The purpose of this page is to describe the existing relationships in the HemOnc ontology and to give examples. Most of the examples are based on adjuvant CapeOx for colon cancer, as described in the XELOXA study's primary publication (Schmoll et al. 2007, JCO). For an overview and information about how to obtain a copy of the ontology please go to this page. You can also follow this link to the Concepts page.

Internal relationships

The vast majority of the relationships in the HemOnc ontology are internal relationships, that is, relationships between two concepts that are native to the HemOnc vocabulary. Below are examples of common and less common internal relationships.

Common internal relationships and examples

These relationships occur at least 100 times in the most recent version of the ontology. This table is sortable; the default arrangement is alphabetical by relationship type. Note that in the actual relationship table, the HemOnc concept code is used, not the concept name as is shown here for clarity. For simplicity, relationships to regimen stubs or sig stubs are not shown, even if they occur more than 100 times.

Concept Type 1	Relationship	Concept Type 2	Example 1	Relationship	Example 2
Study	Began enrollment in	Year	XELOXA	Began enrollment in	2003
Regimen	Can be followed by	Regimen	7 plus 3i (induction) (HO:1095)	Can be followed by	HiDAC (consolidation) (HO:839)
Regimen	Can be followed by	Procedure	FEC (neoadjuvant)	Can be followed by	Surgery
Regimen	Can be preceded by	Regimen	HiDAC (consolidation) (HO:839)	Can be preceded by	7 plus 3i (induction) (HO:1095)
Regimen	Can be preceded by	Procedure	CapeOx (adjuvant)	Can be preceded by	Surgery
Study	Ended enrollment in	Year	XELOXA	Ended enrollment in	2004
Component	Has accepted use	Condition	Capecitabine	Has accepted use	Colon cancer
Regimen	Has accepted use	Condition	CapeOx	Has accepted use	Colon cancer
Regimen	Has immunosuppressor	Component	Dexamethasone monotherapy	Has immunosuppressor	Dexamethasone
Regimen	Has local therapy	Component	IT Cytarabine & Methotrexate	Has local therapy	Cytarabine
Regimen	Has supportive med	Component	Carboplatin & Pemetrexed	Has supportive med	Dexamethasone
Regimen	Has supportive med	Component Class	Bortezomib monotherapy	Has supportive med	Bisphosphonate
Regimen	Has been compared to	Regimen	CapeOx	Has been compared to	FULV
Component	Has brand name	Brand Name	Capecitabine	Has brand name	Xeloda
Regimen	Has context	Context	CapeOx	Has context	Adjuvant therapy
Component	Has FDA indication	Condition	Capecitabine	Has FDA indication	Colon cancer
Component	Has FDA labeling	Context	Erlotinib	Has FDA labeling	Mutation-specific
Reference	Has first author	Author	XELOXA::00	Has first author	Schmoll_Hans Joachim
Reference	Has middle author	Author	XELOXA::00	Has middle author	Tabernero_Jose M
Reference	Has last author	Author	XELOXA::00	Has last author	Haller_Daniel G
Regimen	Has min cycle length	Duration	CapeOx	Has min cycle length	21 days
Regimen	Has max cycle length	Duration	CapeOx	Has max cycle length	21 days
Regimen	Has min cycle num	Numeric	CapeOx	Has min cycle num	1
Regimen	Has max cycle num	Numeric	CapeOx	Has max cycle num	Indefinite
Regimen	Has min duration	Numeric	CapeOx	Has min duration	21 days
Regimen	Has max duration	Numeric	CapeOx	Has max duration	Indefinite
Regimen	Has modality	Modality	CapeOx	Has modality	Chemotherapy
Reference	Has PMID	PubMedURL	XELOXA::00	Has PMID	https://pubmed.ncbi.nlm.nih.gov/17194911
Reference	Has URL	ReferenceURL	XELOXA::00	Has URL	https://doi.org/10.1200/jco.2006.08.1075
Reference	Has title	ReferenceTitle	XELOXA::00	Has title	Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients
Regimen	Is current in	Condition	CapeOx	Is current in	Colon cancer
Regimen	Is historical in	Condition	Edrecolomab monotherapy	Is historical in	Colon cancer
Component	Was FDA approved	Year	Capecitabine	Was FDA approved	1998
Reference	Was published in	Journal	XELOXA::00	Was published in	J Clin Oncol
Reference	Was published year	Year	XELOXA::00	Was published year	2007
Regimen	Has cycle	Cycle Sigs	CapeOx	Has cycle	21-day cycle for 8 cycles
Study	Has reference	Reference	XELOXA	Has reference	XELOXA::00
Study	Has reported endpt	Endpoint	XELOXA	Has reported endpt	OS
Study	Had experimental design	Experimental design	XELOXA	Had experimental design	In-class switch
Component	Has route	Route	Capecitabine	Has route	PO
Study	Has study group	Study Group	ECOG E3200	Has study group	Eastern Cooperative Oncology Group
Study	Has study type	Study Class	X-ACT	Has study type	FDA registration study
Component	Has sig	Sig	Capecitabine	Has sig	1000 mg/m^2 PO twice per day on days 1 to 14
Component	Is a	Component Class	Capecitabine	Is a	Fluoropyrimidine
Component Class	Is a	Component Class	Fluoropyrimidine	Is a	Pyrimidine analog
Condition	Is a	Condition	Colon cancer	Is a	Colorectal cancer
Regimen	Is a	Regimen Class	CapeOx	Is a	Platinum doublet
Component	May have route	Route	Dexamethasone	May have route	PO
Regimen	Was studied in	Study	CapeOx	Was studied in	XELOXA
Context	Was studied in	Study	Adjuvant therapy	Was studied in	XELOXA
Condition	Was studied in	Study	Colon cancer	Was studied in	XELOXA

