Cardio-Oncology Corner

Progress documented, knowledge gaps identified at cardio-oncology workshop

On June 25 and 26, 2018, the National Cancer Institute and the NHLBI held the “Changing Hearts and Minds: Improving Outcomes in Cancer Treatment-Related Cardiotoxicity” workshop focusing on the 5-year progress since an earlier workshop in 2013 outlining research priorities in cardio-oncology.

The meeting convened experts from oncology and cardiology who were charged with identifying research opportunities and needs to advance understanding of cardiotoxicity and its treatment in the setting of cancer therapy. Representatives from the National Cancer Institute (NCI), including Nonniekaye Shelburne, MS, CRNP, AOCN; Lori Minasian, MD, FACP; and Eileen Diamond, RN, MS; and the NHLBI, including Bishow Adhikari, PhD; and Patrice Desvigne-Nickens, MD, discussed new and developing grant opportunities and resources, underscoring an expanded cardiotoxicity portfolio at NIH, which include novel designs of multicenter clinical trials focused on prevention and management of cardiotoxicity and the establishment of an interdisciplinary working group, the NCI Community Oncology Cardiotoxicity Task Force.

Cardiology Today Editorial Board Member Javid Moslehi, MD, from Vanderbilt University, Myrtle Davis-Millin, PhD, from Bristol-Myers Squibb, and Joseph C. Wu, MD, PhD, from Stanford University, addressed basic and translational research platforms to elucidate mechanisms of cardiotoxicity and translation of findings to clinical intervention. There is a need to expand laboratory tool kits with cell-based and animal models that recapitulate cardiotoxic insults of novel therapies.

Patrice Desvigne-Nickens, MD
Patrice Desvigne-Nickens
Bishow Adhikari, PhD
Bishow Adhikari
Lori Minasian, MD, FACP
Lori Minasian
Nonniekaye Shelburne, MS, CRNP, AOCN
Nonniekaye Shelbourne

These platforms need to also consider novel forms of toxicities. For example, vascular damage associated with vascular endothelial growth factor (VEGF) inhibitors and small molecule tyrosine kinase inhibitors is common and triggers hypertension, HF and thrombosis. The potential utility of human induced pluripotent stem cells for disease modeling, cell transplantation, clinical trial and drug discovery may offer novel methods for screening adverse effects.

Saro Armenian, DO, MPH, from City of Hope, Eugenie S. Kleinerman, MD, from MD Anderson Cancer Center, and Eric Chow, MD, MPH, from Fred Hutchinson Cancer Center, reviewed evidence for clinical intervention strategies, including a prevention trial of carvedilol in childhood cancer patients and a preclinical model of exercise to decrease doxorubicin-induced cardiotoxicity.

Critical gaps

Moslehi gave a keynote address on the growing use of cancer immunotherapies and new CV syndromes associated with immune checkpoint inhibitors (ICI). ICI-associated myocarditis, for example, represents an infrequent but fatal complication and there is a growing need to identify patients at risk. Susan Dent, MD, from Duke University, Armenian, Bonnie Ky, MD, MSCE, from the University of Pennsylvania, Colin Ross, PhD, from the University of British Columbia, Marilyn L. Kwan, PhD, from Kaiser Permanente, and Martha Belury, PhD, from The Ohio State University, identified the essential needs and critical gaps in risk assessment to establish patient susceptibility to cardiotoxicity. Gaps in guidelines, lack of standards or discrepant definitions for adverse events as well as the need for precision strategies, common data elements and definitions and methods to improve evidence data sampling and validation were discussed.

Ana Barac, MD, PhD, from Medstar Heart and Vascular Institute, Armenian, Ky, Joerg Herrmann, MD, from Mayo Clinic, and Chau T. Dang, MD, and Anthony Yu, MD, both from Memorial-Sloan Kettering Cancer Center, reviewed and discussed gaps and needs in detecting cardiotoxicity. Cardiotoxicity detection through appropriate use of imaging and biomarker evaluation remains challenging. Attempts of standardization of biomarker and imaging across studies is ongoing. The need for surveillance is keen, but who, what, when, and how and how long must be tailored for specific cancer treatment. Because of substantial costs, timing and test selection are driven by practical issues rather than accepted guidelines. Additional concerns regarding what happens at the end of treatment include latent adverse events which can evolve 10 to 30 years following cancer treatment. The lack of long-term follow-up guidelines due to a paucity of data is a major gap. The use of implementation science methods to improve adherence to detection methods was also discussed.

