Oncology Treatment Proposal

[mgurley]

Oncology Treatments

• Requestor: Michael Gurley (m-gurley@northwestern.edu), Rimma Belenkaya (rimma.belenkaya@gmail.com)

  Background

  We want to represent oncology treatments within the OMOP CDM. Perhaps there is no problem. Why not use DRUG_EXPOSURE and PROCEDURE_OCCURRENCE? Because oncology treatments often create a clinical event welter that thwarts many analytic use cases. Instead, we want a concept that aggregates lower-level clinical events into a higher-level abstraction. Some examples of clinical event welter:

Radiation Therapy Treatment Welter

• Beam IMRT to left breast
  • 15 Fractions at 267 cGy Dose.
  • 27 days
  • Boost Beam IMRT to left breast
  • 6 Fractions at 200 cGy Dose.
  • 5 days

This treatment spawns 72 entries using 11 CPT codes in the PROCEDURE_OCCURRENCE table covering the radiation therapy treatment lifecycle: radiation therapy management, radiation therapy simulation, radiation therapy planning and radiation therapy delivery:

Drug Therapy Treatment Welter

• DOCETAXEL + CARBOPLATIN --- 21-DAY --- NCCN Ovarian Regimen 6 cycles over 115 days

This treatment spawns 22 entries using 5 CPT codes in the PROCEDURE_OCCURRENCE table and 50 entries using 13 RxNorm codes in DRUG_EXPOSURE table.

TREATMENT Concept

In the oncology community there is a widely shared TREATMENT concept: tumor registries, practice guidelines, clinical trials databases and oncology analytic platforms all employ the concept of a TREATMENT. The TREATMENT concept aggregates lower-level clinical events into a higher-level abstraction. But we still want this higher-level abstraction TREATMENT concept to connect to lower-level clinical events.

Can we have both the benefit of a higher-level oncology TREATMENT abstraction and connection to lower-level clinical events? Can we find a place for pre-made oncology TREATMENT abstractions connected to lower-level clinical events? Conversely, can we derive higher-level oncology TREATMENTs from lower-level clinical events ? Finally, can we attach unconnected available pre-made oncology TREATMENT abstractions to lower-level clinical events?

Making room for a TREATMENT concept in the OMOP CDM will afford a number of benefits:

• Allows for a higher-level classification that more closely matches how healthcare professionals categorize oncology treatments.
• Allows for a less fine-grained counting of oncology treatments that more closely matches the number of treatments healthcare professionals conceptualize they are attempting.
• Allows for a data model that more closely matches how oncology analytic use cases are expressed.
• Allows for easier detection of alteration in treatment pathways.
• Allows for the attribution of properties at the level of an oncology treatment that are widely used.

Proposal

Add support for a TREATMENT domain within the OMOP CDM.

• Add tables to the CDM.
• Add vocabularies to the standardized vocabularies.
• Outline algorithms to populate the new tables with the new vocabularies given different source system scenarios.

We will out outline two possible implementation options. Option A and Option B.

Tables (Option A)

TREATMENT Table The TREATMENT table contains records aggregating lower-level clinical events (DRUG_EXPOSURE and PROCEDURE_OCCURRENCE) into a higher-level abstraction representing an extended diagnostic or therapeutic intervention for specific patient condition(s). A TREATMENT can be delivered at regular intervals, cycles or fractions. The temporal grouping of clinical events into cycles will only be instantiated if it is available within a source system. TREATMENT cycles will not be algorithmically derived. Pre-made higher-level TREATMENT abstractions present in a source systems will be directly inserted. Alternatively, when not available within any source system, TREATMENT abstractions will be algorithmically derived from lower-level clinical events.

Field	Required	Type	Description
treatment_id	yes	integer	A unique identifier for each Treatment.
person_id	yes	integer	A foreign key identifier to the Person who is undergoing Treatment. The demographic details of that Person are stored in the PERSON table.
treatment_concept_id	yes	integer	A foreign key that refers to a standard Treatment Concept identifier in the Standardized Vocabularies.
treatment_start_date	yes	date	The start date for the Treatment. If not available within a source system the date is constructed from the individual instances of Standardized Clinical Data tables (Procedure Occurrence and Drug Exposure) comprising the Treatment’s Treatment Concept. It is the start date of the very first chronologically recorded clinical event within a defined window of days after an index date.
treatment_end_date	yes	date	The end date for the Treatment. If not available within the source system the date is constructed from the individual instances of Standardized Clinical Data tables (Procedure Occurrence and Drug Exposure) comprising the Treatment’s Treatment Concept. It is the end date of the final recorded instance of the Treatment within a defined window of days after an index date.
treatment_parent_id	no	integer	A foreign key that refers to a parent Treatment entry representing an entire treatment if the treatment spans multiple cycles.
treatment_cycle_number	no	integer	An ordinal count of cycles for a Treatment that spans multiple cycles
treatment_type_concept_id	yes	integer	A foreign key that refers to a standard Treatment Type Concept identifier in the Standardized Vocabularies reflecting the source data from which the Treatment was recorded, the level of standardization, and the type of occurrence.
treatment_intent_concept_id	no	integer	A foreign key that refers to a standard Treatment Intent Concept identifier in the Standardized Vocabularies reflecting the interventional intent of the Treatment.
treatment_source_value	no	varchar(50)	The source code for the Treatment as it appears in the source data. This code is mapped to a standard procedure Concept in the Standardized Vocabularies and the original code is, stored here for reference.
treatment_source_concept_id	no	integer	A foreign key to a Treatment Concept that refers to the code used in the source.
treatment_status_concept_id	no	integer	A foreign key that refers to a standard Treatment Status Concept identifier in the Standardized Vocabularies reflecting the status the Treatment.

Conventions

• The Treatment Concept defines a fine-grained classification of the oncology treatment. The Treatment Concept is partially based on the NCI CRN ‘Cancer Therapy Look-up Tables’. The Cancer Therapy lookup tables contain lists of NDCs, CPT, and HCPC codes classified by the Treatment Concept that encode low-level clinical events representing receipt of oncology drug therapy or radiation therapy.
• The treatment parent and treatment cycle number fields allow for the representation of oncology treatments delivered at regular intervals, cycles or fractions. The TREATMENT table supports the encoding of oncology treatment cycles or fractions by allowing for a hierarchical parent/child relationship between treatment entries and an ordinal enumeration of treatment cycles. Many source systems will not have treatment cycle information available. A treatment cycle number of NULL should be used for a top level representation of an entire Treatment across all treatment cycles. Each representation of a treatment cycle should refer to the parent Treatment by the parent id column.

TREATMENT_MODIFIER Table The TREATMENT_MODIFIER table contains records that attribute properties to a treatment. These properties should further refine the description of the treatment. Most often these modifiers will point to a TREATMENT table entry but also possibly a PROCEDURE_OCCURRENCE table entry or a DRUG_EXPOSURE table entry. Some examples: attribution of a known Drug Regimen concept to a Drug Therapy treatment; number of fractions, anatomical target, total dose in cGy for Radiation Therapy treatment.

Field	Required	Type	Description
treatment_modifier_id	Yes	integer	A unique identifier for each Treatment Modifier.
treatment_modifier_event_id	Yes	integer	A foreign key identifier to the event (e.g. Treatment, Treatment Cycle, Drug, Procedure etc) record that is being modified.
treatment_modifier_domain_id	Yes	integer	The concept representing the domain of the treatment modifier event, from which the corresponding table can be inferred that contains the entity for which the treatment modifier information is recorded.
person_id	Yes	integer	A foreign key identifier to the Person about whom the Treatment Modifier was recorded. The demographic details of that Person are stored in the PERSON table.
treatmeant_modifier_concept_id	Yes	integer	A foreign key to the standard Treatmenft Modifier concept identifier in the Standardized Vocabularies.
treatment_modifier_date	Yes	date	The date of the Treatment Modifier.
treatment_modifier_datetime	No	datetime	The date and time of the Treatment Modifier. Some database systems don't have a datatype of time. To accomodate all temporal analyses, datatype datetime can be used (combining treatment_modifier_date and treatment_modifier_time)
treatment_modifier_type_concept_id	Yes	integer	A foreign key to the predefined Concept in the Standardized Vocabularies reflecting the provenance from where the Treatment Modifier record was recorded.
operator_concept_id	No	integer	A foreign key identifier to the predefined Concept in the Standardized Vocabularies reflecting the mathematical operator that is applied to the value_as_number. Operators are <, <=, =, >=, >.
value_as_number	No	float	A Treatment Modifier result where the result is expressed as a numeric value.
value_as_concept_id	No	integer	A foreign key to a Treatment Modifier result represented as a Concept from the Standardized Vocabularies (e.g., positive/negative, present/absent, low/high, etc.).
unit_concept_id	No	integer	A foreign key to a Standard Concept ID of Treatment Modier Units in the Standardized Vocabularies.
provider_id	No	integer	A foreign key to the provider in the PROVIDER table who was responsible for initiating or obtaining the Treatment Modifier.
treatment_modifier_source_value	No	varchar(50)	The Treatment Modifier name as it appears in the source data. This code is mapped to a Standard Concept in the Standardized Vocabularies and the original code is stored here for reference.
treatment_modifier_source_concept_id	No	integer	A foreign key to a Concept in the Standard Vocabularies that refers to the code used in the source.
unit_source_value	No	varchar(50)	The source code for the unit as it appears in the source data. This code is mapped to a standard unit concept in the Standardized Vocabularies and the original code is stored here for reference.
value_source_value	No	varchar(50)	The source value associated with the content of the value_as_number or value_as_concept_id as stored in the source data.