Uncommon internal relationships and examples

These relationships occur fewer than 100 times in the most recent version of the ontology. This list is currently incomplete. Note that some very uncommon internal relationships are likely due to logic errors and are actively being reviewed for correction.

Concept Type 1	Relationship	Concept Type 2	Example 1	Relationship	Example 2
Regimen	Has antineoplastic	Component	CapeOx	Has antineoplastic	Capecitabine
Context	Is a	Context	Adjuvant therapy	Is a	Post-definitive therapy
Regimen	Has immunosuppressor	Component Class	Fludarabine & Melphalan	Has immunosuppressor	ATG (type not specified)
Regimen	Has been compared to	Procedure	Cisplatin, Fluorouracil, RT	Has been compared to	Surgery
Regimen	Has been compared to	Regimen Class	Ipilimuamb & Nivolumab	Has been compared to	Platinum doublet

External relationships

In order to increase general utility, the HemOnc ontology has relationships with several external vocabularies/terminologies. Note that external concepts are only present in the OMOP relationship table, and not in the OMOP concept table. These are defined by the vocabulary_id_2 field in the relationship table.

External terminologies that are currently supported

Healthcare Common Procedure Coding System (HCPCS)

HCPCS encodes billable drugs, the majority of which are administered. We update the HCPCS mappings for antineoplastic drugs regularly; we do not focus on mapping supportive medications at this time.

International Classification of Diseases for Oncology (ICD-O-3)

We map a small number of neoplastic conditions that do not have an NCIT code to ICD-O-3. We do not currently plan to map other conditions to ICD-O-3. Once ICD-O-4 is published, we will reconsider this decision.

National Cancer Institute thesaurus (NCIt)

NCI Thesaurus (NCIt) provides reference terminology for many NCI and other systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities. We currently map neoplastic conditions and regimens to NCIt concepts, when available. In the near future we plan to map procedures and potentially drugs.

OncoTree

OncoTree is a condition hierarchy maintained by Memorial Sloan Kettering Cancer Center. We currently map neoplastic conditions, when available.

