Modifiable risk factors for neurocognitive and psychosocial problems after Hodgkin lymphoma

Abstract

Long-term survivors of childhood Hodgkin lymphoma (HL) experience high burden of chronic health morbidities. Correlates of neurocognitive and psychosocial morbidity have not been well established. 1,760 survivors of HL (mean[SD] age 37.5[6.0] years, time since diagnosis 23.6[4.7] years, 52.1% female) and 3,180 siblings (age 33.2[8.5] years, 54.5% female) completed cross-sectional surveys assessing neurocognitive function, emotional distress, quality of life, social attainment, smoking, and physical activity. Treatment exposures were abstracted from medical records. Chronic health conditions were graded according to NCI CTCAE v4.3 (1=mild, 2=moderate, 3=severe/disabling, 4=life-threatening). Multivariable analyses, adjusted for age, sex, and race, estimated relative risk (RR) of impairment in survivors vs. siblings and, among survivors, risk of impairment associated with demographic, clinical, treatment factors and grade 2+ chronic health conditions. Compared with siblings, survivors had significant higher risk (p's<0.05) of neurocognitive impairment (e.g. memory 8.1% vs. 5.7%), anxiety (7.0%%vs. 5.4%),depression (9.1% vs. 7%), unemployment (9.6% vs. 4.4%), and impaired physical/mental quality of life (e.g. physical function 11.2% vs. 3.0%). Smoking was associated with higher risk of impairment in task efficiency (RR=1.56[1.02-2.39]), emotional regulation (RR=1.84[1.35-2.49]), anxiety (RR=2.43[1.51-3.93]), and depression (RR=2.73[1.85-4.04]). Meeting CDC exercise guidelines was associated with lower risk of impairment in task efficiency (RR=0.70[0.52-0.95]), organization (RR=0.60[0.45-0.80]), depression (RR=0.66[0.48-0.92]), and multiple quality of life domains. Cardiovascular and neurologic conditions were associated with impairment in nearly all domains. Survivors of HL are at elevated risk for neurocognitive and psychosocial impairment, and risk is associated with modifiable factors that provide targets for interventions to improve long-term functional outcomes.

Psychological Outcomes in Adolescent and Young Adult Cancer Survivors

“…60 These impairments may persist as studies of long-term survivors (>10 years) of adolescent and early young adult HL self-report significant neurocognitive impairment decades after treatment. 61 In young adulthood, solid tumors become more common, namely thyroid, testicular, and breast cancers. Although not conducted exclusively among AYA patients, several small studies indicate survivors of thyroid cancer experience neurocognitive impairment during therapy.…”

Risk factors and screening for neurocognitive impacts of therapy

“…27 Attention and mem ory prob lems occur at a higher fre quency in longterm sur vi vors of HL com pared with sib lings and com mu nity con trols, and these prob lems are related to car diac and pul mo nary mor bid ity. 11,28 The thresh old for impact from car diac and pul mo nary mor bid ity may be lower in sur vi vors with prior direct neu ro tox ic ity. 22 In addi tion, the effects of car diac and pul mo nary toxic ther a pies may lower the thresh old for cog ni tive impact from other fac tors, such as smok ing and sys temic inflam ma tion.…”

“…22 In addi tion, the effects of car diac and pul mo nary toxic ther a pies may lower the thresh old for cog ni tive impact from other fac tors, such as smok ing and sys temic inflam ma tion. 11 Longterm sur vi vors of HL have been dem on strated to be at ele vated risk for overt ische mic stroke, with a roughly 4fold higher risk than sib ling con trols. 29 Although the spe cific eti ol ogy of the stroke is still under inves ti ga tion (eg, hyper ten sion vs radi a tioninduced vas cu lar dis ease vs obstruc tive sleep apnea), the occur rence of stroke does increase risk for neuro cognitive impair ment in longterm sur vi vors.…”

Late-onset Cognitive Impairment and Modifiable Risk Factors in Adult Childhood Cancer Survivors

“…Younger age at diagnosis and receipt of central nervous system (CNS)–directed therapy are associated with increased risk of neurocognitive impairment in young survivors . Many survivors are also at risk of developing chronic health conditions, which further increase the risk of impairment . The effects of CNS-directed therapies may alter brain development and reduce neurocognitive reserve needed to compensate for brain stressors and chronic health conditions related to typical aging .…”