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INTRODUCTION



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Section:

The accession of aggregate chemotherapy in the 1960s and 1970s has led to ever-increasing aggravation of blight assay regimens. On the base of the success of assertive combinations in abating assertive cancers, multidrug aggregate regimens, about with circuitous sequencing and dosing parameters, accept become common. As a result, an breezy abracadabra based primarily on acronyms arose to facilitate advice amid oncologists and with patients. This abracadabra is appropriate and can accommodate a mix of generic, chemical, and cast names of antineoplastics. For example, the lymphoma dieting CHOP, originally alleged the uninformative “Combination 2,” contains two all-encompassing abbreviations (C for cyclophosphamide and P for prednisone/prednisolone), one brand-name abridgement (O for Oncovin [vincristine]), and one actinic name abridgement (H for hydroxydaunorubicin/hydroxyldaunomycin).1-3 The dieting PAD contains one all-encompassing abridgement (D for dexamethasone), one brand-name abridgement (A for Adriamycin [doxorubicin]), and one cipher name abridgement (P for PS-341 [bortezomib]).4 As the majority of bortezomib-containing regimens abridge it with a “V” (its cast name is Velcade), PAD is sometimes alleged VAD in practice. This creates abashing with an earlier dieting that was a accustomed of affliction for abounding years, VAD,5 breadth V stands for vincristine (as against to Velcade [bortezomib]).



As biologic development accelerates, and an accretion armamentarium of antineoplastics is congenital into assay regimens, examples such as this will become added common. The oncology association needs a lingua franca for documenting the consideration, planning, administration, and history of chemotherapy regimens. There are abounding abeyant downsides to the accustomed accompaniment of nonstandardized representation. Best importantly, analytic affliction can be affected. For example, a tertiary barometer centermost ability alter the “VAD” in a patient’s assay history as accepting independent bortezomib and ability accede the accommodating apparent and aggressive aback they are absolutely bortezomib naïve. In accession to facilitating bigger advice amid clinicians, a connected regimen-naming assemblage would facilitate accessory use of assay acknowledgment abstracts by alien registrars and acquirements bloom systems such as CancerLinQ and for studies application cyberbanking bloom almanac (EHR) data. At atomic in allotment because of difficulties with dieting naming, the blight anthology association has historically abandoned recorded abandoned biologic exposures, aback they are recorded at all. This can advance to ambiguity and bereft detail to accept patterns of assay exposure. For example, R-EPOCH6 and dose-adjusted R-EPOCH7 accommodate the aforementioned drugs but are audible in agreement of doses, indications, administering times, and added details. The anticipated aftereffect is anarchy aback abutting the botheration of accumulation real-world abstracts at a citizenry scale, as is envisioned by the US Food and Biologic Administering (FDA)8 as able-bodied as efforts such as ASCO’s CancerLinQ,9 Flatiron, and American Association for Blight Research Genomics Affirmation Neoplasia Advice Exchange (GENIE).10

CONTEXT



Key Objective

The aim of this assignment was to advance the aboriginal connected nomenclature, to our knowledge, for representation of chemotherapy regimens, which accept been continued accustomed to accept cryptic and nonstandardized allotment conventions.

Knowledge Generated

Rules for the representation of chemotherapy regimens as connected concepts were developed. These rules were activated to map regimens represented by HemOnc.org and the National Blight Institute Thesaurus and to adjudge adopted dieting representations, as able-bodied as to authenticate the amount of ambiguity in dieting representation for assorted myeloma regimens.

Relevance

If adopted, this classification has the abeyant to advance accord in representation of assay concepts, facilitating all-embracing abstracts assay for acquirements bloom systems and cyberbanking bloom record–based investigation.

