Henry Mandeville

Institute of Cancer Research · Division of Radiotherapy and Imaging

Background Parameningeal (PM) site is an unfavorable characteristic in rhabdomyosarcoma (RMS). We described the treatment and outcome for patients with PM RMS and investigated the prognostic value of risk factors. We scored PM site by originating site and by highest risk extension. Methods Patients with PM RMS were treated within the European pedi...

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Background The authors report the prospective evaluation of reduced dose alkylator chemotherapy combined with radiotherapy for European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) standard risk nonalveolar rhabdomyosarcoma (NA‐RMS). Patients and Methods Localized node negative Intergroup Rhabdomyosarcoma Study (IRS) II/III NA‐RMS at favorabl...

INTRODUCTION Low-grade gliomas (LGG) present 10-year overall survival rates of 90%. However, many require multiple lines of treatment. Bevacizumab/Irinotecan is the standard third line treatment for recurrent LGG in the UK; with targeted therapies being accessible only as a fourth or subsequent line for most cases. Access to targeted therapies may...

BACKGROUND Bithalamic gliomas (BTG) are rare brain tumors with dismal prognosis. Optimal management and role of novel therapies have not been established yet. This study aimed to improve our understanding of BTG to guide adapted treatments. METHODS Retrospective case series across 6 Pediatric Neuro-Oncology Units (United Kingdom, Spain) of ≤18-yea...

BACKGROUND High-grade gliomas (HGG) arise in any CNS location with a poor prognosis. HGGs in teenagers/young adults (TYA) are understudied; this project aimed to characterise these tumours and identify therapeutic targets. METHODS HGG samples (histone/IDH-wildtype, n=207, FFPE/FF, 13-30 years) were collected from national/international collaborato...

Simple Summary This article summarises the international Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial for patients with rhabdomyosarcoma. The trial has multiple research questions relating to chemotherapy and radiotherapy and biological and imaging studies as well as to the introduction of novel drugs for patients with very high...

Non-germinomatous germ cell tumours of the central nervous system (CNS NG-GCT) have no standardized treatment at relapse and prognosis is dismal. Additionally, limited patient numbers preclude any clinical trials in this setting. Here we report the case of an adolescent with relapsed metastatic pineal yolk sac tumour treated with induction chemothe...

Background Survivors of childhood medulloblastoma are particularly susceptible to late effects because of the location of the tumour and the treatment required to achieve a cure. Living with these long-term toxicities is challenging and greater understanding of the impact of the disease and treatment have on health-related quality of life (HRQoL) i...

Pediatric diencephalic tumors represent a histopathologically and molecularly diverse group of neoplasms arising in the central part of the brain and involving eloquent structures, including the hypothalamic-pituitary axis (HPA), optic pathway, thalamus, and pineal gland. Presenting symptoms can include significant neurological, endocrine, or visua...

Objective To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) as a predictive imaging marker after neoadjuvant chemotherapy in patients with rhabdomyosarcoma. Material and methods We performed a multicenter retrospective study including pediatric, adolescent and young adult patients with rhabdomyosarcoma, Inter...

Background and purpose Children receiving radiotherapy for head-and-neck tumours often experience severe dentofacial side effects. Despite this, recommendations for contouring and dose constraints to dentofacial structures are lacking in clinical practice. We report on a survey aiming to understand current practice in contouring and dose assessment...

Irradiation of the vertebrae in prepubertal patients, if non-homogenous, can result in future growth deformities including kyphoscoliosis. Vertebral delineation and dosimetry were assessed for 101 paediatric cases reviewed within QUARTET-affiliated trials. Despite the availability of published consensus guidelines, a high variability in vertebral d...

Background: The four different local therapy strategies used for head and neck rhabdomyosarcoma (HNRMS) include proton therapy (PT), photon therapy (RT), surgery with radiotherapy (Paris-method), and surgery with brachytherapy (AMORE). Local control and survival is comparable; however, the impact of these different treatments on facial deformation...

