Joy M. Fulbright

Review of Cardiotoxicity in Pediatric Cancer Patients: During and after Therapy

With the improvement in survival from childhood cancer, late effects of therapy are becoming more apparent. Cardiac disease, one of these late effects, has a significant impact on the life of survivors of childhood cancers. Most survivors are followed by primary care doctors and adult subspecialists after they have graduated from pediatric centers. Since much of the cardiac toxicity of therapy occurs years off of therapy, it is important for these physicians to be aware of how to monitor survivors for the development of cardiac toxicities. In this paper we will discuss the incidence of cardiac disease during treatment and in survivors, what treatment modalities contribute to its development and modalities utilized to screen for cardiac disease. Recommendations for posttherapy monitoring will be emphasized.

Can anthracycline therapy for pediatric malignancies be less cardiotoxic

Anthracyclines have a central role in the treatment of cancer in pediatric patients but confer an increased risk of cardiac dysfunction. Several strategies have been employed to help reduce anthracycline-induced cardiotoxicity, including pretreating the patient with the iron chelator dexrazoxane and infusing the dose of anthracycline over a longer period. Much focus has also been placed on the development of methods that decrease the toxicity of parent compounds, specifically through the use of drug carriers such as liposomes, and on the development of new, potentially less toxic anthracycline derivatives, such as amrubicin and pixantrone. We provide a review of these strategies, focusing on studies in pediatric patients when available, and support the idea that anthracycline therapy can be less cardiotoxic in pediatric patients.

Late Effects of Childhood Leukemia Therapy

As survival rates for children treated for childhood cancers become significantly better, the focus is increasingly on determining the late effects of treatments and the best ways to monitor for them and prevent their occurrence. This review focuses on recent literature discussing the late effects of treatment in patients treated for acute myeloid leukemia and acute lymphoblastic leukemia during childhood. The late effects of therapy for childhood leukemia include secondary malignancy, cardiotoxicity, obesity, endocrine abnormalities, reproductive changes, neurocognitive deficits, and psychosocial effects. As clinicians have become more aware of the late effects of therapy, treatment regimens have been changed to decrease late effects, but patients still require long-term follow-up for their prevention and treatment.

Humanism and professionalism education for pediatric hematology‐oncology fellows: A model for pediatric subspecialty training

Humanism and professionalism are virtues intrinsic to the practice of medicine, for which we lack a standard, evidence‐based approach for teaching and evaluation. Pediatric hematology‐oncology (PHO) fellowship training brings new and significant stressors, making it an attractive setting for innovation in humanism and professionalism training.

A Collaborative Step-Wise Process to Implementing an Innovative Clinic for Adult Survivors of Childhood Cancer

With a 5 year survival rate of approximately 80%, there is an increasing number of childhood cancer survivors in the United States. Childhood cancer survivors are at an increased risk for physical and psychosocial health problems many years after treatment. Long-term follow-up care should include education, development of individualized follow up plans and screening for health problems in accordance with the Childrens Oncology Group survivor guidelines. Due to survivor, provider and healthcare system related barriers, adult survivors of childhood cancer (ASCC) infrequently are receiving care in accordance to these guidelines. In this paper we describe the stepwise process and collaboration between a childrens hospital and an adult academic medical center that was implemented to develop the Survivorship Transition Clinic and address the needs of ASCC in our region. In the clinic model that we designed ASCC follow-up with a primary care physician in the adult setting who is knowledgeable about late effects of childhood cancer treatment and are provided transition support and education by a transition nurse navigator.

Cardiomyopathy in Childhood Cancer Survivors: Lessons from the Past and Challenges for the Future

Childhood cancer survivors are at substantial risk for cancer treatment-related cardiomyopathy. Identification of those at highest risk has presented a longstanding challenge for survivorship researchers. To date, risk stratification approaches to screening and subsequent intervention have largely been driven by demographic and treatment-related exposures, possibly missing an opportunity for a more personalized approach. A growing body of literature suggests associations between cardiomyopathy and a number of genetic and acquired risk factors, supporting a need to incorporate these data into existing surveillance and intervention approaches. Efforts to reduce or eliminate modifiable cardiovascular risk factors are needed; however, the impact of these modifications remains to be seen. Moreover, challenges surrounding identification of effective cardiomyopathy treatment strategies in cancer survivors are ongoing. Despite these uncertainties, more accurate identification of those at highest risk and implementation of early and effective interventions for those with disease will lead to improved outcomes for childhood cancer survivors.

Childhood cancer for the primary care physician.

Childhood cancer is rare among childhood diseases and requires a high index of suspicion by the primary care physician to entertain the possibility of cancer when managing common childhood diseases. This article presents an overview of common pediatric cancers, their presentations, and how the primary care physician can work up patients whom they suspect have a malignancy. The goal is to help primary care doctors in early recognition and appropriate referral of patients, in order for patients to receive required specialized care in a timely manner.

Screening and intervention for treatment-related cardiac dysfunction in childhood cancer survivors

10.2217/FON.15.108

Comparative oncology approach to drug repurposing in osteosarcoma

Background Osteosarcoma is an orphan disease for which little improvement in survival has been made since the late 1980s. New drug discovery for orphan diseases is limited by the cost and time it takes to develop new drugs. Repurposing already approved FDA-drugs can help overcome this limitation. Another limitation of cancer drug discovery is the lack of preclinical models that accurately recapitulate what occurs in humans. For OS using dogs as a model can minimize this limitation as OS in canines develops spontaneously, is locally invasive and metastasizes to the lungs as it does in humans. Methods In our present work we used high-throughput screens to identify drugs from a library of 2,286 FDA-approved drugs that demonstrated selective growth inhibition against both human and canine OS cell lines. The identified lead compound was then tested for synergy with 7 other drugs that have demonstrated activity against OS. These results were confirmed with in vitro assays and an in vivo murine model of OS. Results We identified 13 drugs that demonstrated selective growth inhibition against both human and canine OS cell lines. Auranofin was selected for further in vitro combination drug screens. Auranofin showed synergistic effects with vorinostat and rapamycin on OS viability and apoptosis induction. Auranofin demonstrated single-agent growth inhibition in both human and canine OS xenografts, and cooperative growth inhibition was observed in combination with rapamycin or vorinostat. There was a significant decrease in Ki67-positive cells and an increase in cleaved caspase-3 levels in tumor tissues treated with a combination of auranofin and vorinostat or rapamycin. Conclusions Auranofin, alone or in combination with rapamycin or vorinostat, may be useful new treatment strategies for OS. Future studies may evaluate the efficacy of auranofin in dogs with OS as a prelude to human clinical evaluation.

Medium-term assessment of cardiac function in pediatric cancer survivors. Comparison of different echocardiographic methods, cardiac MRI and cardiac biomarker testing in adolescent cancer survivors

To evaluate the feasibility and correlation of 3D echocardiography (echo) and cardiac biomarkers with cardiac MRI, in surveillance of cardiac function for cancer survivors.