Molecular radiotherapy (MRT) is an evolving form of children’s cancer treatment. Dr Mark Gaze, Caroline Elmagrahi and Georgia Azzopardi, of University College London Hospitals NHS Foundation Trust, tell us more about what it is and what work is being done to develop its usage.
*Caroline Elmagrahi (left), Dr Mark Gaze (middle) and Georgia Azzopardi (right)
MRT is a less well known form of cancer treatment, but can be highly effective, even when the cancer has spread widely. Its uses are growing, and there are increasing numbers of clinical trials of MRT in a variety of types of childhood cancer. There’s a lot of ongoing work in this field to improve, personalise and discover new uses for MRT, aiming for better outcomes for children affected by cancer.
What is MRT and how does it work?
Unlike ‘conventional’ radiotherapy, where a beam of radiation from a machine is directed at a cancer, MRT is a treatment given either by mouth or injection. A radioactive drug accumulates in the cancer cells in a much higher concentration than in most healthy cells. In this way, it delivers a high radiation dose directly to the cancer, sparing healthy, normal tissues. When taken up by the tumour cells, the radiation destroys them. This is a highly targeted treatment.
What is MRT used for, and what trials are there?
The oldest and most common form of MRT is the use of radioactive iodine for the treatment of thyroid cancers. Most patients have a single dose following surgery, to destroy any remaining thyroid cells.
Children who have advanced disease – for example, spread to their lungs – may require multiple treatments over time, and this may still cure the cancer completely. This is an established treatment.
MRT with 131-Iodine mIBG is already an established treatment for high-risk neuroblastoma which has not responded well to initial chemotherapy or has relapsed. 131-Iodine mIBG is currently included in an American front-line high-risk neuroblastoma trial. There’s a range of clinical trials (past, present and future), which try to optimise its use in different ways. These include trials with:
- radiation sensitisers to make tumour cells easier to kill e.g. VERITAS trial
- immunotherapy combinations e.g. MINIVAN trial
- combination with targeted drugs so cancer cells cannot repair themselves e.g. MINT trial
Unlike ‘conventional’ radiotherapy, where a beam of radiation from a machine is directed at a cancer, MRT is a treatment given either by mouth or injection.
The radioactive drug 177-Lutetium DOTATATE targets a cell surface receptor on some cancers. It’s been shown to improve outcomes for neuroendocrine cancers in adults, and its use is being evaluated in children with the same disease in the ongoing NETTER-P trial. The same drug is being tested in children with neuroblastoma. Previous LUDO trial data formed the basis for the current LUDO-N trial, which gives an increased amount of 177-Lutetium DOTATATE over a shorter period, hoping to improve outcomes.
Patients with leukaemia needing bone marrow transplants traditionally receive conditioning with external beam radiotherapy which, although effective, does have long-term side effects. MRT with a monoclonal antibody (immune system protein created in the lab) directed against leukaemia cells has been shown in the RIT trial to be safe, and now the RIT-2 trial will study a much larger number of patients to see how effective it is.
Side effects and isolation?
MRT in general is a very well-tolerated treatment. There’s no hair loss or severe sickness and fatigue, as seen with some chemotherapy regimens. There are some side effects depending on the type of treatment, while another challenge for patients is that they have to be isolated in hospital. Their stay will be a week or more, depending on the treatment. The room is large with an ensuite, as well as a separate side room for a parent to sleep in. As long as comforters and carers follow simple safety measures to keep their personal radiation exposure as low as possible, they can spend as long as necessary with the child during treatment.
Although this treatment may seem daunting for children, with the support from the multiprofessional team including play specialists, nurses, radiographers and physicists, they’re able to cope very well.
From Contact magazine issue 102 - Spring 2024
