Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

A pharmacokinetics study of orally administered higenamine in rats using LC-MS/MS for doping control analysis.

According to WADA guidelines, the presence of Higenamine (HG) in urine should not be ≥10 ng/mL. HG is widely found in materials used in Chinese herbal medicines as well as food and additives. This paper is the first method wherein a rat model has been used to evaluate the pharmacokinetics of orally administered HG by LC-MS/MS and would be helpful in doping control analysis. The method was found to be linear over a concentration range of 0.5(lower limit of quantification, LLOQ)-500 ng/mL for plasma and 0.5(LLOQ)-1000 ng/mL for urine. The values for intra- and inter-day accuracy and precision did not deviate by >12.25% for HG in plasma and 5.87% in urine. Extraction recoveries of HG were 70.30-86.71% from plasma and 74.93%-79.29% from urine. HG was stable in plasma and urine after the extraction process and when exposed to different storage conditions. The findings of this study could provide some reference value for the assessment of HG misuse and for the control of intake and external application of HG-related materials (foods and medicinal herbs). Our key findings are that high levels of external application or oral administration of HG-rich materials may lead to a positive urine test for HG in athletes.

Occurrence, distribution, and potential risks of environmental corticosteroids in surface waters from the Pearl River Delta, South China.

The occurrence, spatiotemporal distribution, and potential risks of 21 glucocorticoids (GCs) and 3 mineralocorticoids (MCs) in four rivers were studied by investigating the surface waters from the Pearl River Delta (PRD), South China. These environmental corticosteroids (ECs) were commonly present in the river surface waters with average concentrations varying from <0.17 ng/L for fluticasone propionate to 5.6 ng/L for clobetasone butyrate; and cortisone had the highest concentration, 32.9 ng/L. The total ECs ranged in concentration from undetectable to 83.3 ng/L, with a mean and median of 8.1 ng/L and 4.8 ng/L, respectively. Spatially the total EC concentration levels in the Pearl River system occurred in the following order: Zhujiang River (ZR) > Dongjiang River (DR) > Shiziyang waterway (SW) > Beijiang River (BR). These levels generally demonstrated a trend of increasing from upstream to midstream or downstream then attenuating toward the estuary. Considerable seasonal variations in the ECs differed among rivers. Higher ECs concentrations in winter were mostly found in the ZR, whereas lower levels were found in the DR. Moreover, the temporal variations of the ECs were marginal in the BR and SW. These spatiotemporal distributions of the ECs might have been simultaneously influenced by pollution sources derived from anthropogenic activities and river hydrologic conditions. Correlation analyses indicated that dissolved organic carbon (DOC) could play a key role in the occurrence and distribution of ECs in an aquatic environment. Risk assessment demonstrated that the occurrence of ECs might have posed medium to high risk to aquatic organisms in the Pearl River.

[Simultaneous determination of 28 corticosteroids in surface water by ultra-high performance liquid chromatography-electrospray tandem mass spectrometry].

A comprehensive analytical method was developed for simultaneous determination of 28 corticosteroids in surface water based on ultra-high performance liquid chromatography- electrospray tandem mass spectrometry (UHPLC-ESI-MS/MS). The solid-phase extraction was performed using hydrophilic-lipophilic balance (HLB) cartridges, and the chromatographic separation was achieved on a reversed-phase C8 column. Qualitative and quantitative analyses were performed in the dynamic multiple reaction monitoring (DMRM) mode using positive and negative electrospray ionization (ESI±). The 28 target compounds were quantified by the internal standard method. Good linear relationships were obtained (R2>0.99) for the 28 analytes in the concentration range of 1.0-100 µg/L. The method limits of detection and quantification were in the range of 0.21-0.48 ng/L and 0.32-0.72 ng/L, respectively. When the matrix spiking levels were at 5.0, 10, and 50 ng/L, the average recoveries for the target compounds ranged from 68.6% to 108.7%, and the relative standard deviations (RSDs) were between 0.1% and 8.1%. Because of its high sensitivity, good precision, and reliability, this method can be widely applied to trace monitoring of glucocorticoids and mineral ocorticoids for investigating their behaviors and risks of corticosteroids in the environment.

Group Sequential Survival Trial Design and Monitoring Using the Log-Rank Test.

