Neurocognitive and Behavioral Outcomes of Chinese Survivors of Childhood Lymphoblastic Leukemia.

BACKGROUND: Increasing attention has been dedicated to investigate modifiable risk factors of late effects in survivors of childhood cancer. This study aims to evaluate neurocognitive and behavioral functioning in a relatively young cohort of survivors of childhood acute lymphoblastic leukemia (ALL) in Hong Kong, and to identify clinical and socio-environmental factors associated with these outcomes. METHODS: This analysis included 152 survivors of childhood ALL who were ≥5 years post-diagnosis (52% male, mean [SD] age 23.5[7.2] years at evaluation, 17.2[7.6] years post-diagnosis). Survivors completed performance-based neurocognitive tests, and reported their emotional and behavioral symptoms using the Child/Adult Behavior Checklist. Socio-environmental variables (living space, fatigue, physical activity, family functioning, and academic stress) were self-reported using validated questionnaires. Clinical variables and chronic health conditions were extracted from medical charts. Multivariable linear modeling was conducted to test identify factors associated with neurocognitive/behavioral outcomes, adjusting for current age, sex, age at diagnosis and cranial radiation. An exploratory mediation analysis was performed to examine the mediating effects of risk factors on neurocognitive and behavioral outcomes. RESULTS: As compared to population norms, a minority of survivors developed mild-moderate impairment in motor processing speed (36.2%), memory (9.2%) and attention measures (4.0%-10.5%). Survivors also reported attention problems (12.5%), sluggish cognitive tempo (23.7%) and internalizing (depressive, anxiety and somatic symptoms) problems (17.1%). A minority of survivors developed mild-moderate treatment-related chronic conditions (n=37, 24.3%). As compared to survivors without chronic conditions, survivors with chronic conditions had more executive dysfunction (B=5.09, standard error [SE]=2.05; P=0.014) and reported more attention problems (B=5.73, SE=1.43; P<0.0001). Fatigue and poor family functioning was associated with multiple measures of behavior problems (all P<0.001). A lower level of physical activity was correlated with more self-reported symptoms of inattention (B= -1.12, SE=0.38, P=0.004) and sluggish cognitive tempo (B=-1.22, SE=0.41, P=0.003). Exploratory analysis showed that chronic health conditions were associated with behavioral measures through fatigue as the mediator. CONCLUSION: The majority of young Chinese survivors of ALL had normal cognitive and behavioral function. Regular monitoring of behavioral function should be performed on survivors who develop treatment-related chronic conditions. Health behavior and socio-environment factors may be potentially modifiable risk factors associated with health outcomes in survivors.

Life Functioning in Chinese Survivors of Childhood Cancer in Hong Kong.

Background: Evidence on self-care ability and occupational outcomes in Chinese survivors of childhood cancer is clearly lacking. This study aims to identify clinical and behavioral factors associated with poor life functioning in this population. Methods: This was a cross-sectional study conducted at an ambulatory clinic of a public hospital in Hong Kong. Licensed occupational therapists administered the Life Functioning Assessment Inventory on survivors diagnosed with cancer <19 years old and ≥5 years post-diagnosis. Survivors' career development self-efficacy, subjective happiness, and motivation were evaluated using structured questionnaires. Clinical information was obtained from medical records. Multivariable linear regression was used to evaluate factors associated with life functioning outcomes, adjusting for clinically relevant variables. Results: Eighty survivors were recruited (58.7% male; age at diagnosis: 6.7 [standard deviation (SD) = 4.8] years; age at evaluation: 24.4 [SD = 6.5] years). Compared to survivors of leukemia, survivors of brain tumor performed worse in social functioning (ß = -0.79, standard error [SE] = 0.36; p = 0.034). Survivors who had been treated with cranial radiation also had lower worker life functioning than those who had not (ß = -0.91, SE = 0.031; p = 0.021). Higher activity motivation was significantly associated with better leisure functioning (ß = 0.086, SE = 0.03; p = 0.008), social functioning (ß = 0.036, SE = 0.02; p = 0.036), and career development self-efficacy (ß = 1.04, SE = 0.26; p < 0.0001). Conclusion: Survivors of brain tumors and survivors who were treated with radiation have poorer life functioning, particularly in social and work domains. Future work includes validating the study findings in a larger cohort of survivors in Hong Kong. Addressing modifiable behavioral factors include motivating survivors to engage in meaningful activities that contribute to self-care and participation in society, as well as providing at-risk survivors with ongoing support from community vocational services.

Neurocognitive impairment in Asian childhood cancer survivors: a systematic review.

