Neurologic morbidity and functional independence in adult survivors of childhood cancer.

OBJECTIVE: To examine associations between neurologic late effects and attainment of independence in adult survivors of childhood cancer treated with central nervous system (CNS)-directed therapies. METHODS: A total of 7881 survivors treated with cranial radiation therapy (n = 4051; CRT) and/or intrathecal methotrexate (n = 4193; IT MTX) ([CNS-treated]; median age [range] = 25.5 years [18-48]; time since diagnosis = 17.7 years [6.8-30.2]) and 8039 without CNS-directed therapy reported neurologic conditions including stroke, seizure, neurosensory deficits, focal neurologic dysfunction, and migraines/severe headaches. Functional independence was assessed using latent class analysis with multiple indicators (independent living, assistance with routine and personal care needs, ability to work/attend school, attainment of driver's license, marital/partner status). Multivariable regression models, adjusted for age, sex, race/ethnicity, and chronic health conditions, estimated odds ratios (OR) or relative risks (RR) for associations between neurologic morbidity, functional independence, and emotional distress. RESULTS: Among CNS-treated survivors, three classes of independence were identified: (1) moderately independent, never married, and non-independent living (78.7%); (2) moderately independent, unable to drive (15.6%); and (3) non-independent (5.7%). In contrast to 50% of non-CNS-treated survivors and 60% of siblings, a fourth fully independent class of CNS-treated survivors was not identified. History of stroke (OR = 2.50, 95% CI: 1.70-3.68), seizure (OR = 9.70, 95% CI: 7.37-12.8), neurosensory deficits (OR = 2.67, 95% CI: 2.16-3.31), and focal neurologic dysfunction (OR = 3.05, 95% CI: 2.40-3.88) were associated with non-independence among CNS-treated survivors. Non-independence was associated with emotional distress symptoms. INTERPRETATION: CNS-treated survivors do not attain full independence comparable to non-CNS-treated survivors or siblings. Interventions to promote independence may be beneficial for survivors with treatment-related neurological sequalae.

The earlier, the better? A review of neoadjuvant immunotherapy in resectable non-small-cell lung cancer.

Immune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non-small-cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD-1) and its ligand (PD-L1), have remarkable antitumor efficacy and have been approved as a standard first- or second-line treatment in non-oncogene-addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long-term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early-phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.

Calreticulin enhances gastric cancer metastasis by dimethylating H3K9 in the E-cadherin promoter region mediating by G9a.

The latest study shows that gastric cancer (GC) ranked the fifth most common cancer (5.6%) with over 1 million estimated new cases annually and the fourth most common cause of cancer death (7.7%) globally in 2020. Metastasis is the leading cause of GC treatment failure. Therefore, clarifying the regulatory mechanisms for GC metastatic process is necessary. In the current study, we discovered that calreticulin (CALR) was highly expressed in GC tissues and related to lymph node metastasis and patient's terrible prognosis. The introduction of CALR dramatically promoted GC cell migration in vitro and in vivo, while the repression of CALR got the opposite effects. Cell migration is a functional consequence of the epithelial-mesenchymal transition (EMT) and is related to adhesion of cells. Additionally, we observed that CALR inhibition or overexpression regulated the expression of EMT markers (E-cadherin, ZO-1, Snail, N-cadherin, and ZEB1) and cellular adhesive moleculars (Fibronectin, integrin ß1and MMP2). Mechanistically, our data indicated that CALR could mediate DNA methylation of E-cadherin promoter by interacting with G9a, a major euchromatin methyltransferase responsible for methylation of histone H3 on lysine 9(H3K9me2) and recruiting G9a to the E-cadherin promoter. Knockdown of G9a in CALR overexpressing models restored E-cadherin expression and blocked the stimulatory effects of CALR on GC cell migration. Taken together, these findings not only reveal critical roles of CALR medicated GC metastasis but also provide novel treatment strategies for GC.

Research on the optimization, key chemical constituents and antibacterial activity of the essential oil extraction process of Thuja koraiensis Nakai.