Conventions

• Even though each Treatment Modifier always have a result, the fields value_as_number and value_as_concept_id are not mandatory. When the result is not known, the Treatment Modifier record represents just the fact that the corresponding Treatment Modifier was carried out, which in itself is already useful information for some use cases.
• Valid Treatment Modifier Concepts (treatment_modifier_concept_id) belong to the 'Treatment Modifier' domain. When the Treatment Modifier Source Value of the code cannot be translated into a standard Treatment Modifier Concept ID, a Treatment Modifier entry is stored with only the corresponding source_concept_id and treatment_modifier_source_value and a treatment_modifier_concept_id of 0.
• Treatment Modifiers are stored as attribute value pairs, with the attribute as the Treatment Modifier Concept and the value representing the result. The value can be a Concept (stored in value_as_concept), or a numerical value (value_as_number) with a Unit (unit_concept_id).
• Valid Concepts for the value_as_concept field belong to the 'Treatment Modifier Value' domain.
• The operator_concept_id is optionally given for relative Treatment Modifiers where the precise value is not available but its relation to a certain benchmarking value is. For example, this can be used for minimal detection thresholds of a test.
• The meaning of Concept 4172703 for '=' is identical to omission of a operator_concept_id value. Since the use of this field is rare, it's important when devising analyses to not to forget testing for the content of this field for values different from =.
• Valid Concepts for the operator_concept_id field belong to the 'Treatment Modider Value Operator' domain.
• The Unit is optional even if a value_as_number is provided.
• The Provider making the observation is recorded through a reference to the PROVIDER table. This information is not always available.

DRUG_EXPOSURE Table Amendments required to the DRUG_EXPOSURE table are as follows:

Field	Required	Type	Description
treatment_id	yes	integer	A unique identifier for each Treatment.

Conventions

• Connect qualifying DRUG_EXPOSURE to the appropriate TREATMENT entry by populating the treatment_id column.

PROCEDURE_OCCURRENCE Table Amendments required to the PROCEDURE_OCCURRENCE table are as follows:

Field	Required	Type	Description
treatment_id	yes	integer	A unique identifier for each Treatment.

Conventions

• Connect qualifying PROCEDURE_OCCURRENCE to the appropriate TREATMENT entry by populating the treatment_id column.

Tables (Option B)

TREATMENT Table The TREATMENT table contains records aggregating lower-level clinical events (DRUG_EXPOSURE and PROCEDURE_OCCURRENCE) into a higher-level abstraction representing an extended diagnostic or therapeutic intervention for a specified patient condition. Pre-made higher-level TREATMENT abstractions present in a source systems will be directly inserted. Alternatively, when not available within any source system, TREATMENT abstractions will be algorithmically derived from lower-level clinical events.

Field	Required	Type	Description
treatment_id	yes	integer	A unique identifier for each Treatment.
person_id	yes	integer	A foreign key identifier to the Person who is undergoing Treatment. The demographic details of that Person are stored in the PERSON table.
treatment_concept_id	yes	integer	A foreign key that refers to a standard Treatment Concept identifier in the Standardized Vocabularies.
treatment_start_date	yes	date	The start date for the Treatment. If not available within a source system the date is constructed from the individual instances of Standardized Clinical Data tables (Procedure Occurrence and Drug Exposure) comprising the Treatment’s Treatment Concept. It is the start date of the very first chronologically recorded clinical event within a defined window of days after an index date.
treatment_end_date	yes	date	The end date for the Treatment. If not available within the source system the date is constructed from the individual instances of Standardized Clinical Data tables (Procedure Occurrence and Drug Exposure) comprising the Treatment’s Treatment Concept. It is the end date of the final recorded instance of the Treatment within a defined window of days after an index date.
treatment_type_concept_id	yes	integer	A foreign key that refers to a standard Treatment Type Concept identifier in the Standardized Vocabularies reflecting the source data from which the Treatment was recorded, the level of standardization, and the type of occurrence.
treatment_intent_concept_id	no	integer	A foreign key that refers to a standard Treatment Intent Concept identifier in the Standardized Vocabularies reflecting the interventional intent of the Treatment.
treatment_source_value	no	varchar(50)	The source code for the Treatment as it appears in the source data. This code is mapped to a standard procedure Concept in the Standardized Vocabularies and the original code is, stored here for reference.
treatment_source_concept_id	no	integer	A foreign key to a Treatment Concept that refers to the code used in the source.
treatment_status_concept_id	no	integer	A foreign key that refers to a standard Treatment Status Concept identifier in the Standardized Vocabularies reflecting the status the Treatment.

Conventions

• The Treatment Concept defines a fine-grained classification of the oncology treatment. The Treatment Concept is partially based on the NCI CRN ‘Cancer Therapy Look-up Tables’. The Cancer Therapy lookup tables contain lists of NDCs, CPT, and HCPC codes classified by the Treatment Concept that encode low-level clinical events representing receipt of oncology drug therapy or radiation therapy.

TREATMENT_MODIFIER Table The TREATMENT_MODIFIER table contains records that attribute properties to a treatment. These properties should further refine the description of the treatment. Most often these modifiers will point to a TREATMENT table entry but also possibly a TREATMENT_CYCLE table entry, a PROCEDURE_OCCURRENCE table entry or a DRUG_EXPOSURE table entry. Some examples: attribution of a known Drug Regimen concept to a Drug Therapy treatment; number of fractions, anatomical target, total dose in cGy for Radiation Therapy treatment.

Field	Required	Type	Description
treatment_modifier_id	Yes	integer	A unique identifier for each Treatment Modifier.
treatment_modifier_event_id	Yes	integer	A foreign key identifier to the event (e.g. Treatment, Treatment Cycle, Drug, Procedure etc) record that is being modified.
treatment_modifier_domain_id	Yes	integer	The concept representing the domain of the treatment modifier event, from which the corresponding table can be inferred that contains the entity for which the treatment modifier information is recorded.
person_id	Yes	integer	A foreign key identifier to the Person about whom the Treatment Modifier was recorded. The demographic details of that Person are stored in the PERSON table.
treatmeant_modifier_concept_id	Yes	integer	A foreign key to the standard Treatmenft Modifier concept identifier in the Standardized Vocabularies.
treatment_modifier_date	Yes	date	The date of the Treatment Modifier.
treatment_modifier_datetime	No	datetime	The date and time of the Treatment Modifier. Some database systems don't have a datatype of time. To accomodate all temporal analyses, datatype datetime can be used (combining treatment_modifier_date and treatment_modifier_time)
treatment_modifier_type_concept_id	Yes	integer	A foreign key to the predefined Concept in the Standardized Vocabularies reflecting the provenance from where the Treatment Modifier record was recorded.
operator_concept_id	No	integer	A foreign key identifier to the predefined Concept in the Standardized Vocabularies reflecting the mathematical operator that is applied to the value_as_number. Operators are <, <=, =, >=, >.
value_as_number	No	float	A Treatment Modifier result where the result is expressed as a numeric value.
value_as_concept_id	No	integer	A foreign key to a Treatment Modifier result represented as a Concept from the Standardized Vocabularies (e.g., positive/negative, present/absent, low/high, etc.).
unit_concept_id	No	integer	A foreign key to a Standard Concept ID of Treatment Modier Units in the Standardized Vocabularies.
provider_id	No	integer	A foreign key to the provider in the PROVIDER table who was responsible for initiating or obtaining the Treatment Modifier.
treatment_modifier_source_value	No	varchar(50)	The Treatment Modifier name as it appears in the source data. This code is mapped to a Standard Concept in the Standardized Vocabularies and the original code is stored here for reference.
treatment_modifier_source_concept_id	No	integer	A foreign key to a Concept in the Standard Vocabularies that refers to the code used in the source.
unit_source_value	No	varchar(50)	The source code for the unit as it appears in the source data. This code is mapped to a standard unit concept in the Standardized Vocabularies and the original code is stored here for reference.
value_source_value	No	varchar(50)	The source value associated with the content of the value_as_number or value_as_concept_id as stored in the source data.

Conventions

• Even though each Treatment Modifier always have a result, the fields value_as_number and value_as_concept_id are not mandatory. When the result is not known, the Treatment Modifier record represents just the fact that the corresponding Treatment Modifier was carried out, which in itself is already useful information for some use cases.
• Valid Treatment Modifier Concepts (treatment_modifier_concept_id) belong to the 'Treatment Modifier' domain. When the Treatment Modifier Source Value of the code cannot be translated into a standard Treatment Modifier Concept ID, a Treatment Modifier entry is stored with only the corresponding source_concept_id and treatment_modifier_source_value and a treatment_modifier_concept_id of 0.
• Treatment Modifiers are stored as attribute value pairs, with the attribute as the Treatment Modifier Concept and the value representing the result. The value can be a Concept (stored in value_as_concept), or a numerical value (value_as_number) with a Unit (unit_concept_id).
• Valid Concepts for the value_as_concept field belong to the 'Treatment Modifier Value' domain.
• The operator_concept_id is optionally given for relative Treatment Modifiers where the precise value is not available but its relation to a certain benchmarking value is. For example, this can be used for minimal detection thresholds of a test.
• The meaning of Concept 4172703 for '=' is identical to omission of a operator_concept_id value. Since the use of this field is rare, it's important when devising analyses to not to forget testing for the content of this field for values different from =.
• Valid Concepts for the operator_concept_id field belong to the 'Treatment Modider Value Operator' domain.
• The Unit is optional even if a value_as_number is provided.
• The Provider making the observation is recorded through a reference to the PROVIDER table. This information is not always available.

