Prof Owen Smith National Clinical Lead NCCP Child, Adolescent and Young Adult Cancer

Ambitious plans that will see cancer treatment designed around the specific needs of 16 to 25 year olds will improve outcomes and support quality of life for patients, according to Prof Owen Smith, NCCP (National Cancer Control Programme) Clinical Lead for Child, Adolescent and Young Adult Cancer. While initially lagging behind improvements in children and adult cancer survival rates, adolescent and young adult cancers (spanning an age range from 16 to 25) have largely caught up over the past five to ten years.  Aiming however to further improve those rates and implement this ambitious plan, Prof Owen Smith, Consultant Paediatric Haematologist at Children’s Health Ireland at Crumlin and Professor of Paediatric and Adolescent Medicine at UCD, this week reflected on the achievements and looks forward to the new standardised service that will be available across the country.

“If we went back 40 years and looked at the survival rates for children and young adolescents (1 – 15 years) with acute lymphoblastic leukaemia – the commonest cancer in children and adolescents up to the age of 20 -  the survival rate was hovering around 45 – 50%.  It’s now up to 90 – 95%.  That’s staggering."

'Great hope'

“It’s such a positive development that gives great hope.  However,  when you look at the same leukaemia in older adolescents and young adults  (16 – 25 age group) survival rates are not as good.  Two main reasons account for this difference – until recently these patients have been treated on adult chemotherapy protocols which are not as effective but also the biology of the leukaemia in this age group is more aggressive.

“We’ve got to change that – we can’t change the biology, but we can change the treatment and that’s what’s happening.  We are now using a more paediatric approach and are seeing big wins in terms of survival.   Next month we will be opening a new clinical trial in Ireland for patients aged 1 – 45 years with this leukaemia. We will be part of a pan European Consortium ‘ALLTogether” involving 14 countries contributing patients to the trial.

Overall, however Prof Smith is very positive and optimistic:  

“Being an adolescent or young adult with cancer in this country – you are currently getting the same treatment you are getting in Boston or Berlin and your overall outcomes are as good if not better.  But we still need to improve on that – we need to get rid of the toxicities, increase life expectancy and quality.  We need to make that cancer journey better, not just for the patient but for the siblings, the family and friends – make it much nicer than it has been in the past.”

Around 200 children are diagnosed every year with cancer up to the age of 16,  with 180-190 adolescents between 16 and 25 diagnosed every year.  Prof Smith says that these numbers are “not as burdensome as adults so it is very manageable and we can do it in a collaborative cohesive way.  

“AYAs with cancer are a very diverse group. They are not defined simply by their age and distinct biology of their cancer but also in terms of the challenges they face regarding adequate access to age-appropriate cancer care, representation on clinical trials, short and long term physicial health and psychosocial issues.  These include fertility preservation considerations, transition to survivorship care after they complete treatment and psychological care.”

 National Cancer Strategy

Prof Smith notes that the 2017 – 2026 National Cancer Strategy recognised Children’s Health Ireland at Crumlin as the ninth designated cancer centre in the country but more importantly that AYAs with cancer are a unique cancer community and made specific recommendations to address their needs. This new programme will see a state of the art AYA cancer care network delivered locally where possible but centralised when necessary by providing separate facilities and specialist care teams in the new Children’s Hospital and in three of the eight adult designated cancer centres across the country. It will bring together all the relevant experts and allow this collective knowledge, experience and interest to work towards better experiences, better outcomes and better long term quality of life. 

“The new strategy also allows Children’s Health Ireland  (the new National Children’s Hospital) when it moves to the campus shared with St. James’s Hospital to act as a hub in a hub and spoke model for Child, Adolescent and Young Adult cancers. 

“Crucically, for those AYA patients being treated in a specialist centre, they will have all their needs met.  While Multi Disciplinary Team (MDT) meetings in most cancer centres bring together all the relevant experts to diagnosis and advise on a treatment plan, for AYA patients that MDT will have a much wider remit.  It will be asking about their psychosocial needs, their college needs, their fertility issues long term as well as the most appropriate treatment that involves recruitment to a clinical trial.

“The age range for AYA differs across European countries, while the Americans see it from 15 up to 39.  Most of the Europeans have a lower age upper limit. We went with what the French and British do – so for us it’s sixteen up to 24 years plus 364 days.   That’s important from a paediatric perspective because within that group of patients, about 70% of these patients have what we call paediatric centric cancers – cancers like leukaemia, lymphoma (Hodgkin and non-Hodgkin), osteogenic sarcoma, Ewings sarcoma, testicular and then you drift into cervical cancer, melanoma, possibly some bowel cancer and some breast cancer at the upper limit.  So we need to be treating these individuals as neither children nor adults but as their own distinct group.”

According to Prof Smith, the UK record in adolescent and young adult cancer is “exceptional. I have worked closely with the Teenage Cancer Trust over the past couple of decades  - they have funded approximately 32 of AYA units where as an 18 year old with cancer, you go in and are sitting with a 19 year old, watching films, videos, and if you want your boyfriend or girlfriend to come in. An 18 year old doesn’t want to be with their mammy or daddy.  They don’t want to be looking at Bob the Builder on the wall or Today with Maura and Daithi on the television.  They want to be with their peers. 