Thuja koraiensis Nakai is a kind of precious economic tree species with fragrance, ornamental and medicinal functions. The essential oil has the satisfactory antibacterial activity. In this paper, the essential oil from the branches and leaves of Thuja koraiensis Nakai was studied by optimization of extraction process, and the optimized parameters mainly include solid-liquid ratio, NaCl concentration, distillation time, storage conditions, etc. Which provided technical scientific basis for the development and utilization of Thuja koraiensis Nakai. The essential oil from the branches and leaves of Thuja koraiensis Nakai was extracted by steam distillation, and the single factor experiment was carried out. The extraction process of the essential oil from the branches and leaves of Thuja koraiensis Nakai was optimized by response surface methodology. The chemical constituents were analyzed by GC-MS. The antibacterial activity of the essential oil was detected by filter paper and plate coating methods. Thuja koraiensis Nakai showed that when the material-to-liquid ratio was 50 g/400 ml, the NaCl concentration was 6.0%, the distillation time was 5 h,the storage condition was dry branch, the oil content was the highest. The response surface optimization method showed that material-to-liquid ratio was 7.8804 ml/g, distillation time was 2.23 h, NaCl concentration was 6.56%, under such condition, the yield was 1.1712%. The chemical constituents of the essential oil were analyzed by GC-MS (gas chromatography-mass spectrometry), and 45 compounds were detected, accounting for 96.03% of the total number. The bacteriostatic activity was detected by filter paper method. The results showed that the essential oil of Thuja koraiensis Nakai had antibacterial effect on three strains (Staphylococcus aureus, Bacillus subtilis and Escherichia coli), among them, the diameter of bacteriostatic circle against S. aureus, B. subtilis and E. coli was 10.00 mm, 15.20 mm and 9.86 mm. The minimum inhibitory concentration (MIC) of the branches and leaves of Thuja koraiensis Nakai to S. aureus was 5 µg/ml, to B. subtilis was 0.625 µg/ml and to E. coli was 2.50 µg/ml. The highest extraction yield of essential oil from the branches and leaves of Thuja koraiensis Nakai by steam distillation was 1.30%. A total of 45 compounds were identified from the essential oils of Thuja koraiensis Nakai, among which carverol acetate was the highest. The essential oil from the branches and leaves of Thuja koraiensis Nakai has obvious antibacterial effect and great development potential, for example, making insect repell0ents, fungicides, essential oil soaps, so it is recommended to collect and use it.

Seizures' impact on cognition and quality of life in childhood cancer survivors.

BACKGROUND: The objective of this study was to determine the impact of seizure-related factors on neurocognitive, health-related quality of life (HRQOL), and social outcomes in survivors of childhood cancer. METHODS: Survivors of childhood cancer treated at St. Jude Children's Hospital (n = 2022; 48.3% female; median age, 31.5 years; median time since diagnosis, 23.6 years) completed neurocognitive testing and questionnaires. The presence, severity, resolution, and treatment history of seizures were abstracted from medical records. Adjusting for the age at diagnosis, sex, and prior cancer therapy, multivariable models examined the impact of seizures on neurocognitive and HRQOL outcomes. Mediation analyses were conducted for social outcomes. RESULTS: Seizures were identified in 232 survivors (11.5%; 29.9% of survivors with central nervous system [CNS] tumors and 9.0% of those without CNS tumors). In CNS tumor survivors, seizures were associated with poorer executive function and processing speed (P < .02); in non-CNS tumor survivors, seizures were associated with worse function in every domain (P < .05). Among non-CNS survivors, seizure severity was associated with worse processing speed (P = .023), and resolution was associated with better executive function (P = .028) and attention (P = .044). In CNS survivors, seizure resolution was associated with improved attention (P = .047) and memory (P < .02). Mediation analysis revealed that the impact of seizures on social outcomes was mediated by neurocognitive function. CONCLUSIONS: Seizures in cancer survivors adversely affect long-term functional and psychosocial outcomes independently of cancer therapy. The resolution of seizure occurrence is associated with better outcomes. Seizure severity is associated with poorer outcomes and should be a focus of clinical management and patient education.

