In Brain News

Welcome to part 3 of this week’s exploration of the key themes highlighted in Tuesday’s BBC Radio 4 programme. In part one we discussed adaptive trials and research funding, you can read this here. And yesterday in part 2 we talked about data for the brain tumour community. Today Helen Bulbeck, brainstrust’s Director of Services and Policy talk about comination therapies and treatments, with part 4 ‘patient experience’ to follow on Monday.

Part 3: Combination therapies and treatments for people with a brain tumour.

It’s been a busy week for Tessa Jowell. Today as I write she is presenting at the House of Lords, following her very brave, eloquent and reasoned words on Tuesday’s BBC’s Today programme. We promised you some thinking around the four key themes that have resonated. We’ve heard about the need for combination therapies and treatments. And then there was discussion about adaptive trial design, so that everyone who is living with a brain tumour can be entered into a trial. And the need too for good data and global data collection and people talking across continents. Finally the programme talked about patient experience. 

Today’s focus is combination therapies and treatments for people with a brain tumour.

 With progress comes complexity.

Actually, it’s so complex that I am not sure where to begin. Let’s begin with a definition:

Combination therapies are when you combine one treatment (monotherapy) with another (it then becomes polytherapy). For example, combining one type of chemotherapy with another. Or combining chemotherapy with radiotherapy.

That’s the easy bit. Now try to get your head around this.

 We used to have one type of glioblastoma (GBM), the most lethal type of brain tumour. We now know, due to advances in understanding the molecular make up of brain tumours, that a GBM is in fact driven by two distinct subsets of cancer stem cells, within which are other subsets.

You can read more about brain tumour types here

In addition, each subtype of glioma stem cells is driven by their own programmes for growth and treatment resistance. And these different cell populations correspond to well-known structural differences within the GBM itself. In other words, one part of a GBM may not be quite the same as another part, because it is made up of different cells.

Now think about when a GBM comes back after treatment. It has changed again. A GBM is what we call heterogeneous, made up of a variety of cells, some of which will respond to treatment and some of which won’t. And these change over time.

So you have two baskets – one with treatment options and one with the tumour in it.

What happens in the middle ground? Firstly, there are the surgical options. The first decision is whether to operate or not. There are clinical guidelines to shape this decision, as well of course, the patient and their family’s wishes. Technology is a great thing, but we now have a situation where surgeons have different tools in their armoury and so the type of brain tumour surgery offered may differ from centre to centre. Surgeons have three intra-operative imaging techniques they can use to visualise tumour margins and improve resection: iMRI, iUS and 5-ALA fluorescence. There is inequality of access to these techniques for patients and centres. A Cochrane Review highlighted a lack of evidence about which techniques have the greatest effect, and a lack of information about the impact on neurological function of more aggressive surgical resection. There are no on-going brain tumour trials investigating the efficacy of these techniques.  It is not known if different techniques could be more effective in adult or paediatric tumours, or according to tumour subtype. A definitive study to assess all techniques in paediatric and adult brain tumour patients is required.

So that’s your first problem. It’s nice that we have these technologies. But we don’t know what works best. More trials are needed.

Responsiveness to chemotherapy

Second line treatment is chemotherapy. At the moment, the gold standard is the Stupp protocol – radiotherapy followed by Temozolomide. But now we know that not all GBMs are going to respond to chemotherapy (chemo-responsive). And then there is radiotherapy. We now have to consider different types of radiotherapy and also how much dose to give. And too we have what are called novel agents – some of which have shown real promise in other cancers, so it makes sense to try them in brain cancer.  These agents can include immunotherapy, antiangiogenic therapies and new technology such as tumour treating fields.

Brain tumour treatment resistance and recurrence

The problem is that these have targeted single mutations and so it leads to eventual treatment resistance and recurrence. It would make sense then to explore mixing up treatments and using combination therapies. But we have quite a few to choose from and you have to think about dose and when on the treatment pathway it would be appropriate to try these, all of which have to be done in controlled way, hence the need for adaptive trial design.

One size does not fit all

Increasingly, it seems that a single, targeted, ‘one-size-fits all’ approach is not going to work. Hence the interest in combination therapies. Recent advances have led to attempts to adapt these treatments to the unique make up of the central nervous system, and clinical trials are ongoing. As we come to appreciate the molecular heterogeneity of GBM, neuro-oncologists are faced with potential new targets and mechanisms for treatment, but also a deepening understanding of the challenges posed by this lethal tumour. Combination therapies, in conjunction with adaptive trial design will afford clinicians and researchers the flexibility and freedom to try new things that may well offer some hope for people with a brain tumour.

If you need help with any of this information, or have a question about your brain tumour treatment, don’t forget you can contact the brainstrust team on hello@brainstrust.org.uk or call us on 01983 292405. 

 

My radiotherapy book: information to help you understand the treatment

We know how confusing a brain tumour diagnosis is and the follow treatments can be. This resource will help you understand, and take control.

My radiotherapy book outlines and explains the range of radiotherapy treatments that are currently available, so that you know what would be the best treatment for the type of brain tumour you are living with, whether you are a carer or a patient.

Click here to download the booklet.

bbc inspiration2
Inspiration from the BBC. What does this mean for you? Part 2.Brain News
bbc inspiration4
Inspiration from Tessa Jowell, Nick Robinson and the BBC – what this means for you. Part 4.Charity News

Introduction

The Brain Tumour Data Dashboard lets you explore up -to-date, population level data about the brain tumours diagnosed in England between 2013 and 2015. Using the drop down menus on the left you can select different groups of patients to view in the charts below. In these charts the number of patients for every 100 diagnoses is displayed as images of people. Patients have been grouped by date of diagnosis, type of tumour, age, gender, and region in England.