Jessica Scott, PhD, from Memorial Sloan Kettering Cancer Center, delivered a keynote highlighting the similarities between space flight and cancer treatment influences on the CV system, and the central role of exercise in providing CV protection against multisystem toxicity. Adhikari, Armenian, Justin E. Bekelman, MD, from the University of Pennsylvania, Deborah Lannigan, PhD, from Vanderbilt University, Chow, Kathryn H. Schmitz, PhD, MPH, from the University of Pennsylvania, Chunkit Fung, MD, from the University of Rochester Medical Center, Jennifer Klemp, PhD, MPH, from the University of Kansas, and Cardiology Today Imaging Section Editor W. Gregory Hundley, MD, from Wake Forest University, reviewed and discussed cardiotoxicity prevention and management strategies.

For many cancer patients, cardiotoxicity is multifaceted, with direct injury from anticancer therapies but also indirect injury such as deconditioning, changes in weight and/or clinical depression. Interventions to improve fitness through exercise are very appealing, although exercise is not acceptable or feasible for everyone. Whenever possible, avoidance of potentially cardiotoxic agents is a key principle. Primary prevention with cardioprotective agents is ongoing, including with statins, beta-blockers, dexrazoxane and more targeted therapies. Evidence is increasing that CV risk factor management, especially BP control and exercise, may be beneficial.

Integrating cardio-oncology into cancer survivorship care was also addressed. Pivotal issues such as definitions of survivorship, algorithms to standardize effective surveillance, shared decision-making, decisions about when a cardiology vs. a primary care provider is needed and when feedback to primary care must be considered were identified. Integrating measures to monitor CV status into NCI/NHLBI existing resources such as epidemiologic and disease cohorts, and clinical trials networks was recommended.

Substantial progress made

In summary, substantial progress on mechanisms of cardiotoxicity, identification and refinement of methods to detect CV injury and investigations to prevent and management of CV complications of cancer treatment has occurred. Nevertheless, critical gaps remain in part because of the rapidly changing landscape of cancer therapies and the growing relevance of CV health in cancer patients. Since the initial NIH meeting in 2013, both the NCI and NHLBI have made cardio-oncology research opportunities a priority. The success of the 2018 meeting will create new resources for cardiologists, oncologists, basic and clinical researchers from all corners of the medical community to continue collaborations and advance the field.

Editor’s Note: This work is solely the responsibility of the authors and does not necessarily represent the official views of the NCI, NHLBI or NIH.

Disclosure: The authors report no relevant financial disclosures.

On June 25 and 26, 2018, the National Cancer Institute and the NHLBI held the “Changing Hearts and Minds: Improving Outcomes in Cancer Treatment-Related Cardiotoxicity” workshop focusing on the 5-year progress since an earlier workshop in 2013 outlining research priorities in cardio-oncology.

The meeting convened experts from oncology and cardiology who were charged with identifying research opportunities and needs to advance understanding of cardiotoxicity and its treatment in the setting of cancer therapy. Representatives from the National Cancer Institute (NCI), including Nonniekaye Shelburne, MS, CRNP, AOCN; Lori Minasian, MD, FACP; and Eileen Diamond, RN, MS; and the NHLBI, including Bishow Adhikari, PhD; and Patrice Desvigne-Nickens, MD, discussed new and developing grant opportunities and resources, underscoring an expanded cardiotoxicity portfolio at NIH, which include novel designs of multicenter clinical trials focused on prevention and management of cardiotoxicity and the establishment of an interdisciplinary working group, the NCI Community Oncology Cardiotoxicity Task Force.

Cardiology Today Editorial Board Member Javid Moslehi, MD, from Vanderbilt University, Myrtle Davis-Millin, PhD, from Bristol-Myers Squibb, and Joseph C. Wu, MD, PhD, from Stanford University, addressed basic and translational research platforms to elucidate mechanisms of cardiotoxicity and translation of findings to clinical intervention. There is a need to expand laboratory tool kits with cell-based and animal models that recapitulate cardiotoxic insults of novel therapies.

Patrice Desvigne-Nickens, MD
Patrice Desvigne-Nickens
Bishow Adhikari, PhD
Bishow Adhikari
Lori Minasian, MD, FACP
Lori Minasian
Nonniekaye Shelburne, MS, CRNP, AOCN
Nonniekaye Shelbourne

These platforms need to also consider novel forms of toxicities. For example, vascular damage associated with vascular endothelial growth factor (VEGF) inhibitors and small molecule tyrosine kinase inhibitors is common and triggers hypertension, HF and thrombosis. The potential utility of human induced pluripotent stem cells for disease modeling, cell transplantation, clinical trial and drug discovery may offer novel methods for screening adverse effects.

