‘CURE IS NOT ENOUGH’

LONG-TERM FOLLOW-UP FOR

CHILDHOOD CANCER SURVIVORS

AZIZA SHAD, MD
AMEY DISTINGUISHED PROFESSOR OF NEURO-
ONCOLOGY AND CHILDHOOD CANCER
DIRECTOR, PEDIATRIC HEMATOLOGY ONCOLOGY,
BLOOD AND MARROW TRANSPLANTATON
LOMBARDI CANCER CENTER
GEORGETOWN UNIVERSITY HOSPITAL
 CHILDHOOD CANCER SURVIVORS
STATISTICS
 Today, almost 80% of all children and adolescents
diagnosed with cancer are surviving more than 5
years, majority are cured
 Currently, there are more than 300,000 childhood
cancer survivors in the USA
 1:1000 adults younger than the age of 45 years,
and 1:570 adults between the ages of 20 – 34 years
is a cancer survivor
 There are almost 100,000 childhood cancer
survivors in college today
 AND THE NUMBERS ARE GROWING!
 FOLLOW-UP CARE FOR CHILDHOOD
CANCER SURVIVORS

 Why should we provide follow-up care for

childhood cancer survivors as they become
adults and for years beyond that?
 TREATMENT IS NOT WITHOUT COST!

 Numerous studies have confirmed that childhood

cancer survivors are vulnerable to complications
related to their cancer or its treatment
 Chemotherapy
 Radiation therapy
 surgery
 Some complications can be identified early during
treatment and follow-up
 Majority of late effects of treatment become
apparent many years after treatment is finished
 SOME SOBERING FACTS

 Children treated in the 1970’s – 1990’s

 75% will develop a chronic disease by 40 years of
age
 Over 40% will develop a serious health problem
 The absolute excess risk of premature
death from
 Second malignancy
 Cardiovascular disease
 Pulmonary disease
Significantly elevated beyond 30 years from
diagnosis
 EXAMPLES OF LATE EFFECTS IN CHILDHOOD
CANCER SURVIVORS
 Heart disease after treatment with anthracycline
chemotherapy or chest radiation
 Learning disabilities in leukemia and brain tumor
survivors treated with radiation and /or
chemotherapy to the brain
 Breast cancer at an early age in female survivors of
Hodgkin lymphoma who received radiation to the
chest in their teens
 Post traumatic stress syndrome in survivors and
parents
 Infertility and premature menopause from radiation
to the abdomen and pelvis for sarcomas
 Chronic pain and fatigue
 THE FUTURE LOOKS BETTER

 Therapy for childhood cancer has evolved

over the years
 Goal of treatment in 21st century
 Improve cure rates
 Decrease the risk of long-term sequelae
 Anticipated result
 ↓ frequency and severity of side effects
 Proactive, risk-based care and healthy
lifestyles will further reduce the severity of
the side effects
CHILDHOOD CANCER SURVIVOR STUDY
(CCSS)
 Largest, most comprehensive, NIH funded,
epidemiological research ‘Long Term Follow-up
Study’ in USA
 17,308 childhood cancer survivors
 Treated between 1970 -1986
 From 26 largest pediatric oncology institutions
 Less than 21 years of age at diagnosis
 Survival of more than 5 years from diagnosis
 Compared the health status of 10,397 adult
childhood cancer survivors to 3034 siblings
 Almost 75% of survivors had at least one chronic
health condition 30 years after diagnosis
CHILDHOOD CANCER SURVIVOR STUDY
(CCSS)
 Late Effects
 Growth and development
 Linear growth, intellectual function, sexual
development
 Vital organ function
 Heart, lungs, thyroid, kidneys, liver, immune system
 Fertility and reproduction
 Second malignancy
 Psychosocial issues
 Post traumatic stress syndrome
 Early mortality
 LATE EFFECTS MOST SURVIVORS
COMMONLY HAVE QUESTIONS ABOUT

 Neurocognitive dysfunction

 Cardiovascular disease

 Infertility and gonadal dysfunction

 Psychosocial problems
 NEUROCOGNITIVE ISSUES

 Range from mild cognitive deficits to major

learning disabilities
 Children with brain tumors and ALL most
susceptible
 Difficulties also seen following SCT or
radiation for tumors of the head and neck
 Disabilities necessitating special education
have been reported in 8 - 50% children
 difficulty in reading, spelling, arithmetic
 impairment of attention and memory
 processing speed
 visual perceptual motor skills
DEVELOPMENT - DEPENDANT LATE EFFECTS