A randomized double-blind placebo-controlled trial of the effectiveness of melatonin on neurocognition and sleep in survivors of childhood cancer.

BACKGROUND: Adult survivors of childhood cancer are at risk of developing sleep and neurocognitive problems, yet few efficacious interventions exist targeting these prevalent late effects. Melatonin has known sleep-promoting effects; however, it has not been well studied among childhood cancer survivors. METHOD: Survivors (n = 580; mean age = 33.5 years; 26 years post-diagnosis) from the St. Jude Lifetime Cohort were randomized (1:1) to a six-month double-blind placebo-controlled trial of 3 mg time-release melatonin within three strata (stratum 1: neurocognitive impairment only; stratum 2: neurocognitive and sleep impairment; stratum 3: sleep impairment only). Neurocognitive performance was assessed at baseline and post-intervention using standardized measures. Sleep was assessed via self-report and actigraphy. Independent sample t tests compared mean change scores from baseline to six months. Post-hoc analyses compared the prevalence of clinically significant treatment responders among melatonin and placebo conditions within and across strata. RESULTS: Intent-to-treat analyses revealed no statistically significant differences in neurocognitive performance or sleep from baseline to post-intervention. However, among survivors with neurocognitive impairment only, a larger proportion randomized to melatonin versus placebo demonstrated a treatment response for visuomotor speed (63% vs 41%, P = 0.02) and nonverbal reasoning (46% vs 28%, P = 0.04). Among survivors with sleep impairment only, a larger proportion treated with melatonin demonstrated a treatment response for shifting attention (44% vs 28%, P = 0.05), short-term memory (39% vs 19%, P = 0.01), and actigraphy-assessed sleep duration (47% vs 29%, P = 0.05). CONCLUSION: Melatonin was not associated with improved neurocognitive performance or sleep in our intent-to-treat analyses; however, a subset of survivors demonstrated a clinically significant treatment response.

Correlation of transrenal DNA with non-small-cell lung cancer in noninvasive disease monitoring.

Background: The study aims to use noninvasive transrenal DNA in advanced non-small-cell lung cancer (NSCLC) patients for treatment monitoring and prognosis. Methods: Urine specimens were collected longitudinally for 103 late-stage NSCLC patients. Detection of targetable mutations in transrenal DNA was achieved by digital droplet PCR. Patients' overall survival outcomes were correlated with levels of transrenal DNA. Results: Corresponding patients' matched tumor results demonstrated concordance rate of 95.6% with transrenal DNA. A significant decline in levels was observed after treatment initiation. We observed changes in transrenal DNA levels to be significantly associated with survival for patients (p < 0.0001). Conclusion: Our results demonstrated strong predictive values of transrenal DNA to better identify patients with poorer survival outcomes and may further complement disease management.

Magnetoactive Soft Drivers with Radial-Chain Iron Microparticles.

Magnetoactive elastomers (MAEs), one kind of typical novel magnetoactive driver applied in the soft robotic area, have become one of the research hotspots as they can provide biologically friendly driving methods with safe, preprogrammed, and easy-to-implement properties. In this study, novel MAEs embedding soft magnetic iron microparticles with radial chains, which can be molded in one piece, achieve 3D deformation, and co-work between multiple MAEs under single homogeneous stimuli, are proposed. Then, two kinds of novel magnetoactive drivers are established based on the proposed MAEs, which can achieve the synchronous pumping behavior of heart and the extension behavior of muscle under applied homogeneous magnetic fields. The experimental data show that (1) for the pumping behavior, the maximum instantaneous flow rate and total pumping volume can reach 200.1 and 52.3 mL/min, respectively, under 120 BPM applied harmonic magnetic field with 0-300 mT amplitude; (2) the muscle extension behavior can achieve a strain of 0.925 without a loading mass and carry a load of 40 times its own weight with a pronounced dynamic movement. It should be emphasized that the behavior of the proposed magnetoactive drivers can be excited by remote homogeneous magnetic fields, and it has great application potential in biomimetic or bioinspired soft driving systems.