Informed primarily by our acquaintance architecture HemOnc.org,11 the better advisedly accessible ability of chemotherapy biologic and dieting information, we accept alien the aboriginal connected cant for chemotherapy regimens in the Empiric Medical Outcomes Partnership accustomed abstracts model, acceptance for transformation of abstracts acquired from audible empiric sources into a compatible format.12 Here, we booty this further, proposing a accustomed classification for chemotherapy regimens. What follows is aggressive by the archetypal of the desiderata angle of Cimino,13 which establishes belief for standardizing medical vocabularies including altered identification of concepts, abstraction permanence, and orientation. It is meant to atom a altercation aural the communities of clinicians (clinical certificate creators), guideline creators, and analytic abstracts consumers (secondary users of EHR data). We adduce 13 rules for allotment chemotherapy regimens on the base of our acquaintance curating HemOnc.org and our circadian acquaintance as clinicians. Subsequently, we appraise the ambit of the accustomed claiming in the breadth of assorted myeloma and accomplish a mapping and allegory of the HemOnc12 and National Blight Institute Thesaurus (NCIT)14 content.

NOMENCLATURE PROPOSAL

Section:

We adduce a action for connected classification of categories of chemotherapy regimens, organized in accretion adjustment of dieting complexity. Our recommendations use the acclimation verbs SHALL, SHOULD, and MAY as authentic in Network Working Accumulation Request for Comment 2119.15 Relevant examples are accustomed in Table 1.

TABLE 1. Examples of Dieting Adjudication According to the Proposed Schema

1. Regimens Composed of a Audible Component

These shall be bidding by the all-encompassing biologic name followed by the suffix “monotherapy.” Alternatively, they can be bidding by the prefix “single-agent” followed by the basic name. The suffix “monotherapy” is preferred, unless apropos to a class (eg, “single-agent chemotherapy”). Application acronyms to represent a audible basic should be avoided, as audible belletrist will be frequently abashed with added EHR artifacts.

2.1. Regimens Absolute Two Components, Abounding Names Used

When the two apparatus are of the aforementioned biologic category, these shall be bidding in alphabetical adjustment of the all-encompassing name, afar by “and” or “&.” Aback one of the apparatus is a cytotoxic and the added is a monoclonal antibody, a steroid, or radiation, the cytotoxic shall be bidding first. For anniversary component, abandoned the aboriginal chat is capitalized.

2.2. Regimens Absolute Two Components, Abounding Name Acclimated for One and Abbreviation/Acronym for the Other

This is about beat except for one case: the abbreviated basic is radiation assay (RT). In this case, the aphorism is the aforementioned as above: “Cisplatin & RT” is correct; “RT & Cisplatin” is not.

2.3. Regimens Absolute Two Components, Abbreviation/Acronym Used

These are decidedly decumbent to ambiguity. For example, the small-cell lung blight (SCLC) dieting absolute cisplatin and etoposide has been variably alleged EC (etoposide & cisplatin), EP (etoposide & Platinol [cisplatin]), and PE (Platinol [cisplatin] & etoposide). In these cases, it is apparently best to aggrandize the acronym and chase the rules categorical in 2.1. Otherwise, there are four guidelines to consider:

Avoid acronyms that are calmly abashed with added medical acronyms (eg, PE is added frequently an abridgement for pulmonary array and EP is an abridgement for electrophysiology).

Avoid acronyms that use a cast name (eg, EP or PE).

Avoid acronyms that are abundant added frequently acclimated for added regimens (eg, EC is a accustomed acronym for the breast blight dieting of epirubicin and cyclophosphamide).

Use the acronym that is best about acclimated in the appear literature.

3.1. Regimens Absolute Three or Added Components, Abounding Names Used

Components shall be afar by a comma, afterwards the use of “and” (eg, “A, B, C, D” not “A, B, C, and D”). Apparatus shall be listed alphabetically aural subcategory, as follows: cytotoxics first, again monoclonal antibodies, again steroids.

3.2. Regimens Absolute Three or Added Components, Abbreviation/Acronym Acclimated for Some but Not All

There are two cases breadth this is acceptable:

As before, the basic of radiation assay can and should be abbreviated as RT.

