Implementing prevention AYA survivors

Department of SurgeryDivision of Public Health Sciences

Reid R. Sacco Adolescent & Young Adult (AYA) Cancer Program

4th Annual LectureDr. Graham ColditzNovember 3, 2017

Implementing prevention to reduce incidence and improve outcomes in AYA survivors

Reid R. Sacco Adolescent & Young Adult Cancer ProgramTufts Cancer Center Friday Nov 3, 2017

Graham A. Colditz, MD DrPH, FAFPHM



Disclosure Information

I have no financial relationships to disclose

I will not discuss off-label use or investigational use of drugs or devices in my presentation


"Aerial view of Sydney Harbour - the bridge is under construction” by Photographic Collection from Australia - Aerial view of Sydney Harbour –the bridge is under construction. 1923


Time frame

• Harbour Bridge

• Opera House

1400 men

15 years

• 8 years

Projected cost 1957 $7M • Final cost $102M when opened in

1973



Goals of talkReview potential for implementation science to improve outcomes and prevention

Issues: • Improving cancer prevention, • Implementing what we know, • Identifying levels for interventions: patients, providers, and systems• What needs to be done to achieve desired effects• Clarifying our time frame for translation of research to practice

Shared understanding of what implementation science is


Long history of accepting preventionPott P, SCC scrotum described in chimney sweeps based on clinic experience 1775

• Chimney Sweeper’s act of 1788 passed by Parliament preventing employment of children under 8; age then increased until 1875 use of young climbing boys forbidden

Cook J. Capt. 1768 -1780• 3 voyages, 3 men lost to scurvy cf standard 50%• British navy adopted citrus in 1795

Smoking cessation reduces cancer, heart disease, stroke, etc

Given this type of evidence why do we still take so long to get from discovery to delivery?

We must speed up implementing prevention



Medical interventions proven to prevent cancer (Sci Trans Med 2012)

Intervention Target Magnitude of reduction

Time (yrs)

Aspirin Colon mortality 40% 20+SERMs Breast incidence 40-50% 5+Salpingooophorectomy

Familial breast caBRCA1/2

50% 3+

Screening for colorectal ca

Colon ca mortality 30-40% 10

Vaccination Cervical ca incidence

50-100% 20+

Liver ca incidence 70-100% 20+Mammography Breast ca

mortality30% 10-20

Serial CT lung Lung ca mortality 20% 6+


Balancing approachesLynch syndrome –Moonshot priority• 1M in USA have Lynch

syndrome, <5% aware• 7,000 CRC cases caused

by Lynch syndrome each year

• Balance against 80% by 2018 national screening call to action,

• 200,000 fewer CRC deaths by 2030


Meester 2015

200,000 fewer CRC deaths within 20 yrs


Behavioral, Social, and Policy interventions that impact Cancer PreventionIntervention Target Type of Ix Evidence

review

Reduce tobacco use

Children and Adolescents

Smokers to quit

Combined Pharmaco/behavioral IxsSmoke-free policiesTobacco taxes

Surgeon General

Increase physical activity

Individuals and community norms

Urban designStairs and workplace

Surgeon General

Reduce Obesity Population School & work environmentPhysical activityFood & beverage

IOM report 2012

Limit alcohol intake Population Taxes WHO

Reduce UV exp Children, AYA All of above WHO


When we implement what we know, we prevent cancerTobacco –lung cancer mortality decreased by one third

• Adolescent smoking decrease 35% (1999) to 18% (2011)

Colorectal cancer screening –steady increase in use and reduction in CRC mortality over time


Burden of AYA cancers

• 70,000 cancer cases diagnosed each year ages 15 to 39 years of age

• This is 6 times greater than new cases children 0 – 14 • For ages 25 to 39 breast cancer and melanoma are the

leading diagnoses

• Contrast strategies to prevent melanoma (well known); premenopausal breast cancer – only high risk strategy with limited uptake


Message

• Avoid too much sun.

• Skin damage starts early in childhood, so it’s especially important to protect children.


Tips• If UV index is above 3 protection is needed.

Avoid direct sunlight between 10:00 a.m. and 4:00 p.m.

• Use hats, long-sleeve shirts, and sunscreens with SPF15 or higher, broad spectrum.

• Don’t use sun lamps or tanning booths.


