The government hopes genome sequencing technology will improve the treatment of cancer
A series of NHS and healthcare events are taking place over the coming weeks to spark a conversation among healthcare professionals about genomics.
They will help educate healthcare professionals about the benefits of genomics – the practice of using people’s DNA and genetic information to inform their clinical care – in improving diagnosis and treatment for patients.
Health Education England (HEE) held its second annual #GenomicsConversation this week to increase health professionals’ familiarity about genomics. HEE’s campaign involves panel events, online courses, the launch of new podcasts and educational resources.
In December last year, health secretary Matt Hancock announced that the 100,000 Genomes Project, led by Genomics England in partnership with NHS England, reached its goal of sequencing 100,000 whole genomes from NHS patients.
The programme was launched in 2012 by then prime minister David Cameron, with the goal of harnessing whole genome sequencing technology to improve diagnosis and treatments for people with rare inherited diseases and cancer. The project laid the foundations for a NHS Genomic Medicine Service, which will provide genomic testing to patients across the NHS from 2019.
HEE wants to make healthcare professionals aware of the roll-out of the new service and whole genome sequencing so that they feel more comfortable discussing genomic testing with patients, and can signpost them to relevant information and services.
Meanwhile, the University of Cambridge will be holding an event on genomics on 13 March as part of Cambridge Science Festival to celebrate the sequencing of all 100,000 genomes and the UK becoming the first nation in the world to apply genome sequencing at scale in healthcare.
Genomics England interim chief executive and chief scientist Mark Caulfield said: ‘The Genomic Medicine Service is the first of its kind where genomics will be embedded into a national health system and transform routine healthcare in the UK.’
Four regional events organised by NHS England in partnership with Macmillan Cancer Support, Cancer Research UK and NHS Horizons will take place in London, Birmingham, Bristol and Leeds, starting from 12 April. Entitled Genomics and Personalisation of Cancer Care, they will explore how genomics can be embedded into personalised cancer care.
They will also enable those working in NHS Genomic Medicine Centres to engage with the public and other healthcare professionals to reflect on the transformation that has already taken place, and consider the changes that will be needed in the future.
Cancer Nursing Practice conference
Genomics will also be among the topics presented at Cancer Nursing Practice’s annual conference on 1 May, where Barts Cancer Institute and Genomics England specialty trainee and clinical research fellow in medical oncology Alison May Berner will present on the implications of genomics for people with cancer and nursing. She will also discuss some of the findings of the 100,000 Genomes Project by drawing on patient case studies.
The overall theme of the conference is patient experience. Topics include dementia and cancer, social prescribing, pain management, managing a large systemic anti-cancer therapy unit and supporting patients with recovery.
Royal Wolverhampton NHS Trust matron for oncology and haematology Doreen Black, who won the top leadership category in NHS England’s 2018 Windrush Awards, will make a keynote address.
The early bird rate for registration expires on 15 March and you can book here
Immunotherapy, in which the body’s own immune system is harnessed to kill cancer cells in patients with advanced disease, is proving a powerful treatment in around 15% of cancer patients. Importantly this type of treatment can be used to treat a broad range of different tumour types including lung, breast and bladder cancers and melanoma.
The patients who are likely to respond to such treatment can be identified by analyzing the tumour biopsy with a special stain called the PD-L1 test. Tests which are able to identify a patient likely to respond to a particular treatment are called companion diagnostic CDx assays. Oncologica, in collaboration with AstraZeneca, has recently completed a study involving the participation of internationally recognised pathologists to assess the performance of one of these tests, called the VENTANA PD-L1 (SP263) Assay in lung cancer.
Preliminary findings were presented at the ESMO 2018 congress in Munich, Germany. The study has now been completed and the findings recently published in the Journal of Thoracic Oncology, a leading journal in the field of lung cancer. We have shown that assessment of tumour cell (TC) scores by expert pathologists is highly reproducible in lung tumour samples using the VENTANA PD-L1 (SP263) Assay, thus building confidence in the performance of this test as a companion diagnostic for anti-PD-L1 immunotherapy.
This will help ensure that patients who may benefit from immunotherapy are correctly identified.
A major trial of an immunotherapy drug has shown it can be effective in some men with advanced prostate cancer.
The men had stopped responding to the main treatment options.
Researchers found that a small proportion of men, described as “super responders”, remained well even after the trial ended, despite a very poor prognosis before treatment.
Last week it was reported the same drug had proved effective in treating advanced head and neck cancers.
What is immunotherapy?
Immunotherapy uses our own immune systems to recognise and attack cancer cells.
It’s already being used as a standard treatment for some cancers such as melanomas – and being tested on many others too.
- Cancer immunotherapy drug ‘prolongs life’
- Prostate cancer drug hailed as ‘big deal’
- Half of people surviving ‘untreatable cancer’
What did the study find?
It found that one in 20 men with advanced prostate cancer responded to the drug pembrolizumab – and saw their tumours actually shrink or disappear altogether.
Although a relatively small number, some of them gained years of extra life, the study in the Journal of Clinical Oncology found.
A further 19% saw some evidence of improvement.
But most patients in the study lived for an average of eight months on the drug.
