Interaction Trees With Censored Survival Data

We propose an interaction tree (IT) procedure to optimize the subgroup analysis in comparative studies that involve censored survival times. The proposed method recursively partitions the data into two subsets that show the greatest interaction with the treatment, which results in a number of objectively defined subgroups: in some of them the treatment effect is prominent while in others the treatment may have a negligible or even negative effect. The resultant tree structure can be used to explore the overall interaction between treatment and other covariates and help identify and describe possible target populations on which an experimental treatment demonstrates desired efficacy. We follow the standard CART (Breiman, et al., 1984) methodology to develop the interaction tree structure. Variable importance information is extracted via random forests of interaction trees. Both simulated experiments and an analysis of the primary billiary cirrhosis (PBC) data are provided for evaluation and illustration of the proposed procedure. Copyright ©2008 The Berkeley Electronic Press. All rights reserved

Interaction Trees with Censored Survival Data

We propose an interaction tree (IT) procedure to optimize the subgroup analysis in comparative studies that involve censored survival times. The proposed method recursively partitions the data into two subsets that show the greatest interaction with the treatment, which results in a number of objectively defined subgroups: in some of them the treatment effect is prominent while in others the treatment may have a negligible or even negative effect. The resultant tree structure can be used to explore the overall interaction between treatment and other covariates and help identify and describe possible target populations on which an experimental treatment demonstrates desired efficacy. We follow the standard CART (Breiman, et al., 1984) methodology to develop the interaction tree structure. Variable importance information is extracted via random forests of interaction trees. Both simulated experiments and an analysis of the primary billiary cirrhosis (PBC) data are provided for evaluation and illustration of the proposed procedure

Interaction Trees with Censored Survival Data

We propose an interaction tree (IT) procedure to optimize the subgroup analysis in comparative studies that involve censored survival times. The proposed method recursively partitions the data into two subsets that show the greatest interaction with the treatment, which results in a number of objectively defined subgroups: in some of them the treatment effect is prominent while in others the treatment may have a negligible or even negative effect. The resultant tree structure can be used to explore the overall interaction between treatment and other covariates and help identify and describe possible target populations on which an experimental treatment demonstrates desired efficacy. We follow the standard CART (Breiman, et al., 1984) methodology to develop the interaction tree structure. Variable importance information is extracted via random forests of interaction trees. Both simulated experiments and an analysis of the primary billiary cirrhosis (PBC) data are provided for evaluation and illustration of the proposed procedure.

Intellectual and academic outcome following two chemotherapy regimens and radiotherapy for average-risk medulloblastoma: COG A9961.

Purpose Assess the intellectual and academic outcomes as well as risk factors associated with treatment for average‐risk medulloblastoma in childhood using 23.4 Gy of craniospinal radiotherapy plus adjuvant chemotherapy. Methods From an overall sample of 379 enrolled in the parent study (COG A9961), 110 patients received a total of 192 assessments over more than 5 years with standardized IQ and academic achievement tests. Random coefficient models of the various outcomes were developed that incorporated covariates including chemotherapy regimen, age at diagnosis, sex, initial Full Scale IQ, and mutism. Results Participants in this study were found to be comparable to the overall sample in all demographic, disease, and treatment factors, except there were more gross total resections in the subsample undergoing intellectual and academic assessment. Major findings include significant decline in both intellectual and academic domains over time that were greater in children who were younger at diagnosis and had higher initial intelligence test scores. Children with mutism were at higher risk for initial effects on intelligence. No effects of sex were found. Conclusion These results show progressive decline over several years post‐treatment in standardized intellectual and academic scores. Despite recent improvements in therapies for these children, most notably a decrease dose of craniospinal radiation, they remain at risk. The pursuit of less toxic treatments, particularly for younger children, should continue. Neuropsychological surveillance should be routine at centers treating children with brain tumors. Pediatr Blood Cancer 2013;601350‐1357. © 2013 Wiley Periodicals, Inc

Long-term follow-up of children treated for high-grade gliomas: Children\u27s Oncology Group L991 final study report

Purpose: High-grade gliomas of the CNS are characterized by poor treatment response and prognosis for long-term survival. The Children\u27s Oncology Group (COG) L991 study investigated the neuropsychological, behavioral, and quality of life (QoL) outcomes after treatment on the Children\u27s Cancer Group (CCG) trial for high-grade gliomas (CCG-945). Patients and Methods: Fifty-four patients (29 males, 25 females) with a median age of 8.8 years at diagnosis (range, 0.2 to 19.5 years) were enrolled at 25 institutions in North America, representing 81% of available survivors; median length of follow-up was 15.1 years (range, 9.5 to 19.2 years), and median age at study evaluation was 23.6 years (range, 11.3 to 36 years). Standardized tests of neuropsychological functioning and QoL were performed. Descriptive statistics summarized principal findings, and one-way analysis of variance identified potential predictors of outcomes. Results: With an average follow-up time of 15 years, survivors demonstrated intellectual functioning within the low-average range. Executive functioning and verbal memory were between the low-average and borderline ranges. In contrast, visual memory and psychomotor processing speed were between the borderline and impaired ranges, respectively. Approximately 75% of patient reported overall QoL within or above normal limits for both physical and psychosocial domains. Nonhemispheric tumor location (midline or cerebellum), female sex, and younger age at treatment emerged as independent risk factors. Conclusion: These results serve as a benchmark for comparison with future pediatric high-grade glioma studies, in addition to identifying at-risk cohorts that warrant further research and proactive interventions to minimize late effects while striving to ensure survival. © 2012 by American Society of Clinical Oncology