A new study hopes to identify which cancer patients would most benefit from radio- and chemotherapy before beginning a course of treatment, writes Eoin Burke-Kennedy
It has long been acknowledged that chemotherapy and radiotherapy improve outcomes for cancer patients.
Individuals, however, can vary in their response to treatment, making it difficult for doctors to predict the usefulness of subjecting patients to a course of therapy.
To overcome this, techniques are being developed to predict the response of patients to treatment so clinicians can identify in advance those most likely to benefit.
Such innovation would also spare patients the prospect of having to endure high levels of toxicity when the chance of a favourable outcome may be low and an alternative treatment strategy, such as surgery or palliative care, may be more appropriate.
To the fore in this field is a team of oncologists at St James's Hospital in Dublin who are attempting to use genetic technology and high-spec imaging tools to predict the response of patients with oesophageal tumours to chemo- and radiotherapy.
"We routinely give chemo and radiotherapy to many different types of cancer," explains Dr Charles Gillham, who has played a leading role in the research. "But from the outset we don't really know if the patient or the tumour is going to respond well to it.
"It is obvious that we are over-treating some patients and under-treating others," he says. "If we could identify in advance those patients who were going to completely respond, we could spare those who were not going to respond the unnecessary toxicity.
"Now that we are moving into an area of looking at cancer at a genetic level, the hope is that treatment can be tailored to the individual to maximise the outcome."
The first part of the research undertaken by the anoesophageal cancer research group at St James's sought to correlate gene expression with a positive response to treatment.
The team took samples of the cancer tissue from patients with oesophageal tumours at the initial diagnosis phase or prior to a standard course of chemo- and radiotherapy.
They then performed what's known as gene expression array analysis to see which genes were under- or over-expressed and attempted to correlate them with a good response to treatment.
"If we could identify a panel of genes that were over- or under- expressed which equated to a good or a bad response then we might have a means of predicting the outcome prior to treatment," explains Gillham.
The team did manage to correlate a panel of overly expressed genes with a positive response but the sample of patients used was not large enough to make the results clinically useful.
"You need dozens of patients to be confident that you have a genetic signature that is associated with a good or a bad response," says Gillham.
Nevertheless, he believes the use of gene-expression signatures, or predictive genomic testing as it is also known, is likely to become a standard feature of cancer therapy in the near future. Clinical trials on breast cancer patients sponsored by the European Organisation for Research and Treatment of Cancer are already under way.
Oesophageal cancer, or cancer of the gullet, is a relatively rare cancer - the ninth most common - affecting less than 0.01 per cent of the population.
The five-year survival rate, however, is poor compared with other cancers - somewhere in the region of 30-40 per cent.
This is largely because the symptoms can be subtle and patients tend to present when the tumour is already at an advanced stage.
The incidence of the disease, particularly in the developed world, is also on the increase.
Figures from the National Cancer Registry in Ireland show there were on average 316 cases per year between 1995 and 2004, with the annual total rising by 3-5 per cent a year.
In the past, the most common form of the disease was a squamous cell carcinoma which usually affects the middle third of the oesophagus.
But more recently oncologists have witnessed a marked rise in the number of adenocarcinomas which normally appear in the lower third of the tract.
This has been associated with a rise in the incidence of obesity. One theory is that obese people are more likely to suffer from acid reflux where acid coming back up from the stomach irritates the lining of the oesophagus.
But experts insist the obesity link is not fully understood, and, while there is an association, it does not explain the whole picture.
The standard treatment in Ireland for oesophageal cancer is a combination of chemotherapy and radiotherapy prior to an operation to remove part or all of the oesophagus.
Before a patient is considered for surgery, he or she must undergo a Positron Emission Tomography (PET) and Computerised Tomography (CT) scan to assess the extent of the cancer. PET and CTare both standard imaging tools which pinpoint the location of cancer.
The former detects the metabolic signal of actively growing cancer cells while the latter provides an image of the internal anatomy of the tumour in terms of location, size and shape.
Alone, each tool has particular benefits and limitations, but recent advances in the technology have allowed for a fusion of both scans, giving doctors a more complete image of the cancer.
"The combination of the two technologies helps us identify more clearly the local extent of the disease and whether there are lymph nodes or other secondaries involved," says Gillham.
"As an add-on to our genetic research, we wondered if a repeated scan, taken shortly after treatment had begun, would detect changes in the tumour that could help us predict who would go on to respond well or poorly."
The team conducted a second scan on a cohort of patients one week after the start of their therapy.
They looked at various parameters to see whether differences with the pre-treatment scan could be useful in determining who was going to respond better to treatment. Unfortunately, this part of the research has so far proved inconclusive. Although the team saw changes to the tumour on the second scans, they could not correlate them with the ultimate outcomes.
But Gillham believes this may have been as a result of using a mixture of squamous cell carcinoma patients and adenocarcinoma patients.
Consequently, the team has begun a new study, this time solely with adenocarcinoma patients, one of the first of its kind, in the hope that they will identify differences on the second scan which might signal how effective the therapy will ultimately be.