The phase II clinical trial, led by the Institute of Cancer Research and the Royal Marsden, involved 258 men with advanced prostate cancer who had run out of all other options on treatment.
What happens next?
The most dramatic responses were seen in patients whose tumours had mutations in genes involved in repairing DNA.
Researchers are now investigating whether this group might benefit the most from immunotherapy in a larger trial.
But first, a test to pick out who will respond best is needed, so that doctors know which patients to give it to.
What is prostate cancer?
It’s the most common cancer in men in the UK, with around 47,700 diagnosed in the UK each year.
The number of people diagnosed has been rising over the last 10 years.
This is probably because the population is getting older and more people are having PSA tests.
Around 30% of men with advanced or stage 4 prostate cancer survive their cancer for five years or more after diagnosis.
What do experts say?
“Immunotherapy has had tremendous benefits for some cancer patients, and it’s fantastic news that even in prostate cancer, where we don’t see much immune activity, a proportion of men are responding well to treatment,” says Professor Paul Workman, chief executive of The Institute of Cancer Research.
“A limitation with immunotherapy is that there’s no good test to pick out those who are most likely to respond.
“It’s encouraging to see testing for DNA repair mutations may identify some patients who are more likely to respond, and I’m keen to see how the new, larger trial in this group of patients plays out.”
Professor Johann de Bono, a consultant medical oncologist at The Royal Marsden NHS Foundation Trust, was one of those who led the study.
He said: “We don’t see much activity from the immune system in prostate tumours, so many oncologists thought immunotherapy wouldn’t work for this cancer type.
“But our study shows that a small proportion of men with end-stage cancer do respond, and crucially that some of these men do very well indeed.
“We found that men with mutations in DNA repair genes respond especially well to immunotherapy, including two of my own patients who have now been on the drug for more than two years.”
Last week, a separate trial found the same drug kept some people’s advanced head and neck cancers at bay for an average of two years – five times longer than under chemotherapy.
Both studies are part of a growing body of research suggesting immunotherapy could offer hope to an increasing number of cancer patients.
An immunotherapy drug that could save some cancer patients from the ordeal of extreme chemotherapy may also help them live longer, researchers say.
In a trial, pembrolizumab kept head and neck cancers at bay for an average of two years – five times longer than under chemotherapy.
The patients also suffered far fewer side-effects.
Cases of head and neck cancers are rising in the UK and most are diagnosed late, when they are harder to treat.
‘I can get on with my life’
Derek Kitcherside, 70, from Leicestershire, believes he wouldn’t be here without pembrolizumab.
He was diagnosed with cancer of the voicebox in 2011. When he started coughing up blood three years later, after receiving standard treatment, he was told the cancer had spread to his lungs and was probably incurable.
Derek asked to go on a drug trial and travelled to London every three weeks for two years for treatment with pembrolizumab.
“My tumour was shrinking all the time and I felt a bit better every time I went,” he said. “It made a huge difference to my life.”
Regular scans show the disease is now stable and the tumour is still getting smaller.
“I’m very pleased I can get on with my life,” Derek said.
“I don’t think I’d be here without it.”
What is immunotherapy?
It is a treatment that does not kill cancer cells itself but instead stimulates the body’s immune system to attack them.
Pembrolizumab is already being used to treat a wide range of advanced cancers, including melanoma – a type of skin cancer that spreads easily.
Experts believe the drug has the potential to treat many more.
When is it used?
Normally, immunotherapy is used after standard treatments like chemotherapy have failed but this trial, in 882 patients from 37 countries, suggests it should be used earlier – and for some people it should be the go-to option.
The drug is given to patients regularly through a drip when their cancer has returned or spread, and is considered incurable.
Why is it better than current treatment?
It is kinder, safer and can keep patients alive for longer, the study in The Lancet found.
But it may not work for everyone.
In people with advanced head and neck cancer who responded to the drug – one in four – their cancer shrank or stabilised for an average of 23 months.
By comparison, although more patients (36%) responded positively to standard chemotherapy treatment, the improvements lasted on average for only four and a half months.
Those with larger, more aggressive tumours were given the drug in combination with chemotherapy to help slow progress of the disease – which was kept in check for an average of seven months.
So who could benefit?
The trick is identifying people with tumours that will respond, says Prof Kevin Harrington, oncologist at The Royal Marsden NHS Founation Trust and professor of biological cancer therapies at the Institute of Cancer Research, who led the study,
A test for the presence of immune marker PD-L1 in the tumour means doctors can work this out.
Prof Harrington says approximately 85% of people with advanced or relapsed head and neck cancer would be eligible for pembrolizumab – around 1,300 patients a year.
Why is it kinder?
At the moment, the recommended treatment is a toxic combination of chemotherapy and antibody therapy, which often makes people feel very sick.
The extreme treatment can also cause damage to the kidneys, hands and feet.
Patients given the immunotherapy drug experienced far fewer side-effects.
“It’s more sensible and less toxic – patients live longer and feel better,” says Prof Harrington.
What does this mean for patients?
“This study is very exciting”, says Prof Paul Workman, from the Institute of Cancer Research.