If two or added apparatus compose a acclaimed “backbone” that is frequently referred to by acronym.

3.3. Regimens Absolute Three or Added Components, Abbreviation/Acronym Acclimated for All Drugs

In abounding cases, a abstract altercation exists over whether abbreviating a dieting is all-important or appropriate for a accurate regimen. Exchanging more-precise for less-precise analogue consistently introduces abeyant ambiguity. There is no a priori way to adjudge this issue, as the specifics of abandoned regimens are important. However, abridgement the names of regimens potentially reduces affidavit accountability for clinicians and registrars, abnormally aback regimens accommodate added than three drugs or absorb alternating combinations of chemotherapy. Regimens should accordingly be abbreviated in some anatomy aback it is accessible to do so in a way that acutely conveys the assay agreement actuality acclimated for a accurate patient.

In adverse to the bearings declared in aphorism 2.3, ambiguity is beneath accustomed in this setting, but it still exists. R-CHOP is a accurate example; 3,952 patients at Vanderbilt University Medical Centermost accept the acronyms “R-CHOP,” “RCHOP,” “CHOP-R,” or “CHOPR”—representing the chemotherapy dieting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone—present in their EHR. In this case a Google Scholar chase is informative; there are 24,100 after-effects for “R-CHOP chemotherapy,” 6,060 for “CHOP-R chemotherapy,” 2,230 for “RCHOP chemotherapy,” and 64 for “CHOPR chemotherapy.” R-CHOP is preferred.

Additional ambiguity arises aback a biologic abettor is added to a chemotherapy courage and is itself abbreviated. In abounding cases, the abbreviated biologic abettor is added on the avant-garde end (R-CHOP, R-GemOx); aback this is done, it is about afar from the chemotherapy courage by hyphenation. In added cases, the accustomed biologic abettor is added on the aback end (BR, FCR), in which case it is about added to the chemotherapy courage with no separation. Empirically, we acquisition that this assemblage about holds, and we adduce that it be followed for atypical akin combinations.

The authors of a cardboard about specify an abridgement for a accurate regimen; in these cases, as continued as this does not battle with an abridgement for an absolute regimen, it is appropriate to use this abbreviation, alike if it does not authority to the conventions defined herein. This facilitates bond of a dieting declared in analytic affidavit or a bump anthology with a agnate advertence in the literature.

4. Regimens That Are Modifications of Added Regimens

Several frequently acclimated regimens are in actuality modifications of earlier regimens that accept overtaken their predecessors in analytic use, usually because of ahead in a randomized trial. We adduce the afterward autograph classification to announce the blazon of modification: e for escalated, m for modified, dd for dose-dense, di for dose-intense, and da for dose-adjusted. If a accurate acuteness of a biologic is used, “high-dose” or “low-dose” are adequate modifiers.

5. Regimens With Cryptic Abbreviations/Acronyms

If one of the belletrist of an abridgement or acronym is acceptable to be abashed with a agnate basic of addition regimen, the name of the abbreviated basic should be provided in parentheses anon afterwards the dieting name.

In some cases, assorted apparatus of a dieting may be abbreviated identically, in which case allegorical the cryptic abettor parenthetically requires accomplishing so assorted times. For some of these, one of the agents has an alternating or cast name that can be abbreviated distinctly. Although all-encompassing names are bigger in the all-inclusive majority of cases, this represents an barring in which a cast name is adopted (Table 2).

TABLE 2. Cast or Nongeneric Names Frequently Acclimated in Dieting Acronyms

Wherever possible, a dieting should not be abbreviated in such a way that makes it identical to an English chat or nonchemotherapy medical abbreviation.

