Author Interviews, Cancer Research, Heart Disease, Pediatrics / 06.09.2016
Iron Chelator Can Reduce Cardiac Toxicity From Some Pediatric Chemotherapy
MedicalResearch.com Interview with:
[caption id="attachment_27606" align="alignleft" width="133"]
Dr. Steven Lipshultz[/caption]
Steven E. Lipshultz, MD, FAAP, FAHA
Schotanus Family Endowed Chair of Pediatrics / Carman and Ann Adams Endowed Chair in Pediatric Research / Professor, Carman and Ann Adams Department of Pediatrics / Professor of Medicine (Cardiology), Oncology, Obstetrics/Gynecology, Molecular Biology/Genetics, Family Medicine/Public Health Sciences, & Pharmacology /Professor in the Center for Molecular Medicine and Genetics
Wayne State University School of Medicine
President, University Pediatricians & Interim Director, Children’s Research Center of Michigan
Pediatrician-in-Chief, Children’s Hospital of Michigan
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Surviving childhood cancer has dramatically and increasing improved to the point where more than 80% will achieve a 5-year event free survival. Many of these survivors look forward to decades of active productive life.
More than half of these survivors have been treated with therapies know to be associated with late cardiotoxicity that can be pervasive, persistent, and progressive and associated with cardiovascular morbidity and mortality. In this article we review both the course and prevention of this cardiotoxicity. We focus in part on anthracycline chemotherapy that is widely used and known to be cardiotoxicity.
We further review studies we and others have conducted to examine the effectiveness of dexrazoxane, an iron chelator, that when given before each anthracycline dose results in anthracycline cardioprotection for long term survivors. In some reported studies this has allowed for higher cumulative anthracycline doses to be safely given. In other cases this has allowed for simultaneously being able to safely treat children with malignancies that would be refractory to conventional therapy more potent therapies that would normally have additive cardiotoxicity.
Dr. Steven Lipshultz[/caption]
Steven E. Lipshultz, MD, FAAP, FAHA
Schotanus Family Endowed Chair of Pediatrics / Carman and Ann Adams Endowed Chair in Pediatric Research / Professor, Carman and Ann Adams Department of Pediatrics / Professor of Medicine (Cardiology), Oncology, Obstetrics/Gynecology, Molecular Biology/Genetics, Family Medicine/Public Health Sciences, & Pharmacology /Professor in the Center for Molecular Medicine and Genetics
Wayne State University School of Medicine
President, University Pediatricians & Interim Director, Children’s Research Center of Michigan
Pediatrician-in-Chief, Children’s Hospital of Michigan
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Surviving childhood cancer has dramatically and increasing improved to the point where more than 80% will achieve a 5-year event free survival. Many of these survivors look forward to decades of active productive life.
More than half of these survivors have been treated with therapies know to be associated with late cardiotoxicity that can be pervasive, persistent, and progressive and associated with cardiovascular morbidity and mortality. In this article we review both the course and prevention of this cardiotoxicity. We focus in part on anthracycline chemotherapy that is widely used and known to be cardiotoxicity.
We further review studies we and others have conducted to examine the effectiveness of dexrazoxane, an iron chelator, that when given before each anthracycline dose results in anthracycline cardioprotection for long term survivors. In some reported studies this has allowed for higher cumulative anthracycline doses to be safely given. In other cases this has allowed for simultaneously being able to safely treat children with malignancies that would be refractory to conventional therapy more potent therapies that would normally have additive cardiotoxicity.
Lindsay Kohler[/caption]
Lindsay Kohler MPH
Mel and Enid Zuckerman College of Public Health
Tucson, Arizona
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Several studies have reported that following health promotion guidelines for diet, physical activity, and maintenance of a healthy body weight may reduce the risk of getting cancer or dying from cancer. We performed a systematic review to examine the associations between established cancer prevention guidelines for diet and physical activity and cancer outcomes. We found that adhering to cancer prevention guidelines set forth by the American Cancer Society or the World Cancer Research Fund/American Institute for Cancer Research consistently reduced the risk of overall cancer incidence and mortality (10-61%) in the studies included in this review. In addition, higher adherence to the guidelines consistently reduced the risk of breast, colorectal, and endometrial cancers. Adherence to a pattern of healthy behaviors may significantly reduce cancer incidence and mortality.
