Genetic test for cancer could result in reduced side effects from treatment in children

2 April 2010

A genetic analysis technique that can identify a less agressive form of a cancer could enable children to be given less intensive treatment than current practice to reduce their risk of damaging side-effects.

A collaboration between scientists at The Institute of Cancer Research (ICR) in London and the Institut Curie in Paris has found a genetic test that can identify patients with a less aggressive form of the childhood cancer alveolar rhabdomyosarcoma. Rhabdomyosarcoma is a cancer that resembles skeletal muscle and can arise in many different locations in the body. The research was published in the Journal of Clinical Oncology this week.

Patients with this less aggressive cancer may be receiving toxic treatment they don’t need. Currently, treatment is based on whether a patient’s cancer is classified as alveolar or embryonal, which is determined by the appearance of a tumour sample under the microscope.

Alveolar rhabdomyosarcoma is considered more aggressive, so these patients are given a more intense combination of chemotherapy, radiotherapy and sometimes surgery.

These treatments have helped improve rhabdomyosarcoma survival rates, but also carry risk of serious and long-term side-effects including the potential to develop another cancer later in life.

When the ICR scientists examined samples from 210 rhabdomyosarcoma patients, they identified 39 cancers that looked like aggressive alveolar type but behaved more like the milder embryonal type. This group of patients had less cancer spread and higher survival rates. Genetic testing revealed that the cancers from these patients lacked a genetic abnormality, known as a PAX/FOX01 fusion gene, which has previously been linked to the alveolar subtype.

ICR scientist Dr Janet Shipley says subsequent analysis of thousands of genes confirmed alveolar rhabdomyosarcomas without a fusion gene are biologically similar to the embryonal subtype but very different from alveolar cancers with a fusion gene.

“We have shown that presence of a fusion gene — not tumour appearance — is a key factor in predicting cancer aggressiveness,” Dr Shipley says. “This study should lead to a re-think in the management of children with the fusion gene-negative alveolar cancer in order to minimise side-effects for these patients. There is no longer any evidence to support treating all alveolar cases the same.”

Dr Shipley says the next step is to hold a clinical trial to see if reducing treatment intensity can improve these patients’ quality of life while maintaining survival rates.

Lynn Lucas, whose son passed away in July 2000 after a three year battle with rhabdomyosarcoma, says the treatment left Chris with serious side-effects including weight loss, difficulty walking and a painful mouth.

“We saw first-hand the horrific side-effects of the treatment for this disease. We will be very pleased if this research leads to some children diagnosed with alveolar rhabdomyosarcoma not suffering in the same way,” Mrs Lucas says.

The research was funded by Chris Lucas Trust, Cancer Research UK, La Ligue Nationale Contre le Cancer, Institut National du Cancer and Enfants et Sante Association.