For randomized group sequential survival trial designs with unbalanced treatment allocation, the widely used Schoenfeld formula is inaccurate, and the commonly used information time as the ratio of number of events at interim look to the number of events at the end of trial can be biased. In this paper, a sample size formula for the two-sample log-rank test under the proportional hazards model is proposed that provides more accurate sample size calculation for unbalanced survival trial designs. Furthermore, a new information time is introduced for the sequential survival trials such that the new information time is more accurate than the traditional information time when the allocation of enrollments is unbalanced in groups. Finally, we demonstrate the monitoring process using the sequential conditional probability ratio test and compare it with two other well known group sequential procedures. An example is given to illustrate unbalanced survival trial design using available software.

A novel sample size formula for the weighted log-rank test under the proportional hazards cure model.

The treatment of cancer has progressed dramatically in recent decades, such that it is no longer uncommon to see a cure or log-term survival in a significant proportion of patients with various types of cancer. To adequately account for the cure fraction when designing clinical trials, the cure models should be used. In this article, a sample size formula for the weighted log-rank test is derived under the fixed alternative hypothesis for the proportional hazards cure models. Simulation showed that the proposed sample size formula provides an accurate estimation of sample size for designing clinical trials under the proportional hazards cure models.

Survival trial design and monitoring using historical controls.

In this paper, we propose a multistage group sequential procedure to design survival trials using historical controls. The formula for the number of events required for historical control trial designs is derived. Furthermore, a transformed information time is proposed for trial monitoring. An example is given to illustrate the application of the proposed methods to survival trial designs using historical controls. Copyright © 2016 John Wiley & Sons, Ltd.

Group Sequential Design for Randomized Phase III Trials under the Weibull Model.

In this article, a parametric sequential test is proposed under the Weibull model. The proposed test is asymptotically normal with an independent increment structure. The sample size for a fixed sample test is derived for the purpose of group sequential trial design. In addition, a multi-stage group sequential procedure is given under the Weibull model by applying the Brownian motion property of the test statistic and sequential conditional probability ratio test methodology.

Critical combinations of radiation dose and volume predict intelligence quotient and academic achievement scores after craniospinal irradiation in children with medulloblastoma.

PURPOSE: To prospectively follow children treated with craniospinal irradiation to determine critical combinations of radiation dose and volume that would predict for cognitive effects. METHODS AND MATERIALS: Between 1996 and 2003, 58 patients (median age 8.14 years, range 3.99-20.11 years) with medulloblastoma received risk-adapted craniospinal irradiation followed by dose-intense chemotherapy and were followed longitudinally with multiple cognitive evaluations (through 5 years after treatment) that included intelligence quotient (estimated intelligence quotient, full-scale, verbal, and performance) and academic achievement (math, reading, spelling) tests. Craniospinal irradiation consisted of 23.4 Gy for average-risk patients (nonmetastatic) and 36-39.6 Gy for high-risk patients (metastatic or residual disease >1.5 cm(2)). The primary site was treated using conformal or intensity modulated radiation therapy using a 2-cm clinical target volume margin. The effect of clinical variables and radiation dose to different brain volumes were modeled to estimate cognitive scores after treatment. RESULTS: A decline with time for all test scores was observed for the entire cohort. Sex, race, and cerebrospinal fluid shunt status had a significant impact on baseline scores. Age and mean radiation dose to specific brain volumes, including the temporal lobes and hippocampi, had a significant impact on longitudinal scores. Dichotomized dose distributions at 25 Gy, 35 Gy, 45 Gy, and 55 Gy were modeled to show the impact of the high-dose volume on longitudinal test scores. The 50% risk of a below-normal cognitive test score was calculated according to mean dose and dose intervals between 25 Gy and 55 Gy at 10-Gy increments according to brain volume and age. CONCLUSIONS: The ability to predict cognitive outcomes in children with medulloblastoma using dose-effects models for different brain subvolumes will improve treatment planning, guide intervention, and help estimate the value of newer methods of irradiation.

Effect of cerebellum radiation dosimetry on cognitive outcomes in children with infratentorial ependymoma.

