Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers

Publication Date: December 5, 2016
Last Updated: December 16, 2022

Risk

It is recommended that cancer patients who meet any of the following criteria should be considered at increased risk for developing cardiac dysfunction.

Treatment that includes any of the following:
  • High dose anthracycline (e.g. ≥250 mg/m2 doxorubicin, ≥600 mg/m2 epirubicin)
  • High dose (≥30 Gy) radiotherapy where the heart is in the treatment field
  • Lower dose anthracycline (e.g. <250 mg/m2 doxorubicin, <600 mg/m2 epirubicin) in combination with lower dose radiotherapy (<30 Gy) where the heart is in the treatment field
  • Treatment with lower dose anthracycline (e.g. <250 mg/m2 doxorubicin, <600 mg/m2 epirubicin) or trastuzumab alone, and presence of any of the following risk factors:
    • Multiple (≥2) cardiovascular risk factors, including: smoking, hypertension, diabetes, dyslipidemia, obesity during or after completion of therapy
    • Older (≥60 years) age at cancer treatment
    • Compromised cardiac function (e.g. borderline low LVEF [50–55%], history of myocardial infarction, ≥moderate valvular heart disease) at any time prior to or during treatment
  • Treatment with lower dose anthracycline (e.g. <250 mg/m2 doxorubicin, <600 mg/m2 epirubicin) followed by trastuzumab (sequential therapy)
( EB , H , H , M )
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No recommendation can be made on the risk of cardiac dysfunction in cancer patients with any of the following treatment exposures:
  • Lower dose anthracycline (e.g. <250 mg/m2 doxorubicin, <600 mg/m2 epirubicin) or trastuzumab alone, and no additional risk factors (as defined in RISK)
  • Lower dose radiotherapy (<30 Gy) where the heart is in the treatment field, and no additional cardiotoxic therapeutic exposures or risk factors (as defined in RISK)
  • Kinase inhibitors
( EB , Ins , B/H , W )
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Prevention

Prevention PRIOR TO Initiation of Therapy

Avoid or minimize the use of potentially cardiotoxic therapies if established alternatives exist that would not compromise cancer-specific outcomes. ( CB , H , B , )
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Clinicians should perform a comprehensive assessment in cancer patients that includes a history and physical examination, screening for cardiovascular disease risk factors (hypertension, diabetes, dyslipidemia, obesity, smoking), and an echocardiogram prior to initiation of potentially cardiotoxic therapies. ( EB , H , B , S )
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Prevention DURING Potentially Cardiotoxic Cancer Therapy

Clinicians should screen for and actively manage modifiable cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) in all patients receiving potentially cardiotoxic treatments.
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Clinicians may incorporate a number of strategies, including use of the cardioprotectant dexrazoxane, or continuous infusion, or liposomal formulation of doxorubicin for prevention of cardiotoxicity in patients planning to receive high-dose (e.g. ≥250 mg/m2 doxorubicin, ≥600 mg/m2 epirubicin) anthracyclines. ( EB , H , H , M )
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For patients who require mediastinal RT which might impact cardiac function, clinicians should select lower radiation doses when clinically appropriate, and use more precise or tailored radiation fields with exclusion of as much of the heart as possible. ( EB , H , B , M )
These goals can be accomplished through use of advanced techniques including:
  • Deep inspiration breath-holding for patients with mediastinal tumors or breast cancer in which the heart might be exposed.
  • Intensity-modulated radiation therapy that varies the radiation energy while treatment is delivered in order to precisely contour the desired radiation distribution and avoid normal tissues.
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Prevention DURING Potentially Cardiotoxic Cancer Therapy

Clinicians should screen for and actively manage modifiable cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) in all patients receiving potentially cardiotoxic treatments. ( IC , H , H , )
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Clinicians may incorporate a number of strategies, including use of the cardioprotectant dexrazoxane, or continuous infusion, or liposomal formulation of doxorubicin for prevention of cardiotoxicity in patients planning to receive high-dose (e.g. ≥250 mg/m2 doxorubicin, ≥600 mg/m2 epirubicin) anthracyclines. ( EB , H , H , M )
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For patients who require mediastinal RT which might impact cardiac function, clinicians should select lower radiation doses when clinically appropriate, and use more precise or tailored radiation fields with exclusion of as much of the heart as possible. ( EB , H , B , M )
These goals can be accomplished through use of advanced techniques including:
  • Deep inspiration breath-holding for patients with mediastinal tumors or breast cancer in which the heart might be exposed.
  • Intensity-modulated radiation therapy that varies the radiation energy while treatment is delivered in order to precisely contour the desired radiation distribution and avoid normal tissues.
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Surveillance