“Firstly because it shows that immunotherapy can have dramatic benefits for some patients with head and neck cancer when used as a first-line treatment, and secondly because the researchers have devised a test for picking out who is most likely to benefit.”
He said all new drugs coming on to the market should be accompanied by a test to target their uses as precisely as possible.
In the US and the EU, pembrolizumab has been approved for use on its own and with chemotherapy for advanced head and neck cancer, but not yet in the UK.
The National Institute for Heath Care and Excellence is currently appraising pembrolizumab and it could be approved for use on the NHS by next summer.
Facts on head and neck cancer
- Around 12,000 people in the UK are diagnosed with head and neck cancer each year
- Half are diagnosed at stage III or IV when it is hard to treat
- Most cases are linked to smoking and alcohol but the recent rise in cases seems to be linked to HPV (human papillomavirus)
- This virus infects the skin and cells lining the inside of the body and can be spread through close skin-to-skin contact
- Boys and girls are now being vaccinated against HPV at school, but it will be several decades before HPV stops being a risk factor
Mapping the binding sites of antibodies utilized in programmed cell death ligand-1 predictive immunohistochemical assays for use with immuno-oncology therapies
Oncologica has participated in a study, led by AstraZeneca, to further improve the tests that are used to pin point the patients most likely to respond to a new type of anti-cancer treatment called “immune-therapy”. These tests are known as Companion Diagnostic (CDx) tests.
Immune-therapy is now becoming a front-line treatment for many tumour types. Immune Checkpoint Therapy, is an immune-therapy which targets a protein called PD-L1, expressed on the surface of tumour cells, which exploits the bodies’ immune system to attack cancer cells. The NHS use Immune Checkpoint Therapy to treat patients with the most serious form of skin cancer (melanoma) and aggressive tumour types such as lung cancer. The impact of this revolutionary new treatment was recently recognized by the award of the Nobel Prize for Medicine to Prof A Prof Allison (University of Texas) and Prof Honjo (Kyoto University) who discovered this new approach to cancer therapy.
Immune-therapy doesn’t work for everyone, in some patients it appears to work incredibility well, completely destroying tumours even after they have begun to spread around the body, but for other patients the response can be less dramatic.
Several PD-L1 CDx tests have been approved for use, including the VENTANA PD-L1 (SP263) Assay, VENTANA PD-L1 (SP142) Assay, Dako PD-L1 IHC 22C3 pharmDx assay and the Dako PD-L1 IHC 28-8 pharmDx assay. PD-L1 CDx tests are used to pin-point which patients are most likely to respond to anti-PD-L1/PD-1 directed immune-therapies. During the clinical use of these CDx tests a degree of variance between their performances has been observed and it has been hypothesized that such variances may be caused by the different PD-L1 antibodies, used in these tests, recognizing different parts (epitopes) of the PD-L1 protein.
The AstraZeneca/Oncologica study, identified that any variances in performance between CDx tests (inter-assay variability) are more likely attributable to tumour heterogeneity or test/instrument variables than they are to the antibody epitope. This information will help to further the understanding of CDx testing in PD-L1 immune-therapy in the clinical testing community, maximize the benefits of this type of treatment for cancer patients and drive the adoption of CDx testing.
Karan Jensen was diagnosed in 2017, aged 48 with cervical cancer. Karan ordered the Oncofocus Test to identify additional treatment options and shares her story here in the following Q&A.
How did your diagnosis come about?
I had been having regular smear tests, but then one came back with irregular cells and the doctor asked to see me in 6 months time. We were moving, so I delayed going back, but when I did get to the doctors, they ended up doing a biopsy. Within 2 weeks I was diagnosed with Stage 2B cervical cancer with lymph node involvement.
What happened after you were diagnosed?
Treatment was started to cure my cancer. I had four cycles of cisplatin chemotherapy plus 32 sessions of radiotherapy.
Did this treatment work?
Unfortunately, the tumour did not change with this type of chemotherapy, so I then started on carboplatin and paclitaxel.
Did the second round of treatment work?
I was meant to have six sessions of this chemotherapy, but after three, I had a scan and found out that the tumour had grown. I was told that there was no point continuing treatment as my cancer was incurable, and to go home and get things in order.
Did you experience any side effects of chemotherapy?
During chemotherapy, I was hospitalised four times with infections and neutropenic sepsis. The chemotherapy also caused swelling of my legs (lymphoedema), and my kidneys had been damaged so that I had to have a nephrostomy bag attached to collect urine.
How did you feel when they told you that you cancer was incurable?
I have an 11-year-old son, so I was not going to give up and did some research online on the best treatments for my cancer.
What did you find searching online?
I found out about the Oncofocus® cancer test by Oncologica on their website and got in touch.
Was it easy getting the Oncofocus test done?
It cost £2000 but it was an easy decision to make. I just had to fill in a few forms and Oncologica did all the work to get the biopsy from my hospital.
What were the results of the Oncofocus test?
The test quickly came back that my tumour was exceptionally high in a protein called PD-L1, so it would respond really well to immunotherapy, which works by boosting a person’s immune system to help it recognise and fight cancer cells.
What happened when you knew the results of the test?