TREATMENT_CYCLE Table

A TREATMENT can be delivered at regular intervals, fractions or cycles. This temporal grouping of clinical events will only be instantiated if it is available within a source system. A TREATMENT_CYCLE will not be algorithmically derived.

Field	Required	Type	Description
treatment_cycle_id	yes	integer	A unique identifier for each Treatment Cycle.
treatment_id	yes	integer	A foreign key identifier to the Treatment that the Treatment Cycle belongs to and subdivides.
person_id	yes	integer	A foreign key identifier to the Person who is undergoing Treatment. The demographic details of that Person are stored in the PERSON table.
treatment_cycle_start_date	yes	date	The start date for the Treatment Cycle.
treatment_cycle_end_date	yes	date	The end date for the Treatment Cycle.
treatment_cycle_number	yes	integer	An ordinal count of cycles for a Treatment that spans multiple cycles

TREATMENT_EVENT Table

Connect qualifying DRUG_EXPOSURE or PROCEDURE_OCCURRENCE to the appropriate TREATMENT entry by populating the TREATMENT_EVENT table.

Field	Required	Type	Description
treatment_event_id	yes	integer	A unique identifier for each Treatment Event.
treatment_event_event_id	yes	integer	A foreign key identifier to the event (Drug Exposure or Procedure Occurrence) record for which cost data are recorded.
treatment_event_domain_id	yes	integer	The concept representing the domain of the treatment event, from which the corresponding table can be inferred that contains the entity connected to the Treatment and Treatment Cycle.
treatment_id	yes	integer	A foreign key identifier to the Treatment that the Treatment Event belongs to.
treatment_cycle_id	no	integer	A foreign key identifier to the Treatment Cycle that the Treatment Event belongs to. If no Treatment Cycle information is present within the source system, his field will be NULL.
person_id	yes	integer	A foreign key identifier to the Person who is undergoing Treatment. The demographic details of that Person are stored in the PERSON table.

Vocabulary

TREATMENT table columns demanding new concepts are as follows:

The Treatment Concept domain is partially based on the NCI CRN ‘Cancer Therapy Look-up Tables’.) https://crn.cancer.gov/resources/codes.html. Entries will be made in the CONCEPT_RELATIONSHIP table using the existing ‘"Maps to" and "Mapped from" relationships based on the NCI CRN ‘Cancer Therapy Look-up Tables’ that link National Drug Codes (NDCs), procedure codes (CPT4, ICD-9, HCPC) and diagnosis codes (ICD-9) to Treatment Concepts.

• treatment_concept_id
  • Drug Therapy
    • Biologic
    • Chemotherapy (molecule)
    • Hormone
    • Immunologic
    • Other
    • Radioactive
  • Surgery
    • Biopsy
    • Resection
  • Radiation Therapy
    • Beam Electron
    • Beam IMRT
    • Beam Neutron
    • Beam NOS
    • Beam Proton
    • Beam SRS
    • Brachytherapy
    • Isotopes
    • General

The Treatment Type vocabulary:

• treatment_type_concept_id
  • Pre-made treatment abstraction with pre-made clinical events connections.
  • Pre-made treatment abstraction with algorithmically derived clinical events connections.
  • Algorithmically derived treatment abstraction and clinical event connections.

The Treatment Intent vocabulary:

• treatment_intent_concept_id
  • Curative
  • Diagnostic
  • Palliative

The Treatment Status vocabulary:

• treatment_status_concept_id
  • Therapy Complete
  • Not Completed due to Progression
  • Not Completed due to Death
  • Not Completed due to Not Tolerated
  • Not Completed due to Provider Discretion
  • Not Completed due to Patient Discretion

TREATMENT_MODIFIER table columns demanding new concepts are as follows:

The Treatment Modifier domain:

• treatment_modifier_concept_id
  • Drug Regimen

The Treatment Modifier Value domain:

The Drug Regimen Value domain is based on National Tariff Chemotherapy Regimens List. See here: https://hscic.kahootz.com/gf2.ti/f/762498/27839109.1/XLSX/-/NatTarChemoRegList1718.xlsx And here: https://hscic.kahootz.com/gf2.ti/f/762498/27838501.1/PDF/-/ChemRegClinCodingStandGuidApl2017.pdf. Entries will be made in the CONCEPT_RELATIONSHIP table using the existing ‘"Maps to" and "Mapped from" relationships to RxNorm ingredients based on the ingredient participation detailed in the National Tariff Chemotherapy Regimens List.