Monitoring During Treatment

Clinicians should complete a careful history and physical examination in patients who are receiving potentially cardiotoxic treatments. (IC, B, S, Ins)
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Recommendation 4.2
Echocardiogram for diagnostic work-up ( EB , H , B , M )
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Cardiac magnetic resonance imaging (MRI) or multi-gated acquisition (MUGA) if echocardiogram is not available or technically feasible (e.g. poor image quality), with preference given to cardiac MRI. ( EB , H , H , M )
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Serum cardiac biomarkers (troponins, natriuretic peptides) or echocardiography-derived strain imaging, in conjunction with routine diagnostic imaging ( EB , H , H , M )
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Referral to a cardiologist based on findings. (EB, B, M, I)
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Routine surveillance imaging may be offered during treatment in asymptomatic patients considered to be at increased risk (See RISK) of developing cardiac dysfunction. In these individuals, echocardiography is the surveillance imaging modality of choice that should be offered. Frequency of surveillance should be determined by healthcare providers based upon clinical judgment and patient circumstances. ( EB , H , H , M )
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No recommendations can be made regarding continuation/discontinuation of cancer therapy in individuals with evidence of cardiac dysfunction. This decision, made by the oncologist, should be informed by close collaboration with a cardiologist, fully evaluating the clinical circumstances, and considering the risks/benefits of continuation of therapy responsible for the cardiac dysfunction. (IC, B, W, Ins)
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Clinicians may use routine echocardiographic surveillance in patients with metastatic breast cancer continuing to receiving trastuzumab indefinitely. The frequency of cardiac imaging for each patient should be determined by healthcare providers, based upon clinical judgment and patient circumstances. ( EB , H , H , W )
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Monitoring After Treatment

Clinicians should complete a careful history and physical examination in cancer survivors previously treated with potentially cardiotoxic therapies. (IC, B, S, Ins)
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Recommendation 5.1.1
Echocardiogram for diagnostic work-up ( EB , H , B , M )
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Cardiac MRI or MUGA if echocardiogram is not available or technically feasible (e.g. poor image quality), with preference given to cardiac MRI ( EB , H , H , M )
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Serum cardiac biomarkers (troponins, natriuretic peptides) ( EB , H , H , M )
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Referral to a cardiologist based on findings (IC, B, S, Ins)
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An echocardiogram may be performed 6–12 months after completion of cancer-directed therapy in asymptomatic patients considered to be at increased risk (See RISK) of cardiac dysfunction. ( EB , H , H , M )
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Cardiac MRI or MUGA may be offered for surveillance in asymptomatic individuals if an echocardiogram is not available or technically feasible (e.g. poor image quality), with preference given to cardiac MRI. ( EB , H , H , M )
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Patients identified to have asymptomatic cardiac dysfunction during routine surveillance should be referred to a cardiologist or a healthcare provider with cardio-oncology expertise for further assessment and management. (IC, B, S, Ins)
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No recommendations can be made regarding the frequency and duration of surveillance in patients at increased risk (See RISK) who are asymptomatic and have no evidence of cardiac dysfunction during their 6–12 month post-treatment echocardiogram. (IC, B/H, W, Ins)
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Clinicians should regularly evaluate and manage cardiovascular risk factors such as smoking, hypertension, diabetes, dyslipidemia, and obesity in patients previously treated with cardiotoxic cancer therapies. A heart-healthy lifestyle, including the role of diet and exercise, should be discussed as part of long-term follow-up care. ( EB , H , H , M )
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Recommendation Grading

Overview

Title

Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers

Authoring Organization

Publication Month/Year

December 5, 2016

Last Updated Month/Year

December 16, 2022

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Target Patient Population

The target population consists of adults with cancer for whom cardiotoxic anticancer therapies are being considered.

Target Provider Population

Oncologists, cardiologists, primary care physicians, specialists, practice providers, and any other

Inclusion Criteria

Female, Male, Adult, Older adult

Health Care Settings

Ambulatory, Long term care

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Prevention

Keywords

cancer, cardiac dysfunction, cancer survivors, cardiotoxic, anticancer therapies

Source Citation

DOI: 10.1200/JCO.2016.70.5400 Journal of Clinical Oncology 35, no. 8 (March 10, 2017) 893-911.