 Cranial irradiation
 timing - < 36 months of age
 dose - > 36 Gy
 this is highest risk group for serious cognitive
impairment and neurological sequelae
 Chemotherapy alone
 Methotrexate, high dose Ara-C, corticosteroids
 Worsening academic performance is related to a
reduced rate of skill acquisition
 Become more evident as children transition to
middle and high school
 RADIATION EFFECT ON GROWTH

 Early onset of puberty

 Direct inhibition of vertebral growth

 following spinal radiation > 35 Gy
 ultimate short stature

 Growth retardation after chemotherapy is

usually temporary
 CARDIOVASCULAR DISEASE

 The developing cardiovascular system is

very vulnerable to cancer therapy

 Exposure to anthracyclines
 Asymptomatic cardio toxicity
 Cardiomyopathy, LV dysfunction, CHF

 Mantle radiotherapy
 Coronary and carotid artery disease
 ASYMPTOMATIC CARDIOTOXICITY (A-CHF)

 Cohort study of 831 survivors treated with

anthracyclines
 Estimated risk of (A-CHF) 20 yrs after the 1st
dose
 9.8% for subjects receiving > 300mg/m2

 Other risk factors

 Female sex
 Younger age at treatment
 Higher cumulative doses of anthracyclines
 Radiotherapy involving the heart region
 FERTILITY AND GONADAL DYSFUNCTION

 Males
 Sterility can occur
 following a dose of 10 g of cyclophosphamide
 low doses of radiotherapy (200 - 300 cGy)

 Females
 Ovaries are relatively resistant to chemotherapy-
induced damage
 They are sensitive to radiation
 pubertal delay and premature ovarian failure
 osteoporosis and early coronary artery disease
 age at treatment is significant
 PREMATURE OVARIAN FAILURE

Risk factors for Premature Ovarian Failure

 age between 13 and 19 years at time of treatment
 high dose chemotherapy including alkylating agents
 whole abdominal radiation (22 - 30 Gy) for Hodgkin’s
disease, Wilm’s tumor or other solid tumors
 cranial irradiation

 highest risk factor - total body irradiation in

preparation for BMT
 100% patients over 10 years of age and 50% under the
age of 10 will develop premature ovarian failure
 PSYCHOLOGICAL ISSUES

 Childhood cancer survivors are more likely to

present with
 Mental health disorders
 Chronic pain
 Fatigue

 One fifth suffer from PTSD

 Can emerge months to years after treatment
 May be associated with anxiety and other
psychological stress
 MISSION OF A LONG TERM FOLLOW-UP
PROGRAM
 To follow survivors carefully for anticipated
late effects
 To educate survivors about their cancer and
its treatment
 To provide education on risk taking
behaviors, healthy life styles, fertility,
employment and health insurance issues
 To transition them to adult programs as
they become older
 All patients 2 years off therapy qualify for a
LTFU program
 HISTORICAL PERSPECTIVE ON LONG
TERM FOLLOW-UP CLINICS
 1960 to mid – 1980’s, little information was
available on long term health of cancer
survivors
 Most survivors treated during that period
were discharged from care 5 -10 years off
therapy
 Were never seen back in a children’s
hospital or cancer center
 HISTORICAL PERSPECTIVE
 Early 1980’s – very few long term follow-up (LTFU)
programs for survivors
 Primarily to document and report any late effects of
treatment
 With increase in awareness of late effects,
institutions started developing LTFU programs
 USA: most COG institutions have a LTFU program
for children
 Hardly any Transition Programs are available
 Ontario, Canada: the only province with a
coordinated system of care for both, pediatric and
adult survivors of childhood cancer
 Netherlands: all pediatric oncology centers have a
LTFU program for children
 DELIVERY OF SURVIVOR HEALTH CARE

 Long Term Follow-up Programs

 Backbone of care for pediatric cancer survivors
 Based at Children’s hospitals or Cancer Centers
 Team: MD, NP, SW, Psychologist
 Multidisciplinary Network

 Core Components
 Cancer summary and plan
 COG Long Term Follow-up Guidelines
 Delivery of risk based care
 TRANSITION PROGRAMS

