HemOnc vocabulary relationships

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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://europepmc.org/article/MED/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.
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