Saro Armenian, DO, MPH, from City of Hope, Eugenie S. Kleinerman, MD, from MD Anderson Cancer Center, and Eric Chow, MD, MPH, from Fred Hutchinson Cancer Center, reviewed evidence for clinical intervention strategies, including a prevention trial of carvedilol in childhood cancer patients and a preclinical model of exercise to decrease doxorubicin-induced cardiotoxicity.

Critical gaps

Moslehi gave a keynote address on the growing use of cancer immunotherapies and new CV syndromes associated with immune checkpoint inhibitors (ICI). ICI-associated myocarditis, for example, represents an infrequent but fatal complication and there is a growing need to identify patients at risk. Susan Dent, MD, from Duke University, Armenian, Bonnie Ky, MD, MSCE, from the University of Pennsylvania, Colin Ross, PhD, from the University of British Columbia, Marilyn L. Kwan, PhD, from Kaiser Permanente, and Martha Belury, PhD, from The Ohio State University, identified the essential needs and critical gaps in risk assessment to establish patient susceptibility to cardiotoxicity. Gaps in guidelines, lack of standards or discrepant definitions for adverse events as well as the need for precision strategies, common data elements and definitions and methods to improve evidence data sampling and validation were discussed.

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Ana Barac, MD, PhD, from Medstar Heart and Vascular Institute, Armenian, Ky, Joerg Herrmann, MD, from Mayo Clinic, and Chau T. Dang, MD, and Anthony Yu, MD, both from Memorial-Sloan Kettering Cancer Center, reviewed and discussed gaps and needs in detecting cardiotoxicity. Cardiotoxicity detection through appropriate use of imaging and biomarker evaluation remains challenging. Attempts of standardization of biomarker and imaging across studies is ongoing. The need for surveillance is keen, but who, what, when, and how and how long must be tailored for specific cancer treatment. Because of substantial costs, timing and test selection are driven by practical issues rather than accepted guidelines. Additional concerns regarding what happens at the end of treatment include latent adverse events which can evolve 10 to 30 years following cancer treatment. The lack of long-term follow-up guidelines due to a paucity of data is a major gap. The use of implementation science methods to improve adherence to detection methods was also discussed.

Jessica Scott, PhD, from Memorial Sloan Kettering Cancer Center, delivered a keynote highlighting the similarities between space flight and cancer treatment influences on the CV system, and the central role of exercise in providing CV protection against multisystem toxicity. Adhikari, Armenian, Justin E. Bekelman, MD, from the University of Pennsylvania, Deborah Lannigan, PhD, from Vanderbilt University, Chow, Kathryn H. Schmitz, PhD, MPH, from the University of Pennsylvania, Chunkit Fung, MD, from the University of Rochester Medical Center, Jennifer Klemp, PhD, MPH, from the University of Kansas, and Cardiology Today Imaging Section Editor W. Gregory Hundley, MD, from Wake Forest University, reviewed and discussed cardiotoxicity prevention and management strategies.

For many cancer patients, cardiotoxicity is multifaceted, with direct injury from anticancer therapies but also indirect injury such as deconditioning, changes in weight and/or clinical depression. Interventions to improve fitness through exercise are very appealing, although exercise is not acceptable or feasible for everyone. Whenever possible, avoidance of potentially cardiotoxic agents is a key principle. Primary prevention with cardioprotective agents is ongoing, including with statins, beta-blockers, dexrazoxane and more targeted therapies. Evidence is increasing that CV risk factor management, especially BP control and exercise, may be beneficial.

Integrating cardio-oncology into cancer survivorship care was also addressed. Pivotal issues such as definitions of survivorship, algorithms to standardize effective surveillance, shared decision-making, decisions about when a cardiology vs. a primary care provider is needed and when feedback to primary care must be considered were identified. Integrating measures to monitor CV status into NCI/NHLBI existing resources such as epidemiologic and disease cohorts, and clinical trials networks was recommended.

PAGE BREAK

Substantial progress made

In summary, substantial progress on mechanisms of cardiotoxicity, identification and refinement of methods to detect CV injury and investigations to prevent and management of CV complications of cancer treatment has occurred. Nevertheless, critical gaps remain in part because of the rapidly changing landscape of cancer therapies and the growing relevance of CV health in cancer patients. Since the initial NIH meeting in 2013, both the NCI and NHLBI have made cardio-oncology research opportunities a priority. The success of the 2018 meeting will create new resources for cardiologists, oncologists, basic and clinical researchers from all corners of the medical community to continue collaborations and advance the field.

Editor’s Note: This work is solely the responsibility of the authors and does not necessarily represent the official views of the NCI, NHLBI or NIH.

Disclosure: The authors report no relevant financial disclosures.