Advice
The technology
The technology
The next-generation sequencing (NGS)-based panel for solid tumour cancers in children is an in-house laboratory test, not a commercial product. It was developed at the Centre for Molecular Pathology at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust and validated in-house for clinical application, following the standardised framework published by Mattocks et al. (2010).
The test provides a genetic profile from a sample of solid tumour tissue for a range of childhood cancers including glioma, medulloblastoma, bone sarcomas, soft tissue sarcomas, renal tumours and neuroblastoma. The test reports whether there are mutations within each target gene in the tissue sample, and may identify whether the child with cancer is eligible for any suitable clinical trial to have targeted treatment.
The current NGS panel design, which is being continually developed, includes 92 genes which are either recurrently altered in childhood cancers, or have clinical implications in adult cancers (and potentially childhood cancers). Specialist genetic sample processing techniques are used to identify mutations in these genes. The test takes 10 working days to complete from receipt of tumour material in the laboratory to final reporting of results.
Innovations
The NGS panel was developed with input from a wide range of clinical and scientific experts. It is highly optimised and tailored specifically to solid tumour cancers in children.
Ongoing clinical trials could contribute to developing molecular stratification approaches to treating cancer in children.
Current NHS pathway or current care pathway
Companion diagnostic tests designed to identify targeted genetic variations in tumour DNA are routinely used for some cancers in adults. However, childhood cancers are biologically different to adult cancers, and there are no targeted therapies available in the NHS. As such, diagnostics are not part of standard care pathway for treating cancer in children.
Targeted therapies are offered to children with cancer only in the context of clinical trials. Children with cancers that do not meet the inclusion criteria of clinical trials may be offered surgery, chemotherapy or radiotherapy, then palliative care for when all other treatment options have been exhausted.
Population, setting and intended user
The NGS panel is intended for use in a clinically accredited laboratory. Because of the relatively low numbers of children with cancer, the test would likely be run from a small number of laboratories that provide a service to centres involved in diagnosing and treating cancer in children. A sample from the tumour, together with corresponding germline DNA or whole blood, would be sent from the laboratory of the referring centre to the laboratory providing the test. The test laboratory would then prepare a formalin-fixed paraffin embedded (FFPE) clinical sample block, run the test and provide the results to the referring pathologist. The results would be used to help decide whether the child is eligible for enrolment in a clinical trial.
Staff using the NGS panel need training in the test, alongside general competency training in line with Good Clinical Laboratory Practice (GCLP) regulations. This would be provided by the test laboratory. The test is in scope for the NHS Genomic Laboratory Services on which NHS England has recently developed a specification for engagement with stakeholders.
Costs
Technology costs
Costs obtained from the Centre for Molecular Pathology at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust vary depending on volume and turnaround time. Table 1 shows the total in-house costs, including the cost of using an Illumina Nextseq 500 NGS sequencer. The panel can be run in batches of 20 paired samples at most, or in smaller batches for faster turnaround or when sample numbers are limited.
Table 1 Cost per sample for NGS panel testing
|
Description |
Cost per sample (20 samples, full capacity) |
Cost per sample (5 samples, faster turnaround) |
|
Reagents only |
£204 |
£325 |
|
Reagents and overheads |
£271 |
£413 |
|
Reagents, overheads and labour* |
£346 |
£651 |
|
* Including all necessary maintenance contracts, data analysis and labour costs, but no additional NHS administrative costs. |
||
Resource consequences
Cancer in children is relatively rare, but around 1,000 children with cancer could be eligible for NGS panel testing each year (Childhood cancer registration in England, 2016).
The resource impact would be cost-incurring at first. However, the NGS panel would mainly use existing laboratory resources and remove the need for expensive sequential testing to inform eligibility decisions for clinical trials in children with solid tumour cancer. Based on the costs outlined in table 1, sequencing all solid tumour cancers in children may cost between £342,194 and £643,839 per year (excluding administration costs).
The genetic information obtained may lead to the development of molecular stratification strategies in paediatric oncology, targeted therapies using biological agents or targeted drugs for children. These would be alternatives to surgery, chemotherapy, radiotherapy and other current treatments in children with solid tumour cancers.