PURPOSE: Cognitive decline is a recognized effect of radiation therapy (RT) in children treated for brain tumors. The importance of the cerebellum and its contribution to cognition have been recognized; however, the effect of RT on cerebellum-linked neurocognitive deficits has yet to be explored. METHODS AND MATERIALS: Seventy-six children (39 males) at a median 3.3 years of age (range, 1-17 years old) were irradiated for infratentorial ependymoma from 1997 to 2008. The total prescribed dose was 54 to 59.4 Gy administered to the postoperative tumor bed with 5- or 10-mm clinical target volume margin. Age-appropriate cognitive and academic testing was performed prior to the start of RT and was then repeated at 6 months and annually throughout 5 years. The anterior and posterior cerebellum and other normal brain volumes were contoured on postcontrast, T1-weighted postoperative magnetic resonance images registered to treatment planning computed tomography images. Mean doses were calculated and used with time after RT and other clinical covariates to model their effect on neurocognitive test scores. RESULTS: Considering only the statistically significant rates in longitudinal changes for test scores and models that included mean dose, there was a correlation between mean infratentorial dose and intelligence quotient (IQ; -0.190 patients/Gy/year; P=.001), math (-0.164 patients/Gy/year; P=.010), reading (-0.137 patients/Gy/year; P=.011), and spelling scores (-0.147 patients/Gy/year; P=.012), where Gy was measured as the difference between the mean dose received by an individual patient and the mean dose received by the patient group. There was a correlation between mean anterior cerebellum dose and IQ scores (-0.116 patients/Gy/year; P=.042) and mean posterior cerebellum dose and IQ (-0.150 patients/Gy/year; P=.002), math (-0.120 patients/Gy/year; P=.023), reading (-0.111 patients/Gy/year; P=.012), and spelling (-0.117 patients/Gy/year; P=.015) scores. CONCLUSIONS: Sparing portions of the cerebellum should be considered in RT planning for children with infratentorial ependymoma because of the potential impact of radiation dose on cognitive function.

Prospective evaluation of local control and late effects of conformal radiation therapy in children, adolescents, and young adults with high-grade glioma.

BACKGROUND: A phase II trial of conformal radiotherapy (CRT) for pediatric high-grade glioma (HGG) was performed to evaluate disease control and late effects. METHODS: Between July 1997 and January 2003, 34 pediatric patients (median age, 13.2 ± 6.7 years) with HGG were enrolled on an International Commission on Radiation Units and Measurements Report 50-compliant prospective trial using CRT with a 2 cm clinical target volume margin. Baseline and serial evaluations were performed to assess functional outcomes. RESULTS: Median follow-up for the entire group was 18 months (range, 2-134 months). Twenty (58.8%) patients developed local progression, and 6 (17.6%) patients developed distant progression. Progression-free and overall survival at 10 years were 18.8% ± 6.9% and 16.8% ± 6.5%, respectively. At baseline, 40% of patients evaluated for intelligence quotient (IQ) scored below 85. Measures of cognitive function obtained during the first 12 months fit a mixed model with a quadratic function. The relationship between IQ and time was -1.1883 points/month for the linear term and 0.07728 points/month for the quadratic term (P = .0454). IQ decreased between baseline and 6 months and then increased slightly through 12 months. The opposite was found for (all P values of the quadratic term) activities of daily living (P = .0155), socialization (P = .0049), and the composite score (P = .0257) of adaptive behavior. CONCLUSION: CRT using a 2 cm clinical target volume margin in pediatric HGG demonstrated tumor control comparable to conventional radiation therapy. Disrupted cognitive and adaptive behavioral functioning were present at baseline and throughout the course of disease.

Prognostic factors that increase the risk for reduced white matter volumes and deficits in attention and learning for survivors of childhood cancers.

OBJECTIVE: In children, CNS-directed cancer therapy is thought to result in decreased cerebral white matter volumes (WMV) and subsequent neurocognitive deficits. This study was designed as a prospective validation of the purported reduction in WMV, associated influential factors, and its relationship to neurocognitive deficits in a very large cohort of both acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT) survivors in comparison to an age similar cohort of healthy sibling controls. PROCEDURES: The effects of host characteristics and CNS treatment intensity on WMV were investigated in 383 childhood cancer survivors (199 ALL, 184 BT) at least 12 months post-completion of therapy and 67 healthy siblings that served as a control group. t-Tests and multiple variable linear models were used to assess cross-sectional WMV and its relation with neurocognitive function. RESULTS: BT survivors had lower WMV than ALL survivors, who had less than the control group. Increased CNS treatment intensity, younger age at treatment, and greater time since treatment were significantly associated with lower WMV. Additionally, cancer survivors did not perform as well as the control group on neurocognitive measures of intelligence, attention, and academic achievement. Reduced WMV had a larger impact on estimated IQ among females and children treated at a younger age. CONCLUSIONS: Survivors of childhood cancer that have undergone higher intensity therapy at a younger age have significantly less WMV than their peers and this difference increases with time since therapy. Decreased WMV is associated with significantly lower scores in intelligence, attention, and academic performance in survivors.