Introduction: Significant differences in outcome and survivorship in childhood cancer still exist across Europe, with poorer results in eastern regions. We aimed to map the provision of paediatric radiotherapy in Romania, identifying the key future requirements and main challenges. Methods: An online survey supported by SIOP Europe was distributed...

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO...

Background and Purpose: SIOP Europe’s QUARTET project launched in 2016; aiming to improve access to high-quality radiotherapy for children and adolescents treated within clinical trials across Europe. The aim of this report is to present the profile of institutions participating in six QUARTET-affiliated trials and a description of the initial indi...

Introduction: Active Breathing Control (ABC) is a motion management strategy that facilitates reproducible breath-hold for thoracic radiotherapy (RT), which may reduce radiation dose to organs at risk (OARs). Reduction of radiation-induced toxicity is of high importance in younger patients. However, there is little published literature on the feas...

Rhabdomyosarcoma (RMS) is a typical tumour of childhood but can occur at any age. Several studies have reported that adolescent and young adult (AYA) patients with RMS have poorer survival than do younger patients. This review discusses the specific challenges in AYA patients with pediatric-type RMS, exploring possible underlying factors which may...

Objectives Children receiving radiotherapy for head and neck tumours can experience severe late dento-facial effects. However, recommendations for delineation and dose assessment to dento-facial structures are lacking. We report on a survey aiming to better understand current practice and establish areas for development. Methods An online survey w...

Objectives Irradiation of the vertebrae in prepubertal patients can result in growth defects and deformities, related to inhomogeneities in dose distribution. In 2019 the SIOPE-ROWG published a consensus on vertebral delineation and constraints in an effort to standardise practice across Europe. QUARTET is a SIOPe project for RTQA in Paediatric Cli...

Objectives Ophthalmological adverse events (OAEs) following local treatment for pediatric head and neck rhabdomyosarcoma (HNRMS) are prevalent. More knowledge on specific radiation dose-toxicity relationships for ophthalmological organs at risk (OARs) in children can help to avoid these OAEs. The aim of the present study is to explore the dose-toxi...

Objectives VMAT Craniospinal irradiation (CSI-VMAT) requires extensive contouring of multiple targets and OARs. Manual contouring of these structures is time consuming (3-5 hours). Using an automatic contouring module within Raystation treatment planning system there is potential to automate outlining and streamline planning. The aim of this projec...

Objectives This trial compared intensity modulated arc therapy (IMAT) with conventional techniques for high-risk neuroblastoma, to establish whether IMAT could enable a higher radiation dose than standard to be given without exceeding normal tissue dose objectives. The aim was to determine the radiotherapy dose for use in a subsequent international...

Purpose The aim of this study is to investigate the spectrum of neurological triad improvement in patients with diffuse intrinsic pontine glioma (DIPG) treated by re-irradiation (re-RT) at first progression. Methods We carried out a re-analysis of the SIOP-E retrospective DIPG cohort by investigating the clinical benefits after re-RT with a focus...

Background: Adolescent and young adult patients with rhabdomyosarcoma often have poorer outcomes than do children. We aimed to compare the findings of adolescent and young adult patients with children enrolled in two prospective clinical protocols. Methods: This retrospective observational analysis was based on data from the European paediatric...

PURPOSE: To investigate the spectrum of neurological triad improvement in patients with diffuse intrinsic pontine glioma (DIPG) treated by re-irradiation (re-RT) at first progression. METHODS: Re-analysis of the SIOP-E retrospective DIPG cohort by investigating clinical benefits after re-RT with focus on the neurological triad. Patients were divide...

Background/objectives: Rhabdomyosarcoma of the perianal/perineal region (PRMS) is rare, with poor survival and limited understanding of the functional consequences of treatment. Design/methods: International Society of Pediatric Oncology (SIOP) malignant mesenchymal tumor (MMT) 95, Italian RMS 96, and European paediatric Soft tissue sarcoma Stud...