Dr. Mikhail Kolonin[/caption]
Mikhail Kolonin, PhD, Associate Professor
Director, Center for Metabolic and Degenerative Diseases
Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research
The Brown Foundation Institute of Molecular Medicine
University of Texas Health Science Center at Houston
Houston, TX 77030
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Epidemiology studies have indicated that in obese patients progression of prostate, breast, colorectal, and other cancers is more aggressive. Adipose (fat) tissue, expanding and undergoing inflammation in obesity, directly fuels tumor growth. Adipose tissue is composed by adipocytes and stromal/vascular cells, which secrete tumor-trophic factors. Previous studies by our group have demonstrated that adipose stromal cells, which support blood vessels and serve as adipocyte progenitors, are recruited by tumors and contribute to cancer progression. Mechanisms underlying stromal cell trafficking from fat tissue to tumors have remained obscure. We discovered that in obesity a chemokine CXCL1, expressed by cancer cells, attracts adipose stromal cells to tumors.
Prof. Frances Balkwill[/caption]
Professor Frances Balkwill OBE, FMedSci
Lead, Centre for Cancer and Inflammation
Barts Cancer Institute
Queen Mary University of London
London
MedicalResearch.com: What is the background for this study?
Prof. Balkwill: We wanted to find out if chemotherapy altered patients immune system especially the immune cells that co-exist with cancer cells in tumors.
We studied women with ovarian cancer who often receive chemotherapy after diagnosis but before surgery. This meant, at least in some of them, we could study a biopsy taken before treatment began and also a biopsy taken during the operation.
Dr. Arjun Balar[/caption]
Dr. Arjun Balar MD
Assistant Professor, Department of Medicine
Co-Leader Genitourinary Cancers Program
NYU Langone Medical Center
Laura and Isaac Perlmutter Cancer Center
MedicalResearch.com: What is the background for this study?
Dr. Balar: Standard treatment for advanced urothelial cancer includes cisplatin chemotherapy. But more than half of patients are not expected to tolerate
it well and alternative treatment is inferior to cisplatin. The average survival for these patients is in the range of 9-10 months with carboplatin-based treatment, which is the most commonly used alternative
to cisplatin. Atezolizumab is a PD-L1 blocking antibody that reactivates
the body¹s immune system to fight bladder cancer and has been recently
FDA approved in the management of advanced urothelial cancer in the
second-line setting after failure of platinum-based chemotherapy.
Dr. Katie Greenzang[/caption]
Katie Greenzang, MD
Dana-Farber/Boston Children’s Cancer and Blood Disorders Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Greenzang: Advances made over the last several decades mean that more than 80 percent of children diagnosed with cancer will become long-term survivors. However, many of these survivors experience physical and cognitive late effects of the treatment that cured them. We surveyed 352 parents of children recently diagnosed with cancer to assess how well they understood their children’s risk of future limitations in physical abilities, intelligence, and quality of life. We found that an overwhelming majority of parents (92 percent) are very interested in learning about possible late effects, and most (86 percent) seek detailed information. Yet, parent and physician predictions of a child’s risk of experiencing late effects of treatment often don’t match. Among children identified by their oncologists as being at high risk for such challenges, only 38 percent of parents recognized this risk in physical abilities, 21 percent in intelligence, and 5 percent in quality of life.
Dr. Gregory Idos[/caption]
Gregory Idos MD
Division of Gastroenterology and Hepatology
Keck School of Medicine
University of Southern California
Los Angeles, CA 90033
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Idos: Identifying individuals at increased risk for hereditary cancer prompts enhanced cancer surveillance as early detection mitigates disease specific morbidity and mortality. This justifies germ line genetic testing for specific cancer risk alleles. In recent years, the field of cancer genetics has moved from a gene by gene sequencing approach to now having the ability to examine multiple genes concurrently. Multiplex gene panel (MGP) testing allows simultaneous analysis of multiple high- and moderate- penetrance genes. As a result, more pathogenic mutations and variants of uncertain significance (VUS) are discovered. MGP tests are increasingly being used by cancer genetic clinics, but questions remain about the clinical utility and complexities of these tests.
We are conducting a multi center prospective trial to measure the added yield of detecting pathogenic mutations using the MGP approach. In our interim analysis of the first 1000 participants, we found that multiplex gene panel testing increased the yield of detection of pathogenic mutations by 26%. In some cases, we found patient’s who had a mutation in the BRCA gene, but their family history did not indicate a history of breast or ovarian cancer.
Dr. Andrea Wickremasinghe[/caption]
Andrea C. Wickremasinghe, MD
Neonatologist
Kaiser Santa Clara California
MedicalResearch.com: What is the background for this study?
Response: Neonatal jaundice is common and is often treated with phototherapy. Phototherapy is typically considered to be benign. In the past decade, phototherapy use has increased and it is sometimes started at bilirubin levels below recommended treatment thresholds. Beginning in the 1970’s, in-vitro and in-vivo studies have shown phototherapy to be associated with cellular changes implicated in the pathogenesis of cancer. Epidemiologic studies have yielded mixed results, with some studies showing associations between phototherapy and leukemia and other studies failing to show this association. In this study, we used a large statewide administrative dataset to investigate the relationship between neonatal phototherapy and cancer in the first year after birth.