what paediatrics can teach us - rcp london

The late medical effects of cancer treatments

What paediatrics can teach us

Rod Skinner, Paediatric and Adolescent Haematology / Oncology Unit

& Children’s BMT Unit,

Great North Children’s Hospital and

Northern Institute for Cancer Research,

Newcastle upon Tyne, UK

What we (in paediatrics) have learnt

• Studying late effects after childhood cancer

• (Childhood) cancer survivor cohort studies

Secondary cancers

Cardiac

Frailty

• Long-term follow-up after childhood cancer

Risk stratification

Models of care

Transition

Treatment summary / care plan

• Evidence-based guidelines

European and international collaboration

“late (premature) mortality”

Childhood cancer survivors

• 5 year survival rate of childhood malignancy is

now about 80%

• ~1 in 700 young adults is a survivor

Estimated numbers of five-year survivors alive at the end

of successive calendar years, by attained age in years

Great Britain, 1971-2005

54%

75% 81%

1978-1982 1993-1997 1995-2002

5 year survival rates for CCS in Europe

Studying late effects in childhood cancer survivors

• Late effects often easier to identify in growing

children

• Much longer follow-up

• Childhood cancer survivor cohort studies

• Clinical trials improved survival (with follow-up)

• Relatively small and close-knit international

community

• National groups

CCLG Late Effects Group – since 1980s

NCSI – all centres involved

Radiation oncologists first

noted late sequelae in

1970s

• Growth (bone/soft tissue)

abnormalities

• SMNs



children





community

• National groups



BCCSS

• British Childhood Cancer Survivor Study

• Retrospective population-based UK

childhood cancer cohort study

34,489 five-year survivors, all cancers

Diagnosed at <15 years age 1940-2006

• National or well validated control data

International survivor cohorts

• ALiCCS (Adult Life after Childhood Cancer in

Scandinavia)

• CCSS (Childhood Cancer Survivor Study)

• EKZ/AMC (Emma Children’s Hospital / Academic

Medical Center, Amsterdam)

• PanCareSurFup (PanCare Childhood and

Adolescent Cancer Survivor Care and Follow-up

Studies)

• SCCSS (Swiss Childhood Cancer Survivor Study)

• SJLIFE (St Jude Lifetime Cohort Study)

Survivors of adult cancer

• Teenage and Young Adult Cancer

Survivor Study

• Retrospective population-based teenage /

young adult cancer cohort study

England and Wales

233,081 five-year survivors, all cancers

Diagnosed at 15-39 years age 1971-2006



children





community

• National groups



Clinical trials improve survival



children





community

• National groups



• High prevalence and wide range of late effects

60-75% of long-term survivors have at least 1

chronic medical problem

25-45% have at least 2 chronic medical

problems

25-40% have at least 1 severe, life-threatening

or disabling chronic condition

• Increasing burden with intensive treatment,

longer follow-up (FU), older age attained

• Most very late excess mortality (>20-25 years

FU) is due to late effects rather than relapse

Wide spectrum of “medical” effects

• Secondary malignant neoplasms (SMNs)

• Cardiovascular

• Respiratory

• Gonadal / reproductive

• Renal

• Endocrine

• Neurological / neurocognitive

• Psychological / psychosocial

• Sensory (hearing / visual)

• Metabolic syndrome

• Bone

• Frailty (accelerated ageing)

• ….

Wide spectrum

• Secondary malignant neoplasms

• Cardiovascular

• Respiratory

• Gonadal / reproductive

• Renal

• Endocrine

• Neurological / neurocognitive

• Psychological / psychosocial

• Sensory (hearing / visual)


• Bone

• Frailty (accelerated ageing)

• ….

Chronic Symptoms - Fatigue/ Low energy - Disrupted sleep - Poor memory/concentration - Chronic pain Self-care - Independent living

Education/Vocation - Academic underachievement - Vocational limitations - Under/unemployment - Loss of job/benefits Insurance discrimination - Access to health care Financial/economic - Debt (medical/other) Social Interaction - Family/peer relationships - Social withdrawal/isolation - Intimacy/marriage/family - Cancer-related stigma

Mental Health -Depression/mood disorders - Cancer-related anxiety - Post-traumatic stress Physical/Body image -Weight loss/gain -Loss of organs/tissues

Long-term and Late Effects of Cancer

Fried criteria

• Low lean muscle mass

• Weakness

• Poor endurance

• Slowness

• Low energy expenditure

Male Female

Pre-Frailty = ≥2 criteria documented 12.9% 31.5%

Frailty = ≥3 criteria documented 2.7% 13.1%

Frailty – the emerging concern

Frailty in childhood cancer survivors

Implications of frailty

Frailty was associated with:

• Presence of an existing chronic health condition

• Increased risk of new chronic conditions (RR 2.2) and

death (RR 2.6)

Long-term follow-up

Overall aim – improve long-term health of survivors

Manage existing late effects – many are treatable

Surveillance for potential future chronic toxicities

Better outcomes if detected and treated early

Easier (and less expensive) to prevent / ameliorate chronic

illness than to treat advanced morbidity

Information provision – for survivors, families, carers

Promotes engagement of survivor

Healthy lifestyle choices

Specialist LTFU care – what?