Pain and functional outcomes in adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort study.

BACKGROUND: Although survivors of childhood cancer are at risk of chronic pain, the impact of pain on daily functioning is not well understood. METHODS: A total of 2836 survivors (mean age, 32.2 years [SD, 8.5 years]; mean time since diagnosis, 23.7 years [SD, 8.2 years]) and 343 noncancer community controls (mean age, 35.5 years [SD, 10.2 years]) underwent comprehensive medical, neurocognitive, and physical performance assessments, and completed measures of pain, health-related quality of life (HRQOL), and social functioning. Multinomial logistic regression models, using odds ratios and 95% confidence intervals (95% CIs), examined associations between diagnosis, treatment exposures, chronic health conditions, and pain. Relative risks (RRs) between pain and neurocognition, physical performance, social functioning, and HRQOL were examined using modified Poisson regression. RESULTS: Approximately 18% of survivors (95% CI, 16.1%-18.9%) versus 8% of controls (95% CI, 5.0%-10.9%) reported moderate to very severe pain with moderate to extreme daily interference (P < .001). Severe and life-threatening chronic health conditions were associated with an increased likelihood of pain with interference (odds ratio, 2.03; 95% CI, 1.62-2.54). Pain with daily interference was found to be associated with an increased risk of impaired neurocognition (attention: RR, 1.88 [95% CI, 1.46-2.41]; and memory: RR, 1.65 [95% CI, 1.25-2.17]), physical functioning (aerobic capacity: RR, 2.29 [95% CI, 1.84-2.84]; and mobility: RR, 1.71 [95% CI, 1.42-2.06]), social functioning (inability to hold a job and/or attend school: RR, 4.46 [95% CI, 3.45-5.76]; and assistance with routine and/or personal care needs: RR, 5.64 [95% CI, 3.92-8.10]), and HRQOL (physical: RR, 6.34 [95% CI, 5.04-7.98]; and emotional: RR, 2.83 [95% CI, 2.28-3.50]). CONCLUSIONS: Survivors of childhood cancer are at risk of pain and associated functional impairments. Survivors should be screened routinely for pain and interventions targeting pain interference are needed.

Cumulative Burden of Chronic Health Conditions in Adult Survivors of Osteosarcoma and Ewing Sarcoma: A Report from the St. Jude Lifetime Cohort Study.

BACKGROUND: Adult survivors of childhood osteosarcoma and Ewing sarcoma are at risk of developing therapy-related chronic health conditions. We characterized the cumulative burden of chronic conditions and health status of survivors of childhood bone sarcomas. METHODS: Survivors (n = 207) treated between 1964 and 2002 underwent comprehensive clinical assessments (history/physical examination, laboratory analysis, and physical and neurocognitive testing) and were compared with community controls (n = 272). Health conditions were defined and graded according to a modified version of the NCI's Common Terminology Criteria for Adverse Events and the cumulative burden estimated. RESULTS: Osteosarcoma and Ewing sarcoma survivors [median age 13.6 years at diagnosis (range 1.7-24.8); age at evaluation 36.6 years (20.7-66.4)] demonstrated an increased prevalence of cardiomyopathy (14.5%; P < 0.005) compared with controls. Nearly 30% of osteosarcoma survivors had evidence of hypertension. By age 35 years, osteosarcoma and Ewing sarcoma survivors had, on average, 12.0 (95% confidence interval, 10.2-14.2) and 10.6 (8.9-12.6) grade 1-4 conditions and 4.0 (3.2-5.1) and 3.5 (2.7-4.5) grade 3-4 conditions, respectively, compared with controls [3.3 (2.9-3.7) grade 1-4 and 0.9 (0.7-1.0) grade 3-4]. Both survivor cohorts exhibited impaired 6-minute walk test, walking efficiency, mobility, strength, and endurance (P < 0.0001). Accumulation of ≥4 grade 3-4 chronic conditions was associated with deficits in executive function [RR: osteosarcoma 1.6 (1.0-2.4), P = 0.049; Ewing sarcoma 2.0 (1.2-3.3), P = 0.01] and attention [RR: osteosarcoma 2.3 (1.2-4.2); P = 0.008]. CONCLUSIONS: Survivors of osteosarcoma and Ewing sarcoma experience a high cumulative burden of chronic health conditions, with impairments of physical function and neurocognition. IMPACT: Early intervention strategies may ameliorate the risk of comorbidities in bone sarcoma survivors.