Summary of evidence: Adolescent exposures relation to risk of BBD and breast cancer

Lifestyle Relative Risk BBD Breast Cancer (premenopausal)

Alcohol

Peak Growth Velocity

Height

Nuts

FiberCarotenoids Fruit and veggies

Vegetable protein

Family history

Physical activityColditz Bohlke Berkey Br Ca Res Treat 2015, Colditz & Bohlke 2014


Increasing burden of new cancer cases under age 50, USASEER data summary available on line… ages 20 to 49

Significant increasing age-adjusted trends 1992 to 2014 for:Pancreas 0.9% /yrColorectal 1.7% /yrMelanoma 1.0% /yr (up to 2005)Testis 1.0% /yrBreast 0.2%/ yr not sig. Myeloma 1.7%/yr (White) and .12% /yr (Black)

https://seer.cancer.gov/


Pancreatic cancer

US incidence 1992 to 2014

Age 20 to 49

Rising incidence 0.9% per year (significant)


Colorectal cancer


Age 20 to 49

Rising incidence 1.7% per year (significant)


Myeloma


Age 20 to 49

Rate increase 1.5% / year since 1975 for whites Increase 2.8% / year overall since 2002


Genkinhger et al 2011

Cohort consortium2135 cases846,340 py

Forest plot of RR for BMI >30 vs 21-22.9

Pancreatic Ca:Baseline BMI


Pancreatic Ca:BMI in early adulthood


All Survivors Grade 3-5 Cumulative Burden By Organ System

Bhaktaetal.Lancet,2017


Cause-specific Mortality Among Aging Survivors

Standardized Mortality Ratio

SMN =15.2Cardiac = 7.0

Armstrong GT, J Clin Oncol,2009


Reduction in Late Mortality Among 5-Year Survivors of Childhood Cancer

Cum

ulat

ive

Mor

talit

y (%

)

0 25 30 352015105Years since diagnosis

0

10

15

5

1970s3.1% (2.7 – 3.5)

1980s2.4% (2.2 – 2.7)

1990s1.9% (1.6 – 2.2)

15-Year Cumulative Mortality

Armstrong GT, N Engl J Med., 2016

Nonrecurrence, Nonexternal Cause


Clinical Heart Failure: CTCAE Grades 3-5

11.8%

6.8%5.0%

0.3%

At 45 Years

Armstrong GT, J Clin Oncol,2013


Modifiable Risk Factors & Major Cardiac Events

Evaluate relative contribution of CV risk factors to development of CHF• Longitudinal evaluation• 10,724 survivors, CCSS• Is risk simply additive?

• Hypertension potentiates anthracycline-associated risk for CHF

• Multiple traditional CV risk factors increase risk

Congestive Heart Failure180160

80

60

40

20

100

0

Rat

e R

atio RR=34.1

HTN,No Anthracycline

RR=8.3

Anthracycline,No HTN

RR=88.5

HTN +Anthracycline

Armstrong GT, et al, J Clin Oncol, 2013


Blood Pressure Status in Survivors

0%

20%

40%

60%

80%

100%

0 5 10 15 20 25 30 35 40 45 50 55 60

Cumulativeprevalen

ce

Age

Expectedbasedonage,sex,race/ethnicityandBMI-specificratesfromNHANES

Cumulative Prevalence of Hypertension by Attained Age in SJLIFE

Gibson et al, Cancer Epidemiol Biomarkers Prev, (in press)

Standardized Prevalence Ratio = 2.6 (1.7-4.7)


Human Papillomavirus Vaccination Rates in Young Cancer Survivors• Recent data from survey AYA survivors 5 Comprehensive Cancer Centers• 982 cancer survivors (9 to 26 years of age; 1 to 5 years postcompletion of

therapy)• Vaccine initiation rates were significantly lower in cancer survivors versus

the general population 23.8% (95% CI, 20.6% - 27.0%) v 40.5% (40.2% - 40.7%)

• Predictors of noninitiation included: • lack of provider recommendation (OR, 10.8; 95% CI, 6.5 to 18.0; P < .001), • survivors’ perceived lack of insurance coverage for HPV vaccine (OR, 6.6; 95% CI,

3.9 to 11.0; P < .001), • male sex (OR, 2.9; 95% CI, 1.7 to 4.8; P < .001), • endorsement of vaccine-related barriers (OR, 2.7; 95% CI, 1.6 to 4.6; P < .001)

Klosky, Hudson et al JCO 2017, Nov 1


Trends in U.S. Vaccination Rates: Ages 13-17 Yrs

Abbreviations: Tdap = tetanus, diphtheria, acellular pertussis vaccine; MenACWY = meningococcal conjugate vaccine; HPV-1= human papillomavirus vaccine, ≥1 dose; HPV-3 = human papillomavirus, ≥3 doses.* Tdap and MenACWY vaccination recommendations were published in March and October 2006, respectively.† HPV vaccination recommendations were published in March 2007.