• value_as_concept_id
  • Drug Regimen Value
    • Abemaciclib
    • ABVD
    • AC
    • ACE (1 day)
    • ACE (3 day)
    • ACE (germ cell)
    • ADE 10+3+5
    • ADE 8+3+5
    • ADOC
    • AFATINIB
    • Afuresertib
    • Alectinib
    • Alemtuz+Cyclophos+Fludara Allo
    • Alemtuz+Fludara+Melphalan RIC MUD
    • Alemtuzumab (INTRAVENOUS)
    • Alemtuzumab (SUBCUTANEOUS)
    • Alemtuzumab + Cyclophos TBI Allo
    • Alemtuzumab cond (RI ALLO CAMP100)
    • Alemtuzumab+Busulfan+CyclophosphMUD
    • AML16 DA 2+5
    • AML16 DA 3+10
    • AML16 DA 3+8
    • AML16 Low Dose Cytarabine
    • Arsenic Triox + Tretinoin Ind W1-4
    • Arsenic Triox + Tretinoin Ind W5-8
    • Arsenic Trioxide (consolidation)
    • Arsenic Trioxide (Induction Week)
    • ATG + Busulf + Fludara + Thiotepa
    • ATG + Busulfan + Fludarabine
    • ATG + Cyclophosphamide TBI Allo
    • Axitinib
    • Azacitidine
    • BCG Intravesical
    • BEACOPP
    • BEACOPP-14
    • BEAM
    • BEAM + Alemtuzumab Allo SCT
    • Bendamustine + prednisolone
    • Bendamustine + Thalidomide +/- Dex
    • Bendamustine +/- Prednisolone
    • Bendamustine+Rituximab (1st Course)
    • Bendamustine+Rituximab(Sub Courses)
    • BEP 3 day
    • BEP 5 Day
    • Bevacizumab + Cape + Irino 14day
    • Bevacizumab + Cape + Irino 21day
    • Bevacizumab + Cape + Oxali 14day
    • Bevacizumab + Cape + Oxali 21day
    • Bevacizumab + Capecitabine
    • Bevacizumab + Irinotecan
    • Bevacizumab + Irinotecan + MdG
    • Bevacizumab + Oxaliplatin +MdG
    • Bevacizumab + Paclitaxel
    • Bevacizumab + Temozolomide
    • Bevacizumab 10mg/kg
    • Bevacizumab 15mg/kg
    • Bevacizumab 5mg/kg
    • Bevacizumab 7.5mg/kg
    • Bevacizumab Maint (wk 10 on) Glio
    • Bevacizumab+Carbo+Gemcitabine
    • Bevacizumab+Carbo+Pacliaxel
    • Bevacizumab+Cisplatin+Gemcitabine
    • Bevacizumab+Irinotecan+Raltitrexed
    • Bevacizumab+temoz+RT (weeks 1 to 6)
    • Bevacizumab+temoz+RT(weeks7 to 9)
    • Bexarotene
    • BGEM
    • Binimetinib
    • BIP
    • Bleomycin + Cisplatin + Vinblastine
    • Bleomycin + Vinblastine
    • BOP
    • BOP (Bendamustine+vinc+pred)
    • Bortezomib (weekly)
    • Bortezomib + Cyclophos + Dex
    • Bortezomib + Cyclophos + Pred
    • Bortezomib + Melphalan +/- Pred
    • Bortezomib + Thalidomide +/- Dex
    • Bortezomib +/- Dexamethasone
    • BOSUTINIB
    • Brentuximab
    • Buparlisib
    • BUSULFAN + CYCLO oral
    • Busulfan + Cyclophos Conditioning
    • BUSULFAN + FLUDARABINE
    • BUSULFAN + FLUDARABINE + METHOTREXATE
    • BUSULFAN + MELPHALAN
    • Busulfan Oral
    • Busulfan po + Fludarabine RIC Allo
    • Busulfan po + Melphalan Auto
    • Cabazitaxel
    • CABOZANTINIB
    • CAIP
    • CAP
    • Cape + Cetuximab +Irinotecan - Load
    • Cape + Cetuximab +Irinotecan - Main
    • Cape +Cetuximab +Oxalip (3 wk) Load
    • Cape +Cetuximab +Oxalip (3 wk)Maint
    • Cape+Cetuximab+Oxalip (2 wk) Load
    • Cape+Cetuximab+Oxalip (2 wk) Maint
    • Cape+Cisplatin+Trastuzumab Load
    • Cape+Cisplatin+Trastuzumab Main
    • Capecitabine
    • Capecitabine (14 day) + Irinotecan
    • Capecitabine (14 days)+Carboplatin
    • Capecitabine (21 day) + Irinotecan
    • Capecitabine (21days) + Carboplatin
    • Capecitabine + Carboplatin + RT
    • Capecitabine + Cisplatin
    • Capecitabine + Cisplatin + RT
    • Capecitabine + Docetaxel
    • Capecitabine + Lapatinib
    • CAPECITABINE + LOMUSTINE
    • Capecitabine + Mitomycin
    • Capecitabine + Oxaliplatin 14day
    • Capecitabine + Oxaliplatin 21day
    • Capecitabine + RT
    • Capecitabine + Streptozocin
    • CAPECITABINE + TEMOZOLOMIDE
    • Capecitabine + Vinorelbine iv
    • Capecitabine+Cisplatin+Streptozocin
    • Capecitabine+Trastuzumab 21day Load
    • Capecitabine+Trastuzumab 21dayMaint
    • Capecitabine+Trastuzumab 7 day Load
    • Capecitabine+Trastuzumab 7day Maint
    • Capecitabine+Trastuzumab SC
    • Carbo + Liposomal Dox + Paclitaxel
    • Carbo + Topotecan (EPSSG RMS 2005)
    • Carbo F
    • CarboPEC-Taxol
    • Carboplatin + Cetux + FU (>Cycle 2)
    • Carboplatin + Cetux + FU (Cycle 1)
    • Carboplatin + Cetuximab (>Cycle 2)
    • Carboplatin + Cetuximab (Cycle 1)
    • Carboplatin + Dexrazoxane + Dox
    • Carboplatin + Docetaxel
    • Carboplatin + Doxorubicin
    • Carboplatin + Etoposide IV 3 day
    • Carboplatin + Etoposide IV 5 day
    • Carboplatin + Etoposide iv&po
    • Carboplatin + Irinotecan
    • Carboplatin + Liposomal Doxorubicin
    • Carboplatin + Methotrexate
    • Carboplatin + Paclitaxel (3 weekly)
    • Carboplatin + Paclitaxel (weekly)
    • Carboplatin + Pemetrexed
    • Carboplatin + Raltitrexed
    • Carboplatin + Thiotepa + Topotecan
    • Carboplatin + Topotecan
    • Carboplatin + Vinblastine
    • Carboplatin + Vincristine
    • Carboplatin + Vinorelbine IV
    • Carboplatin + Vinorelbine IV &PO D8
    • Carboplatin + Vinorelbine Oral
    • Carboplatin 21day + Paclitaxel 7day
    • Carboplatin AUC 2 - 5
    • Carboplatin AUC 6 - 10
    • Carboplatin+Cyclophos+Dox
    • Carboplatin+Fluorouracil 4 or 5 day
    • Carboplatin+Gemcitabine+Paclitax
    • Carfilzomib
    • CAV
    • CCEP
    • CEB 3 day
    • CEB 5 day
    • CEDIRANIB
    • CEOP
    • Ceritinib
    • Cetuximab + FOLFIRI cycle 2 onwards
    • Cetuximab + FOLFIRI cycle1
    • Cetuximab + Irinotecan (Cycle 1)
    • Cetuximab + Oxaliplatin + MdG Load
    • Cetuximab + Oxaliplatin + MdG Maint
    • Cetuximab + Radiotherapy Load
    • Cetuximab + Radiotherapy Maint
    • Cetuximab +Cisplatin + FU (Cycle 1)
    • Cetuximab 14 day
    • Cetuximab 7 day (>Cycle 2)
    • Cetuximab 7 day (Cycle 1)
    • Cetuximab+Cisplatin+FU (> Cycle 2)
    • Cetuximab+Irinotecan (Cyc2 onwards)
    • CEV
    • ChIVPP/EVA
    • Chlorambucil
    • Chlorambucil + Obinutuzumab
    • Chlorambucil + Pred + Rituximab
    • Chlorambucil + Pred + Vinblastine
    • CHLVPP
    • CHLVPP PABLOE
    • CHOEP - 14 days
    • CHOEP - 21 days
    • CHOP - 14 days
    • CHOP - 21 days
    • CHOP R - 14 days
    • CHOP R - 21 days
    • CHOP-Asparaginase
    • CIA
    • CIDEX
    • CIOP
    • Cisplatin
    • Cisplatin + Dacarbazine
    • Cisplatin + Docetaxel
    • Cisplatin + Docetaxel +Fluorouracil
    • Cisplatin + Doxorubicin
    • Cisplatin + Etoposide (3 day)
    • Cisplatin + Etoposide (5 day)
    • Cisplatin + Etoposide + RT
    • Cisplatin + Etoposide 500mg/m2 1day
    • Cisplatin + Etoposide po
    • Cisplatin + Etoposide po&iv 3 day
    • Cisplatin + Fluorouracil + Mtx + FA
    • Cisplatin + Fluorouracil + RT 5day
    • Cisplatin + Gemcitabine (D 1 & 8)
    • Cisplatin + Irinotecan (14 Days)
    • Cisplatin + Irinotecan (21 Days)
    • Cisplatin + Liposomal Doxorubicin
    • Cisplatin + Methotrexate
    • Cisplatin + Modified de Gramont
    • Cisplatin + Paclitaxel
    • Cisplatin + Pemetrexed
    • Cisplatin + Radiotherapy
    • Cisplatin + Teysuno
    • Cisplatin + Topotecan
    • Cisplatin + Vinorelbine (IV)
    • Cisplatin + Vinorelbine (PO)
    • Cisplatin +Fluorouracil (2 wk)
    • Cisplatin +Fluorouracil (3 wk)
    • Cisplatin +FU +Trastuzumab - Load
    • Cisplatin +FU +Trastuzumab - Maint
    • Cisplatin 100 + RT(H&N) 1 day
    • Cisplatin 25 + RT (H&N) 4 day
    • Cisplatin 50 + RT (H&N) 2 day
    • Cisplatin 7 day
    • Cisplatin chemoembolisation
    • Cisplatin+Doxorubicin+Etoposide 21d
    • Cisplatin+Doxorubicin+Etoposide 28d
    • Cisplatin+Epirubicin+Raltitrexed
