The HemOnc Chemotherapy Regimen Ontology

Background and Applications

Jeremy Warner MD, MS, FAMIA, FASCOAssociate Professor of Medicine (Hematology/Oncology) and Biomedical Informatics

Deputy Editor, HemOnc.org

Monday, February 8th, 2021National Childhood Cancer Registry Data Summit2/9/2021 1

Disclosures• Consulting: Westat, IBM Watson Health

advisory council

• Equity: HemOnc.org LLC (no monetary value)

• Funding: NIH, AACR, Vanderbilt University

2/9/2021 2

AcknowledgementsHemOnc.org

• Peter C. Yang (founder)

• Zachary H. Moldwin (intern → FDA)

• The Editorial Board

OHDSI Oncology Subgroup

• Dmitry Dymshyts

• Christian G. Reich

• Michael J. Gurley

• Rimma Belenkaya

• Andrew E. Williams

• Timur Vakhitov

• Anastasios Siapos

Vanderbilt University Medical Center (VUMC)

• Andrew Malty

• Li Wen

Others

• Harry Hochheiser (U Pitt)

• Georgia Tech teams FHIR Hose, Sandhy

• Donna Rivera (NCI SRP → FDA)

• Lyubov Remennik (NCI EVS)

Funding

Current: AACR GENIE BPC; NCI U01 CA194215; U01 CA231840; U24 CA248010; UG3 CA243120

Former: NCI P30 CA068485; U24 CA184407

2/9/20213

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Motivation

Chemotherapeutics are usually given in complex combination regimens and protocols

Efficacy and toxicity are dependent on combinations, dosing, cycle lengths, cycle numbers, etc.

Regimens are not well-represented in current systems, leading to an unmet need in data representation

-500

0

500

1000

1500

2000

2500

3000

3500

4000

9/1/2011 6/1/2012 3/1/2013 12/1/2013 1/26/2015 1/20/2016 1/1/17 12/31/17 7/10/18 5/7/19 2/15/20

Number of Chemotherapy Regimens

HemOnc.org – a growing resource

2020 page views 1,252,575

By the numbers876 primary content pages>700k lines of content235 disease-specific pages

>6300 primary references>3500 context-specific regimens

~1500 registered users36 members of editorial board

2/9/2021

62011 2012 2013 2014 2015 2016 2017 2018 2019 2020

CY20 Stats2019

Users: 213,527

Pageviews: 1,165,947

2020

Users: 259,039

Pageviews: 1,252,575

21% user growth

7% pageview growth

2020 vs 2019

Global Reach181 countries/territories

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Editorial Board

https://hemonc.org/wiki/Editorial Board

Editor-in-ChiefPeter C. Yang, MD

Deputy EditorJeremy L. Warner, MD, MS, FAMIA, FASCO

Clinical PharmacologyDonna Rivera, PharmD, MSc

Evidence-based OncologyBishal Gyawali, MD, PhD

Section EditorsSolid Oncology

BreastH. Deepika Fernandes, MD

Derm-OncElizabeth Buchbinder, MD

EndocrineTo be filled

GI-OncNeeta K. Venepalli, MD, MBA

Head & NeckMichael Gibson, MD, PhD

Gyn-OncSummer B. Dewdney, MD

Neuro-OncSeema Nagpal, MD

SarcomaElizabeth J. Davis, MD

ThoracicTravis Osterman, DO, MS, FAMIA

https://hemonc.org/wiki/Editorial Board

GU-OncAli Raza Khaki, MD

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TBD

Section EditorsMalignant Hematology

Acute leukemiasMartin W. Schoen, MD, MPH

MPN/MDSSanjay R. Mohan, MD, MSCI

Aggressive lymphomasTarsheen Sethi, MD, MSCI

Indolent lymphomasSanjai Sharma, MD

Plasma cell dyscrasiasAndrew J. Cowan, MD

T-cell and NK-cell neoplasmsBhagirathbhai Dholaria, MBBS

Histiocyte disordersGaurav Goyal, MD

TBD

TBD

https://hemonc.org/wiki/Editorial Board

TBD

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Section EditorsClassical Hematology & Cross-Disciplinary

Classical hematologyBenjamin F. Tillman, MD

Peds-OncWayne Liang, MD, MS, FAMIA

Immuno-oncologyMeghan J. Mooradian, MD

TransplantTalal Hilal, MD

https://hemonc.org/wiki/Editorial Board2/9/2021 12

Guidelines

2/9/2021 13

Osteosarcoma

2/9/2021 14

Semi-structured Drug Information

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Semi-structured Drug Information

Semi-structured regimens

Semi-structured Regimens

Semi-structured regimens

Semi-structured Regimens

Biomarker-driven definitionsNon-small cell lung cancer (NSCLC)

IMAGE: FINE ART IMAGES/HERITAGE IMAGES/GETTY IMAGE

Comparison of existing terminologies/ontologies

TerminologyMaps to

DrugsDisease Context

Treatment Context

ModalityLink to

EvidenceNumber of regimens

SNOMED-CT Yes1 No No No No 6

SEER*Rx Yes1 No No Yes No 516

NCI Thesaurus

Yes1 Yes No No2 No 1021

HemOnc Yes Yes Yes Yes Yes 3460*

1Antineoplastics; HemOnc also maps to supportive medications2In some cases, modality can be inferred*Includes 1612 regimen “stubs” which that are incompletely defined

Condition

Study

First authorMiddle author

Last authorTitle

Component

Supportive medications

Regimen

HemOnc Regimen Model (simplified)

Was studied in

Local therapy

Antineoplastics

JournalYear

Study GroupHas study group

Context

RxNormRxNorm Ext.