The treatment that the test recommended was not available on the NHS so my oncologist contacted Christie Hospital in Manchester, which was part of the PROCLAIM-CX-072 clinical trial that is investigating an experimental drug that targets PD-L1.
I was very sick at this stage, and the doctors were not sure that I would be well enough to get into the trial. As my levels of PD-L1 were so high, however, they thought they had to give me the opportunity.
Was this new treatment successful?
I was meant to have four sessions of CX-072 plus ipilumumab every 3 weeks, plus CX-072 maintenance therapy for a year. Although the treatment was not as bad as chemotherapy and I did not lose any hair, it still made me feel very poorly. After the third session, I developed a bad reaction and the level of some of my white blood cells that fight infection, neutrophils, plummeted and could not be restored to normal. It was therefore too risky to continue the treatment.
The good news was that a scan in March this year showed that the new therapy had reduced the tumour by 50%.
Are you still receiving treatment?
Even though the treatment has stopped, my immune system has taken over and is fighting the tumour. I am scanned every 2 months, and every time my tumour reduces by a further 0.5% to 1%. Last week I had another scan, and it had reduced by 3% and I feel better today than I have over the past 3 years.
What are your thoughts on the Oncofocus test?
If I had had the test before receiving chemotherapy, this would have saved the NHS a load of money giving me a treatment that did not work and putting me through so much. I continue to need a nephrostomy bag due to the damage done by chemotherapy, which needs changing once a week and the tubes replaced in hospital every 3 months.
What is happening now?
We are now at the ‘watch and wait’ stage. However, as I have had such a good response to the immunotherapy and feel so much better, I can have more treatment if needed in the future. The swelling in my leg has gone down and I can now wear my shoes and move around normally again. I was so sick that I did not think that I would see last Christmas. Now I will get to experience Christmas again this year.
A “revolutionary” new class of cancer drug that can treat a wide range of tumours has been approved for use in Europe for the first time. Tumour-agnostic drugs do not care where the cancer is growing in the body as long as it has a specific genetic abnormality inside. UK doctors testing the drugs said they were “a really exciting thing”.
They said the approach had the potential to cure more patients and cut side-effects. The drug that has been approved is called larotrectinib. Charlotte Stevenson, a two-year-old from Belfast, was one of the first patients to benefit.
She was diagnosed with infantile fibrosarcoma, a cancer of the body’s connective tissue. She has been treated with larotrectinib as part of a clinical trial at the Royal Marsden Sutton, in London, for the past year. Her mum, Esther, said: “We knew that our options were limited [so] we decided to give it a try and are so glad that we did.
“We have been able to watch Charlotte develop and grow at a rapid rate, making up for lost time in so many ways and amazing us all with her energy and enthusiasm for life.
“She can now have a relatively normal life and, best of all, the drug has had an incredible impact on the tumour.”
Charlotte’s tumour was caused by a genetic abnormality known as an NTRK gene fusion.
One part of her DNA accidentally merged with another and the alteration in the blueprint for her body led to the growth of her cancer.
But NTRK gene fusions are not unique to sarcomas – they also appear in some brain, kidney, thyroid and other cancers.
“It is a really exciting thing, as is it works across a range of cancers. It’s not confined to one,” Dr Julia Chisholm, a children’s cancer consultant at the Royal Marsden Hospital, told the BBC.
NTRK mutations are relatively rare, but other targeted therapies are in development.
It marks a move away from treating a “breast cancer” or “bowel cancer” or a “lung cancer” and towards precision medicine that takes advantage of the genetic make-up of each patient’s tumour.
Dr Chisholm told the BBC: “The beauty is it targets the abnormality.
“There are a number of biochemical pathways that are common in many different tumour types.
“I think this is the way things are going and this is about better outcomes, curing more patients and producing kinder treatments with reduced side-effects.”
The decision by European regulators does not mean it will be instantly available for patients in the UK. But earlier this year, NHS England described tumour-agnostic drugs as a “revolutionary” and “exciting new breakthrough” in cancer and said preparations were under way to ensure patients were given access to them.
“The benefits for patients – in particular children – of being able to treat many different types of cancers with one drug is potentially huge, helping them to lead longer, healthier lives,” NHS England chief executive Simon Stevens said at the time.
Prof Charles Swanton, Cancer Research UK’s chief clinician, said the drugs were “exciting”. He added: “The NHS will need to ensure the right genomic testing is available across the country to identify patients who could benefit so it’s good that the NHS is already thinking about how to get this to patients with cancer as soon as possible.”
Dr Brendon Gray, from Bayer, the drug company that developed larotrectinib, said: “As the first tumour-agnostic medicine approved in Europe, larotrectinib represents a real shift in cancer treatment.”
Molecular genetic testing identified the most precise treatments
Genetic testing not only provides information regarding the chance of developing a particular disease but is also crucial in identifying the most effective anti-cancer therapy for each individual patient suffering from any solid tumour. Thus the battle against the tumour is tailored.