    • Cisplatin+Fluorouracil+Streptozoc
    • Cisplatin+Gemcitabine (Days 1&8&15)
    • Cisplatin+Gemcitabine (gallbladder)
    • Cisplatin+Gemcitabine+Paclitaxel
    • Cisplatin+Irinotecan+Vinorelbine
    • Cladribine (7day continuous IV inf)
    • Cladribine (subcut) 5 days
    • Cladribine + Rituximab
    • Cladribine IV (5 day)
    • Cladribine IV weekly
    • Clofarabine + Cytarabine
    • Clofarabine+Cytarabine+Idarubicin
    • CMD
    • CMF Classical 28 day Oral
    • CMF IV (21 day)
    • CMF IV (28 day)
    • CMV
    • Cobimetinib
    • Cobimetinib + Vemurafenib
    • CODOX M
    • Consolidation - Cycle 1 (ALL)
    • Consolidation - Cycle 2 & 4 (ALL)
    • Consolidation - Cycle 3 (ALL)
    • COPP + Dacarbazine
    • CRIZOTINIB
    • CTD (Thalidomide 100mg)
    • CTD (Thalidomide 150mg)
    • CTD (Thalidomide 200mg)
    • CTD Attenuated (Thalidomide 100mg)
    • CTD Attenuated (Thalidomide 150mg)
    • CTD Attenuated (Thalidomide 200mg)
    • CTD Attenuated (Thalidomide 50mg)
    • CTW
    • CVAD
    • CVAMP
    • CVD (Neuroendocrine)
    • CVD (skin)
    • CVP
    • CVP R
    • CYCLET
    • Cyclophophamide + Mtx (oral)
    • Cyclophos + Dex + Lenalidomide
    • Cyclophos+Docetaxel+TrastuzumabLoad
    • Cyclophosphamide + Dacarbazine + FU
    • Cyclophosphamide + Dex + Rituximab
    • Cyclophosphamide + Docetaxel
    • Cyclophosphamide + Etoposide (iv)
    • Cyclophosphamide + Etoposide (PO)
    • Cyclophosphamide + Fludarabine IV
    • Cyclophosphamide + Pentostatin
    • Cyclophosphamide + Topotecan
    • Cyclophosphamide + Vincristine
    • Cyclophosphamide Fludarabine (Oral)
    • Cyclophosphamide High Dose
    • Cyclophosphamide oral
    • Cyclophosphamide PO +Vinorelbine IV
    • Cyclophosphamide TBI Allograft
    • Cyclophosphamide Weekly IV
    • Cyclophosphamide Weekly PO
    • Cyclophosphamide+Doce+Tras Main
    • Cyclophosphamide+Etopophos HD
    • Cyclophosphamide+Fludara+TBI Allo
    • Cyclophosphamide+Lipo Dox Myocet
    • Cytarabine + Idarubicin
    • Cytarabine + Ifosfamide
    • Cytarabine HD + Methotrexate HD
    • Cytarabine HD + Rituximab
    • Cytarabine High Dose
    • Cytarabine intrathecal
    • Cytarabine low (10to20mg/m2) IV/SC
    • Cytarabine Low Dose
    • Cytarabine+Hydrocortisone Intrathecal
    • Cytarabine+Methotrexate Intrathecal
    • DA 3 + 10
    • DA 3+8
    • DA-EPOCH-R
    • DABRAFENIB
    • DABRAFENIB + TRAMETINIB
    • Dacarbazine
    • Dacarbazine + Ipilimumab
    • Dacarbazine + Vinblastine
    • Dacarbazine 14day
    • Dacomitinib
    • Dactinomycin + Vincristine
    • Dactinomycin 5 day
    • Dartumumab
    • Dasatinib
    • De Angelis (Modified)
    • Defactinib
    • Depocyte Intrathecal
    • DHAP
    • DHAP - R
    • DHAX
    • DJV3
    • Doce + Pertuzumab + Trastuz IV Load
    • Doce + Pertuzumab + Trastuz IV Maint
    • Docetaxel
    • Docetaxel + Gemcitabine (prior RT)
    • Docetaxel + Gemcitabine with GCSF
    • Docetaxel + Irinotecan
    • Docetaxel + Nintedanib
    • Docetaxel + Trastuzumab (Load)
    • Docetaxel + Trastuzumab (Maint)
    • Docetaxel + Trastuzumab (SC)
    • Docetaxel 100mg/m2 (21 day)
    • Docetaxel 75mg/m2 (21 day)
    • Docetaxel+Gemcitabine (no prior RT)
    • Dovitinib
    • Dox + HD Mtx (post PAM)
    • Dox + HD Mtx (post PAM)+Dexrazoxane
    • Doxorubicin + Gemcitabine
    • Doxorubicin + Ifosfamide
    • Doxorubicin + Methotrexate
    • Doxorubicin + Steptozotocin
    • Doxorubicin +Fluorouracil + Streptozocin
    • Doxorubicin 20mg/m2 7 day
    • Doxorubicin chemoembolisation
    • Doxorubin 50mg/m2
    • DPV3
    • DTPACE
    • Duvelisib
    • EC
    • ECarboF
    • ECarboX
    • ECE
    • ECF
    • ECX
    • EE VI
    • EEF or EOF
    • EMA High Dose
    • EMA/CO
    • Encorafenib
    • Entinostat
    • Entinostat + Exemestane
    • EOF
    • EOX
    • EP 1, 2 or 3 day
    • Epirubicin
    • Epirubicin (2 weekly)
    • Epirubicin (weekly)
    • Epirubicin + Ifosfamide
    • Epirubicin + Vinorelbine
    • Epirubicin intravesical
    • Epirubicin+Oxaliplatin+Raltitrexed
    • EpSSG NRSTS 2005
    • Eribulin
    • Erismodegib
    • Erlotinib
    • Erlotinib + Gemcitabine Cycle 1
    • Erlotinib + Gemcitabine Cycle 2
    • Erwinase (Erwinia Asparaginase)
    • Escalated BEACOPP
    • ESHAP
    • ESHAP R
    • ESTRAMUSTINE
    • Etoposide + Ifosfamide (3 days)
    • Etoposide + Ifosfamide (5 days)
    • Etoposide + Ifosfamide + HD Mtx
    • Etoposide Conditioning
    • Etoposide IV
    • Etoposide iv + Mitoxantrone
    • Etoposide oral
    • Etoposide PBSCT Mobilisat (1.6g/m2)
    • EV
    • EVEROLIMUS
    • EZ
    • FAD
    • FAM
    • FBC Conditionining
    • FCarboSt
    • FCiSt
    • FCM (IV)
    • FCMR (Cycle 1)
    • FCMR (Cycle 2 onwards)
    • FCR IV - Cycle 1
    • FCR IV - Cycle 2 onwards
    • FCR Oral - Cycle 1
    • FCR Oral - Cycle 2 onwards
    • FCR Oral Lite
    • FEC 100
    • FEC 60 or 75
    • FLAG
    • FLAG + Idarubicin
    • FLUDAP
    • Fludarabine (iv) + Rituximab
    • Fludarabine (po) + Rituximab
    • Fludarabine + Melphalan RIC Allo
    • Fludarabine IV
    • Fludarabine oral
    • Fluorouracil + Folinic + RT Bossett
    • Fluorouracil + Folinic Acid (Mayo)
    • Fluorouracil + Folinic Acid Weekly
    • Fluorouracil + Streptozocin
    • Fluorouracil + Streptozocin 3day
    • Fluorouracil + Streptozocin 5day
    • Fluorouracil 96hr infusion+R(4g/m2)
    • Fluorouracil PVI + Mitomycin 21day
    • Fluorouracil PVI + Mitomycin 42 day
    • Fluorouracil+Mitomycin+RT (Anal Ca)
    • Fluorouracil+Mitomycin+RT (Bladder)
    • Fluorouracil+Streptozocin 7day Load
    • Fluorouracil+Streptozocin 7day Main
    • Fluorouracil96hr infusion+RT(3g/m2)
    • Fluorouricil + Folonic Acid (MdG)
    • Fluouracil continuous infusion
    • FMD Oral
    • Folfirinox/ Folfoxiri
    • Galunisertib
    • GANETESPIB
    • GCP
    • GDCVP
    • GDP
    • Gefitinib: 1 to 2 & 4 onwards
    • Gefitinib: Cycle 3 only (PAS)
    • GELOX
    • Gem-Dex
    • GEM-P
    • GemCarbo Days 1+8
    • Gemcitabine + Capecitabine
    • Gemcitabine + Methylprednisolone
    • Gemcitabine + Oxaliplatin
    • Gemcitabine + Paclitaxel
    • Gemcitabine + RT pancreas
    • Gemcitabine + Treosulfan (iv)
    • Gemcitabine + Treosulfan (po)
    • Gemcitabine + Vinorelbine IV
    • Gemcitabine 1000mg/m2 D1 8 15
    • Gemcitabine 1250mg/m2 D1 8 15
    • Gemcitabine 300mg/m2 + RT
    • Gemcitabine day 1&8
    • Gemcitabine weekly
    • Gemcitabine+Paclitaxel (Neo-tAnGo)
    • Gilteritinib
    • HCX (Cape + Cisp + Tras) - Load
    • HCX (Cape + Cisp + Tras) - Main
    • Hydroxycarbamide
    • HYDROXYCARBAMIDE + IMATINIB
    • HyperCVAD
    • Ibritumomab Tiuxetan Y90+Rituximab
    • IBRUTINIB
    • ICE (no GCSF)
    • ICE + GCSF
    • ICE-R (Cycle 1)
    • ICE-R (Cycle 2 onwards)
    • IDARAM
    • Idarubicin + Tretinoin (Consolidation course 1)
    • Idarubicin + Tretinoin (Consolidation course 3)
    • Idarubicin + Tretinoin (Induction course)
    • Idarubicin 20mg/m2 oral
    • Idelalisib
    • Idelalisib + Rituximab
    • Ifos + Liposomal Doxorubicin (Pump)
    • Ifosfamide
    • Ifosfamide + Liposomal Doxorubicin
    • Ifosfamide 3g/m2 5 day
    • Ifosfamide PVI 1g/m2 14day
    • Imatinib 100mg
    • Imatinib 200mg
    • Imatinib 400mg
    • Imatinib 600mg
    • Intensification 1 2 3(ALL) (Mtx)
    • Intrahepatic-Fluorouracil+Mitomycin
    • Ipilimumab
    • IPM
    • IPO
    • Irinotecan
    • Irinotecan + De Gramont
    • Irinotecan + Modified De Gramont
