LATE EFFECTS OF

CHILDHOOD CANCERMariana Kruger

M Med Paed, M Phil, PhD

Paediatrics & Child Health, Faculty of Medicine &

Health Sciences

Stellenbosch University

“Cure is not

Enough!”Dr Gulio D’Angio

Kate Moss

Connecticut Children’s Medical Center

Childhood cancer survival

• Childhood cancer = success story

Current aim of childhood cancer

treatment

Maximize Cure

Minimize toxicity

Background

• 1 in 285 children will develop a cancer

before 20 years of age

• +/- 1000 children diagnosed annually in

South Africa

• Well established treatment centers since

1987

– Known number of Survivors - ?????

Definition of survivorship

• Survivor of childhood cancer 5 years post

treatment for a childhood/adolescent

cancer (Clinical definition)

Childhood cancer survivors

• 72% long term childhood cancer survivors

know their diagnosis and past treatment

• Only 35% know that their serious health

problems were due to childhood cancer

treatmentLandier W, et al. Pizzo & Poplack Section 6

Barriers to Health Care

• Less than 25% of childhood cancer

survivors have adequate follow up

• Reasons

– Historical less emphasis on long term

survivors

– Anxiety or post traumatic stress syndrome

– Poor transition to adult health services

What determine long term

effects?• Cancer type

• Individual patient’s genetics

• Treatment modalities – each with unique

toxicities

– Surgery

– Chemotherapy

– Radiotherapy

– Stem cell or bone marrow transplant

Late effects of childhood cancer

• 75% will suffer a long term effect

– 40% will suffer a significant late effect ranging from

severe to fatal

• Need lifelong surveillance for long term effects

of previous treatments

Landier W, et al. Pizzo & Poplack Section

Auditory long term effects

Auditory screening• Ototoxicity

– Cancer treatment: Platinum-based chemotherapy,

aminoglycoside antibiotics, radiation

– Audiologic evaluation at end of treatment

• Platinum-based therapy

• 30Gy or more cranial irradiation: Ongoing as radiotherapy

can cause progressive hearing loss

• Crucial to identify hearing loss early in young children as

speech is still in development

• Ongoing audiology follow up

• School assistance if hearing impaired

Occular late effects

Occular screening• Occular

– Treatment modalities: Surgery, steroids, radiotherapy

– Cataracts, glaucoma, retinopathy, xeropthalmia,

orbital hypoplasia

– Opthalmoscopic examination – depending on

treatment modality annually when >30Gy

radiotherapy received or every three-years if less

– Visual acuity annually

– School assistance if visually impaired

Dental and oral sequelae

Dental and oral screening• Teeth abnormalities due to chemotherapy

(alkylating agents < 5 years of age) & radiation >

20 Gy to mouth

– Tooth or root agenesis, thinning & shortening

– Micordontia

– Enamel dysplasia

• Mouth complications after head & neck

radiotherapy

– Xerostomia, salivary gland dysfunction

– Peridontal disease

– Osteoradionecrosis if mandible was involved

Neurocognitive sequelae

Neurocognitive sequelae• Cranial radiation & antimetabolite chemotherapy

– Especially young children with brain tumours very vulnerable

for radiotherapy

– Usually 1-2 years post treatment

– Failure to acquire new abilities

– Learning disabilities

• Inattention, slow in processing new information, memory

impairment, verbal impairment

– Receptive and expressive language problems

– Genetic susceptibility

– Annual assessment: Baseline assessment to be repeated at key

transition points and assist with vocational training

Cardiovascular sequelae

Cardiovascular sequela• Anthracyclines specifically

– Direct myocardial toxicity (formation of free radicals)

– Early (1st year of treatment) or delayed

– Cumulative dose <300 mg/m2 less likely to cause damage

– Worsened

• Young age & concomitantly radiation to mediastinum

• Interindividual variability

• Mediastinal Radiation

• Constrictive pericarditis, cardiomyopathy, valvular or coronary

heart disease, conduction abnormalities

Cardiovascular sequela• Management

– Cardioprotection during treatment

• liposomal anthracyclines & cardioprotectants

• Long term – more prone to hypertension, dislipidemia

• Screening recommendations

• Serial echocardiogram – annually to 5-year intervals depending on

cumulative dose of anthracyclines

• Exercise

– Aerobic exercise should be encourages

– Avoid isometric activities

• Weight lifting & wrestling

Pulmonary sequelae

Pulmonary sequelae

• Pulmonary fibrosis

– Mediastinal Radiation

– Chemotherapy

• Bleomycin – dose dependent

• Stem cell transplantation (SCT)

