Hocking Laboratory Research Overview

Survivors of pediatric brain cancer are at increased risk for poor social connectedness, diminished health-related quality of life, and reduced psychological well-being, but the associations between these factors and the underlying mechanisms impacting the trajectory of social connectedness are poorly understood. This project will use an accelerated longitudinal design to compare the social connectedness and well-being among survivors of malignant and non-malignant brain tumors, determine the influence of social connectedness on health and well-being, and evaluate risk and mechanistic factors for social connectedness. Our findings will significantly advance our understanding of the importance of social connectedness in pediatric brain cancer survivorship and inform the development of effective interventions that target mechanistic factors.

Brain tumors account for approximately 20% of all pediatric tumors. Treatment generally involves surgery, chemotherapy and/or radiation therapy.

Photon-based radiotherapy, which is used in most pediatric treatment centers to treat brain tumors, can be associated with significant toxicity on the developing brains of infants and young children, and profound late effects on survivors including vision and hearing loss, endocrine problems, and neurocognitive deficits. These toxicities and side effects result from the destructive effects of conventional photon therapy scattered on surrounding normal brain tissue.

In contrast, proton therapy, an emerging radiotherapy, is a more precise radiotherapy modality and offers greater normal tissue sparing. We think the precision of proton therapy will result in reduced toxicities and side effects and we hypothesize improved long-term neurocognitive outcomes for children with brain tumors. However, the long-term effects of proton therapy on neurocognitive development in infants and young children have not been well studied.

Researchers at the CCCR, including Jane E. Minturn, MD, PhD, Christine E. Hill-Kayser MD, and Iris Paltin, PhD, are evaluating the effects of proton therapy and long-term clinical and neurocognitive outcomes on infants and young children with a variety of pediatric brain cancers, including medulloblastoma, atypical teratoid rhabdoid tumor, low-grade glioma and other tumors.

Early results from these clinical studies reveal that proton therapy is well-tolerated by very young children with minimal acute toxicity and excellent disease control. Additional long-term follow-up studies are currently underway to assess the longer-term clinical and neurocognitive effects (greater than three years) of proton therapy on children with brain tumors.

Many children with brain and skull base tumors are treated with radiation therapy. Cranial radiation therapy can have significant adverse cognitive effects such as changes to attention, working memory, processing speed, long-term memory, executive functioning, emotional regulation, and social skills.

Proton therapy is a new way to deliver radiation therapy. Because proton therapy can better target the tumor and spare healthy brain tissue, it is expected to be associated with reduced neurocognitive morbidity. Given the novelty of proton therapy, little data is available describing cognitive changes after treatment.

Iris Paltin, PhD, is evaluating children prior to proton therapy and then annually/bi-annually after treatment completion to learn about the effects of cranial proton radiation. These assessments evaluate thinking and learning in many ways, with a specific focus on attention, executive functions, processing speed, and memory. The information gained during these evaluations helps inform future treatment and intervention design. It is expected that pediatric proton radiation therapy will be associated with preserved long-term functioning compared to conventional (photon) radiation therapy. Researchers also aim to identify individual risk and protective factors that influence the emergence of cognitive late effects.

We collaborate with other institutions to compare the neurocognitive effects of proton and photon radiation therapy.

Children receiving treatment such as chemotherapy, radiation and surgery for brain tumors often experience social difficulties after tumor-directed therapy has concluded. These difficulties can mirror problems commonly seen with children diagnosed with autism spectrum disorder (ASD), including deficits with facial expression recognition, fewer friendships, and greater social isolation compared to other children. Previous studies have suggested that injuries to specific brain regions commonly seen with brain tumors can lead to impairments similar to ASD. Considering the overlapping social difficulties in both groups of children, research that examines shared and distinct mechanisms of social adjustment among children with ASD and those treated for brain tumors is needed.

Researchers at the Center for Childhood Cancer Research, including Dr. Hocking, are collecting data on long-term brain tumor survivors to help identify specific areas of social difficulty and the factors that contribute to or hinder their social abilities. In one study, children are being assessed on measures capturing multiple elements of social abilities including facial recognition, emotional recognition, and social attention (i.e. where one attunes their gaze when watching social stimuli). Findings from these measures are then being compared with analogous data collected from a group of children diagnosed with ASD. MRI scans are also incorporated, to allow researchers to identify the particular brain structures responsible for commonalities and differences in social abilities among these children.

Results of this study will aid in the development of interventions for child brain tumor survivors, targeting specific areas of post-treatment social difficulties. Furthermore, the study will increase our knowledge of biological underpinnings of ASD and factors influencing social abilities of these children.