The International Soft Tissue Sarcoma Database Consortium (INSTRuCT) consists of a collaboration between the Children's Oncology Group (COG) Soft Tissue Sarcoma Committee, the European pediatric Soft Tissue Sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS). As part of the larger initiative of INSTRuCT to provide c...

The International Soft-Tissue Sarcoma Database Consortium (INSTRuCT) consists of a collaboration between the Children’s Oncology Group (COG) Soft Tissue Sarcoma Committee, the European pediatric Soft-Tissue Sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS). As part of the larger initiative of INSTRuCT to provide c...

In-transit metastases (ITM) are defined as metastatic lymph nodes or deposits occurring between the primary tumor and proximal draining lymph node basin. In extremity rhabdomyosarcoma (RMS), they have rarely been reported. This study evaluates the frequency, staging and survival of patients with ITM in distal extremity RMS. Methods Patients with e...

Aims To determine if multi-isocentric volumetric modulated arc radiotherapy for craniospinal irradiation (CSI-VMAT) can be implemented safely and accurately using robust optimisation in a commercially available treatment planning system. Our initial clinical experience is reported for the first 20 patients treated with the technique. Materials and...

Objective Clinical diagnostic sequencing of circulating tumour DNA (ctDNA) is well advanced for adult patients, but application to paediatric cancer patients lags behind. Methods To address this, we have developed a clinically relevant (67 gene) NGS capture panel and accompanying workflow that enables sensitive and reliable detection of low-freque...

Appropriate imaging is essential in the treatment of children and adolescents with rhabdomyosarcoma. For adequate stratification and optimal individualised local treatment utilising surgery and radiotherapy, high-quality imaging is crucial. The paediatric radiologist, therefore, is an essential member of the multi-disciplinary team providing clinic...

Background/objectives The primary aim of this study was to analyse and evaluate the impact of different local treatments on the pattern of relapse in children with primary head and neck non-parameningeal (HNnPM) rhabdomyosarcoma (RMS), treated in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 study. The secondary aim was to...

Purpose: There is limited evidence to define the role of radiotherapy in children with metastatic rhabdomyosarcoma (mRMS). In the international XXXX study, children with mRMS or non-RMS soft tissue sarcoma were randomized to receive standard chemotherapy with/without bevacizumab, with radiotherapy recommended to all disease sites after chemotherap...

Background and purpose Magnetic resonance guided radiotherapy (MRgRT) has been successfully implemented for several routine clinical applications in adult patients. The purpose of this study is to map the potential benefit of MRgRT on toxicity reduction and outcome in pediatric patients treated with curative intent for primary and metastatic sites....

Rhabdomyosarcoma is a heterogeneous disease both in presentation and histology. Improvements in a multimodality therapy resulted in the improved overall survival for patients with a low‐risk and intermediate‐risk disease but not for patients with a metastatic disease. We reviewed and contrasted the North American and European practice patterns, tho...

Non‐rhabdomyosarcoma soft‐tissue sarcomas (NRSTS) comprise 4% of childhood cancers and consist of numerous histologic subtypes. Prognostic factors associated with poor outcome include high histologic grade, large tumor size, presence of metastases, and unresectability. Complete surgical resection is critical for the best oncologic outcomes and is p...

The Children's Oncology Group (COG) has a strong quality assurance (QA) program managed by the Imaging and Radiation Oncology Core (IROC). This program consists of credentialing centers and providing real‐time management of each case for protocol compliant target definition and radiation delivery. In the International Society of Pediatric Oncology...

High grade gliomas (HGG) have a dismal prognosis with survival rates of 15-35%. Approximately 10-12% of pediatric HGG occur in young children and their molecular biology and clinical outcomes differ from those arising at older ages. We report on four children aged <5 years newly diagnosed with non-brainstem HGG between 2011 and 2018 who were treate...

Background and Purpose 4D and midposition MRI could inform plan adaptation in lung and abdominal MR-guided radiotherapy. We present deep learning-based solutions to overcome long 4D-MRI reconstruction times while maintaining high image quality and short scan times. Methods Two 3D U-net deep convolutional neural networks were trained to accelerate...

