Heather Conklin, PhD

As the survival rates for children with cancer improve, the consideration of long-term effects has taken on increased importance. For those receiving treatment for pediatric brain tumors, there can be significant effects from the presence of cancer and its treatment on a child’s neurocognitive skills, calling for more neurocognitive protective measures to be taken during treatment and interventions to lessen their impact when they occur. My research concentrates on characterizing these cognitive impacts and developing neurocognitive interventions so we can approach therapy in a way that uses the best curative approaches but also seeks to preserve and promote the continued development of vital cognitive skillsets that improve the outcomes and quality of life for the patient.

The preservation of neurocognition in pediatric cancer patients is essential. While this is true of all pediatric cancer patients, it is especially essential for those receiving central nervous system (CNS)-directed therapy, such as patients with pediatric brain tumors or some cases of acute lymphoblastic leukemia (ALL). Previous research demonstrated that the use of more focal irradiation for brain tumors or intrathecal and systemic chemotherapy as opposed to prophylactic cranial irradiation for ALL resulted in high survival rates without the decline in cognitive functioning. These findings laid the groundwork for new studies, in which we seek to identify, via molecular, genetic and neuroimaging screening, patients who are at greatest risk for developing cognitive deficits during cancer-directed therapy. When we know which patients are at greatest risk for developing neurocognitive deficits, we are able to direct front-line treatments that aim to preserve cognitive function and simultaneously work toward a cure.

Impacts to cognition have often been measured as a global neural phenomenon with limited nuance given to specific neural systems and the particular cognitive impact of cancer and its treatment on those systems. From our previous research, working memory emerged as a cognitive ability that was particularly sensitive to therapeutic approaches in patients with pediatric brain tumors and ALL. This work showed that cognitive performance was related to white matter integrity and specific genetic polymorphisms, which provided insights that serve to guide prognostication for cognitive late effects, selection of front-line treatments with neurotoxic effects in mind and novel pharmacological interventions. With this knowledge, I have developed collaborative research that uses neuroimaging technology to identify specific neural systems related to disease, treatment and cognitive dysfunction as we continue our work to identify patients at risk of neurocognitive effects and tailor treatment and targeted interventions to preserve neurocognitive function. 

As children move from patients to survivors, they need empirically validated interventions for cognitive preservation. My previous research, through randomized controlled trials, documented the safety and efficacy of methyphenidate as a pharmaceutical intervention for attention and social skills in childhood cancer survivors. Like all pharmaceuticals, methylphenidate is not a viable option for some cancer survivors, so my research has extended to nonpharmacologic interventions with an emphasis on computerized training. With functional neuroimaging to guide our work, we’ve shown training-based neuroplasticity as a mechanism for cognitive improvement. We’ve additionally been able to identify predictors of response to intervention, which has helped shape development of new strategies for cognitive remediation and/or protection in children treated for cancer that continue to move earlier in treatment and reach younger patients.  

All of my research efforts seek to characterize impaired cognitive effects and the impacted neural pathways associated with cancer and its treatment so we can best modify treatment to support both the cure and care that prioritizes survival and quality of life for our patients.