Children receiving treatment such as chemotherapy, radiation and surgery for brain tumors often experience neurodevelopmental challenges after tumor-directed treatment has concluded. They may have trouble with decreased processing speed, attention, memory and general executive functioning, all of which can affect them academically and socially.

Dr. Hocking and researchers at the CCCR are working to identify the basic predictors of how well children function socially over time after they have finished tumor-directed treatment. One longitudinal study uses different assessment tools to measure different domains potentially relevant to social functioning, including neurocognitive functioning, family functioning, and survivor processing of social information.

These tools assess how well survivors are able to understand the perspectives of others, how well they can recognize facial expressions, how well they can interpret social influences, and how well they're able to handle different hypothetical social dilemmas. Pediatric brain tumor survivors will be compared with survivors of non-central nervous system tumors to determine the influence of treatments on neurocognitive and social functioning.

The results of this study will enhance our understanding of how much post-treatment neurocognitive functioning contributes to the social functioning of pediatric brain tumor survivors.

Some cancer survivors face significant challenges following treatment. Chemotherapy, radiation, surgery, or stem cell transplant may result in late effects including cognitive effects, infertility, cardiovascular effects, endocrinopathies, psychosocial concerns, and risk of developing new malignancies. Adding to this complexity is that some of these late effects don’t emerge until years or decades after the completion of cancer therapy when survivors have moved on from pediatric oncology care.

Survivorship care seeks to keep cancer survivors healthy, off therapy, and well into adulthood. Survivors are educated about potential late effects of therapy and undergo screening for late effects based on their treatment-specific risk. As survivors age and assume more responsibility for their care, it is recommended that each survivor have his or her own individualized plan to ensure that he or she knows about these health risks, and recommended screening to advocate for themselves across multiple care settings.

Working at the level of patient care, researchers at the Center for Childhood Cancer Research, including Dava Szalda, MD, developed algorithm-based online portable individual survivorship care plans for cancer survivors. Care plans can be created by survivors themselves and shared with healthcare teams or be created by clinicians. Care plans incorporate predictive models of risk and are tailored to the specifics of the survivor’s case, such as type and location of cancer, types of treatment, gender, age, and other data.

These care plans can then educate the survivor and the survivor’s clinicians about potential late effects of cancer therapy. Care plans also contain information about diet, exercise, smoking and other variables that can affect everyone’s health. Psychosocial resources are also provided, offering information about education, employment and other support for survivors in general. All plans contain detailed information as well as a survivor and clinician summary.

Studies are currently underway to determine how survivors are accessing healthcare as long-term survivors and what predicts meaningful engagement in follow-up care.

Concerning the use of care plans, results from a pilot study of long-term survivors of leukemia and Hodgkin’s lymphoma have been promising, demonstrating that survivors are finding the care plans useful. Feedback from the pilot study informed adaptions to the care plan generator and have improved the efficiency of how patients are cared for in long-term follow-up clinic. Ongoing work is expanding the population utilizing care plans to both (1) understand the effects of care plans on knowledge and health behaviors and (2) use survivorship care plans coupled with a self-management mobile health intervention.

Dr. Szalda works clinically in survivorship clinics and both CHOP and the Abramson Cancer Center and is focused on the care of adolescent and young adult cancer survivors, seeing survivors of pediatric, adolescent, and young adult cancers, and helping them manage chronic health conditions and coordinating their healthcare. Her clinical and research program collaborators include Jill Ginsberg, MD, Linda Jacobs, PhD, CRNP, Lisa Schwarz, PhD, Marilyn Schapira, MD, MPH, and Chrissie Hill-Kayser, MD.

A large body of research confirms the presence of psychosocial distress and resiliencies of families as they initiate and complete pediatric cancer treatment. Although most families adapt and are able to cope with the stressors associated with a cancer diagnosis and treatment for their child, there are currently many missed opportunities for identifying problems for which we have effective preventative or early interventions. If untreated, psychosocial stress has the potential to escalate and impact cancer care and outcomes. For example, psychological factors are important, across cancers, in adherence to treatment and ongoing medical monitoring and health-promoting behaviors.

While evidence-based assessment and intervention approaches relevant across the course of treatment have been developed, efforts continue to integrate psychosocial screening into clinical care on a systematic basis. As a result, researchers at the CCCR, led by Lamia P. Barakat, PhD are analyzing the acceptability, feasibility, and validity of tools used for psychosocial assessment or screening at various time points across the course of treatment to help predict and improve outcomes for children with cancer and their families. Additionally, identifying factors associated with ongoing distress for pediatric cancer patients and their families can facilitate cancer care and ensure the timely provision of evidence-based psychosocial services.