 As childhood cancer survivors become

young adults, they need to be transitioned
from the sheltered environment of
pediatrics to the independent environment
of adult medicine
 MODELS OF CARE

 Specialized Long Term Follow-up Clinics

 Multi-disciplinary teams provide life long follow-
up at pediatric oncology treatment centers
 Relationship established with primary health care
provider in community
 Annual comprehensive follow-up at pediatric
facility
 Routine health care needs with primary health
care provider
 Complete treatment summary provided to
primary MD and close communication
maintained between the two services
TRANSITION FOLLOW-UP PROGRAMS

 Formalized transition programs for adult

survivors of childhood cancer

 Children’s Hospital of Philadelphia and Live Well

After Cancer program at University of PA

 Children’s Memorial Hospital, Chicago

transitions to STAR (Survivors Taking Action and
Responsibility) Program at Northwestern
University
 OTHER MODELS OF CARE

 Adult Oncology Directed Care

 Monitoring for disease recurrence is easy
 Unfamiliar with late effects of multi-agent chemotherapy
and radiation given to children

 Community Based Care

 Care provided by primary care provider – internist, family
practitioner
 Maintains ongoing communication with pediatric oncology
treatment team
 Limited access to sub-specialists
 Survivor may eventually lose contact with oncology team
 RISK-STRATIFIED SHARED CARE MODEL

 Integration of primary care physicians (PCP)

into this model
 Survivors are stratified into 3 groups based
upon their risk of late effects:
 Low risk group:
 Surgery only, no radiation, minimal
chemotherapy
 Following 1st LTFU clinic visit, patient is
transitioned to PCP with summary of treatment
 LTFU clinic staff communicates with PMD every
3-5 years to get updates
 RISK-STRATIFIED SHARED CARE MODEL

 Moderate risk group:

 No radiation, low or moderate dose
chemotherapy with alkylating agents,
anthracycline, bleomycin or epipodophyllotoxin
 Annual follow-up in LTFU clinic for 5 – 10 years
 Education on healthy lifestyles provided
 Monitoring for late effects and recurrence
 Transition to PMD with updated treatment
summary and surveillance plan
 LTFU clinic staff communicates with PMD every
year to get updates
 LTFU program also serves as a ‘consult service’
 RISK-STRATIFIED SHARED CARE MODEL

 High risk group:

 Any radiation, high dose chemotherapy with
alkylating agents, anthracycline, bleomycin
or epipodophyllotoxin, SCT
 Followed only at LTFU program
 Continued communication with PCP
regarding new health problems
 PCP remains involved for non-cancer care
 CANCER SURVIVORSHIP PROGRAM
LOMBARDI CANCER CENTER
 Established 5 years ago
 1 oncologist
 Off-therapy summaries
 Expanded to fully staffed program 2 years
ago
 Grant from Children’s Cancer Foundation and
Hyundai Motor Cars
 Support from patient families
 CANCER SURVIVORSHIP PROGRAM
LOMBARDI CANCER CENTER
 Team
 Oncologist
 Nurse practitioner
 Social worker
 Art Therapist
 Neuropsychologist
 Psychologist
 Multidisciplinary sub-specialist team
 CANCER SURVIVORSHIP PROGRAM
LOMBARDI CANCER CENTER
 Achievements
 Health Behaviors Study
 CD-ROM on Late Effects
 3 conferences on Late Effects
 2002 –Local meeting
 2006 – Regional conference “Rise to Action”
 2008 – Regional conference “Rise to Action II”
 Bridges Art Therapy Project
 Manual for Childhood cancer survivors
 ‘The Next Step….Crossing the Bridge to Survivorship’
 Education for primary care givers
 CANCER SURVIVORSHIP PROGRAM
LOMBARDI CANCER CENTER

 Current Model of Care

 Specialized Long Term Follow-up Clinic
 ‘Shared Care’
 Partner with primary health care providers

 Planned Model of Care

 Formalized Transition Program with Adult Oncology
Department at Lombardi Cancer Center
 ‘Shared Care’
 Partner with primary care providers
 SUMMARY

 Late effects of therapy are frequent and

serious
 Proactive and anticipatory risk-based care
can reduce the frequency and severity of
treatment based morbidity
 The primary care physician should be an
integral partner in risk-based care of
survivors