    • Irinotecan + Raltitrexed
    • Irinotecan + Temozolomide
    • Irinotecan 14day
    • Irinotecan weekly
    • IVA
    • IVAC
    • IVAD
    • IVADo
    • IVE
    • IVE-R
    • Ixazomib
    • LACE
    • Lapatinib
    • LENALIDOMIDE + MELPHALAN
    • Lenalidomide 10mg (Cycle 1 to 25)
    • Lenalidomide 15mg (Cycle 1 to 25)
    • Lenalidomide 25mg (Cycle 1 to 25)
    • Lenalidomide 5mg (Cycle 1 to 25)
    • Lenalidomide Cycle 26 onwards (PAS)
    • Lenvatinib
    • Letrozole + Palbociclib
    • Liposomal daunorubicin
    • Liposomal Doxorubicin (20mg/m2)
    • Liposomal Doxorubicin (Myocet)
    • Liposomal Doxorubicin + Trabectedin
    • Liposomal Doxorubicin 40mg/m2
    • Liposomal Doxorubicin 50mg/m2
    • Lomustine
    • LOMUSTINE + PROCARBAZINE
    • MA (Cytarabine 1g/m2)
    • MA (Cytarabine 3g/m2)
    • MACE
    • MACOP-B
    • MAE
    • Maintenance Therapy ALL
    • Masitinib
    • MaxiCHOP (>Cycle 2)
    • MaxiCHOP (Cycle 1)
    • MCF
    • MCX
    • MDT
    • MeAD
    • MeAD (peg-asparaginase)
    • Melpahan IV Low dose
    • Melphalan + Treosulfan - HD
    • Melphalan IV High dose
    • Melphalan oral
    • Mercaptopurine
    • Mereletinib
    • Methotrexate + Folinic acid
    • Methotrexate + Vinblastine
    • Methotrexate + Vinorelbine iv
    • Methotrexate 10mg/m2 po 7day
    • Methotrexate 25-50mg/m2 iv 7day
    • Methotrexate 35mg/m2 iv (D1,8)
    • Methotrexate High Dose (3g/m2)
    • Methotrexate Intermed dose (1g/m2)
    • Methotrexate intrathecal
    • Methotrexate+Hydrocortisone Intrathecal
    • MIC
    • MidAC
    • Midostaurin
    • Mifamurtide weeks 1-12
    • Mifamurtide weeks 13-36
    • Mini BEAM
    • Mini-ICE
    • Mitomycin + MdG
    • Mitomycin Intravesical
    • Mitotane 2.5g
    • Mitotane 2g
    • Mitotane 3 - 3.5g
    • Mitotane 4 - 4.5g
    • Mitotane 5.5 - 10g
    • Mitotane 5g
    • Mitoxantrone
    • Mitoxantrone + Paclitaxel
    • Mitoxantrone + Tretinoin (Consolidation course 2)
    • MM
    • MMM
    • Momelotinib
    • MPT
    • MPV (cycle 1-4)
    • MPV (cycle 5-9) - maintenance
    • MVAC
    • MVAC Accelerated
    • MVCarbo
    • MVP
    • Nelarabine
    • Neratinib
    • Nilotinib
    • Nintedanib
    • Niraparib
    • Nivolumab
    • OEPA
    • Ofatumumab Loading
    • Ofatumumab Monthly
    • Ofatumumab Weekly
    • Olaparib
    • OMB (Mtx 1g/m2)
    • Osimertinib
    • Oxaliplatin + Modified de Gramont
    • Oxaliplatin + Raltitrexed
    • PAC-E
    • PAC-PLAT
    • PACE-BOM
    • Packer Induction Vincristine + RT
    • Packer Maintenance Regimen
    • Paclitaxel (2 or 3 weekly)
    • Paclitaxel + Trastuzumab (SC)
    • Paclitaxel 7 day
    • Paclitaxel albumin (Abraxane) 21day
    • Paclitaxel albumin (Abraxane) 7 day
    • Paclitaxel Priming
    • Paclitaxel+Trastuzumab 21 day Maint
    • Paclitaxel+Trastuzumab 21day Load
    • Paclitaxel+Trastuzumab wkly Loading
    • Paclitaxel+Trastuzumab wkly Maint
    • Pacritinib
    • PAD
    • Palbociclib
    • PAM x 2 post-surgery (cycles 3&4)
    • PAM x 2 pre-surgery (cycles 1&2)
    • Panitumumab
    • Panitumumab + Irinotecan + MdG
    • Panitumumab +Oxaliplatin +MdG
    • Pazopanib
    • PCE2BO (Etopophos®)
    • PCV
    • PEC (Germ cell)
    • PEI
    • Pembrolizumab
    • Pemetrexed
    • Pentostatin
    • Pentostatin (for GVHD)
    • Perifosine
    • Pertuzumab + Trastuzumab IV
    • Phase 2 Induction (ALL)
    • Pixantrone
    • PMB
    • PMitCBOM + HD Methotrexate week 1
    • PMitCBOM + HD Methotrexate week 2
    • PMitCEBO
    • PMitCEBO-R
    • PMitCEBOM
    • PNET 4 HIT-SIOP Chemo + RT
    • PNET 4 HIT-SIOP Maintenance
    • POMALIDOMIDE
    • POMB
    • PONATINIB
    • Procarbazine
    • PVD
    • Quizartinib
    • R ABVD
    • R CAIP
    • R Chlorambucil
    • R CHLVPP
    • R CODOX M
    • R FMD
    • R GCVP
    • R IVAC
    • R Mini BEAM
    • R-CHOEP
    • R-GDP
    • R-GEM-P
    • R-GIV
    • R-Hyper-CVAD Course A
    • R-Hyper-CVAD Course B
    • R-PCE2BO (Etopophos®)
    • R-PMitCEBOM
    • R-VP
    • Ralitrexed
    • RCEOP
    • REGORAFENIB
    • Resminostat
    • Resminostat + Sorafenib
    • RFluCy RIC
    • Rituximab
    • Rituximab (INTRAVENOUS Maintenance)
    • Rituximab (SUBCUTANEOUS Maintenance)
    • Rituximab + Temozolomide
    • Rituximab Intrathecal
    • Rociletinib
    • Romidepsin
    • Rucaparib
    • RUXOLITINIB
    • SAPACITABINE
    • Selumetinib
    • Shamash LBCMVD-56
    • SIROLIMUS
    • SMILE
    • Sonidegib
    • Sorafenib
    • SORAFENIB + SUNITINIB
    • Spanish Maintenance (Months 1-3)
    • Spanish Maintenance (Months 4-24)
    • Streptozocin + MdG
    • Sunitinib
    • TAC
    • Talazoparib
    • Talimogene laherparepvec
    • Taselisib
    • TCH (21 day Trastuzumab) Loading
    • TCH (21 day Trastuzumab) Maint
    • TCH (7 day Trastuzumab) Loading
    • TCH (7 day Trastuzumab) Maint
    • TCH(SC)
    • Tegafur
    • Telatinib
    • Temozolomide + RT
    • Temozolomide 100mg/m2 21/28day
    • Temozolomide 150mg/m2
    • Temozolomide 200mg/m2
    • Temsirolimus weekly
    • TEYSUNO
    • Thalidomide 100mg
    • Thalidomide 150mg
    • Thalidomide 200mg
    • Thalidomide 50mg
    • TIDE
    • TIP
    • Tivantinib
    • Tivozanib
    • Topotecan (intravenous)
    • Topotecan (oral)
    • Topotecan IV 7 day
    • Tosedostat
    • Trabectedin
    • Trametinib
    • Trastuzumab (SC) + Vinorelbine (IV)
    • Trastuzumab (SC) + Vinorelbine (Oral)
    • Trastuzumab Intrathecal
    • Trastuzumab IV & Vinorelbine (Loading)
    • Trastuzumab IV +Vinorelbine IV 3wk Main
    • Trastuzumab IV 21 day loading dose
    • Trastuzumab IV 21 day maintenance
    • Trastuzumab IV 7 Day (Loading Dose)
    • Trastuzumab IV 7 Day (Mainten Dose)
    • Trastuzumab IV+Vinorelbine (Maint.)
    • Trastuzumab IV+Vinorelbine IV 3wk Load
    • Trastuzumab IV+Vinorelbine PO 3wk Load
    • Trastuzumab IV+Vinorelbine PO 3wk Main
    • Trastuzumab Subcutaneous
    • Trastuzumab(Kadcyla®) (1st cycle)
    • Trastuzumab(Kadcyla®) (Maintenance)
    • Treosulfan
    • Tretinoin
    • Trifluridine + Tipiracil
    • Triple Intrathecal
    • UKALL XII Consolidation 1
    • UKALL XII Consolidation 2 & 4
    • UKALL XII Consolidation 3
    • UKALL XII Induction Phase 1
    • UKALL XII Induction Phase 2
    • UKALL XII Intensification
    • UKALL XII Maintenance (3 months)
    • UKALL14- Cons Cycle 1
    • UKALL14- Cons Cycle 1 + Imatinib
    • UKALL14- Cons Cycle 2
    • UKALL14- Cons Cycle 2 + Imatinib
    • UKALL14- Cons Cycle 3
    • UKALL14- Cons Cycle 3 + Imatinib
    • UKALL14- FMC (1 day) Conditioning
    • UKALL14- FMC (2 day) Conditioning
    • UKALL14- Intens/CNS Proph
    • UKALL14- Intens/CNS Proph +Imatinib
    • UKALL14- Maintenance
    • UKALL14- Maintenance + Imatinib
    • UKALL14- Ph 1 Induction
    • UKALL14- Ph 1 Induction + Imatinib
    • UKALL14- Ph 2 Induction
    • UKALL14- Ph 2 Induction + Imatinib
    • VAC
    • VAD
    • VAI (Ifos 3g/m2)
    • VANDETANIB
    • VANDETANIB + RT
    • VDC
    • VDT-PACE
    • VE - Vinorelbine + Epirubicin
    • VEDex
    • VeIP
    • Veliparib
    • Vemurafenib
    • Venetoclax
    • VEPEMB
    • VIA (Ifos 1.5g/m2)
    • VIDE
    • Vinblastine
    • Vinblastine weekly
    • Vincristine (weekly)
    • Vindesine
    • Vinflunine
    • Vinorelbine (oral)
    • Vinorelbine (weekly iv)
    • Vinorelbine 25mg/m2 14 day
    • Vinorelbine 25mg/m2 28 day
    • Vinorelbine IV
    • VIP
    • VISMODEGIB
    • VTDPACE  
    • Z-Dex