For each group of patients you can explore the different routes to diagnosis, the proportion of those who received chemotherapy or radiotherapy, as well as the survival of the patients within each group. For more information about what these metrics mean please see the glossary.

How to use

  1. Select the year of diagnosis using the drop down menu.
  2. Select your patient group of interest from the four drop down menus in the following order:
    1. Tumour group
    2. Age at diagnosis
    3. Region of England
    4. Gender of patient
  3. To view a second chart to compare different groups of patients, click the ‘compare’ button.The second chart will appear below the first chart.

*Note that the tool is best used on a laptop or tablet rather than a mobile phone*

Unavailable data

Some of the data in these charts is not available.There are two main reasons for this:

  1. How the data has been grouped

If you cannot select a patient group from the drop down menus, the data is unavailable because of how the data has been organised.

Public Health England has grouped the data like a branching tree. The bottom of the tree contains all the patients with brain tumours, and then each branch divides the data by a certain characteristics, like age, or location of tumour. But the data is divided in an order, starting with location of the tumour (endocrine or brain), then by age, region, and gender. Age is at the start because it makes a bigger difference to survival rates and treatment rates than gender or region. Sometimes, after the data has been split by type of tumour and age, there is not enough data to be split again. This is because to protect patient confidentiality groups cannot contain less than 100 patients. Because some groups cannot be split further, you cannot create ‘totals’ for everyone by region or gender. For example, you cannot see results for all ages by region, or all brain tumours by gender. If these totals were calculated and released, it might be possible to identify patients, which is why Public Health England cannot release this data.

  1. Statistical reasons and data availability

If you can select a patient group from the chart menus, but the chart does not display, the data is unavailable for one of several reasons:

  1. Data is not yet available for the selected year from Public Health England.
  2. Data is not available because the data quality is too poor to release this statistic.
  3. Data is not available as the statistic is not appropriate for this group.
  4. Data is not available because the standard error of the estimate was greater than 20% and so the estimate has been supressed.

Up to date brain tumour data

Brain tumour data may influence the decisions you make about your care. Data also helps you understand the bigger picture, or landscape, in which you find yourself.

Brain tumour data and statistics influence the focus, and work of organisations like brainstrust. The information helps us to understand the scale and impact of the problems we are setting out to solve.

This tool helps you understand the landscape in which you find yourself having been diagnosed with a brain tumour. This landscape can be particularly tricky to navigate as there are many different types of brain tumour, all of which have a different impact.

The information you see represents the most up-to-date, official, population level brain tumour data available for England. Over time we will be adding to the brain tumour data available and publishing reports, with recommendations, as a result of what we learn from this data.

The data behind this content has come from Public Health England’s National Cancer Registration and Analysis Service (NCRAS) and is a direct result of the ‘Get Data Out’ project.

This project provides anonymised population level brain tumour data for public use in the form of standard output tables, accessible here: http://cancerdata.nhs.uk/standardoutput

Incidence

The number or rate (per head of population) of new cases of a disease diagnosed in a given population during a specified time period (usually a calendar year). The crude rate is the total number of cases divided by the mid-year population, usually expressed per 100,000 population.

Malignant

Malignant tumours which grow by invasion into surrounding tissues and have the ability to metastasise to distant sites

Mortality

The number or rate (per head of population) of deaths in a given population during a specified time period (usually a calendar year). The crude rate is the total number of deaths divided by the mid-year population, usually expressed per 100,000 population.

Non-malignant

Not cancerous. Non-malignant tumours may grow larger but do not spread to other parts of the body.

Survival

The length of time from the date of diagnosis for a disease, such as cancer, that patients diagnosed with the disease are still alive. In a clinical trial, measuring the survival is one way to see how well a new treatment works. Also called ‘overall survival’ or ‘OS’.

Routes to Diagnosis

Under the ‘Routes to Diagnosis’ tab in the Brain Tumour Data Dashboard, you can explore the ways patients have been diagnosed with brain tumours. There are many ways, or routes, for cancers to be diagnosed in the NHS. A ‘route to diagnosis’ is the series of events between a patient and the healthcare system that leads to a diagnosis of cancer. The routes include:

  1. Two Week Wait

Patients are urgently referred by their GP for suspected cancer via the Two Week Wait system and are seen by a specialist within 2 weeks where they are diagnosed.

  1. GP referral

Diagnosis via a GP referral includes routine and urgent referrals where the patient was not referred under the Two Week Wait system.

  1. Emergency Presentation

Cancers can be diagnosed via emergency situations such as via A&E, emergency GP referral, emergency transfer or emergency admission.

  1. Outpatient

Outpatient cancer diagnoses include diagnoses via an elective route which started with an outpatient appointment that is either a self-referral or consultant to consultant referral. (It does not include those under the Two Week Wait referral system).

  1. Inpatient elective

Diagnosis via an inpatient elective route is where diagnosis occurs after the patient has been admitted into secondary care from a waiting list, or where the admission is booked or planned.

  1. Death Certificate Only

Diagnoses made by Death Certificate Only are made where there is no more information about the cancer diagnosis other than the cancer related death notifications. The date of diagnosis is the same as that of the date of death.

  1. Unknown

For some patients with a cancer diagnosis, there is no relevant data available to understand the route to diagnosis.

 

More information

If any of the statistical terms in this section of the brainstrust website are hard to understand, we recommend looking them up here:

Cancer Research UK’s Cancer Statistics Explained

http://www.cancerresearchuk.org/health-professional/cancer-statistics/cancer-stats-explained/statistics-terminology-explained#heading-Seven

If you are looking for help understanding terms relating specifically to brain tumours, and treatment, then the brainstrust glossary is available here:

https://www.brainstrust.org.uk/advice-glossary.php