Insomnia and Neurocognitive Functioning in Adult Survivors of Childhood Cancer.

BACKGROUND: In noncancer populations, insomnia is known to affect neurocognitive processes. Although the prevalence of insomnia appears to be elevated in survivors of childhood cancer, relatively little is known about its association with neurocognitive performance in this at-risk population. METHODS: A total of 911 survivors (51.9% female; mean [SD] age, 34 [9.0] years; time since diagnosis, 26 [9.1] years) completed direct assessments of attention, memory, processing speed, and executive functioning and self-reported symptoms of sleep (Pittsburgh Sleep Quality Index), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), and daytime sleepiness (Epworth Sleepiness Scale). Sex-stratified general linear models were used to examine associations between insomnia and neurocognitive performance, with adjustment for treatment exposures and chronic health conditions. All statistical tests were two-sided. RESULTS: Insomnia was reported by 22.1% of females and 12.3% of males (P < .001). After adjustment for neurotoxic treatment exposures, insomnia (vs healthy sleepers with no daytime fatigue or sleepiness) was associated with worse neurocognitive performance in the domains of verbal reasoning, memory, attention, executive function, and processing speed (verbal reasoning: males ß = -0.34, P = .04, females ß = -0.57, P < .001; long-term memory: males ß = -0.60, P < .001, females ß = -0.36, P = .02; sustained attention: males ß = -0.85, P < .001, females ß = -0.42, P = .006; cognitive flexibility: males ß = -0.70, P = .002, females ß = -0.40, P = .02). Self-reported sleep disturbance without daytime fatigue or sleepiness or daytime fatigue or sleepiness alone were not consistently associated with poorer neurocognitive performance. CONCLUSIONS: Insomnia was highly prevalent and contributed to the neurocognitive burden experienced by adult survivors of childhood cancer. Treatment of insomnia may improve neurocognitive problems in survivors.

Cerebral microbleeds in adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiation.

Cranial radiation therapy is associated with white matter-specific brain injury, cortical volume loss, mineralization, microangiopathy and neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia. In this retrospective cross-sectional analysis, neurocognitive testing and 3 T brain MRI's were obtained in 101 survivors treated with cranial radiation. Small focal intracerebral hemorrhages only visible on exquisitely sensitive MRI sequences were identified and localized using susceptibility weighted imaging. Modified Poisson regression was used to assess the effect of cranial radiation on cumulative number and location of microbleeds in each brain region, and multiple linear regression was used to evaluate microbleeds on neurocognitive outcomes, adjusting for age at diagnosis and sex. At least one microbleed was present in 85% of survivors, occurring more frequently in frontal lobes. Radiation dose of 24 Gy conveyed a 5-fold greater risk (95% CI 2.57-10.32) of having multiple microbleeds compared to a dose of 18 Gy. No significant difference was found in neurocognitive scores with either the absence or presence of microbleeds or their location. Greater prevalence of microbleeds in our study compared to prior reports is likely related to longer time since treatment, better sensitivity of SWI for detection of microbleeds and the use of a 3 T MRI platform.

Recent progress on anti-Toxoplasma drugs discovery: Design, synthesis and screening.