Genetic tests are basically of two types: the first is the predictive one, which allows asymptomatic people to reveal all the hidden secrets of their DNA and to quantify their risks of falling ill with certain diseases, cancer in particular, especially tumours of breast and ovary, colorectal and prostate and other diseases such as juvenile Alzheimer’s and cardiovascular diseases. The second type of test is aimed at people already suffering from cancer, a precision cancer test that is able to identify the most effective cancer therapy, especially biological, for each individual patient suffering from any solid tumour. From the routine paraffin blocks containing the excised or biopsied tumour tissues of the individual patient, stored in the pathology archive of the treating hospital, a piece of this material is sent to the precision oncology laboratory, for example Oncologica UK, based in Cambridge, UK. Here the sample is analysed using the Oncofocus test and within 10 – 15 days the report is issued which provides Oncologists with the linkage between the identified genetic mutations and the targeted drugs approved by the major world organizations as well as those undergoing clinical trials and additionally the immunological drugs that have recently entered clinical practice.
There is now a major change in direction regarding the method used for treatment selection in cancer. This modern approach, rather than recommending treatments based solely on the fact that the individual has a specific type of cancer, such as lung, breast, colorectal, etc., instead bases therapy selection by examining the disease at a molecular level. The best way to treat cancer with modern anti-cancer drugs is therefore “agnostic of cancer type”, meaning regardless of the type of cancer a patient may have developed. This is an approach that has been approved by the US Food and Drug Administration (FDA) and that has been adopted by many other countries such as Australia.
These “tumour-agnostic” therapies are beginning to show promising results in the clinical setting, helping patients with a wide variety of different tumours types that have previously been difficult to treat using conventional drugs, especially those patients in second line after the failure of first line treatment. In the tumour center of the Tirelli Medical Group (www.tirellimedical.it) based in Pordenone we have already treated a hundred patients with this therapeutic strategy based on the recommendations of the American Food and Drug Administration (FDA) with often surprisingly favourable results.
Notably this is in keeping with a study recently published in the journal “Oncotarget” by a group of Stanford University in California showing that the use of therapy based on precision oncology (e.g. Oncofocus Test) improves the survival of refractory cancer patients while decreasing the costs of treatment.
Mutations that play a fundamental role in the development of neoplasms have been called “driver” mutations since they are able to confer a growth advantage in the affected cells. Approximately 350 driver genes involved in cancer development have been identified in human tumours. Investigations by massive sequencing have shown that tumours exhibit numerous mutations, most of which are not drivers but “passengers”, i.e. not involved in tumour development but randomly occurring and selected by rapid neoplastic growth.
Knowing the genetic drivers, that is those genetic alterations that are the basis of tumour cell multiplication, means that it is possible to develop precision treatments that specifically and in a completely new way address the choice of biological and immunological drugs.
At the moment, oncologists have limited information in trying to find the right anti-cancer drug for their patient. There are in fact more than 300 anti-cancer drugs and hundreds of different types of cancer, each of these also possesses different genetic mutations that respond differently to therapies, it follows that, even for a good oncologist the chances of finding an effective drug mix can be low.
The use of genetic testing of the tumour biopsy sample is able to help the oncologist in making the right choice by increasing the probability of prescribing an effective drug. Immunological therapy is also identified through this type of testing. Prof. Riccardo Dolcetti, who is a professor of oncological medicine at the University of Queensland in Australia and who has been at the Cancer Institute of Aviano for a long time, tells me that there genetic testing on the tumour tissue is done following diagnosis in the major tumour types (e.g. lung, breast, colorectal, prostate, etc.) but that they also carry out genetic testing on the tumour biopsy taken following relapse if feasible. At the Tirelli Medical Group of Pordenone we carry out genetic testing only in cases of tumoural relapse, that is in patients in whom the first line therapy has failed, even though testing could take place at diagnosis to identify the best treatment available.
Even though the clinical implementation of genetic testing is still not such as to be used in routine clinical practice, it may be in the near future according to what was recently reported in the “New England Journal of Medicine”. The first so-called tumour histology-independent treatment, that is “agnostic of cancer type” was recently recommended by the European for approval in relation to the drug called Larotrectinib. This is a drug that targets a specific genetic mutation called NTRK i.e. the gene coding for the neurotropic tyrosine kinase receptor. Larotrectinib is indicated for the treatment of all pediatric and adult solid tumours that have the NTRK mutation regardless of their tumour type, i.e. whether it is breast, lung, colon, melanoma, etc.
This drug was approved in November 2018 in the United States and is considered an example of a targeted drug that radically changes the approach to cancer treatment. The data that have been recently published in the “New England Journal of Medicine” show an overall response of 76% which is quite unusual for patients heavily pre-treated with conventional therapies who have subsequently been administered Larotrectinib. This genetic alteration can be found in lung, colon, breast, thyroid and melanoma tumours.
Prof. Umberto Tirelli
Director of Tumor Center, Chronic Fatigue, Fibromyalgia and Oxygen-Ozone Therapy,
Tirelli Medical Group Clinic of Pordenone.
Oncologist, National Tumor Institute of Aviano
Sherrie Hewson was due on stage when her phone rang with shattering news.
The Coronation Street favourite’s beloved elder brother Brett had been diagnosed with an incurable brain tumour. He was given 18 months to live. Sherrie, 68, burst into floods of tears in her dressing room.
The actress, who played stroppy hotel manager Joyce Temple-Savage in Benidorm, was about to appear in a stage version of the ITV sitcom.
