Germ cell tumours develop from cells in the ovaries or testes. They are extremely rare in childhood – fewer than 45 children are diagnosed each year in the UK with the disease – but the number of cases increases as children reach adolescence.
Most children who develop germ cell tumours are successfully treated using established medicines such as chemotherapy, but not all types respond as well, and if chemotherapy fails there may not be any secondary treatments to turn to.
A new review by an international team of researchers – including Professor Robert Huddart here at The Institute of Cancer Research – looks at how clinical trials have been used to improve the treatment options for germ cell tumours.
Chemotherapy can also lead to serious side-effects for patients later in life, like nerve damage and cardiovascular problems, so there is a real need for new treatments for germ cell tumours to provide better options for patients who don’t respond to standard therapy.
At the ICR, we’ve campaigned for cancer drugs developed for adults to be tested in children whenever they could be effective, as one way of expanding children’s access to innovative new treatments.
But the search for new ways to treat childhood germ cell tumours has faced more fundamental problems. One of the largest obstacles has been that children with the disease may receive different diagnoses or treatments depending on where they live in the world and their age at the time of diagnosis.
It’s clear that the disease affects adults and children differently, indicating different biological origins, but researchers haven’t been able to agree on what factors were most likely to affect patients’ response to treatment.
It’s also common for adults, adolescents, and younger children with germ cell tumours to be treated separately, without reference to each other.
Without a common ground for talking about the disease, testing new treatments in a robust way across different patient groups has been very difficult.
Collaboration is key
One of the first collaborative studies for childhood germ cell tumours was carried out in the US in the 1990s. It aimed to develop treatment strategies for low-risk and high-risk germ cell tumours based on the location of the tumour and stage of the disease.
This study recognised the importance of collaboration to bring together larger groups of patients for testing treatments and reducing administration. Unfortunately, in the UK and elsewhere, the lack of consensus continued to hinder progress.
A major turning point came in 2009, when the Malignant Germ Cell International Collaborative (MaGIC) initiative was established.
MaGIC brought together data obtained over 25 years from clinical trials of over 1,000 paediatric patients with germ cell tumours – and was an important first step toward developing treatment strategies based on predictions of outcome, taking into account factors like age and tumour staging.
The study showed that children over 11 were at risk of more aggressive germ cell tumours and were more likely to suffer relapse of their disease than younger children, even those with more advanced disease.
Findings from other groups found adolescents with germ cell tumours fared consistently worse than either children or adults with the disease.
Differences in how childhood and adult germ cell tumours are classified mean researchers have needed to take care when comparing treatment outcomes across different ages, but their studies are now helping to develop the common language needed to make informed decisions about treatment.
Paediatric groups in the UK and US are now exploring opportunities for collaboration in future clinical trials that include both children and adults with germ cell tumours.
Several strategies have been tested in clinical trials for patients with poor-prognosis disease, including use of alternative forms of chemotherapy, high-dose chemotherapy with stem cell treatments, and more complex multi-drug regimens.
And the ICR is leading a new trial in the UK called TIGER, which will compare conventional chemotherapy with high-dose chemotherapy for patients with germ cell tumours whose disease has relapsed.
These trials will continue to enhance our understanding of the disease, and help doctors to select treatments based on the most relevant information available. The research will play a vital role in ensuring that whatever their age, patients with germ cell tumours have access to the most effective cancer treatments.
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