RxNorm

RxNorm provides normalized names for clinical drugs and links its names to many of the drug vocabularies commonly used in pharmacy management and drug interaction software, including those of First Databank, Micromedex, and Gold Standard Drug Database. By providing links between these vocabularies, RxNorm can mediate messages between systems not using the same software and vocabulary. We currently map both antineoplastic and supportive drugs to RxNorm, and also have direct pointers from regimens to RxNorm drugs, as shown in the examples below.

RxNorm extension

The RxNorm extension is developed and maintained by OHDSI to capture drugs that are outside the normal scope of RxNorm. We currently map a small number of drugs to the RxNorm extension.

SEER Site Recode

The values of SEER site recode variables are based on the primary site and histology data fields submitted to SEER by the registries. The site recode variables define the major cancer site/histology groups that are commonly used in SEER's reporting of cancer incidence data and published statistics. The site recode variables are added to the SEER databases as a convenience for researchers. We currently map neoplastic conditions, when available.

Common external relationships and examples

These relationships occur at least 100 times in the most recent version of the ontology.

Concept Type 1	Relationship	Concept Type 2	Example 1	Relationship	Example 2
Regimen	Has antineopl Rx	RxNorm CUI	CapeOx	Has antineopl Rx	194000
Regimen	Has immunosuppr Rx	RxNorm CUI	Dexamethasone monotherapy	Has immunosuppr Rx	3264
Regimen	Has local therap Rx	RxNorm CUI	CHOP-14	Has local therap Rx	3041
Regimen	Has support med Rx	RxNorm CUI	Carboplatin & Pemetrexed	Has support med Rx	3264
Component	Maps to	RxNorm CUI	Capecitabine	Maps to	194000
Component	Maps to	HCPCS code	Capecitabine	Maps to	J8520; J8521
Condition	Maps to	NCIT CUI	Colon cancer	Maps to	C4910
Condition	Maps to	OncoTree CUI	Colon cancer	Maps to	COAD
Condition	Maps to	SEER Site Recode	Colon cancer	Maps to	21049

Uncommon external relationships and examples

These relationships occur less than 100 times in the most recent version of the ontology.

Concept Type 1	Relationship	Concept Type 2	Example 1	Relationship	Example 2
Condition	Maps to	ICD-O-3 code	Acute promyelocytic leukemia	Maps to	9866
Regimen	Has antineopl Rx	RxNorm Extension CUI	Pixantrone monotherapy	Has antineopl Rx	OMOP997118
Component	Maps to	RxNorm Extension CUI	Pixantrone	Maps to	OMOP997118

Further explanation of some relationships

Treatment modalities

In the HemOnc data model, treatment modalities are directed from regimen to drug (component), not vice versa. What this means is that the intent of the use of the drug defines the modality of the drug, not any intrinsic properties of the substance itself. For most drugs, the mechanism of action and the intent align in a 1:1 relationship, and there is no potential problem. However, there are several drugs, most notably the glucocorticoids and some drugs with cytotoxic chemotherapeutic properties, which can have different mechanisms of actions and different intents in different treatment contexts. Due to constraints of the OMOP data model, the names for these relationships ("Relationship ID") are by necessity abbreviated; longer forms are provided in the "Relationship expanded" column for additional guidance.

The following relationships are currently supported in the HemOnc model, as of July 2022:

Concept Type 1	Relationship ID	Concept Type 2	Intent	Example 1	Relationship expanded	Example 2
Regimen	Has AB-drug cjgt	Component	Systemic anticancer	A-AVD	Has antibody-drug conjugate therapy¹	Brentuximab vedotin
Regimen	Has antineoplastic	Component	Systemic anticancer	R-CHOP	Has antineoplastic therapy²	Doxorubicin
Regimen	Has cytotoxic chemo	Component	Systemic anticancer	R-CHOP	Has cytotoxic chemotherapy	Doxorubicin
Regimen	Has endocrine tx	Component	Systemic anticancer	Letrozole monotherapy	Has endocrine tx	Letrozole
Regimen	Has immunosuppressor	Component	Non-cancer	Alemtuzumab monotherapy	Has immunosuppressive therapy³	Alemtuzumab
Regimen	Has immunotherapy	Component	Systemic anticancer	Ipilimumab & Nivolumab	Has immunotherapy⁴	Nivolumab
Regimen	Has local therapy	Component	Local anticancer	Hyper-CVAD/MA	Has local therapy⁵	Methotrexate⁶
Regimen	Has pept-drug cjgt	Component	Systemic anticancer	Melphalan flufenamide monotherapy	Has peptibody-drug conjugate therapy¹	Melphalan flufenamide
Regimen	Has radioconjugate	Component	Systemic anticancer	Ibritumomab tiuxetan protocol	Has radioconjugate therapy¹	Ibritumomab tiuxetan
Regimen	Has radiotherapy	Component	Local anticancer	Carboplatin & RT	Has radiation therapy	External beam radiotherapy
Regimen	Has steroid tx	Component	Systemic anticancer	R-CHOP	Has systemic glucocorticoid therapy	Prednisone
Regimen	Has supportive med	Component	Supportive	R-CHOP	Has supportive medication	Filgrastim
Regimen	Has targeted tx	Component	Systemic anticancer	R-CHOP	Has targeted therapy	Rituximab

¹Some consider these drugs to be targeted therapy. While they do target a specific cell surface receptor, the antineoplastic action is through the drug or radiotherapy conjugate, which is usually a cytotoxic chemotherapy or radiotherapy.
²This is a more generic category, and we try to minimize its use.
³This category is used almost exclusively for non-malignant conditions, such as autoimmune cytopenia and graft-versus host disease.
⁴This category includes drugs that exert an indirect antineoplastic effect through activation of the immune system. Immune checkpoint inhibitors are the most commonly used drugs in this category.
⁵This category refers to drugs that are delivered to a local tissue, tumor, or space. This includes intrathecal administration of drugs that could have a systemic effect in other settings.
⁶In this regimen, methotrexate is used both as a systemic therapy and as an intrathecal therapy; the latter is the local therapy in this example.

Temporal relationships

Can be followed by

This directed relationship is phrased as an optional because there is always the possibility, even in a pre-defined protocol, that the patient will not go on to receive the second (or third, etc.) part of a treatment protocol.

Can be preceded by

This directed relationship is phrased as an optional because it is contextual; in many treatment contexts it is not necessary that the first treatment occurs before the second. In some treatment contexts the relationship is absolute, e.g., chemotherapy given in the adjuvant setting must by definition be preceded by a surgical procedure. This subtle distinction is not yet captured by the ontology.

FDA relationships

Has FDA indication

With very few exceptions, the FDA approves drugs, not regimens. Currently, all of these relationships in HemOnc are between components (drugs) and conditions.

Has FDA labeling

Most oncology labels issued by the FDA have specific contextual restrictions, which we are beginning to incorporate into HemOnc. Initially, we are focusing on labels that have a protein-expression or gene mutation requirement, i.e., a biomarker requirement. For example, the drug Erlotinib (Tarceva) is approved for first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) substitution mutations.

Has route and May have route

Components with only one route of administration are related to that route using "Has route". Conversely, components with multiple routes of administration are related to those routes using "May have route".

Study-specific relationships

Has been compared to

This non-directional relationship is the pairwise comparison of two regimens in a randomized clinical trial. In the most common scenario one regimen is a control arm and the other is experimental arm, although this is not always the case.

Has reported endpt

For "negative" studies, which we define as those having p>0.10 regardless of the predeclared level of alpha, the reported endpoint is the primary endpoint. For "positive" studies, the reported endpoint is that which is the least surrogate with a p<0.10.

Has study type

Right now there is only one defined study class: FDA registration trials. We will plan to expand this in the near future to include details such as phase of study, whether a study was a cooperative group trial, etc.

Was replaced by

This is a special relationship type used to associate current and deprecated concepts. For example, "Imatinib monotherapy, high dose" has been replaced by "Imatinib monotherapy" and the replacement is captured by this relationship.

HemOnc vocabulary relationships

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