Investigating the relationship between COMT polymorphisms and working memory performance among childhood brain tumor survivors.

BACKGROUND: Survivors of childhood brain tumors are at increased risk for neurocognitive impairments, including deficits in abilities supported by frontal brain regions. Catechol-O-methyltransferase (COMT) metabolizes dopamine in the prefrontal cortex, with the Met allele resulting in greater dopamine availability and better performance on frontally mediated tasks compared to the Val allele. Given the importance of identifying resiliency factors against the emergence of cognitive late effects, the current study examined the relationship between COMT genotype and working memory performance among childhood brain tumor survivors. PROCEDURE: Children treated for a brain tumor with conformal radiation therapy (N = 50; mean age at irradiation = 7.41 ± 3.41; mean age at assessment = 13.18 ± 2.88) were administered two computerized measures of working memory (self-ordered search verbal and object tasks). Buccal (cheek) swabs were used to provide tissue from which DNA was extracted. RESULTS: Findings revealed an association between COMT genotype and performance on the self-ordered verbal (P = 0.03) but not object task (P = 0.33). Better performance was found for the Met/Val group compared to either Met/Met or Val/Val. CONCLUSIONS: COMT may indicate a potential resiliency factor against neurocognitive effects of cancer and its treatment; however, there is a need for replication with larger samples of childhood brain tumor survivors.

Single-Arm Phase II Group Sequential Trial Design with Survival Endpoint at a Fixed Time Point.

In this paper, three non-parametric test statistics are proposed to design single-arm phase II group sequential trials for monitoring survival probability. The small-sample properties of these test statistics are studied through simulations. Sample size formulas are derived for the fixed sample test. The Brownian motion property of the test statistics allowed us to develop a flexible group sequential design using a sequential conditional probability ratio test procedure (Xiong, 1995). An example is given to illustrate the trial design by using the proposed method.

Slower processing speed after treatment for pediatric brain tumor and acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) and brain tumor (BT) survivors are at risk for post-treatment IQ declines. The extent to which lower scores represent global cognitive decline versus domain-specific impairment remains unclear. This study examined discrepancies between processing speed and estimated IQ (EIQ) scores and identified clinical characteristics associated with score discrepancies in a sample of pediatric cancer survivors. PROCEDURE: Survivors (50 ALL, 50 BT) ages 12-17 years completed cognitive testing. The Wechsler Abbreviated Scale of Intelligence provided an untimed measure of general reasoning ability (EIQ). The age-appropriate Wechsler Intelligence Scale provided a Processing Speed Index (PSI) score. Scores were examined and compared. RESULTS: Survivors' PSI scores were lower than their EIQ scores (BT t(45) =6.3, p<0.001; ALL t(49) =6.9, p<0.001). For BT survivors, lower PSI scores were associated with history of craniospinal irradiation, t(44) =3.3, p<0.01. For ALL survivors, lower PSI scores were associated with male gender, grade retention, and time since diagnosis, F(3, 46) =10.1, p<0.001. Clinically significant EIQ-PSI score discrepancies were identified in 41.3% of BT and 14.0% of ALL survivors. CONCLUSIONS: Many pediatric BT and ALL survivors exhibit slower processing speed than expected for age, whereas general reasoning ability remains largely intact. Risk factors associated with larger EIQ-PSI discrepancies include the following: BT diagnosis, craniospinal irradiation (BT only), male gender, and younger age at diagnosis (ALL only). Grade retention was frequent and associated with lower EIQ scores (both groups) and PSI scores (ALL only). Describing post-treatment cognitive declines using global measures of intellectual ability may underestimate dysfunction or fail to isolate specific underlying deficits contributing to impairment.

The utility of parent report in the assessment of working memory among childhood brain tumor survivors.