In the months that followed Sherrie would turn her life upside down to help Brett fight the killer disease and to be by his side.
She said: “I wouldn’t take it in. I think it was my way of dealing with it because I knew I was due on stage and because I just didn’t want to believe it.
“Brett is my big brother who I have always looked up to and he has always led a charmed life.
“Everything he touched had turned to gold and suddenly I was hearing this. It didn’t make sense.
“Part of me wanted to throw everything up in the air and go to him there and then. But another voice in my head said, ‘No. You need to keep on earning, girl, because Brett is going to need you now.’ You’d better get out here and do your job.”
Sherrie, who first trod the boards aged four, wiped aways the tears and got ready for the show at Belfast’s Grand Opera House. Fellow actors Tony Maudsley, who plays Kenneth, and Jake Canuso, who is Mateo, helped Sherrie through the show.
Sherrie said: “Not a soul in the audience knew what I was going through. Every part of me wanted to be with Brett but I had to stay strong.” That night her performance brought the house down and, despite all the heartache in the following months, Sherrie did not miss a show.
After taking her bow she dashed to Belfast airport to be by Brett’s side. On April 4, just a few days after the diagnosis, Brett, 71, was admitted to the Walton Centre, a neurological hospital in Liverpool, where a golf ball sized tumour was removed from his brain in a nine-hour operation. His daughter Chloe, 37, had insisted former DJ, male model and TV actor Brett have a check-up after his tongue stopped moving properly.
He was also sensing mysterious powerful odours and was constantly feeling tired.
At an A&E near his home in Llandudno, Conwy – where he runs a tea shop with his wife of 40 years Annie, 68, – a scan revealed a massive swelling on the brain.
Fluid had built up and Brett would have died within days without surgery.
The operation was a success but three days later he suffered a massive bleed on the brain and needed another four-hour op to remove a blood clot which had formed in the cavity where the tumour had been.
Again he pulled through and then faced radiotherapy and chemo in a bid to keep the aggressive cancer at bay. Tests showed the tumour was a grade 4 glioblastoma – the most common and aggressive brain tumour in adults.
Now Sherrie aims to be by Brett’s side as much as possible in the time he has left.
She has also become an ambassador of The Brain Tumour Charity to raise awareness of the symptoms and is seeking new treatments and drugs which could help prolong Brett’s life beyond 18 months.
She also has plans to rent a home in Llandudno to be near Brett and has arranged to do Christmas panto in the town so all the family will be together.
Sherrie, who was dizzy Maureen Webster in Corrie and has been a regular on Loose Women, said: “You never think it’s going to happen to you or your family but it doesn’t matter if you’re famous or not, young or old, brain tumours can affect any one.
“Brett wants to leave a legacy and he wants to raise awareness of this awful illness which can creep up on people.
“So becoming an ambassador for The Brain Tumour Charity was something I had to do for him and the people we may be able to help.
“I think about Brett’s prognosis every minute of the day. As a family we have vowed to live in the moment for Brett and for ourselves to get the very most out of the time we all have together with him. Fear touches everything now. It overshadows everything we do.
“I don’t allow myself to look too far into the future – it’s too frightening, so I don’t let my mind go there. He’s selfless and all he worries about is the impact on his family – that’s when he breaks down.”
Sherrie has now enlisted the help of a special medical company called Oncologica, which runs a DNA service and, after testing Brett’s tumour, has come up specifics drugs which may help him live longer.
Sherrie said: “The NHS has been amazing, they saved Brett’s life, now it is all about buying him as much time as we can.
“I’ll do everything I can to get him the very best treatment and if I have to work 365 days a year so be it. I’ll do anything.”
Sherrie, who revealed her own breast cancer scare in 2015, is aiming to raise £50,000 for The Brain Tumour Charity by offering a lunch date with herself on the good causes website Rafful – as well as an overnight stay in a London hotel for the winner.
Meanwhile her family is doing all it can to support Brett, who said his little sister and the rest of his family have been “amazing”. He said: “Sherrie and I are incredibly close and I confide my feelings and fears in her – I can tell her anything.
“We’re bound together by love and humour.
“Sherrie will always be my Shez – I’ve always called her that and always will. People think there must be ‘side’ to her because she’s an actress but she’s the same lovely, down-to-earth girl she’s always been.
“She is such a loving person with a fabulous big heart and would do anything to help anyone, especially her big brother. I’ve always told my family I love them but now I tell them I love them every time I see them and hug them closer.
“I’m grateful I’ve had such a rich, full life right up to my 70s, and I feel blessed I’ve got such a loving, supportive family around me.
“Every one of them is amazing. Chloe saved my life and Annie is my rock. I don’t know what I’d do without her. I know nothing about brain tumours. When doctors told me I had a glioblastoma I asked, ‘Is that serious?’
“The answer was, ‘It doesn’t get any worse.’ When I was told it was terminal I just couldn’t take it in. It feels like it’s a story being told about someone else.
“You’re in such a heightened state of emotion and shock that you can’t process it at first. You have to face your own mortality. This is what you’ve got and it’s going to kill you in 12-18 months. I’m learning to accept it, one step at a time.