Childhood cancer survivors are at higher risk of developing neurocognitive deficits due to the intensive treatment they received at an early age. Most studies on childhood cancer survivorship have so far focused on the Western populations. Due to the ethnic, genetic, environmental, and cultural differences, clinical data of the Western populations may not be representative of Asian countries. This scoping review systematically summarized the existing clinical evidence of the neurocognitive impairment of Asian childhood cancer survivors. We searched the Embase and Medline databases for studies assessing the neurocognitive functions of survivors in Asia, who were diagnosed with cancer before the age of 19 and completed active treatment. The literature search identified 13 studies involving 2212 participants from five Asian countries: South Korea (n = 4, 30.8%), Taiwan (n = 3, 23.1%), Japan (n = 3, 23.1%), Hong Kong (n = 2, 15.4%), and Thailand (n = 1, 7.7%). The included studies focused on CNS tumors (n = 10, 76.9%), hematological malignancies (n = 7, 53.8%), or heterogeneous cancer diagnoses (n = 3, 23.1%). Collectively, mild-to-moderate impairment in intelligence was observed in 10.0 to 42.8% of survivors, which seemed higher than the reported rate in Western survivors. We speculate that the ethnic and genetic variations in drug responses and susceptibility to adverse chronic toxicities may have contributed to the differences in the prevalence and severity of neurocognitive impairment between these two populations. To better understand the effects of culturally relevant and region-specific environmental risk factors on the post-treatment neurocognitive development in cancer survivors, a holistic approach that addresses the complex interactions between biological, physical, and psychosocial factors is needed. This will aid the development of effective intervention strategies to improve the functional and psychosocial outcomes of cancer survivors in Asian societies.

Clinical ascertainment of health outcomes in Asian survivors of childhood cancer: a systematic review.

PURPOSE: Survivorship in children with cancer comes at a cost of developing chronic treatment-related complications. Yet, it is still an under-researched area in Asia, which shares the largest proportion of the global childhood cancer burden given its vast population. This systematic review summarizes existing literature on clinically ascertained health outcomes in Asian survivors of childhood cancer. METHODS: A search was conducted on Ovid Medline and EMBASE for studies that focused on survivors of childhood cancer from countries in East and Southeast Asia; adopted post-treatment clinical ascertainment of organ-specific toxicities or/and secondary malignancy. Studies were excluded if health outcomes were assessed during the acute treatment. RESULTS: Fifty-nine studies, enrolling a total of 13,442 subjects, were conducted on survivors of leukemia (34%), CNS tumor (14%), and cohorts of survivors with heterogeneous cancer diagnoses (52%). The studies used different medical evaluation methods to assess cardiovascular (15%), metabolic and infertility (32%), and neurological/neurocognitive (20%) outcomes in survivors. The collective findings suggest potential differences in the prevalence of certain late effects (e.g., secondary malignancy and obesity) among Asian and non-Asian populations, which may reflect differences in treatment regimens, practice, genetic variations, or/and socioeconomic disparity. CONCLUSIONS: We recommend developing collaborative initiatives to build a regional repository of systematically assessed health outcomes and biospecimens to investigate treatment, social-environmental and genetic predictors, and interventions for late effects in this population. IMPLICATIONS FOR CANCER SURVIVORS: The existing types of chronic health problems identified in this review suggest the need for active screening, better access to survivorship care, and promotion of protective health behavior in Asia.

Effect of heat treatments on the essential oils of kumquat (Fortunella margarita Swingle).

Kumquats (Fortunella margarita Swingle) cultivated in Taiwan are eaten raw or made into candied fruit or fruit tea. For the experiments described in this paper, essential oils were obtained from kumquat peels or whole fruit by cold pressing, steam distillation or heating in water at 90°C for 15 min followed by steam distillation. The volatile components contained in the essential oils were identified by direct injection (DI) or headspace-solid phase microextraction (HS-SPME) coupled with gas chromatography (GC). A total of 43 compounds were identified, of which 37 were verified by DI/GC and 31 by HS-SPME/GC. Hot water heating increased the yields of essential oils from both peels and whole fruit. The principal constituents of the oils were similar except for the minor compounds, including linalool, terpinen-4-ol and α-terpineol, the levels of which increased after steam distillation. The whole fruit also contained higher levels of terpene alcohols.

Identification of di-isononyl phthalate metabolites for exposure marker discovery using in vitro/in vivo metabolism and signal mining strategy with LC-MS data.

Di-isononyl phthalate esters (DINPs) are endocrine-disrupting chemicals and have replaced di(2-ethylhexyl) phthalate (DEHP) as the major plasticizer for poly(vinyl chloride) (PVC) products in recent years. Exposure marker discovery of DINPs is crucial, because of their high potential for human exposure and toxicity. Here, we propose an alternative approach for tracing signals derived from stable isotope-labeled precursors with varied labeling ratios to efficiently filter probable metabolite signals. The statistical process, which involves a signal mining algorithm with isotope tracing (SMAIT), has effectively filtered 13 probable DINP metabolite signals out of the 8867 peaks in the LC-MS data obtained from incubated stable isotope-labeled precursors with liver enzymes. Seven of the 13 probable metabolite signals were confirmed as DINP structure-related metabolites by preliminary MS/MS analyses. These 7 structure-related metabolite signals were validated as effective DINP exposure markers, using urine samples collected from DINP-administered rats without time-consuming comprehensive structure identification. We propose that the 7 identified possible DINP metabolite signals of m/z 279.1, 293.1, 305.1, 307.1, 321.1, 365.1, and 375.1 are potential markers for DINP exposure and should be investigated further. The integrated approach described here can efficiently, and systematically, filter probable metabolite signals from a complex LC-MS dataset for toxic exposure marker discovery. It is a relatively low-cost/rapid workflow for exposure marker discovery.