Childhood brain tumor survivors are at increased risk for neurocognitive impairments, including working memory (WM) problems. WM is typically assessed using performance measures. Little is known about the value of parent ratings for identifying WM difficulties, the relationship between rater and performance measures, or predictors of parent-reported WM problems in this population. Accordingly, the current study examined the utility of parent report in detecting WM difficulties among childhood brain tumor survivors treated with conformal radiation therapy (n = 50) relative to siblings (n = 40) and solid tumor survivors not receiving central nervous system-directed therapy (n = 40). Parents completed the Behavior Rating Inventory of Executive Function (BRIEF). Participants were administered WM measures (digit span, self-ordered search tasks). Findings revealed parents rated brain tumor survivors as having significantly more WM problems (p < .01) compared to controls. However, the BRIEF-WM scale demonstrated poor sensitivity and specificity for detecting performance-based problems. Significant, albeit modest, correlations were found between the BRIEF-WM scale and performance measures (r = -.24-.22; p < .05) for the combined group. Age at testing, socioeconomic status, and IQ were significant predictors of parent reported WM problems. Rater and performance measures offer complimentary yet different information in assessing WM, which reiterates the importance of using both within the context of clinical assessment.

Supratentorial ependymoma: disease control, complications, and functional outcomes after irradiation.

PURPOSE: Ependymoma is less commonly found in the supratentorial brain and has known clinical and molecular features that are unique. Our single-institution series provides valuable information about disease control for supratentorial ependymoma and the complications of supratentorial irradiation in children. METHODS AND MATERIALS: A total of 50 children with newly diagnosed supratentorial ependymoma were treated with adjuvant radiation therapy (RT); conformal methods were used in 36 after 1996. The median age at RT was 6.5 years (range, 1-18.9 years). The entire group was characterized according to sex (girls 27), race (white 43), extent of resection (gross-total 46), and tumor grade (anaplastic 28). The conformal RT group was prospectively evaluated for neurologic, endocrine, and cognitive effects. RESULTS: With a median follow-up time of 9.1 years from the start of RT for survivors (range, 0.2-23.2 years), the 10-year progression-free and overall survival were 73% + 7% and 76% + 6%, respectively. None of the evaluated factors was prognostic for disease control. Local and distant failures were evenly divided among the 16 patients who experienced progression. Eleven patients died of disease, and 1 of central nervous system necrosis. Seizure disorders were present in 17 patients, and 4 were considered to be clinically disabled. Clinically significant cognitive effects were limited to children with difficult-to-control seizures. The average values for intelligence quotient and academic achievement (reading, spelling, and math) were within the range of normal through 10 years of follow-up. Central hypothyroidism was the most commonly treated endocrinopathy. CONCLUSION: RT may be administered with acceptable risks for complications in children with supratentorial ependymoma. These results suggest that outcomes for these children are improving and that complications may be limited by use of focal irradiation methods.

Disease control after reduced volume conformal and intensity modulated radiation therapy for childhood craniopharyngioma.

PURPOSE: To estimate the rate of disease control after conformal radiation therapy using reduced clinical target volume (CTV) margins and to determine factors that predict for tumor progression. METHODS AND MATERIALS: Eighty-eight children (median age, 8.5 years; range, 3.2-17.6 years) received conformal or intensity modulated radiation therapy between 1998 and 2009. The study group included those prospectively treated from 1998 to 2003, using a 10-mm CTV, defined as the margin surrounding the solid and cystic tumor targeted to receive the prescription dose of 54 Gy. The CTV margin was subsequently reduced after 2003, yielding 2 groups of patients: those treated with a CTV margin greater than 5 mm (n=26) and those treated with a CTV margin less than or equal to 5 mm (n=62). Disease progression was estimated on the basis of additional variables including sex, race, extent of resection, tumor interventions, target volume margins, and frequency of weekly surveillance magnetic resonance (MR) imaging during radiation therapy. Median follow-up was 5 years. RESULTS: There was no difference between progression-free survival rates based on CTV margins (>5 mm vs ≤5 mm) at 5 years (88.1% ± 6.3% vs 96.2% ± 4.4% [P=.6386]). There were no differences based on planning target volume (PTV) margins (or combined CTV plus PTV margins). The PTV was systematically reduced from 5 to 3 mm during the time period of the study. Factors predictive of superior progression-free survival included Caucasian race (P=.0175), no requirement for cerebrospinal fluid shunting (P=.0066), and number of surveillance imaging studies during treatment (P=.0216). Patients whose treatment protocol included a higher number of weekly surveillance MR imaging evaluations had a lower rate of tumor progression. CONCLUSIONS: These results suggest that targeted volume reductions for radiation therapy using smaller margins are feasible and safe but require careful monitoring. We are currently investigating the differences in outcome based on host factors to explain the results.