Toxoplasma gondii severely threaten the health of immunocompromised patients and pregnant women as this parasite can cause several disease, including brain and eye disease. Current treatment for toxoplasmosis commonly have high cytotoxic side effects on host and require long durations ranging from one week to more than one year. The regiments lack efficacy to eradicate T. gondii tissue cysts to cure chromic infection results in the needs for long treatment and relapsing disease. In addition, there has not been approved drugs for treating the pregnant women infected by T. gondii. Moreover, Toxoplasma vaccine researches face a wide variety of challenges. Developing high efficient and low toxic agents against T. gondii is urgent and important. Over the last decade, tremendous progress have been made in identifying and developing novel compounds for the treatment of toxoplasmosis. This review summarized and discussed recent advances between 2009 and 2019 in exploring effective agents against T. gondii from five aspects of drug discovery.

Growth hormone deficiency and neurocognitive function in adult survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: The impact of growth hormone deficiency (GHD) on neurocognitive function is poorly understood in survivors of childhood acute lymphoblastic leukemia (ALL). This study examined the contribution of GHD to functional outcomes while adjusting for cranial radiation therapy (CRT). METHODS: Adult survivors of ALL (N = 571; 49% female; mean age, 37.4 years; age range, 19.4-62.2 years) completed neurocognitive tests and self-reported neurocognitive symptoms, emotional distress, and quality of life. GHD was defined as a previous diagnosis of GHD or a plasma insulin-like growth factor1 level less than -2.0 standard deviations for sex and age at the time of neurocognitive testing. Hypothyroidism, hypogonadism, sex, age at diagnosis, CRT dose, and intrathecal and high-dose intravenous methotrexate were included as covariates in multivariable linear regression models. RESULTS: Of the 571 survivors, 298 (52%) had GHD, and those with GHD received higher doses of CRT (P = .002). Survivors who had GHD, irrespective of prior growth hormone treatment, demonstrated poorer vocabulary (z-score, -0.84 vs -0.61; P = .02), processing speed (z-score, -0.49 vs -0.30; P = .04), cognitive flexibility (z-score, -1.37 vs -0.94; P = .01), and verbal fluency (z-score, -0.74 vs -0.44; P = .001), and they self-reported more neurocognitive problems and poorer quality of life compared with survivors who did not have GHD. Multivariable and mediation models revealed that GHD was associated with small effects on quality of life (general health, P = .01; vitality, P = .01; mental health, P = .01); and CRT dose accounted for the lower neurocognitive outcomes. CONCLUSIONS: Adult survivors of childhood ALL who receive CRT are at risk for GHD, although poor neurocognitive outcomes are determined by CRT dose and not by the presence of GHD.

Alcohol consumption behaviors and neurocognitive dysfunction and emotional distress in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

AIMS: To estimate the level of alcohol consumption behaviors in adult survivors of childhood cancer and to test associations between alcohol consumption behaviors and symptoms of neurocognitive impairment and emotional distress. DESIGN: Retrospective cohort study with longitudinal follow-up of self-reported health outcomes. SETTING: Childhood Cancer Survivor Study (CCSS), a 26-center study of ≥ 5-year survivors of childhood cancer diagnosed ≤ 21 years of age between 1970 and 1986 in the United States and Canada. PARTICIPANTS: A total of 4484 adult survivors of childhood cancer [mean (standard deviation) age at evaluation = 34.8 (6.1) years; time from diagnosis = 24.8 (4.4) years] and 1651 sibling controls who completed surveys reporting on alcohol use, neurocognitive impairment and emotional distress. MEASUREMENTS: Survivor report of alcohol use included age at drinking initiation and quantity and frequency of alcohol consumption. Neurocognition was assessed using the CCSS Neurocognitive Questionnaire. Emotional distress symptoms were measured using the Brief Symptoms Inventory-18 and the Posttraumatic Stress Diagnostic Scale. FINDINGS: After adjustment for childhood cancer treatment exposures, including cranial radiation therapy, drinking initiation prior to 18 years of age was associated with 30% increased risk of subsequent memory problems [risk ratio (RR) = 1.3; 95% confidence interval (CI) = 1.1-1.5]. Younger age at drinking initiation was associated with future risk of depression (RR = 1.3; 95% CI = 1.1-1.5), anxiety (RR = 1.6; 95% CI = 1.3-2.1), and somatization (RR = 1.2; 95% CI = 1.1-1.4). Persistent heavy/risky drinking was associated with 80% increased risk of persistent psychological distress (RR = 1.8, 95% CI = 1.4-2.3). CONCLUSIONS: Drinking initiation during adolescence is associated with modest increased risk for memory impairment and emotional distress in adult survivors of childhood cancer.

