Received: 13 October 2016 Revised: 10 December 2016 Accepted: 12 December 2016 DOI: 10.1002/pbc.26442 Pediatric Blood & Cancer The American Society of Pediatric Hematology/Oncology RESEARCH ARTICLE Systematic review and meta-analysis of health-related quality of life in pediatric CNS tumor survivors Fiona Schulte 1,2 K. Brooke Russell 3,4 Patricia Cullen 5 Leanne Embry 6 Taryn Fay-McClymont 1,7 Donna Johnston 8 Abby R. Rosenberg 9 Lillian Sung 10 1 Departments of Oncology and Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada 2 Haematology, Oncology and Transplant Pro- gram, Alberta Children’s Hospital Research Institute, Alberta Children’s Hospital, Calgary, Alberta, Canada 3 Haematology, Oncology and Transplant Program, Alberta Children’s Hospital, Calgary, Alberta, Canada 4 Departments of Oncology and Psychology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada 5 Loretto Heights School of Nursing, Regis University, Denver, Colorado 6 Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas 7 Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada 8 Department of Haematology/Oncology, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada 9 Department of Hematology/Oncology, Seattle Children’s Hospital, Seattle, Washington 10 Department of Haematology/Oncology, SickKids Hospital, Toronto, Ontario, Canada Correspondence Fiona Schulte, Departments of Oncology and Paediatrics, Cumming School of Medicine, Uni- versity of Calgary, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada. Email: Fiona.schulte@albertahealthservices.ca Abstract Background: Pediatric central nervous system (CNS) tumor survivors are at high risk for numer- ous late effects including decreased health-related quality of life (HRQOL). Our objective was to summarize studies describing HRQOL in pediatric CNS tumor survivors and compare HRQOL out- comes in studies that included a comparison group. Procedure: EMBASE, MEDLINE, and PsychINFO were used to identify relevant articles published until August, 2016. Eligible studies reported outcomes for pediatric CNS tumor survivors diag- nosed before age 21, at least 5 years from diagnosis and/or 2 years off therapy and used a stan- dardized measure of HRQOL. All data were abstracted by two reviewers. Random-effects meta- analyses were performed using Review Manager 5.0. Results: Of 1,912 unique articles identified, 74 were included in this review. Papers described 29 different HRQOL tools. Meta-analyses compared pediatric CNS tumor survivors to healthy com- parisons and other pediatric cancer survivors separately. HRQOL was significantly lower for CNS (n = 797) than healthy comparisons (n = 1,397) (mean difference = –0.54, 95% confidence interval [CI] = –0.72 to –0.35, P < 0.001, I 2 = 35%). HRQOL was also significantly lower for CNS (n = 244) than non-CNS survivors (n = 414) (mean difference = –0.56, 95% CI = –0.73 to –0.38, P < 0.00001, I 2 = 0%). Conclusions: Pediatric CNS tumor survivors experience worse HRQOL than healthy comparisons and non-CNS cancer survivors. Future HRQOL work should be longitudinal, and/or multisite stud- ies that examine HRQOL by diagnosis and treatment modalities. KEYWORDS CNS tumors, late effects of cancer treatment, pediatric oncology, psychosocial, quality of life 1 INTRODUCTION Pediatric central nervous system (CNS) tumors are the second most common cancer diagnosis among children. Advanced therapies have improved survival rates and currently there are more than 115,000 Abbreviations: CI, confidence interval; CNS, central nervous system; CRT, cranial radiation therapy; HRQOL, health-related quality of life; HUI, Health Utilities Index; MCID, minimally clinically important difference; PedsQL, Pediatric Quality of Life Inventory; SD, standard deviation pediatric CNS tumor survivors in North America. 1,2 There is consid- erable evidence documenting the potential negative late effects for pediatric CNS tumor survivors, particularly in neurological and psy- chosocial domains. 3 Neurologically, these survivors are more likely to experience cognitive deficits such as attention and memory prob- lems, hearing impairments, visual impairments, motor problems, and seizure disorders. 4–6 Psychosocially, CNS tumor survivors may expe- rience overall impaired mental health, activity limitations, educa- tional setbacks, and difficulty making and maintaining close friend- ships in comparison to healthy controls and other pediatric cancer Pediatr Blood Cancer 2017; 00: e26442 c  2017 Wiley Periodicals, Inc. 1 of 9 wileyonlinelibrary.com/journal/pbc