MMWR Vol 63, #29, July 25, 2014

Tdap

MenACWY

≥1 dose

3 doses≥1 dose

3 doses

Girls

Boys

Tdap*MenACWY†

≥1 HPV (females)3 HPV (females≥1 HPV (males)3HPV (males)

% v

acci

nate

d


Sample, studies addressing uptake HPVAuthor Year Journal Location

and nIntervention Vaccination

Rates/Results

Vanderpool 2010 J CommHealth

USA, rural SE

KentuckyN = 247

Education, free HPV vaccine voucher and

$25 for time

44.9% of women enrolled accepted

Brotherton 2013 Med J Aust

Australia, no n

reported

Governmental school-based vaccination

program, free vaccine

83% initiated, 70%completed

McClure 2015 Vaccine CanadaN = 1443, girls AND

boys

Dedicated school-basedRN, info packet to

parents, free vaccine

Girls: 85% completionBoys: 79% completion


Gaps è Research opportunitiesTarget vaccine: whole population• Convenient dosing current vaccines• Next generation vaccine / broader protection, easier

storage, etc, fewer doses• Oropharyngeal HPV infections and cancer• More effective ways to communicate about HPV-associated

disease and HPV vaccines - to address vaccine hesitancy• Determine how best to integrate HPV vaccination and

cervical cancer screening

President’s Cancer Panel Annual Report 2012-13




High Priority: much is known (p37)

Colorectal screening

HPV vaccination

Tobacco control

Identification of individuals with genetic predisposition to cancer


Moving from Discovery to Delivery

Translation scientific evidence base to population health

• Implementation of what works• Evidence è guidelines (clinical or public health

community)• Benefit estimates è time frame for risk reduction• Disparities è Worsened, improved, or unchanged?

Understanding how to sustain changes


Sustaining change

Target automatic, unreflective processes to sustain behavior change• Alter environment• Target automatic associative processes (activate existing

associations; create new associations, etc)

Marteau et al Science 2012;337:1492-


Why are we not preventing more cancer now?Multiple challenges:1. Skepticism that cancer can be prevented2. Short term focus of cancer research3. Interventions deployed too late in life4. Research focused on treatment not prevention5. Debates among scientists6. Societal factors ignored7. Lack of transdisciplinary training 8. Complexity of implementation

Colditz et al Sci Transl Med 2012: March 28


Definition –implementation science

Scientific study of how to move evidence-based interventions into practice and policy

Includes study of how to sustain changes to improve population health

**NIH program announcement for funding opportunities. PAR 13-055 and PAR 16-238


Implementation OutcomesFeasibility

FidelityPenetrationAcceptabilitySustainability

UptakeCosts

*IOM Standards of Care

Conceptual Model: Implementation Research

What?Evidence Based Practices

How?

ImplementationStrategies

Implementation Research Methods

ServiceOutcomes*Efficiency

SafetyEffectiveness

EquityPatient-

centerednessTimeliness

Patient Outcomes

Clinical/health status

SymptomsFunction

Satisfaction

Proctor et al 2009 Admin. & Pol. Mental Health Services

CONTEXT

CONTEXT

CO

NTE

XT C

ON

TEX

T


Impact evaluation?

Objective: to quantify the impact of using information (risk stratification models) on behavior/decision making of provider or individuals

• Ultimately change in health outcomes• Effectiveness of care• Cost-effectiveness of care

Moons et al Risk prediction models II Heart 2012


What we currently knowWe have established and effective cancer prevention strategies, including:

• Colorectal cancer screening – 50% reduction CRC • HPV and HepB vaccines – 70 to 100% reduction

(cervix and liver cancer)• SERMs – 40 to 50% reduction in breast cancer• Aspirin – 40% reduction in colon cancer• Smoking cessation – 75 % in lung cancer• Avoid adult weight gain, alcohol use, & eat healthy

dietColditz et al Sci Transl Med 2012


Programs for survivors?At Siteman we have slowly evolved a range of services to meet specific needs:• Pediatric late effects and survivor clinic• Reproductive endocrinology, banking harvesting and fertility

assistance• In collaboration with adult oncology enhanced cancer

predisposition genetic counseling and surveillance• Neuro-oncology joint peds and adult clinic for cognitive and

functional interventions/outcomes

• System wide – PROMIS modules being implemented in all clinics


LOGIC MODEL FOR PROGRAM STAKEHOLDERS,W. K. Kellogg Foundation Evaluation Handbook 1998


Community Health Model –applies to cancer prevention


Cancer Prevention Gaps to Fill

• Where do we strengthen science?• How do we sharpen focus: on prevention of

cardiovascular disease, diabetes, and other major complications among cancer survivors

• Speed translation and delivery to all members of society

• Even when program is implemented, research gaps remain to achieve full population coverage and cancer prevention benefits, reducing or eliminating cancer disparities


“In the beginning of every enterprise we should know, as distinctly as possible, what we propose to do, and the means of doing it… We desire to lay the foundation and to mature some parts of the plan. Those who come after us must finish the work.”

William Greenleaf Eliot, co-founder Washington University in St Louis1854



Graham Colditz, MD, DrPHNiess-Gain Professor of Surgery

Chief, Division of Public Health Sciences, Dept. of Surgery

Campus Box 8100660 South Euclid

St. Louis, MO 63110(314) 454-7939

[email protected]©2014

Implementing prevention AYA survivors

Health & Medicine