LATE EFFECTS OF CHILDHOOD CANCER

Kerry Moss, MDConnecticut Children’s Medical CenterAlex’s Lemonade Stand FoundationNovember 16, 2014

Thanks to Alex’s Lemonade Stand!

Today’s Topic: The Late Effects of Childhood Cancer

“Cure is not enough”

----Dr. Giulio D’Angio

Childhood Cancer Today…the Numbers

• Approximately 12,000 Children and Adolescents are Diagnosed with Cancer Each Year in the US• ~46 new diagnosis each

day (2-3 during webinar today)

• One in every 285 Children Develop Cancer by the Age of 20

Childhood Cancer Today…the Numbers

• On Average, 1 in every 4 Elementary Schools has a Child with Cancer

• The Average High School has Two Students who are Childhood Cancer Survivors

• Cure Rates Today are > 80%

• Estimated 4800 children each year will be long-term survivors

Distribution of Childhood Cancer in the US

Lymphoma

11%

Kidney

6%

Bone

5%

CNS

20%

Leukemia

32%

Sarcoma

7%

Other

11%

Neuroblastoma

8%

SEER Data, 1975-95

7

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10

20

30

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50

60

70

80

90

1960 1970 1980 1990 2000 2005

Year

% r

ela

ps

e f

ree

1950’s: ~10-20%

2014: >80%

1950s

1960s

1970s

1980s

Childhood ALL: Dramatic Survival Improvements

Pui, NEJM 1995; 332: 1618

How Did We Get From There to Here?

• Earlier detection/improved modalities• CT

• Improved disease understanding• MRD/Minimal residual

disease

• Targeted therapies• TKIs/Tyrosine kinase

inhibitors

Our Current Approach to Childhood Cancer

MinimizeToxicities

Maximize Cure

The Facts on Childhood Cancer Survivorship

• 1 /10 Cancer Survivors < 40 yo

• 379,112 Childhood Cancer Survivors are Living in the US Currently

• 1 of Every 539 Young Adults (Ages 20-39) is a Childhood Cancer Survivor

The American Cancer Society's publication,

Cancer Facts & Figures 2014.

The Facts on Childhood Cancer Survivorship

• Less than 25% of Survivors Obtain FU By Cancer Centers

• Documented Barriers to Care Include:• Historical Lack of

Emphasis/Importance• Survivors Prototype• PTSD/Anxiety s/p Cancer

Treatment

The Advent of Survivor Clinics and Survivor Focused Care

• First Survivor Clinic Started at CHOP in 1983

• Currently 42 National Clinics• 13 CONNECCS Members

• CCSS• NIH Funded The LTFU Study• Started in 1994• 20,000 Identified/13,000 Participated

Survivors Between 1970 and 1986

• NCI 1996~Office of Cancer Survivorship

The Shift of Focus to Survivorship

• Survivorship Has Entered Into Politics, Pop-Culture & Sports

• Livestrong Democratic Cancer Forum

• “I’m Too Young For This”• Lauded by Time as one of the Best

Websites

How Do We Define Survivorship?

Clinical

• An individual at least 2-5 years off therapy for childhood or adolescent cancer

Research

An individual diagnosed with cancer at age less that 21 years, surviving five years from date of diagnosis without evidence of persistent cancer

Office CancerSurvivorship NCI

• “An individual is considered a cancer survivor from the time of cancer diagnosis, through the balance of his/her life”

What Defines the Survivorship Experience?

• Family experience during treatment (family factors, medical history, supportive services)

• Combination:• Long-term effects of illness

• Long-term effects of treatment

• Personal, social and cultural meanings associated to survivorship

• …No two survivors are the same!

What Contributes to Late Effects?

• Cancer/Tumor Type

• Treatment Modalities

• Individual Patient Genetics

• …No two survivors are the same!

The Different Modalities of Childhood Cancer Therapy

Surgery

Chemotherapy

Radiation

Bone Marrow Transplantation

…Each Modality Has Different Acute

And Late Side Effects

..

Kenney, in Nathan and Oski, Copyright © 2010 Elsevier Inc. All rights reserved.

Treatment Associated Late Effects

The Heart of the Matter…the Cardiac Late Effects

• Chemotherapy (Anthracyclines) Can Lead to Heart Cell Damage Causing heart weakening (heart failure)• Many Risk Factors• Echocardiogram• Medical management & Lifestyle Modifications

• Radiation to the Chest/Neck Can Lead to plaque build up (atherosclerosis) • Dose Dependent• Blood Test• Medical Management and Lifestyle Modifications

Take My Breath Away…Pulmonary Complications of Cancer Therapy

Chemotherapy (Bleomycin) Can Lead to Lung Scarring• Dose Dependent

• Chest Xray/Pulmonary Function Tests

• Medication Management and Lifestyle Modification

Fertility Concerns in Childhood Cancer Survivors

• Males: Chemotherapy (AlkylatingAgents) and Radiation Can Decrease Sperm Production and Function

◦ Sperm Analysis◦ Proactive Cryopreservation/Reproductive

Counseling/Adoption

• Females: Chemotherapy and Radiation Can Lead to absence of menses/decreased ovarian function

◦ Laboratory/Ultrasound Confirmation◦ Reproductive Counseling/ Adoption

• Offspring do not demonstrate an increased risk of cancer!!!• Green et al (CCSS)

• 4029 pregnancies in 1915 survivors • No evidence of adverse outcomes

• Genetic predisposition is the exception• Wilm’s Tumor, Retinoblastoma, Li-

Fraumeni

The Offspring of Childhood Cancer Survivors

Endocrine Late Effects

• Obesity

• Thyroid Disease

• Osteoporosis

• Growth Hormone Deficiency

Risk: Chemotherapy (Alkylating Agents and Epipodophyllotoxins) and Radiation Therapy

