ArticlePDF AvailableLiterature Review

Managing teenage/young adult (TYA) brain tumors: a UK perspective

Authors:

Abstract

SUMMARY Tumors of the CNS are among the commonest malignancies occurring in teenage/young adult patients (i.e., those aged between 15 and 24 years). The treatment of this patient population is challenging. Adolescence and young adulthood are a turbulent period of life, with physical, emotional, social and cognitive changes. Best practice advocates their treatment in dedicated teenage/young adult units, with multidisciplinary team input and access to clinical trials. Treatment of CNS malignancies is dependent upon histological subtype and staging, with varying combinations of surgery, radiotherapy and chemotherapy used. Clinical trials directly targeted at this patient population are rare; treatments are based on pediatric protocols as studies have demonstrated improved outcomes in patients (with other malignancies) treated as such. Scope for improvement lies in minimizing patient risk of recurrence and long-term sequelae of treatment. Molecular characterization of tumors may provide further information.
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Article
Background The adolescent and young adult (AYA) cancer population, aged 15-39, carries significant morbidity and mortality. Despite growing recognition of unique challenges with this age group, there has been little documentation of unmet need in their care, trial participation, and quality of life, particularly in those with primary brain tumors. Methods A systematic literature review of four databases was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Studies included editorials, reviews, and practice guidelines on the challenges and limitations faced by the AYA population. Papers had to address CNS tumors. Results Sixty-eight studies met inclusion criteria. The challenges and limitations in clinical trials in the AYA population were synthesized into 11 categories: molecular heterogeneity, tumor biology, diagnostic delay, access to care, physician factors, patient factors, primary brain tumor (PBT) factors, accrual, limited trials, long term follow up, and trial design. The published papers’ recommendations were categorized based on the target of the recommendation: providers, coordination of care, organizations, accrual, and trial design. The AYA cancer population was found to suffer from unique challenges and barriers to care and construction of trials. Conclusions The AYA CNS cancer population suffers from unique challenges and barriers to care and construction of trials that makes it critical to acknowledge AYAs as a distinct patient population. Additionally, AYAs with primary brain tumors are underrecognized and underreported in current literature. More studies in the AYA primary brain tumor patient population are needed to improve their care and participation in trials.
Article
Full-text available
Primary brain tumors are a leading cause of death worldwide and are characterized by extraordinary heterogeneity and high invasiveness. Current drug and radiotherapy therapies combined with surgical approaches tend to increase the five-year survival of affected patients, however, the overall mortality rate remains high, thus constituting a clinical challenge for which the discovery of new therapeutic strategies is needed. In this field, novel immunotherapy approaches, aimed at overcoming the complex immunosuppressive microenvironment, could represent a new method of treatment for central nervous system (CNS) tumors. Chemokines especially are a well-defined group of proteins that were so named due to their chemotactic properties of binding their receptors. Chemokines regulate the recruitment and/or tissue retention of immune cells as well as the mobilization of tumor cells that have undergone epithelial–mesenchymal transition, promoting tumor growth. On this basis, this review focuses on the function and involvement of chemokines and their receptors in primary brain tumors, specifically examining chemokine-targeting immunotherapies as one of the most promising strategies in neuro-oncology.
Article
Full-text available
Medulloblastoma (MB) is a childhood malignant brain tumour but also occurs in teenagers and young adults (TYA). Considering that MB is heterogeneous, this study aimed to define the molecular landscape of MBs in TYAs. We collated more than 2000 MB samples that included 287 TYA patients (13–24 years). We performed computational analyses consisting of genome-wide methylation and transcriptomic profiles and developed a prognostics model for the TYAs with MB. We identified that TYAs predominantly comprised of Group 4 (40%) and Sonic Hedgehog (SHH)-activated (33%) tumours, with Wingless-type (WNT, 17%) and Group 3 (10%) being less common. TYAs with SHH tumours displayed significantly more gene expression alterations, whereas no gene was detected in the Group 4 tumours. Across MB subgroups, we identified unique and shared sets of TYA-specific differentially methylated probes and DNA-binding motifs. Finally, a 22-gene signature stratified TYA patients into high- and low-risk groups, and the prognostic significance of these risk groups persisted in multivariable regression models (P = 0.001). This study is an important step toward delineating the molecular landscape of TYAs with MB. The emergence of novel genes and pathways may provide a basis for improved clinical management of TYA with MB.
