Cardiopulmonary function and cerebral blood flow in Hodgkin Lymphoma survivors

PROJECT ABSTRACT Hodgkin Lymphoma (HL) is a cancer whose principal therapies are associated with an increased risk for cardiopulmonary complications and cerebrovascular disease when compared to sibling. Reduced cardiopulmonary functional reserve and lung morbidity are associated with poor neurocognitive outcomes. The pathophysiology of how HL treatment and cardiopulmonary complications are related to increased cerebrovascular and neurocognitive risks are not well understood. We hypothesize that impaired regulation of cerebral blood flow (CBF), which is primarily driven by oxygen and carbon dioxide levels in the blood, is caused by impaired gas diffusion in the lungs and reduced cardiopulmonary function and functional reserve. The specific aims of this research are: 1) to evaluate how CBF and oxygenation change during exercise in survivors compared to controls; 2) to examine if CO2 clearance differs in survivors compared to controls during rest and exercise; and 3) to examine associations among CBF, reduced cardiopulmonary functional reserve, cardiopulmonary function, and neurocognitive outcomes in HL survivors. This study will utilize a cross-sectional assessment of community controls and adult survivors of HL who were treated with bleomycin and/or chest and neck radiation. Participants will be recruited from the St. Jude Lifetime Cohort (SJLIFE) study. As part of this study, they will undergo complete pulmonary function tests, echocardiogram, and neurocognitive testing. In addition to this standard testing, CBF will be assessed immediately prior to and during cardiopulmonary exercise using a wearable, near infrared spectroscopy system. Participants will complete maximal (100% of predicted heart rate) cardiopulmonary exercise testing with continuous 12-lead electrocardiogram (ECG) monitoring. Expired gas will be collected with a two-way non- rebreather valve and monitored continuously using a breath-by-breath gas analysis system to evaluate cardiopulmonary functional reserve and lung ventilation and gas diffusion measures. Demographic and treatment factors will be compared to cardiopulmonary functional reserve outcomes. Gas diffusion (ETCO2/DLCO) and CBF will be compared between HL survivors and community controls and identified differences will be referenced to the chemotherapy, chest and neck radiation dose, pulmonary function test, ECG, and neurocognitive testing. This study will improve our understanding of the relationship between cardiopulmonary health and functional reserve, CBF regulation, and late-onset neurocognitive impairments in HL survivors. This can be translated to improved screening and monitoring, and development of interventions to reduce cancer related late-effects.