“As most cancers in AYA population are curable, one question that comes up regularly is what happens to their fertility.  They say to me that I have just been told that they have a 90% chance of being alive and at the Christmas party in 20 years time but they tell me I haven’t said anything about their chances of having their own children. Fertility preservation is a hot topic for cancer survivors and it’s not just in the AYA group.  Even parents are asking that about the younger children.”

 Clinical trials

Another essential area is clinical trial participation: “Currently 65% of our children receiving cancer treatment are on clinical trials.  It’s not higher because a lot of the clinical trials are not open at the moment.

“But when you get to Adolescent and Young Adult Clinical Trials, they drop dramatically.  It goes down to less than 10% and one of the reasons for this is that some trials exclude AYA cancer patients from trial entry on the basis of age – this has to stop.  

“We know that clinical trials are the paradigm – you live longer, your quality of life is better if you are on a clinical trial.  So we are addressing that through the AYA programme.  That’s why CHI are taking charge in a hub and spoke model that will recruit all cancer patients from 0 – 25 years into clinical trials when available and this has been funded by the Health Research Board for the next 60 months in partnership with UCD.

Crucially too, Prof Smith explains that they are looking at clinical trials on an all island basis.  Generally, he says “we know very little about the biology of adolescent and young adult cancers.  We know far more about lung cancer in a 70 year old than we know about a lymphoma in an 18 year old.  We know an awful lot about what’s happening in children too so this particular focus on clinical trials and the investment and involvement will be hugely important and will have significant impact.

“We are going to create this new programme in CHI on St James’s campus when it opens during the first three months of 2024.  There we will be able to take individuals with cancer up to 20 years of age.  The three designated adolescent and young adult centres that we will be nominating shortly  – they will be able to take, as they do at the moment, 16 to 24/25 year olds (one in Dublin, and two outside Dublin, one in the west and one in the south).  We are going to concentrate expertise in oncological medicine and nursing, together with allied health care professionals, especially psychological and social care professionals into these three units.  So every 16 – 24/5 year old will be referred into one these expert centres.  That will allow for a cohesive network of adolescent and young adult cancer units to be established.”  

Speaking fondly of Dr Karen O’Neill currently a Specialist Registrar in Paediatrics, Prof Smith remembers her well when he was treating her for Acute Myeloid Leukaemia in Crumlin 14 years ago.  He also vividly remembers her stating her ambition was to take over his job when she qualified as a doctor.  They are now friends and colleagues.

“Karen is a cancer survivor – she had a lot of chemotherapy to get to where she is.  The question is where does she go next.  She should have regular follow ups.  That is a new area of medicine that I call ‘survivorship medicine’ and is a rapidly developing field as there are so many survivors now.  They are living which is great, but some are coming out with long term toxicities.  If you are a survivor of childhood acute lymphoblastic and you live 50 years you will accumulate around 17 chronic toxicities (compared to seven in normal individuals of the same age) because of your treatment back as a child.  So we want to know how to follow those patients up and also to detect early some of those toxicities and intervene earlier so we can improve quality of life in these survivors.”

Concept of cure

Working with colleagues in UCD and Trinity , Prof Smith says we are “trying to re-define the concept of cure.   Cure to many people is being cancer free in three to five years.  But to me it’s having your fertility preserved, not having these long term chronicities; it’s living a normal life.

“We can do that by changing the drug approach with introducing immunotherapeutics and getting rid of some of the chemotherapy but also by looking at the host genomes of the patient – what genes they have variants in that make them more pre-disposed to toxicities.

“One in every ten of the girls we treat over the age of ten, who are treated for acute lymphoblastic leukaemia, develop bone disease and some have to have some type of joint replacement. This toxicity usually occurs within the first six months of treatment.  So, who are these 10% of patients?

“We can  pick them out at the beginning of their treatment journey genomic analysis. Two to three per cent of our children who are treated for cancer end up with a second cancer so they are genetically pre disposed to cancer and especially after they have had cancer causing agents like chemotherapy.  There is a whole lot of these toxicities and issues where you can get insights by looking at the genomic landscape of their germline and pulling out those gene variants that predict toxicities to a given anticancer drug.”

Stressing the need for ongoing vigilance around symptoms Prof Smith says: “When you are an adolescent or a young adult, you are infallible.  Because these things are rare, you are not mixing with friends who have had cancer.  At my age a lot of my friends have cancer.  So the teens and young adults tend to hide it.”

Recently appointed as the Chair of the European Society of Paediatric Oncology Adolescent and Young Adult Programme (taking up the position in August this year) Prof Smith concludes with his own aspirations of wanting to “spear head a standard plan for the treatment and management of childhood, adolescent and young adult cancers across the European Union.  Hopefully it will go in parallel with what we are going to do with the NCCP across the island of Ireland.”