6. Regimens With Eponymous or Appropriate Names

Although about to be avoided, some regimens and protocols are actual able-bodied accustomed by the name of an abandoned or a accumulation study. In these cases, if there is a readily accustomed noneponymous dieting name it should be used, with the eponym parenthetically anon afterwards the dieting name. If no such classification readily exists, it should be adumbrated as a regimen, either by admittance of the chat “regimen” or with alternating modifiers allegorical the above-mentioned acronym. This is abnormally important aback because protocols involving abounding audible regimens administered over months to years (see area 9 for added discussion).

7. Regimens Absolute Two or Added Alternating Sets of Components

These regimens abide of subsets of regimens that cannot be accordingly unlinked because of the alternation agenda (eg, A is followed by B, again A, again B, again A, again B). In these cases, aback the subsets are acronyms, abandoned subsets should be afar by a “/”. The “/” indicator shall be aloof for this purpose only; application it abroad creates ambiguity as to whether the drugs afar by “/” are accustomed sequentially or together. If the subsets are abounding names, the separator should be “alternating with.”

8. Variant Naming

Many broadly acclimated regimens are variants of added regimens, involving the aforementioned drugs on an alternating dosage akin or agenda that does not calmly fit into the modification archetype as explained above. Sometimes these variants abide to abstain toxicity in the ambience of anterior agency dysfunction or to amusement patients who were too breakable to be advised in antecedent trials. If such variants are adumbrated by broadly accustomed modifiers, these should be used, as they can abstain cogent aggravation in dieting allotment while carrying the aforementioned meaning. If not, the modification to the absolute dieting should be adumbrated as succinctly as possible, with the adapted biologic adumbrated in the aforementioned appearance as in the antecedent regimen.

9. Protocols Absolute Two or Added Regimens

These are about circuitous treatments that abide of two or added consecutive procedures or regimens accumulated into a absolute protocol. Anniversary temporally audible dieting or action should be afar by “, then.” There are some exceptions to this; for example, some broadly acclimated consecutive breast blight regimens absorb a arrangement of an anthracycline/cyclophosphamide brace and a taxane, and the banausic break amid regimens is represented by a birr (eg, AC-T). Unless such representations are about ubiquitous, they should be avoided.

EVALUATION

Section:

Use Case 1: NCIT to HemOnc Dieting Mapping

We manually mapped the adopted audible dieting names in the HemOnc cant to the agnate adopted concepts in the NCIT. The purpose of this was two-fold: 1) accouterment added alien mappings in HemOnc (eg, procedures are mapped to Systematized Classification of Medicine-Clinical Agreement [SNOMED-CT]; drugs to RxNorm; and altitude to NCIT and SNOMED-CT), and 2) free the amount to which the adopted names in the vocabularies adjust with these proposed rules.

There were 527 auspiciously mapped regimens; of these 285 (54.1%) are declared analogously on NCIT, aback accounting for semantic differences in punctuation and labeling concepts as “regimens” (Data Supplement). This leaves 242 (45.9%) in which the aforementioned abstraction is represented abnormally by the two databases. Of these, the action aloft was able to analyze a acutely bigger dieting for 217 (90.0%); the HemOnc classification was adopted in 194 cases (89.4%), and the NCIT classification was adopted in 23 cases (10.6%). Rationales for allocating a bigger dieting are abbreviated in Figure 1.

For 25 discrepancies, the proposed rules could not admeasure a adopted name. The two sources about chose means to abridge regimens that were appropriately actual and potentially useful, are distinct, and accept agnate representation in the literature. It is arduous to adjudge these cases until one accurate classification is adopted added widely. Beyond the classification evaluation, this mapping offers account to the community. For example, built-in NCIT users can band HemOnc relationships into their applications (Fig 2).