Longitudinal investigation of adaptive functioning following conformal irradiation for pediatric craniopharyngioma and low-grade glioma.

PURPOSE: Children treated for brain tumors with conformal radiation therapy experience preserved cognitive outcomes. Early evidence suggests that adaptive functions or independent-living skills may be spared. This longitudinal investigation prospectively examined intellectual and adaptive functioning during the first 5 years following irradiation for childhood craniopharyngioma and low-grade glioma (LGG). The effect of visual impairment on adaptive outcomes was investigated. METHODS AND MATERIALS: Children with craniopharyngioma (n=62) and LGG (n=77) were treated using conformal or intensity modulated radiation therapy. The median age was 8.05 years (3.21-17.64 years) and 8.09 years (2.20-19.27 years), respectively. Serial cognitive evaluations including measures of intelligence quotient (IQ) and the Vineland Adaptive Behavior Scales (VABS) were conducted at preirradiation baseline, 6 months after treatment, and annually through 5 years. Five hundred eighty-eight evaluations were completed during the follow-up period. RESULTS: Baseline assessment revealed no deficits in IQ and VABS indices for children with craniopharyngioma, with significant (P<.05) longitudinal decline in VABS Communication and Socialization indices. Clinical factors associated with more rapid decline included females and preirradiation chemotherapy (interferon). The only change in VABS Daily Living Skills correlated with IQ change (r=0.34; P=.01) in children with craniopharyngioma. Children with LGG performed below population norms (P<.05) at baseline on VABS Communication, Daily Living Indices, and the Adaptive Behavior Composite, with significant (P<.05) longitudinal decline limited to VABS Communication. Older age at irradiation was a protective factor against longitudinal decline. Severe visual impairment did not independently correlate with poorer adaptive outcomes for either tumor group. CONCLUSIONS: There was relative sparing of postirradiation functional outcomes over time in this sample. Baseline differences in functional abilities before the initiation of irradiation suggested that other factors influence functional outcomes above and beyond the effects of irradiation.

Are the psychological needs of adolescent survivors of pediatric cancer adequately identified and treated?

OBJECTIVES: To describe the psychological needs of adolescent survivors of acute lymphoblastic leukemia (ALL) or brain tumor (BT), we examined the following: (i) the occurrence of cognitive, behavioral, and emotional concerns identified during a comprehensive psychological evaluation and (ii) the frequency of referrals for psychological follow-up services to address identified concerns. METHODS: Psychological concerns were identified on measures according to predetermined criteria for 100 adolescent survivors. Referrals for psychological follow-up services were made for concerns previously unidentified in formal assessment or not adequately addressed by current services. RESULTS: Most survivors (82%) exhibited at least one concern across domains: behavioral (76%), cognitive (47%), and emotional (19%). Behavioral concerns emerged most often on scales associated with executive dysfunction, inattention, learning, and peer difficulties. Cranial radiation therapy was associated with cognitive concerns, χ(2) (1, N = 100) = 5.63, p < 0.05. Lower income was associated with more cognitive concerns for ALL survivors, t(47) = 3.28, p < 0.01, and more behavioral concerns for BT survivors, t(48) = 2.93, p < 0.01. Of the survivors with concerns, 38% were referred for psychological follow-up services. Lower-income ALL survivors received more referrals for follow-up, χ(2) (1, N = 41) = 8.05, p < 0.01. Referred survivors had more concerns across domains than non-referred survivors, ALL: t(39) = 2.96, p < 0.01; BT: t(39) = 3.52, p < 0.01. Trends suggest ALL survivors may be at risk for experiencing unaddressed cognitive needs. CONCLUSIONS: Many adolescent survivors of cancer experience psychological difficulties that are not adequately managed by current services, underscoring the need for long-term surveillance. In addition to prescribing regular psychological evaluations, clinicians should closely monitor whether current support services appropriately meet survivors' needs, particularly for lower-income survivors and those treated with cranial radiation therapy.