“I’m not scared or sad for myself but I am scared and sad for my family – what lies ahead of them and the grief they’ll face.
“We’re all doing our best to live in the moment.
“I have everything I want or need – my family – and I just want to spend time with them. Now it’s about living the best life I can in the time I’ve got left.”
THOUSANDS of pounds have been donated within just two days to help a young Co Donegal mother-of-five access life saving cancer treatment.
Sonya Hamilton McCloskey (35) – who is originally from St Johnston close to the Derry border but lives with husband Michael in Ballybofey – has been fighting cancer for the past two years.
The businesswoman, who gave up work to look after her children who are aged from three to 15, first thought she had pulled a muscle.
Following various treatments for the pain, it was confirmed in April this year that she had cancer. It was later discovered that the disease had spread to her pancreas, lungs and liver.
Following a number of weeks separated from her four youngest children in an oncology ward, Mrs Hamilton McCloskey was transferred to Galway Hospital last Tuesday to have a stent inserted into her liver.
Unable to undergo chemotherapy she now hopes that UK-based specialists Oncologica will be able to provide a course of treatment which will give her a “fighting chance” against her illness.
The Donegal woman’s family set up a GoFundMe page last Wednesday hoping to raise the €2,000 (£1,785) necessary to cover the cost of having biopsies sent to Oncologica for analysis.
However, nothing could have prepared them for the public reaction to her appeal. Within just two days, a massive €36,000 (£32,139) was raised through the GoFundMe page and other donations.
The family has been overwhelmed by the support shown by the public. One man alone donated €5,000 (£4,464).
In a message issued from her hospital bed in Galway, Mrs Hamilton McCloskey and her husband thanked everyone who had donated, giving her some hope.
Her parents also took to social media to thank those who have donated.
In a post on the Sonya’s Struggle Facebook page, they wrote: “From the Hamilton family we would like to thank everyone for their support in these hard times. Sonya is one that brings our family together.”
They said their daughter had a heart of gold.
“We couldn’t ask for a better daughter. Keep on fighting dear,” they said.
Mrs Hamilton McCloskey’s Gofundme page can be accessed at https://www.gofundme.com/qap9y-sonyas-battle
Medicine has always been personal to some extent – a doctor looks for the best way to help the patient sitting in front of them.
But with advances in technology, it is becoming possible to use the most unique of characteristics – our genomes – to tailor treatments for individuals.
Genomes are made up of a complete set of our DNA, including all of our genes, and are the instruction manual on how to build and maintain the 37 trillion cells in our bodies.
Any two people share more than 99% of their DNA. It’s the remaining less than 1% that makes us unique, and can affect the severity of a disease and effectiveness of treatments.
Looking at these small differences can also help us understand the best way to treat a patient for a range of diseases – from cancer and heart disease to depression.
Cancer is the most advanced area of medicine in terms of developing personalised treatments. In the UK, differences in the DNA sequence are being used by the NHS to help doctors prevent and predict cancer. For example, women with an increased risk of developing breast or ovarian cancer have been identified by screening for changes to the BRCA1 or BRCA2 genes.
Mutations in these genes increase a woman’s risk of breast cancer by four-to-eightfold and can explain why some families see many relatives with the disease. A BRCA1 mutation gives women a lifetime risk of ovarian cancer of 40-50%.
Screening has helped women make informed choices about treatment and prevention – for example, whether to have a mastectomy.
It is steps like these – splitting patients into ever smaller groups to identify the best treatments – that is taking us towards personalisation.
- ‘New era’ of personalised cancer drugs
- ‘Dismantling cancer’ reveals weak spots
- Targeted checks ‘prevent 10% of heart attacks’
For certain cancers, measuring gene activity is becoming commonplace. Gene activity is a little like the dimmer switch on a light – it can be set to low, high or anywhere in between.
Measuring this allows us to see how active a particular gene is in a tissue or cell.
In breast cancer, a test measuring the activity of 50 genes in tumours can be used to guide decisions about whether the patient will benefit from chemotherapy.
To extend this approach to other cancers, researchers are switching off all of the genes in hundreds of tumours grown in the laboratory. In doing so, scientists are looking for cancer’s weaknesses – to try to produce a detailed rule book for precision treatment.
The development of personalised medicine
- Genome sequencing is being offered in England to children with rare diseases – and has led to a change of treatment for some
- An 11-year-old became the first patient to use a leukaemia drug called CAR-T, which re-programmes the immune system to fight cancer
- The entire genetic code of women diagnosed with breast cancer is being mapped by scientists in Cambridge
- There are plans to sequence one million genomes in the UK in the next five years
The development of such techniques raises the question: how far can personalisation go?
For illnesses like heart disease, diabetes and infectious diseases, a combination of genetic, lifestyle and life events also play a part. This means that information about small differences in the DNA sequence alone will not be enough to predict susceptibility and outcome.
Measuring the activity of our genes also captures information about current stresses to the body. For example, certain genes will have a higher or lower activity depending on the type of infection.
Yuvan Thakkar, 11, is the first to receive a drug called CAR-T.