Most Common/Most Preventable: Skin Cancers

Less Common: Secondary Leukemia, Colon Cancer, Breast Cancer

Hodgkin’s Disease Survivors~Breast Cancer

Secondary Malignancies in Childhood Cancer Survivors

More Than Just Medical…The Psychosocial Issues

• Approximately 25% of Childhood Cancer Survivors Experience some form of depression/anxiety

• Post-traumatic Stress Symptoms in 5-20%

• 30% Report Issues 20-30 Years After Treatment

Educational Concerns

• Radiation to the Brain and Certain Chemotherapies Can Affect Learning

• Radiation Leads to Short Term Memory Loss Causing School Decline

• School Absence, Avoidance and Peer Interactions Can Lead to Decreased Performance

• Risk Taking Behaviors Can Lead to School Performance Decline

• Resources school system dependent

Insurance Issues• Long term medical expenses due to late effects may

result in more out of pocket expenses

• Late effects may result in more missed days of working with loss of job and health insurance

• Good news – most pediatric cancer survivors have some form of health insurance

Where is the Silver Lining…It is important to put our findings into context…

“Cancer is a deadly disease and to cure it often requires fairly toxic therapy. Because children and teens have organs still in the growing stage, they're particularly vulnerable to the effects of these therapies, so it's

common to see chronic health problems years after.

The silver lining, however, is that cancer survivors need to realize that some of these conditions can be prevented, and many can be reduced in

severity,“

~Kevin Oeffinger, MDNEJM 2006

The Positive Side of Survivorship

• “Positive Benefit Finding”• Positive Changes in Focus• Reordering of Life Priorities• Strengthened Relationships• Increased Resilience• Renewed spirituality/religiosity• Greater Appreciation of Life• Overall, Childhood Cancer Survivors Exhibit

Lower Levels of Aggression, Antisocial Behavior and Substance Abuse

• Fear of Late Relapse >>>> Reality

• CURE = 5 years

• Highly Variable by Disease and Treatment Modalities

• Historical Reality

What We Know About Recurrent Disease in Survivorship

0

10

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50

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70

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90

1960 1970 1980 1990 2000 2005

Year

% r

ela

ps

e f

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1950’s: ~10-20%

2014: >80%

• 5-year survivor cumulative incidence of recurrent disease:• 4.4% at 10 years• 5.6% at 15 years• 6.2% at 20 years

• Cumulative incidence varies by diagnosis

• Greatest Risk: earlier treatment era

Late Recurrence in Pediatric Cancer: A Report From the Childhood Cancer Survivor Study

Karen Wasilewski-Masker,

JCNI, 2009

• Research, Research, Research

• Minimize Toxicities/Alter Therapies

• Develop Novel Approaches

• Paradigm Shift To Prevention/Early Detection of Late Effects

• Education, Education, Education…Healthy Living Focus

What Are We Doing to Minimize Late Effects and Relapses?

Next Steps For Survivors/Parents

• Participate in a Survivorship Clinic

• Re-establish care with Primary Care Physician• Transition to Adult PCP

• Serve as an advocate for yourself/your child

• Ask Questions

• Empower Your Survivor/ Yourself

STAR Clinic at Connecticut Children’s Medical Center• Multidisciplinary Clinic

• One time vs annual

• Each Patient Evaluated by:• Pediatric Oncologist• Social Worker• Nutritionist• Nurse Educator• +/- Endocrinologist

• 2-3 hours long• Passport for Care

created/distributed

Components Of Successful Long-term Follow-Up

•Prevention

•Surveillance

•Intervention

•Coordination

From Cancer Patient to Cancer Survivor: Lost in Transition

(Institute of Medicine 2005)

Resources…

“Help, I Need Somebody…Not Just Anybody”

~The Beatles

• American Society of Clinical Oncology• www.cancernet.org• Patient website from the American Society of Clinical Oncology. Provides

information on cancer type, coping, and survivorship issues.

• Children's Oncology Group• www.survivorshipguidelines.org• Long-term follow-up guidelines for survivors of childhood, adolescent and

young adult cancers

• Oncolife/Oncolink• www.oncolink.org

Oncolife’s on-line survivorship care plan tool. Included is patient education and resources for cancer survivors

• LIVESTRONG foundation• www.livestrong.org• 1-866-673-7205• SurvivorCare offers one-on-one support for counseling, local resources,

financial, insurance, job concerns and discussing your cancer. Website offers patient education, support and advocacy.

Resources

• National Cancer Institute• www.cancer.gov• 1-800-4-CANCER

• Information on physiological and psychosocial effects, clinical trials, caregivers.

• Facing Forward Series: Life After Cancer Treatment

• American Cancer Society• www.cancer.org• 1-800-ACS-2345• Information, education, support and local resources. Cancer Survivor’s Network provides

on-line community for survivors to share their stories, use discussion boards and chat rooms to meet other survivors.

• National Coalition for Cancer Survivorship• www.canceradvocacy.org• 1-888-650-9127

• NCCS provides education resources, such as A Cancer Survivor's Almanac: Charting Your Journey, the Cancer Survival Toolbox and a patient resource guide.

Resources

Finally…the Take Home Reminders

We Have Come a Long Way, Baby!

Late Effects are the Price We Pay for Curing Cancer…Thankfully an Ounce of Prevention is Worth a Pound of Cure

Today’s Treatment Modalities Take Into Consideration Toxicities/Late Effects

Individuals Vary Greatly in Their Response to Disease and Treatment…Late Effects are Not “One Size Fits All”

Thanks to you for Being Here Today!

“I’m Sorry for You…I’m Sorry for You that You Do Not Believe in Miracles”

~Lance Armstrong