Algorithms

• Treatment records should be inserted into TREATMENT table using one of three standardized algorithms. Algorithm choice is dependent on two factors:
  • Presence of pre-made treatment abstractions in source system(s): The presence of oncology treatments encoded at the required higher-level of abstraction within source system(s).
  • Presence of pre-made connection to lower-level clinical events: The presence of connection from oncology treatments encoded at the required higher-level of abstraction to lower-level clinical events within source system(s).

Option A Algorithms

• Option A Algorithm 1: Pre-made treatment abstractions in source system that have pre-made connections to lower-level clinical events.
  • Insert pre-made treatment abstraction into TREATMENT table.
  • Make pre-made connections to the inserted TREATMENT entry by populating the treatment_id column in the corresponding clinical event table: DRUG_EXPOSURE or PROCEDURE_OCCURRENCE.
  • No derivation logic necessary.
• Option A Algorithm 2: Pre-made treatment abstractions in source system(s) that do not have pre-made connections to lower-level clinical events.
  • Insert pre-made treatment abstraction into the TREATMENT table.
  • Identify qualifying clinical events of the TREATMENT entry’s treatment concept falling within treatment begin date and treatment end date.
  • Connect qualifying clinical events to the appropriate TREATMENT entry by populating the treatment_id column in the corresponding clinical event table: DRUG_EXPOSURE or PROCEDURE_OCCURRENCE.
• Optin A Algorithm 3: No pre-made treatment abstractions in source system(s).
  • Treatment records will be derived from the records in the DRUG_EXPOSURE and PROCEDURE_OCCURRENCE. tables.
  • Identify the first-course treatment of each treatment concept by finding all qualifying clinical events of each treatment concept category within 10 days of treatment start date (index date). Treatment start date is the date of the first qualifying clinical event after diagnosis date of each treatment concept.
  • Identify qualifying clinical events of the treatment concept not occurring during the period. If new qualifying clinical events for the treatment concept are found outside of the 10-day period for the first course, insert another entry into the TREATMENT table and update the treatment end date of the prior course to the date of the last qualifying clinical event. New clinical events is defined as events not present in the first period. Treatment start date (index date) for the second-course is the date of the new clinical event. Second course includes all clinical events of the treatment concept within 10 days of the second-course treatment’s start date. Repeat until no additional clinical events of the treatment concept are identified.
  • Connect qualifying clinical events to the appropriate TREATMENT entry by populating the treatment_id column in the corresponding clinical event table: DRUG_EXPOSURE or PROCEDURE_OCCURRENCE.

Option B Algorithms

• Option B Algorithm 1: Pre-made treatment abstractions in source system that have pre-made connections to lower-level clinical events.
  • Insert pre-made treatment abstraction into TREATMENT table.
  • Make pre-made connections to the inserted TREATMENT entry by inserting into the TREATMENT_EVENT table a reference to the corresponding clinical event table: DRUG_EXPOSURE or PROCEDURE_OCCURRENCE.
  • No derivation logic necessary.
• Option B Algorithm 2: Pre-made treatment abstractions in source system(s) that do not have pre-made connections to lower-level clinical events.
  • Insert pre-made treatment abstraction into the TREATMENT table.
  • Identify qualifying clinical events of the TREATMENT entry’s treatment concept falling within treatment begin date and treatment end date.
  • Connect qualifying clinical events to the appropriate TREATMENT entry by inserting into the TREATMENT_EVENT table a reference to the corresponding clinical event table: DRUG_EXPORSURE or PROCEDURE_OCCURRENCE.
• Option B Algorithm 3: No pre-made treatment abstractions in source system(s).
  • Treatment and Treatment Event records will be derived from the records in the DRUG_EXPOSURE and PROCEDURE_OCCURRENCE. tables.
  • Identify the first treatment of each treatment concept by finding all qualifying clinical events of each treatment concept category within 10 days of treatment start date (index date). Treatment start date is the date of the first qualifying clinical event after diagnosis date of each treatment concept.
  • Identify qualifying clinical events of the treatment concept not occurring during the first period. If new clinical events for the treatment submodlity are found outside of the 10-day period for the first treatment, insert another entry into the TREATMENT table and update the treatment end date of the prior treatment to the date of the last qualifying clinical event. New clinical events is defined as events not present in the first period. Treatment start date (index date) for the second treatment is the date of the new clinical event. Second treatment includes all clinical events of the treatment concept within 10 days of the second treatment’s start date. Repeat until no additional clinical events of the treatment concept are identified.
  • Connect qualifying clinical events to the appropriate TREATMENT entry by inserting into the TREATMENT_EVENT table a reference to the corresponding clinical event table: DRUG_EXPOSURE or PROCEDURE_OCCURRENCE.

Algorithm Inspiration
Based on an algorithm in paper “Algorithm to Identify Systemic Cancer Therapy Treatment Using Structured Electronic Data”: http://ascopubs.org/doi/pdf/10.1200/CCI.17.00002. Attempts to characterize first-course systemic therapy and all subsequent course systemic therapy. Uses ‘Cancer Therapy Look-up Tables’ maintained by the NCI Cancer Research Network (CRN) listing National Drug Codes (NDCs), procedure codes (CPT4, ICD-9, HCPC) and diagnosis codes (ICD-9) to filter clinical events in a Health Care Systems Research Network (HCSRN) virtual data warehouse (VDW). https://crn.cancer.gov/resources/codes.html

Open Issues

• This solution provides Oncology Treatments pre-abstracted and pre-connected to lower-level clinical events a place within the OMOP CDM.
• The solution also provides an admittedly simplistic compendium-based/persistence window algorithm to derive oncology treatments and clinical event connections when they are not available within source systems.
• Hopefully the future will bring better compendiums and better algorithms to increase accuracy of deriving Oncology Treatments abstractions and connections to lower-level clinical events.
• A authoritative source of known drug ingredient/regimens administered outside of a 10-day window and storage of the window in some location within the CDM would enable data-driven look-aheads by a configurable window in the data for receipt of the additional systemic therapy drugs. Perhaps look to NCCN Chemotherapy Order Templates and/or NHS National Tariff Chemotherapy Regimens List.
  • https://www.nccn.org/professionals/OrderTemplates/Default.aspx
  • https://isd.digital.nhs.uk/trud3/user/guest/group/61/pack/10
• Perhaps a default of 10 day window does not make sense for radiation therapy or some radiation therapy subtypes. An authoritative source of known radiation therapy subtypes administered outside of a 10-day fractionation window and storage of the window in some location within the CDM would enable data-driven look-aheads by a configurable window in the data for receipt of the additional radiation therapy clinical events.
• Surgical Oncology Compendium: The NCI CRN ‘Cancer Therapy Look-up Tables’ do not currently cover surgical therapies. A comparable compendium linking oncology surgical procedure codes to a high-level classification of oncology surgery types will need to be developed/found.
• The NCI Cancer Therapy Evaluation Program (CTEP) provides a list of therapy codes based on MedDRA v10.0. This list of therapy codes points to other Treatment Types and/or Treatment Subtypes that need a compendium of micro-clinical event codes: Anti-retroviral Therapy, Antisense, Bone Marrow Transplant, Gene Transfer, Hematopoietic Stem Cell Transplantation, Image Directed Local Therapy, Oncolytic Virotherapy and Vaccine.
• Should we find a place for attribution of properties or modifiers at the level an Oncology Treatment? Waiting to see evolution of condition modifiers proposal. For example NAACCR radiation therapy treatment properties (http://datadictionary.naaccr.org/). For example:
  • Rad--Regional Dose: cGy
  • Rad--Boost Dose cGy
  • Rad--Treatment Volume
• Should we make room for representing an even higher level abstraction of Treatment Courses? A treatment course is a grouping of Oncology Treatments into a set. For example, a radiation therapy and a drug therapy. Each treatment is considered a co-equal participant in a treatment course.

[ColinOrr2008]

Good proposal. As per my forum message on tracking patient treatments I have a similar requirement to store treatment level data related to various cancer treatment methods. And as the proposal suggests there a bunch of data that relates to the overall course of treatment that has no natural location within OMOP today that is easily / efficiently accessible. Option A of the proposal is the most appropriate approach from the perspective of my use cases anyway. My use cases at present all relate to cancer treatment but the approach suggested can be used for any chronic condition where there is a course of treatment. I image that CNS conditions would benefit from such a construct.

The TREATMENT domain in conjunction with the TREATMENT_MODIFIER would support all of the my requirements. I have a whole series of “modifiers” that I need to capture at a treatment level such as “whether it was completed or not” or specific side effects and their date of occurrence. These “modifiers” could also easily be considered OBSERVATIONS and I believe in my case all of the data that would be collected as part of a TREATMENT could just as easily be stored in the OBSERVATION table. In which case the OBSERVATION table should also have a TREATMENT_ID column added in to relate them to a specific treatment.

The proposal of adding a TREATMENT ID to the DRUG_EXPOSURE and PROCEDURE_OCCURRENCE table to link these events to a specific treatment I suggest should also be extended to the VISIT_OCCURRENCE table. This would allow for any events related to a patient visit whether they are related to a specific procedure, drug exposure or otherwise to be linked back to a treatment where the visit is part of a specific treatment.

Just a few thoughts…..

[shawndo]

Is there any reason this cannot be used for non-cancer treatments that have some or all of the same requirements/challenges? Seems it has been designed without cancer specificity enough to accommodate others. ?

[mgurley]

@ColinOrr2008 @shawndo

Thanks for the feedback.

• TREATMENT beyond Oncology: Yes, I think the TREATMENT structures/domains could likely be applied/expanded outside of Oncology. As mentioned: to the treatment of any chronic/long-running condition. Here are some discussions in the forums about concepts closely related to the treatment concept: an 'Episode of Care' concept and a 'Care Plan' concept. See here: http://forums.ohdsi.org/t/how-to-capture-pregnancy-data-edc-gestation-length-etc/4250 http://forums.ohdsi.org/t/how-to-capture-care-plan-data/4273

@ColinOrr2008

• EAV: We are proposing the TREATMENT_MODIFIER structure/domain instead of using references to OBSERVATION/MEASUREMENT via FACT_RELATIONSHIP in order move to more tightly-scoped EAV structures/domains. We are doing likewise in a separate Diagnosis Modifier proposal for the myriad oncology diagnosis modifiers: staging, grade, lymphatic invasion, biomarker results, etc. EAV is a necessary evil in healthcare. But there are ways to make it less evil. To quote @cgreich, OBSERVATION is a "garbage can". We are just trying to organize our garbage cans. Like separating into compost, waste, paper, aluminum/plastic.