Social adjustment in adolescent survivors of pediatric central nervous system tumors: A report from the Childhood Cancer Survivor Study.

BACKGROUND: The purpose of this study was to examine the prevalence and predictors of social difficulties in adolescent survivors of central nervous system (CNS) tumors. METHODS: Six hundred sixty-five survivors of CNS tumors (53.8% male and 51.7% treated with cranial radiation therapy [CRT]), who had a current median age of 15.0 years (range, 2.0-17.0 years) and were a median of 12.1 years (range, 8.0-17.7 years) from their diagnosis, were compared with 1376 survivors of solid tumors (50.4% male), who had a median age of 15.0 years (range, 12.0-17.0 years) and were a median of 13.2 years (range, 8.3-17.9 years) from their diagnosis, and 726 siblings (52.2% male), who had a median age of 15.0 years (range, 12.0-17.0 years). Social adjustment was measured with parent-proxy responses to the Behavior Problems Index. Latent profile analysis defined social classes. Multinomial logistic regression, adjusted for age, sex, and age at diagnosis, identified predictors of class membership. Path analyses tested mediating effects of physical limitations, sensory loss, and cognitive impairment on social outcomes. RESULTS: Caregivers reported that survivors of CNS tumors were more likely to have 0 friends (15.3%) and to interact with friends less than once per week (41.0%) in comparison with survivors of solid tumors (2.9% and 13.6%, respectively) and siblings (2.3% and 8.7%, respectively). Latent profile analysis identified 3 social classes for survivors of CNS tumors: well-adjusted (53.4%), social deficits (16.2%), and poor peer relationships (30.4%). However, 2 classes were identified for survivors of solid tumors and siblings: well-adjusted (86.2% and 91.1%, respectively) and social deficits (13.8% and 8.9%, respectively). CRT predicted class membership for CNS survivors (odds ratio [OR] for poor peer relationships, 1.16/10 Gy; 95% confidence interval [CI], 1.08-1.25; OR for social deficits 1.14/10 Gy; 95% CI, 1.04-1.25; reference, well-adjusted). Cognitive impairment mediated the association between all social outcomes and CRT (P values < .001). CONCLUSION: Almost 50% of survivors of CNS tumors experience social difficulties; the pattern is unique in comparison with solid tumor and sibling groups. Cognitive impairment is associated with increased risk, and this highlights the need for multitargeted interventions.

Perceptions of future health and cancer risk in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Survivors of childhood cancer are at significant risk for serious chronic health conditions and subsequent cancers because of their prior treatment exposures. However, little is known about survivors' perceptions of their future health risks. METHODS: This study examined self-reported levels of concern about future health and subsequent cancer in 15,620 adult survivors of childhood cancer (median age, 26 years; median time since diagnosis, 17 years) and 3991 siblings in the Childhood Cancer Survivor Study. The prevalence of concerns was compared between survivors and siblings, and the impact of participant characteristics and treatment exposures on concerns was examined with multivariable modified Poisson regression to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: A substantial proportion of survivors were not concerned about their future health (31%) or developing cancer (40%). The prevalence of concern in survivors was modestly higher (RR for future health, 1.12; 95% CI, 1.09-1.15) or similar (RR for subsequent cancer, 1.02; 95% CI, 0.99-1.05) in comparison with siblings. Survivors exposed to high doses of radiation (≥20 Gy) were more likely to report concern (RR for future health, 1.13; 95% CI, 1.09-1.16; RR for subsequent cancer, 1.14; 95% CI, 1.10-1.18), but 35% of these high-risk survivors were not concerned about developing cancer, and 24% were not concerned about their future health. CONCLUSIONS: A substantial subgroup of survivors were unconcerned about their future health and subsequent cancer risks, even after exposure to treatments associated with increased risk. These survivors may be less likely to engage in beneficial screening and risk-reduction activities. Cancer 2018. © 2018 American Cancer Society.

