows important fibres involved in specific functions, for example, speech/language, vision, and movement to be seen during surgery. This means that potential damage to these functions might be avoided during the procedure. This study aims to see if surgery to remove a GB with these additional imaging added to present standard techniques improves HRQoL. This will be assessed though participants completing HRQoL questionnaires before and after surgery for up to 2 years.
Glioblastoma (GB) is a cancer with unmet needs.
GB is the most frequent and aggressive form of brain cancer, with an incidence of 4.64/100,000/year in the UK. Prognosis remains extremely poor with median survival just over 12 months and as the tumour grows patients experience a progressive decline in health-related quality of life (HRQoL), and caregivers report high levels of distress and carer burden. Resistance to treatment leads to poor survival, with high costs to the patient, relatives, society, and the economy.
Although primary brain tumours represent only 3% of all cancers, a brain tumour reduces life expectancy by an average of 20 years, the highest of any cancer, and accounts for more average years of life lost than any other cancer. GB affects adults in their economic prime, and is a leading cause of death in those under 40 years, costing the economy £578M per year.
AIMS AND OBJECTIVES
In patients with GB suitable for surgery, is removing as much tumour as possible (tumour resection), guided by preoperative imaging (MRI) and intraoperative 5-ALA (the dye which allows the tumour to become more clear with a certain light), both of which are standard care, with the addition of two futher technologies, DTI (neuronavigation,
which allows important fibres involved in specific functions, for example, speech/language, vision, and movement to be seen during surgery), and intraoperative US (high frequency sound waves which create an image), associated with an increase in patient quality of life measured by deterioration free survival (DFS) score?
The secondary objectives are to assess the patient impact of using these additional surgical tools (DTI and intraoperative US) during GB removal, with reference to DFS, overall and progression free survival (survival without a progression on imaging or of symptoms), extent of tumour removal, surgical complications/adverse events, number of patients eligible for chemotherapy and radiotherapy (adjuvant therapy) following surgery, and functional outcome (cognitive/ physical performance) post operatively.
FUTURE-GB is a 2- Stage trial. The first Stage of the trial (called IDEAL 2B study) will be a 6 month period when surgeons participating in the trial will familiarise themselves with the protocol, and combining the additional technologies. Participants will be enrolled into this section of the trial. There are information leaflets for both stages.
Stage 2 is a blinded, parallel 2-arm, multicentre, randomised controlled trial of standard care surgery (neuronavigation based on preoperative imaging and intraoperative use of 5-ALA) versus standard care surgery (neuronavigation based on preoperative imaging and intraoperative use of 5-ALA) with the addition of intraoperative US and DTI. This means that patients from a number of centres in the UK will be allocated by chance to either standard care or the use of additional technologies as well as standard care. Neither the patient or the research team collecting assessment information will be aware of what tools have been used during the operation.
Potential participants will be identified through Neuro-oncology Multi-Disciplinary Team meetings if imaging shows a likely GB tumour where the aim is to remove as much tumour as
present standard NHS guidelines all eligible participants will be seen in a dedicated neuro oncology clinics to discuss management of their GB tumour and the FUTURE-GB trial.
Written trial information sheets and Informed Consent forms will be presented to the participants detailing: the exact nature of the study; what it will involve for the participant; the implications and constraints of the protocol; the known side effects and any risks involved in taking part. The participant will be allowed as much time as desired to consider the information, and will also be given the opportunity to question the Investigator/ a member of the research team, their GP or other independent parties to decide whether they will participate in the study. Written Informed Consent will then be obtained by means of participant dated signature and dated signature of the person who presented and obtained the Informed Consent.
At the same time as taking consent, the participant will be asked to provide the name of a proxy, such that should he/she lose function, this individual would be able to provide answers to the questionnaires on the participant’s behalf. Over time, a participant may deteriorate, due to progressive cognitive problems due to the cancer and/or surgery. However, this may not affect the ability to complete HRQoL questionnaires during follow-up. If the participant is not able to complete the HRQoL questionnaires, whether due to physical and/or cognitive/psychological reasons, a proxy, if provided by the patient at the time of enrolment, will be asked to complete the questionnaires. The proxy and the participant will both be asked to complete questionnaires at baseline.
Following screening and consent, participants will be enrolled to the Stage 1(IDEAL 2b) study or the Stage 2 randomised study, randomly allocated to a treatment group by a computer, depending on the phase of the study. In Stage 2 the participant will have an equal chance (50%) of being allocated to either treatment, like the toss of a coin.
There is a 50% chance the participant will be put into the group in which the new technologies will be used during their operation in addition to the standard techniques(the experimental arm), and a 50% chance they will be in the group where the surgeon uses the present standard techniques (the control arm).
Participants in the randomised study will remain blinded as to which arm of the trial they have been allocated.
Postoperatively, the radiologist (reviewing the postoperative scans), and the therapist/research nurse (conducting the postoperative assessments and collecting the data) will be blinded to study arm.
All participants will undergo a routine preoperative neuronavigation MRI scan. For all participants in the initial Stage 1 (IDEAL 2b study), and those randomised to the experimental arm of the randomised study, there will be an additional. DTI sequence (extra 5 minutes scanning time).
In Stage 2 participants will complete questionnaires about their health and activity, and quality of life prior to surgery, post operatively, 6 and 12 weeks after surgery, and then every 3 months. These time points will be when participants would usually come back to the hospital for routine NHS care. Questionnaires can also be completed online or taken away and posted back to the Trials Unit. Participants clinical performance status, side effects of treatment (surgery, radiotherapy, chemotherapy), will be recorded by a research nurse at each planned hospital visits. Participants will also have MRI brain scans as part of standard care pathway, with no additional MRI scans for the FUTURE-GB trial.
There will be minimal deviation from the standard care pathway for GB participants undergoing surgery, and no alteration to the standard radiotherapy and chemotherapy dosing regimen or treatment schedule for participants.