Article
Adolescents and Young Adults (AYA), have distinct endocrine and psychosocial peculiarities. Brain tumors occur less among AYAs, compared to other age groups and with better prognosis. There is however a paucity of literature about brain tumors in AYA in sub-Saharan Africa. We aim to describe the clinical characteristics of brain tumors in AYA across five neurosurgical centers in Nigeria and the associated factors. We report results for older children (10-14 years), adolescents (15-19 years) and young adults (20-24 years). This was a retrospective review of AYA with brain tumors over a 10-year period (2010-2019). Data analysis was by descriptive statistics, Chi square test and multinomial regression at a0.05. There were 104 AYAand the male to female ratio was 1.2:1. Headache (79.8%) and visual symptoms (65.4%) were the most common presenting symptoms. Focal limb weakness (44.1%) occurred less frequently. Median duration of symptoms prior to presentation was 9 months. Glioma was the most common tumor (31, 29.8%) while pituitary adenoma and craniopharyngioma constituted 30.8% of the tumors. Patients with symptom duration of one year were more likely to have infratentorial tumors. There was no significant association between the KPS following intervention and the AYA characteristics. Age group was not significantly associated with any of the presenting symptoms except ataxia, which was significantly higher among the 10 to 14 years group.We have described the epidemiology of brain tumors within AYA in Nigeria and highlighted a need to maximize their care and meet their special needs.
Article
Background Disparities in survival by race/ethnicity, socioeconomic status (SES), and geography in adolescent and young adult (AYA) patients with central nervous system (CNS) tumors have not been well studied. Procedure A retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results (SEER) database was conducted for AYA patients diagnosed with primary CNS tumors. Adjusted hazard ratios (aHR) were calculated using a multivariate Cox proportional hazard model to evaluate the association between race/ethnicity, SES, rurality, and hazard of death. Results All minority groups showed an increased hazard of death with greatest disparities in the high‐grade glioma cohort. Lower SES was associated with an increased hazard of death in non‐Hispanic White (NHW) patients (aHR 1.12; 95% confidence interval [CI] 1.01–1.24), non‐Hispanic Black (NHB) patients (aHR 1.34; 95% CI 1.00–1.80), and patients aged 25–29 years (aHR 1.29; 95% CI 1.07–1.55). Mediation analysis showed an indirect effect of SES on the effect of race/ethnicity on the hazard of death only among NHB patients, with SES accounting for 33.7% of the association between NHB and hazard of death. Rurality was associated with an increased hazard of death for patients in the lowest SES tertile (aHR 1.31; 95% CI 1.08–1.59) and NHW patients (aHR 1.20; 95% CI 1.08–1.34). Conclusions Patients identified as a racial/ethnic minority, patients with a lower SES, and patients residing in rural areas had an increased hazard of death. Further studies are needed to understand and address the biological, psychosocial, societal, and economic factors that impact AYA neuro‐oncology patients at highest risk of experiencing poorer outcomes.
Article
Purpose: While central nervous system (CNS) tumors account for only 10% of adolescent and young adult (AYA) cancers, they are the leading cause of cancer death in this age group. Using national data for Australia, we describe the presentation, treatment, and survival for AYAs diagnosed with CNS tumors. Methods: A population-based study of 15-24 year-olds diagnosed with CNS tumors (low- and high-grade glioma [LGG, HGG], medulloblastoma [MB], primitive neuroectodermal tumors [PNET], ependymoma [EP]) or other (e.g., low-grade neuronal tumor) between 2007 and 2012. Clinical details were extracted from hospital medical records for each patient. Treatment centers were classified as pediatric or adult services. Results: Two hundred seventy-five patients (129 LGG, 77 HGG, 23 MB, 10 PNET, 19 EP, 17 other) were identified, with 17% treated at pediatric hospitals. Symptoms (headache [53%], nausea [31%]) were present for a median of 3 weeks before consulting a health professional. Of LGG patients, 15% had radiotherapy (RT) and 12% chemotherapy (CT). Of HGG patients, 81% had RT and 75% CT. All MB and PNET were managed with surgery, and 74% of MB and 80% of PNET had both RT and CT. Treatment did not differ by treatment center type. Five-year survival for LGG and EP was over 80%, but was 42% for HGG and 20% for PNET. Conclusions: This national, population-based study indicates similar treatment for AYA patients with CNS tumors between pediatric and adult services. Poor outcomes for HGG and PNET patients highlight the need for clinical trials of novel approaches for these tumors.
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