Sleep and mood during hospitalization for high-dose chemotherapy and hematopoietic rescue in pediatric medulloblastoma.

OBJECTIVE: Disrupted sleep is common in pediatric cancer, which is associated with psychological distress and may impact neural recovery. Information regarding sleep during pediatric brain tumor treatment is limited. This study aimed to describe objective sleep-wake patterns and examine the sleep-mood relation in youth hospitalized for intensive chemotherapy and stem cell rescue. METHODS: Participants included 37 patients (M age = 9.6 ± 4.2 years) enrolled on a medulloblastoma protocol (SJMB03) and their parents. Respondents completed a mood disturbance measure on 3 days, and patients wore an actigraph for 5 days as an objective estimate of sleep-wake patterns. General linear mixed models examined the relation between nocturnal sleep and next-day mood, as well as mood and that night's sleep. RESULTS: Sleep duration was deficient, sleep efficiency was poor, and daytime napping was common, with large between-subjects variability. There were minimal mood concerns across all days. The sleep and next-day mood relationship was nonsignificant (P > .05). Greater parent-reported child mood disturbance on day 2 was associated with decreased same-night sleep (P < .001) and greater patient-reported mood disturbance was associated with greater same-night sleep latency (P = .036). CONCLUSIONS: Patients with medulloblastoma are vulnerable to disturbed sleep during hospitalization, and mood may be an important correlate to consider. Sleep and mood are modifiable factors that may be targeted to maximize daytime functioning.

The role of body image dissatisfaction in the association between treatment-related scarring or disfigurement and psychological distress in adult survivors of childhood cancer.

OBJECTIVE: To examine the potential mediating role of body image dissatisfaction on the association between treatment-related scarring/disfigurement and psychological distress in adult survivors of childhood cancer. METHODS: Participants included 1714 adult survivors of childhood cancer (mean [SD] age at evaluation = 32.4 [8.0] years, time since diagnosis = 24.1 [8.1] years) enrolled in the St. Jude Lifetime Cohort Study. Survivors completed measures of body image, emotional distress, and posttraumatic stress symptoms (PTSS). Body image dissatisfaction (BID) was categorized into 2 groups (cancer-related and general) based on factor analysis. Using causal mediation analysis, we estimated the proportion of psychological distress associated with treatment-related scarring/disfigurement that could be eliminated by resolving BID through a hypothetical intervention. RESULTS: Among survivors with scarring/disfigurement of the head, a sizable proportion of the relative excess of psychological distress could be eliminated if BID was successfully treated (males: [cancer-related BID: depression: 63%; anxiety: 100%; PTSS: 52%]; [general BID: depression: 70%; anxiety: 100%; PTSS: 42%]; females: [cancer-related BID: depression: 20%; anxiety; 36%; PTSS: 23%]; [general BID: depression: 32%; anxiety: 87%; PTSS: 38%]). The mediating effect of BID was less pronounced for the association between scarring/disfigurement of the body and psychological distress for both males and females. CONCLUSIONS: Body image dissatisfaction mediates the association treatment-related scarring/disfigurement and psychological distress among adult survivors of childhood cancer, particularly among survivors with scarring/disfigurement of the head and male survivors. Successful treatment of body image dissatisfaction has the potential to eliminate a substantial proportion of psychological distress related to scarring/disfigurement among adult survivors of childhood cancer.