• Add treatment_id to VISIT_OCCURRENCE Good idea. We will bring this idea to the Oncology Workgroup for inclusion.

[vojtechhuser]

I am confused by Option A statements on derivation. see blue text (start and end)

[vojtechhuser]

If we ingest into OMOP Vocab NCI CRN ‘Cancer Therapy Look-up Tables, we should think of non-US contries. The knowledge base is in "non-standard" CPT codes.

see these examples from here https://crn.cancer.gov/resources/Radiation%20Therapy%20Codes_Procedures.csv

If we formulate smart constructs in OMOP Vocab, we should not do it off copyrighted CPT4 codes.

[mgurley]

@vojtechhuser Regarding your comment: "I am confused by Option A statements on derivation. see blue text (start and end)"

One of the main issues this proposal is trying accomodate is the varying levels of grouping/abstraction of lower-level clinical events available within various source systems. Sometimes:

• You have an Oncology EMR that goes beyond simply recording administrations/prescriptions of the drugs in a chemotherapy regimen or each fraction of a radiation therapy treatment, actually containing TREATMENT and TREATMENT_CYCLE groupings/abstractions natively. No derivation necessary. Insert both the low-level clinical events, the grouping/abstraction structures (TREATMENT and TREATMENT_CYCLE) and the connections between them.
• You have an EMR that simply records administrations/prescriptions of the drugs in a chemotherapy regimen or each fraction of a radiation therapy treatment. With no grouping/abstraction present within the source system that these clinical events are part of a TREATMENT or TREATMENT_CYCLE. Insert the low-level clinical events. Algorithmically derive TREATMENT abstractions/groupings. Do not Algorithmically derive TREATMENT_CYCLE abstractions/groupings because it is not likely possible.
• You have a Tumor Registry that only records that a chemotherapy regimen or a radiation therapy treatment occurred. With no connection to low-level clinical events. Plus you have an EMR that that simply records administrations/prescriptions of the drugs in a chemotherapy regimen or each fraction of a radiation therapy treatment. Insert both the low-level clinical events and the grouping/abstraction structures. Algorithmically derive connections between TREATMENT abstractions/groupings and low-level clinical events. Do not algorithmically derive TREATMENT_CYCLE abstractions/groupings or connections to low-level clinical events because it is not likely possible.
• You just have a Tumor Registry that only records that a chemotherapy regimen or a radiation therapy treatment occurred. With no connection to low-level clinical events. Do not algorithmically derive anything.

[gowthamrao]

Add support for a TREATMENT concept

I think we mean, TREATMENT domain. i.e. just like we have Visit domain, condition domain.

A TREATMENT can be delivered at regular intervals, cycles or fractions. The temporal grouping of clinical events into cycles will only be instantiated if it is available within a source system. TREATMENT cycles will not be algorithmically derived. Pre-made higher-level TREATMENT abstractions present in a source systems will be directly inserted. Alternatively, when not available within any source system, TREATMENT abstractions will be algorithmically derived from lower-level clinical events.

Could you please clarify - 'treatment cycles will not be algorithmically derived' vs. 'Treatment abstractions will be algorithmically derived'

Treatment table

Can the person have different treatment_id's with the same or overlapping treatment start date and treatment end date? (I think the answer is yes). Could you please give some examples?

treatment_cycle_number an ordinal enumeration of treatment cycles. Each representation of a treatment cycle should refer to the parent Treatment by the parent id column.

can you please elaborate this field with an example. E.g. if this is the third chemoRx cycle of a planned treatment of 6 cycles, what value would be in treatment_cycle_number. I think it is proposed to be increment count - e.g. in this case, it would treatment_cycle_number = 3? What is a 'parent Treatment' in this case - maybe the treatment that encompasses all six chemoRx cycles? How can the analyst know for example -- 6 chemoRx were planned, and only 3 were done so far?

table contains records aggregating lower-level clinical events Treatment_modifier.treatment_modifier_domain_id Treatment_modifier.treatment_modifier_event_id

To identify if the table is procedure_occurrence, condition_occurrence, visit_occurrence etc., I think it is best if we support this proposal (use table_concept_id instead of ambiguous domain_concept_id )

TREATMENT_MODIFER

This table seems like a detail of the TREATMENT table. For every record in the TREATMENT table there may 0 or more records in TREATMENT_MODIFIER table? Can the attributes in the TREATMENTMODIFIER table be considered measurements? It has value, unit_

[mgurley]

@vojtechhuser

If we formulate smart constructs in OMOP Vocab, we should not do it off copyrighted CPT4 codes.

We need to find a mapping from vocabulary codes used to represent oncology treatment low-level clinical events to a high-level typing of oncology treatments. This is what NCI CRN ‘Cancer Therapy Look-up Tables' provides. For radiation therapy, it maps 'CPT4', 'HCPC' and 'ICD9' codes. This was based on the actual codes present in the VDW instance upon which it was developed. Since CPT4 is not a standard procedure vocabulary within OMOP (because of licensing), our ingestion of the 'NCI CRN ‘Cancer Therapy Look-up Tables' would likely need to enrich the native mappings to include all standard procedure concepts mappable from CPT4.

On related note, The NCI has recently released a parallel effort called the 'Observational Research in Oncology Toolbox'. See here: https://seer.cancer.gov/oncologytoolbox/. This effort similarly maps vocabulary codes used to represent oncology treatment low-level clinical events to a high-level typing of oncology treatments. A very attractive feature of the 'Observational Research in Oncology Toolbox' is that its high-level typing of oncology treatments is based on and can be connected to tumor registry NAACCR/SEER treatment variables. So far the 'Observational Research in Oncology Toolbox' has only released a mapping for Oncology Drugs, but it is planning on releasing mappings for radiation therapy and surgical oncology. I will be replacing the 'NCI CRN ‘Cancer Therapy Look-up Tables' within the proposal with the 'Observational Research in Oncology Toolbox'. However, your advice about making sure the mappings do not rely on copyrighted non-standard codes will still hold true.

[mgurley]

@gowthamrao

I think we mean, TREATMENT domain. i.e. just like we have Visit domain, condition domain.

You are right. Changed it.

Could you please clarify - 'treatment cycles will not be algorithmically derived' vs. 'Treatment abstractions will be algorithmically derived'

See my response to @vojtechhuser first comment. But basically, in the best case neither Treatments nor Treatment Cycles will need to be algorithmically derived if they are present within your source system. However, if Treatments and Treatment Cycles are not present within your source system, I think it will only be possible to derive Treatments and not Treatment Cycles.

Can the person have different treatment_id's with the same or overlapping treatment start date and treatment end date? (I think the answer is yes). Could you please give some examples?

Yes, a person could have two Treatments with overlapping start and end dates. For example, my Radiation Therapy Beam IMRT treatment could overlap with my Drug Therapy Hormonal treatment.

can you please elaborate this field with an example. E.g. if this is the third chemoRx cycle of a planned treatment of 6 cycles, what value would be in treatment_cycle_number. I think it is proposed to be increment count - e.g. in this case, it would treatment_cycle_number = 3? What is a 'parent Treatment' in this case - maybe the treatment that encompasses all six chemoRx cycles? How can the analyst know for example -- 6 chemoRx were planned, and only 3 were done so far?

The treatment_cycle_number field is supposed to represent the actual number cycle that was executed. So not necessarily incrementing, if for some reason a cycle is skipped.
The treatment_parent_id (in Option A) is always the treatment that encompasses all six chemoRx cycles. (Option B makes this relationship more explicit, which is why I prefer it, the table structure being more isomorphic with reality). Right now the model does not allow for tracking planned versus executed cycles. To allow for this, perhaps we should add a treatment_cycle_status_concept_id field. What do you think?

To identify if the table is procedure_occurrence, condition_occurrence, visit_occurrence etc., I think it is best if we support this proposal (use table_concept_id instead of ambiguous domain_concept_id )

Sounds good. We should follow the emerging OMOP/OHDSI standards. I will change the proposal to adhere to the proposal you pointed to.

This table seems like a detail of the TREATMENT table. For every record in the TREATMENT table there may 0 or more records in TREATMENT_MODIFIER table? Can the attributes in the TREATMENTMODIFIER table be considered measurements? It has value, unit_

This response is a repeat of what I have said to @ColinOrr2008. We are proposing the TREATMENT_MODIFIER structure/domain instead of using references to OBSERVATION/MEASUREMENT via FACT_RELATIONSHIP or adding foreign keys to them in order move to more tightly-scoped EAV structures/domains. We are doing likewise in a separate Diagnosis Modifier proposal for the myriad oncology diagnosis modifiers: staging, grade, lymphatic invasion, biomarker results, etc. EAV is a necessary evil in healthcare. But there are ways to make it less evil. To quote @cgreich, MEASUREMENT and OBSERVATION are "garbage cans". We are just trying to organize our garbage cans. Like separating into compost, waste, paper, aluminum/plastic.

[vojtechhuser]

It would be nice to have same sample data and show all the issues in an example context.

[cgreich]

Agree 100%. Will have to create that.

[mgurley]

@vojtechhuser @cgreich

I will create some sample data. Sample data will make it concrete how source systems (EHR data and Tumor Registry data) with varying degrees of treatment abstractions natively can ETL into the model.

[clairblacketer]

closing as this is covered by #216