NCIT

NCITSNOMED-CT

OncoTreeICD-O-3

SEER Site

PMID

URL

Included in OHDSI releases 1 & 2

Third OHDSI release

Internal relationships

External relationships

Future OHDSI releases

Modality

Concepts: 86,564 Relationships: 230,1282021-01-27

Warner et al. J Biomed Inform 2019 https://doi.org/10.1016/j.jbi.2019.103239

Has…

com

po

nen

t

Reference

1855 5559 983

630

35

19

219

6278

6086

40,000+

294

6323

68

00

+

16978000+

In progress

Example for regimen FOLFOX in Athenahttps://athena.ohdsi.org/search-terms/start

Regimen

Use Case #1: Mapping Components to Regimens

RxNorm

Included in first OHDSI releaseInternal relationships

External relationships

Condition

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“Has antineoplastic RxNorm”

FOLFOX

(35806596)

Fluorouracil (955632)

Leucovorin (1388796)

Oxaliplatin (1318011)

Method

https://github.com/ABMI/treatmentCycleExtraction

Courtesy of Hokyun Jeon, Seng Chan You, Jimyeong Park and Rae Woong Park

(Ajou University)

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Check the drug conditions

Method

“Has antineoplastic RxNorm”

FOLFOX

(35806596)

Fluorouracil (955632)

Leucovorin (1388796)

Oxaliplatin (1318011)

https://github.com/ABMI/treatmentCycleExtraction

Courtesy of Hokyun Jeon, Seng Chan You, Jimyeong Park and Rae Woong Park

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Method

https://github.com/ABMI/treatmentCycleExtraction

Courtesy of Hokyun Jeon, Seng Chan You, Jimyeong Park and Rae Woong Park

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Jeon et al. https://www.jmir.org/preprint/25035/submitted(in press)

Matching drugs to HemOnc regimens in AACR Project GENIE

• Small (N=36) breast cancer cohort

• Data had been curated and stored in REDCap by line of therapy

• N=195 treatment exposures

1%

49%

6%

44%

Data Types

No data

Drugs only

Regimens only

Regimens & Drugs

Results, cont.

• 178 (91%) of the lines of therapy matched to a HemOnc regimen

• Of these, all but 6 (3.4%) were determined automatically

• 49 mapped regimens (84.5%) had an accepted use in breast cancer

Reason for no match # of

instances

Example

No drug or regimen names 3 N/A

Regimen name only, with

only experimental drugs

3 PI3K inhibitor

GDC-0032

Regimens modeled

differently in HemOnc

1 EC-T

Regimen not present in

HemOnc; no data to

support combination found

10 Gemcitabine,

Vinorelbine,

Bevacizumab

Total 17

Condition

Study

Reference

Regimen

Use Case #2: HemOnc Regimen Browser (alpha)

Was studied in

Context

PMID

URL

Included in first OHDSI release

Second OHDSI release (planned)

Internal relationships

External relationships

Future OHDSI releases

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LIVE DEMOhttps://smartpcm-

dev.app.vumc.org/regimen/

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Condition

StudyRegimen

Use Case #3: Landscape Analyses

Was studied in Study GroupHas study group

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Pediatric oncology studies

Adult and Childhood Leukaemia Working Parties of the Medical Research Council

Children's Cancer Group

Children's Leukemia Cooperative Group of the European Organiztaion for Research and Treatment of Cancer

Children's Leukemia Group of the European Organisation for Research and Treatment of Cancer (EORTC)

Children's Oncology Group

Childrens Cancer Group

Dutch Childhood Oncology Group

EORTC Children Leukemia Group

French Society of Pediatric Oncology (SFCE)

Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups

Medical Research Council Childhood Leukaemia Working Party

Pediatric Oncology Group

Societe Francaise d'Oncologie Pediatrique (SFOP)

UK Medical Research Council's Working Party on Childhood Leukaemia

United Kingdom Children's Cancer Study Group (UKCCSG) and the Medical Research Council Bone Sarcoma Working Party

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Study Groups (N=15) Studies (N=56)Berg et al. 2005 COG AALL1131 Matthay et al. 1999

CCG 102 COG AALL1231 MRC UKALL XI

CCG 1882 COG AAML0123 OS2006

CCG 1962 COG AAML0531 POG 8101

CCG 213 COG ANBL0032 POG 8615

CCG 241 COG ANBL1221 POG 8704

CCG 251 COG ARST0332 Arm D POG 9005

CCG 2891 COG ARST0431 POG 9006

CCG 2961 COG CCG-1961 POG 9315

CCG 5942 COG CCG-1991 POG 9404CCG-105 COG D9803 POG 9457

CCG-106 COG P9425 Ravindranath et al. 1996

CCG-1922 DCOG ALL-9 Saylors et al. 2001CCG-521 DCOG ALL-VI SFOP OS94

COG A3961 EORTC 58881 UK MRC ALL97

COG A9952 EORTC 58921 UK MRC AML10

COG AALL0031 EORTC CLG 58951

COG AALL0232 ET-1

COG AALL0434 Finlay et al. 1995

COG AALL07P4 GIMEMA AIDA 0493

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6%

5%

4%

85%

STUDIES BY REGIMEN (N=74)

L-Asparaginase, Vincristine, Dexamethasone

Mercaptopurine and Methotrexate

DCTER

Other

19%

29%

10%

7%

35%

STUDIES BY CONDITION

AML B-ALL T-ALL Neuroblastoma Other

Ontology Availability

https://dataverse.harvard.edu/dataverse/HemOnc/

http://athena.ohdsi.org/vocabulary/list

Retrospective research (any user) Non-commercial user (any use)

Commercial user (any use other than retrospective)