• Multidisciplinary team

• Doctor(s) with experience of late effects

• Specialist nurse(s)

• Other health and social care professionals

• Co-ordination of care (key worker)

• Treatment summary

• Individualised survivorship care plan

• Including transition plan

• Risk stratification

• Education – survivor, family, non-specialists

• Supporting self-management

Risk stratification

• Level 1 – low risk survivors

• Level 2 – medium risk survivors

• Level 3 – high-risk survivors

Characteristics may include: No routine outpatient attendances Information “prescription” and/or an educational intervention Automated surveillance tests with results by post or phone Ability to re access system with/without reference to GP

Characteristics may include: Planned review of care e.g. hospital, community, face to face or phone Clinical examination if required Patients with significant co-morbidities Those who are unable/decline to self manage

Characteristics may include: 20% Complex rapidly changing health Complex treatment complications or symptomatic needs Complex ongoing treatment regimes Other input required e.g. Cardiology, Haematology, Gastroenterology Requiring regular MDT reviews

Differing needs

LTFU care – how? Models of care

• Level 1 – low risk survivors Self-management in primary care

• Level 2 – medium risk survivors Several options including nurse-led FU (hospital or

community), telephone FU, shared care …

• Level 3 – high-risk survivors Hospital-based LTFU clinics

• Ability to move between levels and re-access

specialist LTFU service as appropriate

Treatment summary / care plan

Transition – what?

30

Transition – how?

• Transition policy

• Transition plan

• Timeline

• Treatment summary / care plan

• Health promotion, education, autonomy

• General information

• Multidisciplinary meeting

• Key worker

• Readiness assessment tool

Long-term follow-up

Overall aim – improve long-term health of survivors

Manage existing late effects – many are treatable

Surveillance for potential future chronic toxicities

Better outcomes if detected and treated early

Easier (and less expensive) to prevent / ameliorate chronic

illness than to treat advanced morbidity

Information provision – for survivors, families, carers

Promotes engagement of survivor

Healthy lifestyle choices

Long-term follow-up (LTFU) guidelines

LTFU guidelines

• Improve the quality of care provided

• Improve health outcomes and hence quality of life

• Increase consistency of healthcare decisions and access

to care

Equality

• Stimulate communication and collaboration

Health care professionals

…. and patients

• Eliminate unnecessary components of care and reduce

health care costs

Existing long-term follow-up guidelines …

Guideline themes

• Surveillance for late adverse effects

(PCSF WP6 / IGHG)

• Delivery of LTFU (PCSF WP6) Transition

Models of LTFU care

Health promotion

Completed surveillance guidelines

• Methodology – Kremer, PBC 2013

• Breast cancer surveillance – Mulder, TLO 2013

• Cardiomyopathy surveillance – Armenian, TLO 2015

• Premature ovarian insufficiency surveillance – van Dorp, JCO 2016

• Male gonadotoxicity surveillance – Skinner, TLO (in press)

• Thyroid cancer surveillance – Clement (under review)

Surveillance guidelines under development

• Secondary CNS neoplasms surveillance

• Mental health


• Pituitary dysfunction

• Pulmonary dysfunction

• Ototoxicity

• Vasculopathy (cardiac)

• Renal

• Bone

• Secondary GIT malignancies

• Neurocognitive

Delivery of LTFU

• Transition

Definition – Mulder, EJC 2016

Recommendations

• Transition

• Models of care

• Health promotion

Physical activity

Smoking

Diet / nutrition

What paediatrics has learnt

(or is still learning)

• We should (can) not continue to follow-up all survivors

• We should (can) not work in isolation

• Communication is key

Survivors / families

Colleagues

Acknowledgements and thanks

• PCSF WP6 collaborators

• IGHG collaborators

Including but not limited to: Children’s Oncology Group

Dutch Children’s Oncology Group

Scottish Intercollegiate Guideline Network

United Kingdom Children’s Cancer and Leukemia Group

Nordic Society for Paediatric Haematology Oncology

Japanese Childhood Cancer and Leukemia Study Group

Peter MacCallum Cancer Centre, New Zealand

Children’s Cancer Institute Australia

Numerous individuals

• PanCare

Secondary cancers

Secondary malignant neoplasms

Overall standardised incidence ratio

(SIR) 4x expected

• CNS

• Skin (non-melanoma)

• Digestive

• Genitourinary

• Breast

• Bone

… in middle age

Highest absolute excess risk

(AER) at >40 years age

• CNS

• Skin (non-melanoma)

• Digestive

• Genitourinary

• Breast

• Bone

Cardiovascular

All cardiac events

Date of download: 2/4/2015 Copyright © 2015 American Medical

Association. All rights reserved.

From: Long-term Cause-Specific Mortality Among Survivors of Childhood Cancer

JAMA. 2010;304(2):172-179. doi:10.1001/jama.2010.923

British Childhood Cancer Survivor Study: Percentages of survivors

on hospital follow-up by decade of treatment.

Ca

teg

ory

of S

urv

ivo

rs (

Nu

mb

ers

in

Ca

teg

ory

)

1950-1959

(502)

1960-1969

(1511)

1970-1979

(3425)

1980-1989

(4885)

1990-1991

(614)

Decade of

Treatment

0%

12%

26%

48%

63%

10% 20% 30% 40% 50% 60% 70%

9%

Percentage of number in category who are on hospital follow-up

Lost to follow-up - is it important?

Complex cases - Where do these adults go?

Who coordinates care?

Do they require expert advice?

ALL, allogeneic BMT • Endocrinopathy – adult GHD, insulin resistance,

metabolic syndrome and gonadal failure • Cardiotoxicity • Neurocognitive • cGvHD – obliterative bronchiolitis • Bone – avascular necrosis and osteoporosis • Nephrotoxicity and hypertension • Cataracts • Psychosocial, employment • Potential for (and reality of) SMNs

Expertise, effective triage and coordinated care

• How many centres of

excellence required?

– Who mans them?

• Would virtual MDTs

assist management

– Who hosts them?

• Can this model work

across all ages?

Expertise, effective

triage and management

Specialists

Tumour boards

Survivors

GPs

what paediatrics can teach us - rcp london

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