Paediatric Molecular Radiotherapy: Challenges and Opportunities

Published on Feb 1, 2021in Clinical Oncology3.113
· DOI :10.1016/J.CLON.2020.11.007
Matthew D. Aldridge5
Estimated H-index: 5
(UCLH: University College London Hospitals NHS Foundation Trust),
Connie Peet1
Estimated H-index: 1
(UCLH: University College London Hospitals NHS Foundation Trust)
+ 4 AuthorsMark N. Gaze28
Estimated H-index: 28
(UCLH: University College London Hospitals NHS Foundation Trust)
The common contemporary indications for paediatric molecular radiotherapy (pMRT) are differentiated thyroid cancer and neuroblastoma. It may also have value in neuroendocrine cancers, and it is being investigated in clinical trials for other diseases. pMRT is the prototypical biomarker-driven, precision therapy, with a unique mode of delivery and mechanism of action. It is safe and well tolerated, compared with other treatments. However, its full potential has not yet been achieved, and its wider use faces a number of challenges and obstacles. Paradoxically, the success of radioactive iodine as a curative treatment for metastatic thyroid cancer has led to a 'one size fits all' approach and limited academic enquiry into optimisation of the conventional treatment regimen, until very recently. Second, the specialised requirements for the delivery of pMRT are available in only a very limited number of centres. This limited capacity and geographical coverage results in reduced accessibility. With few enthusiastic advocates for this treatment modality, investment in research to improve treatments and broaden indications from both industry and national and charitable research funders has historically been suboptimal. Nonetheless, there is now an increasing interest in the opportunities offered by pMRT. Increased research funding has been allocated, and technical developments that will permit innovative approaches in pMRT are available for exploration. A new portfolio of clinical trials is being assembled. These studies should help to move at least some paediatric treatments from simply palliative use into potentially curative protocols. Therapeutic strategies require modification and optimisation to achieve this. The delivery should be personalised and tailored appropriately, with a comprehensive evaluation of tumour and organ-at-risk dosimetry, in alignment with the external beam model of radiotherapy. This article gives an overview of the current status of pMRT, indicating the barriers to progress and identifying ways in which these may be overcome.
📖 Papers frequently viewed together
7 Citations
2 Citations
1 Citations
#1Mechteld C de Jong (UCLH: University College London Hospitals NHS Foundation Trust)H-Index: 1
#1Mechteld C. de Jong (UCLH: University College London Hospitals NHS Foundation Trust)H-Index: 1
Last. Tom R Kurzawinski (UCLH: University College London Hospitals NHS Foundation Trust)H-Index: 3
view all 21 authors...
AIM Differentiated thyroid cancer (DTC) in children and adolescents is rare and data about its presentation and management are not well known. The aim of this study was to provide evidence of the current practice in the United Kingdom before the launch of the Rare National Paediatric Endocrine Tumours Guidelines (to be published in 2020). METHODS Seventy-two children and adolescents with DTC (<18 years) who were treated at our institution between 2003 and 2018 were identified and their presentat...
2 CitationsSource
#1Mariam Aboian (Yale University)H-Index: 3
#2Shih-ying Huang (UCSF: University of California, San Francisco)H-Index: 11
Last. Youngho Seo (UCSF: University of California, San Francisco)H-Index: 29
view all 10 authors...
: The metaiodobenzylguanidine (MIBG) scan is one of the most sensitive noninvasive lesion detection modalities for neuroblastoma. Unlike 123I-MIBG, 124I-MIBG allows high-resolution positron emission tomography (PET). We evaluated 124I-MIBG PET/CT for its diagnostic performance directly compared to paired 123I-MIBG scans. Methods: Prior to 131I-MIBG therapy, standard 123I-MIBG scans (5.2 MBq/kg) that include whole-body (anterior-posterior) planar scans and focused field of view (FOV) single photo...
4 CitationsSource
#1Chantal A Lebbink (UU: Utrecht University)H-Index: 2
#2B L Dekker (UMCG: University Medical Center Groningen)H-Index: 1
Last. H M van Santen (UU: Utrecht University)H-Index: 15
view all 21 authors...
Background Currently, there are no European recommendations for the management of pediatric thyroid cancer. Other current international guidelines are not completely concordant. In addition, medical regulations differ between for instance the US and Europe. We aimed to develop new, easily accessible national recommendations for differentiated thyroid carcinoma (DTC) patients <18 years of age in the Netherlands as a first step towards a harmonized European Recommendation. Methods A multidisciplin...
1 CitationsSource
#1Cédric Desmonts (UNICAEN: University of Caen Lower Normandy)H-Index: 10
Last. Nicolas Aide (UNICAEN: University of Caen Lower Normandy)H-Index: 28
view all 6 authors...
BACKGROUND: Evaluate the physical performance of the VERITON CzT camera (Spectrum Dynamics, Caesarea, Israel) that benefits from new detection architecture enabling whole-body imaging compared to that of a conventional dual-head Anger camera. METHODS: Different line sources and phantom measurements were performed on each system to evaluate spatial resolution, sensitivity, energy resolution and image quality with acquisition and reconstruction parameters similar to those used in clinical routine....
