Permissive Cardiotoxicity :  The Clinical Crucible of Cardio-Oncology

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Abstract

The field of cardio-oncology was born from the necessity for recognition and management of cardiovascular diseases among patients with cancer. This need for this specialty continues to grow as patients with cancer live longer as a result of lifesaving targeted and immunologic cancer therapies beyond the usual chemotherapy and/or radiation therapy. Often, potentially cardiotoxic anticancer treatment is necessary in patients with baseline cardiovascular disease. Moreover, patients may need to continue therapy in the setting of incident cancer therapy–associated cardiotoxicity. Herein, we present and discuss the concept of permissive cardiotoxicity as a novel term that represents an essential concept in the field of cardio-oncology and among practicing cardio-oncology specialists. It emphasizes a proactive rather than reactive approach to continuation of lifesaving cancer therapies in order to achieve the best oncologic outcome while mitigating associated and potentially off-target cardiotoxicities.

Central Illustration

Highlights

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Permissive cardiotoxicity is a terminology that represents a vital concept in cardio-oncology
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It emphasizes continued cancer therapy if appropriate, while mitigating cardiotoxicities.
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Its application is guided by understanding the cancer treatment, alternatives, and prognosis.

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Most cited references 50

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Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline

Julie Brahmer, Christina Lacchetti, Bryan J Schneider … (2018)

Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process. The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017. Results The systematic review identified 204 eligible publications. Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports. Due to the paucity of high-quality evidence on management of immune-related adverse events, recommendations are based on expert consensus. Recommendations Recommendations for specific organ system-based toxicity diagnosis and management are presented. While management varies according to organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert to grade 1 or less. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids (prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d). Corticosteroids should be tapered over the course of at least 4 to 6 weeks. Some refractory cases may require infliximab or other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, with the exception of endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .

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Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.

Dennis J Slamon, Brian Leyland-Jones, Steven Shak … (2001)

The HER2 gene, which encodes the growth factor receptor HER2, is amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers, increasing the aggressiveness of the tumor. We evaluated the efficacy and safety of trastuzumab, a recombinant monoclonal antibody against HER2, in women with metastatic breast cancer that overexpressed HER2. We randomly assigned 234 patients to receive standard chemotherapy alone and 235 patients to receive standard chemotherapy plus trastuzumab. Patients who had not previously received adjuvant (postoperative) therapy with an anthracycline were treated with doxorubicin (or epirubicin in the case of 36 women) and cyclophosphamide alone (138 women) or with trastuzumab (143 women). Patients who had previously received adjuvant anthracycline were treated with paclitaxel alone (96 women) or paclitaxel with trastuzumab (92 women). The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression (median, 7.4 vs. 4.6 months; P<0.001), a higher rate of objective response (50 percent vs. 32 percent, P<0.001), a longer duration of response (median, 9.1 vs. 6.1 months; P<0.001), a lower rate of death at 1 year (22 percent vs. 33 percent, P=0.008), longer survival (median survival, 25.1 vs. 20.3 months; P=0.01), and a 20 percent reduction in the risk of death. The most important adverse event was cardiac dysfunction of New York Heart Association class III or IV, which occurred in 27 percent of the group given an anthracycline, cyclophosphamide, and trastuzumab; 8 percent of the group given an anthracycline and cyclophosphamide alone; 13 percent of the group given paclitaxel and trastuzumab; and 1 percent of the group given paclitaxel alone. Although the cardiotoxicity was potentially severe and, in some cases, life-threatening, the symptoms generally improved with standard medical management. Trastuzumab increases the clinical benefit of first-line chemotherapy in metastatic breast cancer that overexpresses HER2.

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Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline.

Susan Dent, Saro Armenian, Ana Barac … (2017)

Purpose Cardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers. Methods Recommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology. Results A total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. Recommendations It is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.

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Author and article information

Contributors

Charles Porter: @charlesporter99

Tariq U. Azam: @TariqAzamMD

Divyanshu Mohananey: @dmohananey

Susan Dent: @sdent_duke

Sarju Ganatra: @SarjuGanatraMD

Gary S. Beasley: @GarySBeasley

Tochukwu Okwuosa: @DrTochiOkwuosa

Journal

Journal ID (nlm-ta): JACC CardioOncol

Journal ID (iso-abbrev): JACC CardioOncol

Title: JACC: CardioOncology

Publisher: Elsevier

ISSN (Electronic): 2666-0873

Publication date PMC-release: 20 September 2022

Publication date Collection: September 2022

Publication date (Electronic): 20 September 2022

Volume: 4

Issue: 3

Pages: 302-312

Affiliations

[a ]Department of Cardiovascular Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA

[b ]Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA

[c ]Division of Cardiology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

[d ]Division of Medical Oncology, Department of Medicine, University of Louisville, Louisville, Kentucky, USA

[e ]Department of Medicine, Rush University, Chicago, Illinois, USA

[f ]International Cardio-Oncology Society, Tampa, Florida, USA

[g ]Duke Cancer Institute, Duke University, Durham, North Carolina, USA

[h ]Cardio-Oncology Program, Division of Cardiovascular Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts, USA

[i ]Division of Cardiology, Department of Pediatrics, University of Iowa Stead Family Children’s Hospital, Iowa City, Iowa, USA

[j ]Division of Cardiology, Department of Internal Medicine, Rush University, Chicago, Illinois, USA

Author notes

[∗ ] Address for correspondence: Dr Charles Porter, University of Kansas Medical Center, 4000 Cambridge, MS 1023, Kansas City, Kansas 66160, USA. cbporter@ 123456kumc.edu @charlesporter99

Article

Publisher Item ID: S2666-0873(22)00321-0

DOI: 10.1016/j.jaccao.2022.07.005

PMC ID: 9537074

PubMed ID: 36213359

SO-VID: 1fd5a348-5cf0-4e9d-bf9f-04e2624dc057

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 6 June 2022

Date revision received : 22 July 2022

Date accepted : 27 July 2022

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Permissive Cardiotoxicity : The Clinical Crucible of Cardio-Oncology

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Abstract

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Related collections

Karger: Oncology

Most cited references 50

Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline

Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.

Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline.

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Cited by 8

Most referenced authors 1,192