His mother, Sapna, said: ‘This new therapy is our last hope’
Looking at gene activity could also provide important clues as to how to best treat a patient.
One life-threatening illness where these techniques could help is sepsis.
It is a condition in which the immune system damages its own organs when trying to fight an infection. Anyone can develop sepsis and it kills 52,000 people each year in the UK – more than breast, bowel and prostate cancer combined. Worldwide, a third of patients who develop sepsis die.
To save lives, general antibiotics are given first to reduce the infection. A blood test is done to find out which particular bacteria have caused the sepsis, so a more targeted antibiotic can be given. But these blood tests take precious time and cannot always identify the bacterium causing the infection.
In our research, we are looking at gene activity in sepsis patients’ immune systems, to give us clues as to why different people respond in different ways.
We hope to pinpoint which part of their immune systems are not working properly – helping doctors decide how other drugs could be used.
This demonstrates how personalised medicine could be used for short-term treatment in intensive care, as well as for longer-term illnesses like cancer.
About this piece
This analysis piece was commissioned by the BBC from an expert working for an outside organisation.
Note: In order to respect the privacy of the patient, his/her identity will not be revealed.
I was diagnosed with terminal bowel cancer in March 2018. I started radiotherapy, which worked well. The tumour then started to cause a build up of fluid in my abdomen, which chemotherapy helped to reduce. However, when the first line chemotherapy stopped working after 5 months and then the second line chemotherapy failed to work at all, the fluid returned and I had two stays in hospital to help drain it.
Having exhausted standard therapy and become bedbound, I found out about the Oncofocus Test from an online search. The overall process from submitting the form to Test results was easy and rapid. The company called to talk me through the process and to explain the results of the Test, and also took care of the logistics of collecting the sample from the hospital. It turned out that I have a rare cancer mutation and was lucky to have had a response at all to the initial chemotherapy.
I had a remarkably effective and rapid response to the drugs that the Test recommended for my cancer mutation. After just 2 weeks of treatment, my abdomen returned to normal size. After 4 weeks of treatment, I was swimming, walking and fully enjoying all that life has to offer again. I am truly grateful for the significant improvement in quality of life I experienced, especially as I had no side effects from the new drugs. The extra months that this gave me meant that I had further quality time with my family and could prepare them better for life without me.
The results of a new study, underscoring the value of precision medicine in advanced sarcoma, showed that patients with heavily pretreated sarcoma who received treatment in accord with their mutational profile attained better outcomes than patients who did not (Abstract 11018). Most notably, median overall survival reached 22.1 months for patients treated with agents targeting mutations identified by genomic profiling, compared with 15.5 months for patients who received treatment unguided by genomic profiling (HR 0.70, 95% CI [0.50, 0.98]; p = 0.031).
“Drug development in sarcomas remains challenging, with few effective U.S. Food and Drug Administration–approved therapies,” lead investigator Shiraj Sen, MD, PhD, of the Sarah Cannon Research Institute, said. “Fortunately, recent genomic analyses have revealed many potentially actionable mutations across sarcoma subtypes. However, the actionability of these potential driver mutations remains unclear, and whether patients enrolled on genomically matched early-phase trials have improved outcomes over patients enrolled on nongenomically matched trials remains unknown.”
To clarify the value of genomic profiling in sarcoma, the investigators leveraged clinical data and next-generation sequencing information for 406 patients with advanced disease who were treated within phase I trials at The University of Texas MD Anderson Cancer Center over a 12-year period (2006 to 2018). Patients had received a median of three prior lines of therapy (range, 0 to 9) before being enrolled in a phase I trial, and collectively they featured a diverse array of soft tissue sarcomas (e.g., leiomyosarcoma, 16%; liposarcoma, 13%; gastrointestinal stromal tumor, 11%; and synovial sarcoma, 3%) and bone sarcomas (e.g., osteosarcoma, 8%; chondrosarcoma, 7%; and Ewing sarcoma, 6%).
Within the 406-patient cohort, 23% of patients had potentially actionable alterations identified through next-generation sequencing and were enrolled in clinical trials of genomically matched therapies. The remaining 77% of patients who participated in nongenomically matched trials served as the comparator group.
The results revealed no difference in the objective response rate for patients who were and were not matched to treatment based on their genomic profile (11% vs. 6%, respectively; odds ratio [OR] 1.97, 95% CI [0.88, 4.44]; p = 0.10). However, significant differences favoring the genomically matched group over the unmatched group were observed for the clinical benefit rate (41% vs. 19%, respectively; OR 2.91, 95% CI [1.77, 4.80]; p < 0.0001), the median time to progression (3.7 vs. 2.7; HR 0.72, 95% CI [0.57, 0.91]; p = 0.0048), and median overall survival (22.1 vs. 15.5 months; HR 0.70, 95% CI [0.50, 0.98]; p = 0.031).
“In our study, while response rates in genomically matched trials were low (11%), occasional responses were seen with experimental therapies targeting alterations such as NTRK, LRRC15, cMET, mTOR, VEGF, MDM2, and FGFR. This suggests that molecular profiling should be considered in metastatic, refractory sarcomas and clinical trial enrollment should be considered for these patients,” Dr. Sen said.
Kara Nyberg, PhD