Children’s Oncology Group Long-Term Follow-

Up Guidelines for Survivors of Childhood,

Adolescent, and Young Adult Cancers

Matt Ehrhardt, MD, MS

Evidence-Based Guidelines for Childhood Cancer

Survivors: A Hybrid Model

EvidenceEvidenceEvidenceEvidence linking linking linking linking

late effects with late effects with late effects with late effects with

therapeutic therapeutic therapeutic therapeutic

exposuresexposuresexposuresexposures

Screening Screening Screening Screening

recommendations recommendations recommendations recommendations

based on based on based on based on expert expert expert expert

clinical experienceclinical experienceclinical experienceclinical experience

Matches magnitude of risk Matches magnitude of risk Matches magnitude of risk Matches magnitude of risk

with intensity of screeningwith intensity of screeningwith intensity of screeningwith intensity of screening

Allows identification of highAllows identification of highAllows identification of highAllows identification of high----

risk categoriesrisk categoriesrisk categoriesrisk categories

National Comprehensive Cancer Network

“Categories of Consensus”• Category 1 Category 1 Category 1 Category 1 – Uniform consensus of the panel that: (1) there is high-level evidence linking

the late effect with the therapeutic exposure and (2) the screening recommendation is

appropriate based on the collective clinical experience of panel members

• Category 2A Category 2A Category 2A Category 2A - Uniform consensus of the panel that: (1) there is lower level evidence linking

the late effect with the therapeutic exposure and (2) the screening recommendation is

appropriate based on the collective clinical experience of panel members

• Category 2B Category 2B Category 2B Category 2B – Non-uniform consensus of the panel that: (1) there is lower level evidence

linking the late effect with the therapeutic exposure and (2) the screening

recommendation is appropriate based on the collective clinical experience of panel

members

• Category 3Category 3Category 3Category 3 – There is major disagreement that the recommendation is appropriate

COG Guideline Example

• Organized around

risk-based exposure

and appropriate

follow-up care

• Exposure specific

sections can be

found, with

corresponding

agents listed

COG Guideline Example

• “Info Links” are

interspersed to

clarify components

of individual

sections

• E.g., anthracycline

conversion ratios

are including in the

anthracycline

associated toxicity

section

COG Guideline Example

• Pertinent late

effects are

individually listed

COG Guideline Example

• Individual risk

factors are listed,

stratified by

increasing degree of

risk

COG Guideline Example

• Suggested

evaluations are then

outlined pertinent to

the exposure and

degree of risk

COG Guideline Example

• Lastly, the level of

evidence is scored

according to the

National

Comprehensive

Cancer Network

“Categories of

Consensus”

Pertinent Upcoming CV Revisions

• Cardiomyopathy surveillance for at risk survivors

• Doxorubicin equivalent anthracycline doses

• Pregnancy related cardiomyopathy surveillance

• Approach to exercise in at risk survivors (discussed

separately)

Cardiomyopathy Surveillance in at Risk Survivors

Armenian et al, Lancet Oncol 2015; Blanco et al, J Clin Oncol 2012; Chow et al, J Clin Oncol

2015; Haddy, Circ 2016; Mulrooney, Br Med J 2009; Mulrooney, Ann Intern Med 2016;

Ramjaun et al, Pediatr Blood Cancer 2015; Wong et al, Ann Intern Med 2014; Yeh et al, Ann

Intern Med 2014

????

Doxorubicin Equivalent Anthracycline Doses

Feijen et al, J Clin Oncol 2015

Pregnancy Related Cardiomyopathy Surveillance

• Women with no prior history of cardiac dysfunction and

normal cardiac function at the outset of pregnancy are at low

risk to develop pregnancy-induced cardiomyopathy

– Hines et al, J Cancer Surviv 2016; van Dalen et al, Eur J Cancer 2006

Pregnancy Related Cardiomyopathy Surveillance

• Echocardiogram at pre- or early-pregnancy baseline for patients who

received: 1) ≥250 mg/m2 anthracyclines, 2) ≥35 Gy chest radiation, or 3)

any dose of anthracycline plus any dose of chest radiation who are

pregnant or planning to become pregnant

• If no prior abnormalities and normal pre-/early-pregnancy echo, follow-up

echocardiograms may be obtained at the treating provider’s discretion

• Those with abnormalities prior to pregnancy or on pre-/early-pregnancy

baseline echo are at highest risk for pregnancy-associated

cardiomyopathy and should be monitored periodically during pregnancy

and during labor and delivery due to risk of cardiac failure

International Guideline Harmonization Group

Armenian et al, Lancet Oncol 2015

COG Guidelines Cardiovascular Task ForceCOG Guidelines Cardiovascular Task ForceCOG Guidelines Cardiovascular Task ForceCOG Guidelines Cardiovascular Task ForceMemberMemberMemberMember ExpertiseExpertiseExpertiseExpertise

Saro Armenian, DO, MPH (Mentor, Liaison to CWG)Saro Armenian, DO, MPH (Mentor, Liaison to CWG)Saro Armenian, DO, MPH (Mentor, Liaison to CWG)Saro Armenian, DO, MPH (Mentor, Liaison to CWG) Pediatric OncologyPediatric OncologyPediatric OncologyPediatric Oncology

Anne Anne Anne Anne BlaesBlaesBlaesBlaes, MD, MD, MD, MD Medical Medical Medical Medical OncologyOncologyOncologyOncology

