These findings suggest that many patients with early stage disease could be cured with chemotherapy alone, without experiencing long-term side effects like heart disease and second cancers.
Hodgkin lymphoma is a cancer that affects white blood cells in the lymphatic system. Around 1700 people are diagnosed with the condition each year in the UK. The average age at diagnosis is around 40 and it can affect teenagers and young adults too, so side effects long after treatment are especially important.
What did the trial do?
The ‘RAPID’ trial – largely funded by Leukaemia & Lymphoma Research and led by researchers in Manchester – recruited 602 patients with early stage Hodgkin lymphoma. After the initial cycles of standard chemotherapy, patients were given a PET scan to detect any traces of disease remaining and to predict an individual’s outlook.
Those whose PET scans flagged cancerous growth (a 'positive' result) were then given a course of radiotherapy, as is usual. For the 420 patients whose PET scans didn't detect anything (a 'negative' result), though, were divided into two groups. Half were given the usual radiotherapy but the other half were not.
The question was: did the group not receiving radiotherapy fare any worse than those who did?
What did the trial show?
The results, published in the New England Journal of Medicine, were very promising. Three years on, in all groups, over nine in 10 patients were still alive – testament to the advances made over the decades in treating this blood cancer.
The researchers measured not only whether a patient survived but whether their disease had come back or had got worse. Of those with negative PET results, 94.6% of patients in the radiotherapy group survived without their lymphoma getting worse, compared with 90.8% in the non-radiotherapy group.
But overall survival – the simple measure of whether a patient is alive or not after a set period of time – was slightly improved after three years in the non-radiotherapy group (99%) compared with their radiotherapy counterparts (97.1%). This could be because the radiotherapy damages some healthy tissue as well as cancerous cells, creating more health problems that may prove too harmful for a few patients.
What does this mean for patients?
So it seems that whilst radiotherapy can bring marginal improvements in keeping the disease at bay in the short-term, the collateral damage may slightly reduce the longer-term survival chances.
In other words, most patients with a favourable PET scan after chemotherapy do not need further treatment. A few may need additional treatment to tackle later disease flare-ups, but in the long-run it's probably safer to avoid the blanket use of radiotherapy. Given this, doctors and patients may well opt out of radiotherapy if their PET scan is favourable.
Professor John Radford, who led the trial and is based at The University of Manchester’s and the Christie NHS Foundation Trust, said: “This research is an important step forward. The results of RAPID show that in early stage Hodgkin lymphoma radiotherapy after initial chemotherapy marginally reduces the recurrence rate, but this is bought at the expense of exposing to radiation all patients with negative PET findings, most of whom are already cured.”
This is one more example of how research is driving a more personalised approach to treating blood cancers. By using information about an individual's risk of disease progression, doctors can tailor the treatment plan accordingly. If treatment can be reduced for patients without affecting their chances of a cure, this would very welcome news – aside from causing later health problems, radiotherapy can be a gruelling experience so cutting it out could seriously improve their treatment journey.
Shiv Meaker, who was diagnosed with Hodgkin lymphoma in 2012 at the age of 33, found her PET test hugely reassuring . "When my end of chemo PET scan came back clean I cannot tell you the relief and joy I felt," she says. "It meant my chemo had worked and the possibility of radiotherapy, more uncertainty, yet more pressing hold on my life, was lifted."
The results provide a snapshot three years after the last patient entered the trial. Further work will need to follow these patients for longer to see whether the majority of the chemotherapy-only group remain disease-free. The researchers would also like to see whether, as predicted, there proves to be substantially fewer cases of heart disease and second cancers.
We hope that these results and the ongoing follow-up of patients in the trial will be taken up as standard practice by the health service. Knowing that costs are a crucial consideration at the moment, it could certainly save the health service money – both in the short-term in the reduction of expensive radiotherapy, but also the long-term by reducing the number of treatment-related complications.
And we hope to do the same for younger patients too. A new trial, run in the UK by Dr Stephen Daw at University College Hospitals, aims to reduce the use of radiotherapy in patients who respond well to initial chemotherapy, and to reduce the intensity of radiotherapy in those patients who still need it. It is the same principle as UKALL 2011, the national trial for children with acute lymphoblastic leukaemia we're also supporting – using information about an individual's disease to scale back the intensity of chemotherapy for some patients.
It goes to the heart of what our charity is about – not just stopping people from dying but giving people the best quality of life possible.
- Radford et al (2015). Results of a Trial of PET-Directed Therapy for Early-Stage Hodgkin’s Lymphoma. N Engl J Med 372;17.