Molecular analysis of adolescent and young adult high grade gliomas in the SPECTA-AYA study: Poorly characterised tumours with frequent germline alterations.

Background: Adolescent and young adult (AYA) high grade gliomas (HGG) have the worst survival of AYA malignancies yet are poorly represented in large-scale molecular datasets.

Methods: 50 AYAs aged 12-29 with newly diagnosed or recurrent HGG and other high risk central nervous system (CNS) tumours were prospectively recruited to the EORTC SPECTA platform study and underwent whole exome sequencing, RNA sequencing and methylation profiling, with central pathological review. Actionable mutations were reported and patients followed up for therapies and outcome.

Radiological Predictors of Cognitive Impairment in Paediatric Brain Tumours Using Multiparametric Magnetic Resonance Imaging: A Review of Current Practice, Challenges and Future Directions.

Paediatric brain tumours and their treatments are associated with long-term cognitive impairment. While the aetiology of cognitive impairment is complex and multifactorial, multiparametric Magnetic Resonance Imaging (MRI) can identify many risk factors including tumour location, damage to eloquent structures and tumour phenotype. Hydrocephalus and raised intracranial pressure can be observed, along with risk factors for post-operative paediatric cerebellar mutism syndrome or epilepsy.

Incidence and survival of European adolescents and young adults diagnosed with sarcomas: EUROCARE-6 results.

Background: Epidemiological data for sarcoma in adolescents and young adults (AYAs) and across age groups are limited. We aim to: 1) update sarcoma incidence, survival, and changes over time in European AYAs; 2) provide an updated comparison of sarcoma survival in AYAs versus children and mature adults.

Methods: We calculated crude incidence rates (IR) per 100,000 European population per year from 2006 to 2013.

Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial.

Importance: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.

Objective: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.

Design, Setting, And Participants: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America.

The Multimodality Management of Malignant Peripheral Nerve Sheath Tumours.

Malignant peripheral nerve sheath tumours (MPNST) are aggressive sarcomas that have nerve sheath differentiation and can present at any anatomical site. They can arise from precursor neurofibroma in the context of neurofibromatosis type 1 (NF1) or as de novo and sporadic tumours in the absence of an underlying genetic predisposition. The primary therapeutic approach is most often radical surgery, with non-surgical modalities playing an important role, especially in locally advanced or metastatic cases.

CT- and MR-based image-based data mining are consistent in the brain.

Purpose: Image-based data mining (IBDM) is a voxel-based analysis technique to investigate dose-response. Most often, IBDM uses radiotherapy planning CTs because of their broad accessibility, however, it was unknown whether CT provided sufficient soft tissue contrast for brain IBDM. This study evaluates whether MR-based IBDM improves upon CT-based IBDM for studies of children with brain tumours.

Impact of age on safety of Busulfan-Melphalan followed by autologous hematopoietic stem-cell transplantation versus standard chemotherapy in the patients of the EURO-E.W.I.N.G. 99 and Ewing 2008 clinical trials.

Introduction: Ewing sarcoma (ES), is a rare cancer affecting children, adolescents and adults. After VIDE (vincristine-ifosfamide-doxorobucin-etoposide) induction chemotherapy, Busulfan-Melphalan (BuMel) high-dose chemotherapy followed by autologous hematopoietic stem cells transplantation improved outcomes in unfavourable localized ES, but with more toxicities than conventional chemotherapy (VAI: Vincristine-dactinomycin-Ifosfamide). We evaluated whether the risk of acute toxicity associated with BuMel compared to VAI varied according to age in patients recruited in the R2Loc and R2Pulm randomised trials of the Euro-E.

Emerging therapies in Ewing sarcoma.

Purpose Of Review: There is an unmet need to improve outcomes for patients for Ewing sarcoma, a rare, aggressive sarcoma with a peak incidence in adolescents and young adults (AYA). Current therapy at diagnosis involves multiagent chemotherapy and local therapy, but despite intensification of treatment, those with metastases at diagnosis and recurrent disease have poor outcomes.

Recent Findings: Improved understanding of Ewing sarcoma biology has identified novel targets with promising activity in Ewing sarcoma patients, including tyrosine kinase inhibitors that are now undergoing evaluation as combination and maintenance therapy.

Protocol for the 'Supporting Young Cancer Survivors who Smoke' study (PRISM): Informing the development of a smoking cessation intervention for childhood, adolescent and young adult cancer survivors in England.

Background: Childhood, adolescent and young adult (CAYA) cancer survivors are vulnerable to adverse late-effects. For CAYA cancer survivors, tobacco smoking is the most important preventable cause of ill-health and early death. Yet, effective strategies to support smoking cessation in this group are lacking.

The development and validation of a needs assessment tool for use with YOUng adult survivors of a CentrAl Nervous system tumor (YOU-CAN).