– Major cause of morbidity/mortality

– Restrictive or obstructive lung disease

– Intensity of SCT therapy plus cumulative previous therapy

– Total body irradiation (TBI) – obliterative bronchiolitis,

Pulmonary sequelae

• Baseline pulmonary functional tests & repeated

as clinically indicated

– Repeat if significant surgery is to be done

• Annual assessment for chronic cough or

dyspnea

• Smoking to be avoided at all costs

• Best – preventative: carefully monitoring

cumulative doses during treatment

Kidney sequelae

Kidney sequelae

• Chemotherapy nephrotoxicity

– Acute irreversibly renal failure

– Progressive chronic renal failure

– Renal tubular dysfunction

– Ifosfamide – up to 30% with residual disease: proximal tubular

dysfunction

• 5% significant Fanconi renal syndrome

– Cis-Platinum – Damage to glomerulus and distal tubule

• Radiation nephropathy

– Same as above

– Hyperfiltration injury

– Radiation nephritis lasting 3-12 months post radiation

Bladder sequelae

Bladder abnormalities

• Chemotherapy especially alkylating agents

– Haemorrhagic cystitis

– Bladder fibrosis

– Neurogenic bladder

• Radiation

• Similar with reduced bladder capacity

• Partial cystectomy

• Screening & follow up

– Careful history especially regarding voiding pattern

– Screen for culture negative haematuria (at least 2 occasions) &

refer to nephrologist

– Bladder dysfuntion – Urology opinion

Genitourinary follow up• Monitoring of urea and creatinine with

electrolytes

• Blood pressure monitoring

• Avoidance of nephrotoxic medicines eg

aminoglycosides, ibuprofen

• Sport participation – careful risk/benefit

assessment as certain sport can cause renal

injury e.g. marathon, iron man competitions

Gastro-intestinal sequelae

Gastro-intestinal sequelae

• Radiation

– Enteritis & fibrosis

• Strictures, ulcers, fistulas

• Stomach & small intestine more susceptible

• Liver toxicity

– Veno-occlusive disease & portal hypertension – 6-thioguanine

– Viral hepatitis

– Cirrhosis

• Screening & follow up

– Liver biopsy if indicated clinically

– Monitor for hepatomegaly, malabsorption & icterus

Endocrinology sequelae

Endocrinology sequelae• Thyroid

– Radiation – hypothyroidism

– Physical examination & annual thyroid function tests

• Gonadal function – Radiation, chemotherapy & surgery

related

– Males

• Testis radiation – Azzoospermia

• Infertility - Alkylating agents, heavy metals, dacarbazine, procarbazine

• Surgery can lead to impotence & retrograde ejaculation

– Females – alkylating agents

• Acute ovarian failure – loose ovarian function during cancer treatment

• Premature ovarian failure – early menopause before 40 yrs of age

• Screening – history, physical examination, serum

gonadotrophin levels

Pregnancy

Pregnancy

• In general not more adverse events reported in

successful pregnancies of long term survivors

• Probability of live birth less than for male

siblings

• Radiation to pelvis

– Increased risk of prematurity & low birth weight

– Malposition of fetus

– Threatened labour

– May require high risk obstetric servicesLandier W, et al. Pizzo & Poplack Section

Musculoskeletal complications

Musculoskeletal complications

• Functional & cosmetic disabilities

– Scoliosis

– Avascular necrosis

– Reduced bone mineral density

– Osteoporosis especially brain tumour survivors after radiation

• Screening & follow up

– Scoliosis risk – 6-monthy evaluation during growth spurt in

adolescence

– Diagnostic radiographs

Growth

Growth

• Decreased linear growth

– Brain tumours with >30Gy to hypothalamus & pituitary

gland

– Direct inhibition of spinal growth – radiation

– Chemotherapy induce temporary growth retardation

• Screening and management

– Monitoring serial height and weight

– Growth hormone prior to closure of epiphysis if

indicated

Obesity

Obesity• Body mass index > 30 kg/m2

• Brain tumours and ALL patients

• Insulin resistance – ALL

– Central obesity

– Elevated blood glucose

– Dyslipidemia

– Hypertension

– Pro-inflammatory & prothrombotic state

• Screening & follow up

– Annual follow up with blood glucose monitoring

– Life style management

Second malignancies

Second malignancies

• Therapy-related

– Myelodysplastic syndromes or AML – 2% 15 years after treatment

for ALL , lymphomas or sarcomas

• Alkylating agents & topoisomerase II inhibitor-related type

– Solid tumours

• Breast cancer, lung cancer & thyroid cancer after Hodgkin lymphoma with

radiation to chest or neck

• Radiation related sarcomas

• Melanoma – Stem cell transplantation and retinoblastoma survivors

• Brain tumours – meningiomas or gliomas after radiation to brain

• Nonmelanoma skin cancers

• Genetic susceptibility

– Li-Fraumeni syndrome

Challenges for Health Care

System• Transition of care

– Transfer from paediatric oncologist to adult physician

• No dedicated interesting group of physicians to take over such care

• Education of long term survivors

– Need to recognize their health care problems and seek early

health care assistance

• Adherence to follow up and life style plans

• Permanent and regular updated health care record

Models for long term care

• USA – Passport for Care (NCI, COG &

National Cancer Survivor Study – NCSS)

• EU Survivorship Passport (European

Network for Cancer Research in Children

and Adolescents - ENCCA)

Passport of

Care

• Internet-based tool

• Individualized,

accurate, & timely

health care

information

• Monitoring &

management

recommendations

Challenges for the childhood

cancer survivor• Education

– Learning disabilities

– Difficult placement in appropriate school

environment

– College & vocational training

Challenges for the childhood

cancer survivor• Economic issues

– Cost of health care

• Difficult to access medical care coverage

with high costs due to previous history of

cancer

– Insurance coverage

• Reluctance in issuing life coverage

– Employment – 1.37 times more likely

not to be employed

Recommendation for SA

• Develop electronic “passport of care” for all chronic

diseases in childhood

• Engage with adult physicians to establish health care

pathways for continuing health care and follow up for

childhood cancer survivors in adulthood

• Advocacy with medical aids and insurance

companies to assist survivors

• Engagement with education system to ensure

appropriate education with vocational training

• Advocacy with employers to ensure fair chance in

seeking employment

Needs Team work

Thank your for your attention

Dankie vir u aandag

Nkosi