Supplemental Methodology Resources

Data Supplement, Methodology Supplement

Methodology

Number of Source Documents
160
Literature Search Start Date
January 1, 1996
Literature Search End Date
February 16, 2016
Description of External Review Process
ASCO has a rigorous review process for guidelines. After the draft has been approved by the Expert Panel, the guideline is independently reviewed and approved by the Clinical Practice Guideline Oversight Committee (CPGC). Select members of the CPGC are asked to critically review the guideline prior to the next scheduled CPGC meeting. The CPGC members then present the results of their reviews to the full committee, discuss the review with the full committee, and the CPGC votes on whether to approve the guideline (with recusals from members who have relationships with affected companies). Approved ASCO Guidelines are then submitted to the Society’s journal for consideration of publication.
Specialties Involved
Cardiology, Family Medicine, Internal Medicine General, Oncology, Post Acute And Long Term Care, Preventive Medicine, Cardio Oncology, Medical Oncology, Cardiology, Oncology
Description of Systematic Review
The Protocol specifies the purpose of the guideline product, target patient population, clinical outcomes of interest, key features of the systematic literature review, and a proposed timeline for completion. ASCO staff, the Expert Panel Co‐Chairs, and possibly other panel members selected by the Co‐Chairs (the Expert Panel Steering Committee), will typically draft the protocol for full panel review. A standard protocol worksheet is used for consistency. Once the Co‐Chairs have approved a first draft of the Protocol, the Protocol will be shared with the full Expert Panel. At the discretion of the Guidelines Director, the CPGC leadership and/or the CPGC Methodology Subcommittee may review the Protocol to make suggestions for revision intended to clarify aspects of the plan for developing the guideline. These suggestions are sent to the Expert Panel Co‐Chairs. Work on the systematic literature review can proceed upon the sign‐off of the Protocol by the Expert Panel.
List of Questions
See full text
Description of Study Criteria
see supplement
Description of Search Strategy
Upon approval of the Protocol, a systematic review of the medical literature is conducted. ASCO staff use the information entered into the Protocol, including the clinical questions, inclusion/exclusion criteria for qualified studies, search terms/phrases, and range of study dates, to perform the systematic review. Literature searches of selected databases, including The Cochrane Library and Medline (via PubMed) are performed. Working with the Expert Panel, ASCO staff complete screening of the abstracts and full text articles to determine eligibility for inclusion in the systematic review of the evidence. Unpublished data from meeting abstracts are not generally used as part of normal ASCO guideline development (“Meeting Data”). However, abstract data from reputable scientific meetings and congresses may be included on a case‐by‐case basis after review by the CPGC leadership. Expert Panels should present a rationale to support integration of abstract data into a guideline. The CPGC leadership will consider the following inclusion criteria for the unpublished scientific meeting data: 1) whether the data were independently peer reviewed in connection with a reputable scientific meeting or congress; 2) the potential clinical impact of the unpublished data; 3) the methodological quality and validity of the associated study; 3) the potential harms of not including the data; and 4) the availability of other published data to inform the guideline recommendations.
Description of Study Selection
Literature search results were reviewed and deemed appropriate for full text review by two ASCO staff reviewers in consultation with the Expert Panel Co-Chairs. Data were extracted by two staff reviewers and subsequently checked for accuracy through an audit of the data by another ASCO staff member. Disagreements were resolved through discussion and consultation with the Co-Chairs if necessary. Evidence tables are provided in the manuscript and/or in Data Supplement.
Description of Evidence Analysis Methods
ASCO guideline recommendations are crafted, in part, using the GuideLines Into DEcision Support (GLIDES) methodology. ASCO adopted a five‐step approach to carry out quality appraisal, strength of evidence ratings and strength of recommendations ratings. The ASCO approach was primarily adapted from those developed by the AHRQ,, USPSTF, and GRADE, however with the validation of the GRADE methodology, the sole use of GRADE is being evaluated by the Clinical Practice Guidelines Committee.
Description of Evidence Grading
High: High confidence that the available evidence reflects the true magnitude and direction of the net effect (i.e., balance of benefits v harms) and that further research is very unlikely to change either the magnitude or direction of this net effect. Intermediate: Moderate confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research is unlikely to alter the direction of the net effect; however, it might alter the magnitude of the net effect. Low: Low confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research may change either the magnitude and/or direction this net effect. Insufficient: Evidence is insufficient to discern the true magnitude and direction of the net effect. Further research may better inform the topic. The use of the consensus opinion of experts is reasonable to inform outcomes related to the topic.
Description of Recommendation Grading
ASCO uses a formal consensus methodology based on the modified Delphi technique in clinically important areas where there is limited evidence or a lack of high‐quality evidence to inform clinical guidance recommendations. Evidence Based: There was sufficient evidence from published studies to inform a recommendation to guide clinical practice. Formal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. Therefore, the Expert Panel used a formal consensus process to reach this recommendation, which is considered the best current guidance for practice. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). The results of the formal consensus process are summarized in the guideline and reported in the Data Supplement (see the Supporting Documents" field). Informal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. The recommendation is considered the best current guidance for practice, based on informal consensus of the Expert Panel. The Panel agreed that a formal consensus process was not necessary for reasons described in the literature review and discussion. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). No recommendation: There is insufficient evidence, confidence, or agreement to provide a recommendation to guide clinical practice at this time. The Panel deemed the available evidence as insufficient and concluded it was unlikely that a formal consensus process would achieve the level of agreement needed for a recommendation.
Description of Funding Source
ASCO provides funding for Guideline Development.
Company/Author Disclosures
ASCO Conflict of Interest Policy complies with the CMSS Code for Interactions with Companies. ASCO requires disclosure by individuals involved in drafting, reviewing, and approving guideline recommendations.
Percentage of Authors Reporting COI
100