7 CitationsSource
#1Jennifer E. Gains (UCLH: University College London Hospitals NHS Foundation Trust)H-Index: 9
#2Veronica Moroz (University of Birmingham)H-Index: 9
Last. Mark N. Gaze (UCLH: University College London Hospitals NHS Foundation Trust)H-Index: 28
view all 9 authors...
PURPOSE: The objective of this phase IIa, open-label, single-centre, single-arm, two-stage clinical trial was to evaluate the safety and activity of 177-lutetium DOTATATE (LuDO) molecular radiotherapy in neuroblastoma. METHODS: Children with relapsed or refractory metastatic high-risk neuroblastoma were treated with up to four courses of LuDO. The administered activity was 75 to 100 MBq kg(-1) per course, spaced at 8- to 12-week intervals. Outcomes were assessed by the International Neuroblastom...
6 CitationsSource
#1Ruth Ladenstein (Boston Children's Hospital)H-Index: 53
#2Ulrike Pötschger (Community College of Rhode Island)H-Index: 43
Last. Holger N. LodeH-Index: 39
view all 24 authors...
To explore the effects of immunotherapy in the International Society of Paediatric Oncology Europe Neuroblastoma Group SIOPEN high-risk neuroblastoma 1 trial (HR-NBL1 trial), two cohorts were studied: one prior to and one after the introduction of dinutuximab beta. All patients received standard induction and high-dose therapy (HDT) with autologous stem cell rescue (ASCR); the local control comprised surgery and radiotherapy to the primary tumour site, followed by isotretinoin. A landmark timepo...
18 CitationsSource
#1Julie Voeller (UW: University of Wisconsin-Madison)H-Index: 2
#2Amy K. Erbe (UW: University of Wisconsin-Madison)H-Index: 8
Last. Paul M. Sondel (UW: University of Wisconsin-Madison)H-Index: 51
view all 18 authors...
Background Unlike some adult cancers, most pediatric cancers are considered immunologically cold and generally less responsive to immunotherapy. While immunotherapy has already been incorporated into standard of care treatment for pediatric patients with high-risk neuroblastoma, overall survival remains poor. In a mouse melanoma model, we found that radiation and tumor-specific immunocytokine generate an in situ vaccination response in syngeneic mice bearing large tumors. Here, we tested whether...
13 CitationsSource
#1Vivek Subbiah (University of Texas MD Anderson Cancer Center)H-Index: 48
#2Peter M. Anderson (Cleveland Clinic)H-Index: 52
Last. Eric M. Rohren (BCM: Baylor College of Medicine)H-Index: 40
view all 17 authors...
Purpose: The prognosis of metastatic osteosarcoma continues to be poor. We hypothesized that alpha-emitting, bone-targeting radium 223 dichloride (223RaCl2) can be safely administered to patients with osteosarcoma and that early signals of response or resistance can be assessed by quantitative and qualitative correlative imaging studies and biomarkers. Experimental Design: A 3+3 phase I, dose-escalation trial of 223RaCl2 (50, 75, and 100 kBq/kg) was designed in recurrent/metastatic osteosarcoma ...
13 CitationsSource
#1Yana Dekempeneer (Vrije Universiteit Brussel)H-Index: 4
#2Tom Bäck (University of Gothenburg)H-Index: 4
Last. Matthias D'Huyvetter (Vrije Universiteit Brussel)H-Index: 18
view all 13 authors...
The use of nanobodies (Nbs) as vehicles in targeted alpha therapy (TAT) has gained great interest because of their excellent properties. They combine high in vivo affinity and specificity of binding with fast kinetics. This research investigates a novel targeted therapy that combines the α-particle emitter astatine-211 (211At) and the anti-HER2 Nb 2Rs15d to selectively target HER2+ cancer cells. Two distinctive radiochemical methodologies are investigated using three different coupling reagents....
10 CitationsSource
#1Karla A. LeeH-Index: 10
#2M.T.A. Sharabiani (Imperial College London)H-Index: 1
Last. Katie L. NewboldH-Index: 22
view all 10 authors...
Abstract Aims To obtain an overview of the management and outcomes of children aged 18 years or younger diagnosed with differentiated thyroid carcinoma of follicular cell origin across the UK, by collecting and analysing data from the limited number of centres treating these patients. This multicentre data might provide a more realistic perspective than single-institution series. Materials and methods Six centres submitted data extracted from historical records on patients aged 18 years or young...
4 CitationsSource
Cited By1
#1Ioannis KyriakidisH-Index: 10
#2Eleni VasileiouH-Index: 2
Last. Athanasios TragiannidisH-Index: 14
view all 6 authors...
Since 1985 when the first agent targeting antigens on the surface of lymphocytes was approved (muromonab-CD3), a multitude of such therapies have been used in children with hematologic malignancies. A detailed literature review until January 2021 was conducted regarding pediatric patient populations treated with agents that target CD2 (alefacept), CD3 (bispecific T-cell engager [BiTE] blinatumomab), CD19 (denintuzumab mafodotin, B43, BiTEs blinatumomab and DT2219ARL, the immunotoxin combotox, an...
1 CitationsSource