Background: Adolescent and young adult (AYA) survivors of a central nervous system (CNS) tumor represent a vulnerable group who can experience: social isolation, low rates of employment, and achieving independence can be compromised, leading to poorer quality of life compared with survivors of other cancer types. The aim of this study is to develop and evaluate the validity of a needs assessment tool (NAT) for AYA survivors of a CNS tumor.

Methods: Items generated using data from 29 qualitative studies and cognitive interviews ( = 8) produced NAT V1.

Protocol for the development of a Core Outcome Set (COS) for Adolescents and Young Adults (AYAs) with cancer.

Background: Adolescents and young adults (AYAs) with cancer, defined as individuals aged 15-39 years at initial cancer diagnosis, form a unique population; they face age-specific issues as they transition to adulthood. This paper presents the protocol for the development of a core outcome set (COS) for AYAs with cancer.

Methods: The methodological standards from the Core Outcome Measures in Effectiveness Trials (COMET) and the International Consortium for Health Outcomes Measurement (ICHOM) for COS development will guide the development of the COS for AYAs with cancer.

Precision Medicine for Childhood Cancer: Current Limitations and Future Perspectives.

Greater collaboration needed to realize potential of molecular profiling initiatives for pediatric cancers.

Experiences and Unmet Needs of Adolescent and Young Adult Survivors of a Brain Tumor (Aged 15-39 Years): A Systematic Review and Meta-ethnography.

Background: Brain tumors account for 15% of all adolescent and young adult cancers, and survivors are at risk of ongoing late effects that can severely impact their ability to reach independence. Despite follow-up initiatives advocating a personalized approach, survivors continue to experience ongoing sequelae. A better understanding of the survivorship experience is required to ensure services are able to deliver personalized support.

Delivered relative dose intensity in adolescent and young adult germ cell tumours in England: Assessment of data quality and consistency from clinical trials compared to national cancer registration data.

Adolescent and young adults (AYA) with germ cell tumours (GCT) have poorer survival rates than children and many older adults with the same cancers. There are several likely contributing factors to this, including the treatment received. The prognostic benefit of intended dose intensity is well documented in GCT from trials comparing regimens.

Measurement Properties of Patient-Reported Outcome Measures for Adolescent and Young Adult Survivors of a Central Nervous System Tumor: A Systematic Review.

To identify and evaluate patient-reported outcome measures (PROMs) for assessing survivorship-related concepts for adolescent and young adult (AYA) survivors of central nervous system (CNS) tumors. We searched five electronic databases. Two researchers independently screened all titles for inclusion and used consensus-based standards for the selection of health measurement instruments (COSMIN) guidance to grade the quality of evidence for each measurement property.

Comprehensive molecular profiling of sarcomas in adolescent and young adult patients: Results of the EORTC SPECTA-AYA international proof-of-concept study.

Background: Adolescent and young adult (AYA) patients with cancer are poorly recruited to molecularly targeted trials and have not witnessed the advances in cancer treatment and survival seen in other age groups. We report here a pan-European proof-of-concept study to identify actionable alterations in some of the worst prognosis AYA cancers: bone and soft tissue sarcomas.

Design: Patients aged 12-29 years with newly diagnosed or recurrent, intermediate or high-grade bone and soft tissue sarcomas were recruited from six European countries.

Amplification of the PLAG-family genes-PLAGL1 and PLAGL2-is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification.

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type.

International variation in childhood cancer mortality rates from 2001 to 2015: Comparison of trends in the International Cancer Benchmarking Partnership countries.

Despite improved survival rates, cancer remains one of the most common causes of childhood death. The International Cancer Benchmarking Partnership (ICBP) showed variation in cancer survival for adults. We aimed to assess and compare trends over time in cancer mortality between children, adolescents and young adults (AYAs) and adults in the six countries involved in the ICBP: United Kingdom, Denmark, Australia, Canada, Norway and Sweden.

Development of Randomized Trials in Adults with Medulloblastoma-The Example of EORTC 1634-BTG/NOA-23.

Medulloblastoma is a rare brain malignancy. Patients after puberty are rare and bear an intermediate prognosis. Standard treatment consists of maximal resection plus radio-chemotherapy.

Oral etoposide as a single agent in childhood and young adult cancer in England: Still a poorly evaluated palliative treatment.

Background: Oral etoposide is commonly used in palliative treatment of childhood and young adult cancer without robust evidence. We describe a national, unselected cohort of young people in England treated with oral etoposide using routinely collected, population-level data.

Methods: Patients aged under 25 years at cancer diagnosis (1995-2017) with a treatment record of single-agent oral etoposide in the Systemic AntiCancer Dataset (SACT, 2012-2018) were identified, linked to national cancer registry data using NHS number and followed to 5 January 2019.