Use Case 2: Assorted Myeloma Dieting Nomenclature

The consequence of this botheration absolutely comes into focus aback analytical the mural of assorted myeloma regimens. There are 17 FDA-approved drugs for the assay of this malignancy, 7 of which were accustomed in 2012 or later; added than 100 regimens accept been evaluated in assorted myeloma in appearance II or III studies. Several contempo randomized controlled trials accept approved above progression-free adaptation for three-drug combinations compared with two biologic combinations in a array of assay settings.16-18 Four-drug combinations are currently beneath alive investigation.19 Because of these developments, added circuitous regimens accumulation chemotherapeutic agents and monoclonal antibodies are acceptable the accustomed of care. An added aggravation arises because lenalidomide additional high-dose dexamethasone has been compared with lenalidomide additional low-dose dexamethasone.20 These are altered regimens and are about represented audibly (“RD” for high-dose dexamethasone, “Rd” for low-dose dexamethasone). One can brainstorm that representation of these regimens is not homogeneous, both in the abstract and in analytic documentation. Some examples of variants of frequently acclimated regimens are listed in Table 3.

TABLE 3. Archetype Myeloma Regimens Alleged According to the Proposed Schema

We advised the 130 assorted myeloma regimens independent aural HemOnc. On the base of the representation of these regimens in the abstract and our empiric acquaintance in analytic practice, we accept recorded 1,138 acronyms apery these regimens (Data Supplement). This is not advised to be absolute but about illustrates the ambit of the problem. Abandoned regimens accept a average of six audible representations, with a best of 31 for one four-drug aggregate (bortezomib, cyclophosphamide, lenalidomide, and dexamethasone). This adverse in representation creates challenges in free above-mentioned assay exposure, and accordingly accommodation for consecutive assay at relapse, which is assured for this cureless malignancy.

Using the rules-based access for compatible nomenclature, we burst these myeloma regimens into representations applicable our action (Table 4).21 Although alternating representations for these concepts exist, this access does so in a way that allows cogent abridgement and basal ambiguity as to the dieting actuality used. To our knowledge, this is the aboriginal angle for a action to adapt chemotherapy dieting nomenclature. We accept approved with two use cases that this action is advantageous to disambiguate dieting representation. Our action can be acclimated to adjudge differences in dieting representation and can collapse an added circuitous mural of dieting representation into a short, comestible account of concepts.

TABLE 4. Putative Representations of Myeloma Regimens

We accede that altered abeyant methodologies abide to assimilate chemotherapy dieting representation. We do not affirmation or aim to authenticate that our angle is definitively above to accessible alternatives. Because no acclimation action yet exists, were the accustomed presented in this cardboard adopted, the accord of assay representation in the abstract and in analytic affidavit could increase. As regimens abound added circuitous and complex over time, it is acceptable added important to advance a priori best practices for allotment new regimens. Adopting a accustomed nomenclature, whether the one proposed actuality or an alternative, would facilitate this. We achievement that this accomplishment stimulates altercation surrounding acclimation of chemotherapy nomenclature. This would facilitate a array of efforts, including ability aggregation, real-world abstracts analysis, and developing an oncology acquirements bloom system.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The afterward represents acknowledgment advice provided by authors of this manuscript. All relationships are advised compensated unless contrarily noted. Relationships are self-held unless noted. I = Actual Family Member, Inst = My Institution. Relationships may not chronicle to the accountable amount of this manuscript. For added advice about ASCO’s battle of absorption policy, amuse accredit to www.asco.org/rwc or ascopubs.org/cci/author-center.

Open Payments is a accessible database absolute advice appear by companies about payments fabricated to US-licensed physicians (Open Payments).

Peter C. Yang

Stock and Added Ownership Interests: Merck, Pfizer, Cyclacel

Other Relationship: HemOnc.org

Andrew J. Cowan

Stock and Added Ownership Interests: Doximity

Consulting or Advisory Role: Doximity, Sanofi, Cellectar Biosciences

Research Funding: Bristol-Myers Squibb, Janssen, AbbVie, Celgene

Jeremy L. Warner

Stock and Added Ownership Interests: HemOnc.org

Consulting or Advisory Role: Westat, IBM

Travel, Accommodations, Expenses: IBM

No added abeyant conflicts of absorption were reported.

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