Gregory Aune, MD, PhDGregory Aune, MD, PhDGregory Aune, MD, PhDGregory Aune, MD, PhD Pediatric Pediatric Pediatric Pediatric OncologyOncologyOncologyOncology

Andrew Dietz, MD, MSAndrew Dietz, MD, MSAndrew Dietz, MD, MSAndrew Dietz, MD, MS Pediatric Pediatric Pediatric Pediatric OncologyOncologyOncologyOncology

Matthew Ehrhardt, MD, MS (Chair)Matthew Ehrhardt, MD, MS (Chair)Matthew Ehrhardt, MD, MS (Chair)Matthew Ehrhardt, MD, MS (Chair) Pediatric Pediatric Pediatric Pediatric OncologyOncologyOncologyOncology

Joy Fulbright, MD (Chair)Joy Fulbright, MD (Chair)Joy Fulbright, MD (Chair)Joy Fulbright, MD (Chair) Pediatric Pediatric Pediatric Pediatric OncologyOncologyOncologyOncology

Kasey Leger, MDKasey Leger, MDKasey Leger, MDKasey Leger, MD Pediatric Pediatric Pediatric Pediatric OncologyOncologyOncologyOncology

Thomas Walwyn, MDThomas Walwyn, MDThomas Walwyn, MDThomas Walwyn, MD Pediatric Pediatric Pediatric Pediatric OncologyOncologyOncologyOncology

Vickie Massey, MDVickie Massey, MDVickie Massey, MDVickie Massey, MD Pediatric Radiation Pediatric Radiation Pediatric Radiation Pediatric Radiation OncologyOncologyOncologyOncology

Shawn Pun, MDShawn Pun, MDShawn Pun, MDShawn Pun, MD CardiologyCardiologyCardiologyCardiology

Ming Ming Ming Ming HuiHuiHuiHui Chen, MD, Chen, MD, Chen, MD, Chen, MD, MMScMMScMMScMMSc CardiologyCardiologyCardiologyCardiology

Julia Steinberger, MDJulia Steinberger, MDJulia Steinberger, MDJulia Steinberger, MD Pediatric CardiologyPediatric CardiologyPediatric CardiologyPediatric Cardiology

COG Guidelines CoreCOG Guidelines CoreCOG Guidelines CoreCOG Guidelines Core Working GroupWorking GroupWorking GroupWorking GroupSaro Armenian, DO, MPHSaro Armenian, DO, MPHSaro Armenian, DO, MPHSaro Armenian, DO, MPH Wendy Wendy Wendy Wendy LandierLandierLandierLandier, PhD, RN, CPNP, CPON, PhD, RN, CPNP, CPON, PhD, RN, CPNP, CPON, PhD, RN, CPNP, CPON

F. Daniel Armstrong, PhDF. Daniel Armstrong, PhDF. Daniel Armstrong, PhDF. Daniel Armstrong, PhD Marcia Leonard, RN, PNPMarcia Leonard, RN, PNPMarcia Leonard, RN, PNPMarcia Leonard, RN, PNP

K. Scott Baker, MD, MSK. Scott Baker, MD, MSK. Scott Baker, MD, MSK. Scott Baker, MD, MS Anna Meadows, MDAnna Meadows, MDAnna Meadows, MDAnna Meadows, MD

SmitaSmitaSmitaSmita Bhatia, MD, MPHBhatia, MD, MPHBhatia, MD, MPHBhatia, MD, MPH Paul Nathan, MD, MSc, FRCPCPaul Nathan, MD, MSc, FRCPCPaul Nathan, MD, MSc, FRCPCPaul Nathan, MD, MSc, FRCPC

Louis Louis Louis Louis ConstineConstineConstineConstine, MD, FASTRO, MD, FASTRO, MD, FASTRO, MD, FASTRO Joseph Joseph Joseph Joseph NegliaNegliaNegliaNeglia, MD, MPH, MD, MPH, MD, MPH, MD, MPH

JoanJoanJoanJoan Darling, PhDDarling, PhDDarling, PhDDarling, PhD Kirsten Ness, PT, PhDKirsten Ness, PT, PhDKirsten Ness, PT, PhDKirsten Ness, PT, PhD

Matthew Ehrhardt, MD, MSMatthew Ehrhardt, MD, MSMatthew Ehrhardt, MD, MSMatthew Ehrhardt, MD, MS Kevin Oeffinger, MDKevin Oeffinger, MDKevin Oeffinger, MDKevin Oeffinger, MD

Daniel Green, MDDaniel Green, MDDaniel Green, MDDaniel Green, MD Leslie Robison,Leslie Robison,Leslie Robison,Leslie Robison, PhDPhDPhDPhD

Melissa Hudson, MDMelissa Hudson, MDMelissa Hudson, MDMelissa Hudson, MD Charles Charles Charles Charles SklarSklarSklarSklar, MD, MD, MD, MD

Nina Nina Nina Nina KadanKadanKadanKadan----LotticLotticLotticLottic, MD, MSPH, MD, MSPH, MD, MSPH, MD, MSPH Julia Steinberger, MDJulia Steinberger, MDJulia Steinberger, MDJulia Steinberger, MD

Matthew Krasin, MDMatthew Krasin, MDMatthew Krasin, MDMatthew Krasin, MD