Purpose/objective About 20% of children with solid tumours (ST) present with distant metastases (DM). Evidence regarding the use of radical radiotherapy of these DM is sparse and open for personal interpretation. The aim of this survey was to review European protocols and to map current practice regarding the irradiation of DM across SIOPE-affiliat...

Background and purpose Recently, the SIOP-RTSG developed a highly-conformal flank target volume definition for children with renal tumors. The aims of this study were to evaluate the inter-clinician delineation variation of this new target volume definition in an international multicenter setting and to explore the necessity of quality assurance....

Purpose/Objective Total body irradiation (TBI) remains a key component of conditioning for allogeneic haemopoietic stem cell transplant (HSCT), with interstitial pneumonitis (IP) and chronic kidney disease (CKD) important late sequelae. We undertook a retrospective service evaluation of TBI patients treated with a forward-planned intensity modulate...

Paediatric high grade glioma and diffuse midline glioma (including DIPG) are comprised of multiple biological and clinical subgroups, the majority of which urgently require novel therapies. Patient-derived in vitro primary cell cultures represent potentially useful tools for mechanistic and preclinical investigation based upon their retention of ke...

TP53 pathway alterations are well-described events in medulloblastoma (MB) and are predictive of poor clinical outcome. Alterations are rare at diagnosis in Group3 (Gr3) and Group4, but enriched in Sonic Hedgehog and WNT subgroups. However, TP53 mutations are observed in all subgroups at relapse. Radiation therapy, along with surgery and chemothera...

BACKGROUND There are global variations in radiotherapy approaches for icGCT. An understanding of patterns of disease recurrence correlated with radiation techniques and doses is important in standardising and improving the quality of radiotherapy using high-precision techniques. METHODS AND RESULTS Data from 20 patients with tumour recurrence afte...

Background Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define a better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissu...

For decades, radiotherapy with two opposing photon beams has been the standard technique used to cover the flank target volume in paediatric patients with renal tumours. Nowadays, many institutes are implementing advanced radiotherapy techniques that spare healthy tissue. To decrease the radiotherapy dose to healthy structures while preserving onco...

Chapter 7 discusses paediatric extracranial solid tumours. Paediatric extracranial solid tumours are very diverse. They include soft tissue and bone sarcomas, embryonal tumours such as neuroblastoma and Wilms tumour, and carcinomas. The prognosis of each type varies considerably depending on stage, tumour biology, and other factors. Careful risk st...

Rhabdomyosarcoma of the extremities present with two main challenges: correct evaluation of initial regional nodal involvement and define adequate local treatment. Methods Pediatric patients with localized rhabdomyosarcoma of the extremity included in the EpSSG‐RMS2005 study between 2005 and 2014 were evaluated for staging, treatment, and survival...

Little is known about pseudoprogression in brain tumours other than gliomas. A 9‐year‐old male child with a pineal teratoma/germinoma underwent surgical resection followed by adjuvant chemo‐radiotherapy. The magnetic resonance imaging scan 4 months post‐radiotherapy showed a contrast‐enhancing lesion within the surgical cavity suspicious of recurre...

Objective To derive evidence-based recommendations for the optimal utilisation of resources during unexpected shortage of radiotherapy capacity. Methods and materials We have undertaken a rapid review of published literature on the role of radiotherapy in the multimodality treatment of paediatric cancers governing the European practice of paediatri...

Objective To derive evidence-based recommendations for the optimal utilisation of resources during unexpected shortage of radiotherapy capacity. Methods and materials We have undertaken a rapid review of published literature on the role of radiotherapy in the multimodality treatment of paediatric cancers governing the European practice of paediatr...

Aims: Cancer remains a leading cause of death in children and adolescents in the developed world. Despite advances in oncological management, rates of primary treatment failure remain significant. Radiation of recurrent or metastatic disease improves survival in adults but there is little data to support clinical decision making in the paediatric/...