People receiving treatment for cancer are at risk of developing a sore mouth and ulcers as a side effect. This side effect is called oral mucositis and affects over 75% of high-risk patients (those receiving radiotherapy to the head and neck or high-dose chemotherapy). The pain caused by this condition can be severe and can stop the person’s ability to eat and drink, which may mean they need to take strong pain killers, stay in hospital and be fed through a tube into their stomach, or even into their veins. This in turn can lead to disruption to their cancer treatment, meaning they are not receiving the best possible treatment. The results may be a reduction in the patient’s chances of survival, and increased costs to the healthcare system. Cancer patients have weakened immune systems due to their treatment, meaning that their bodies are less able to fight infections. This can be a problem if bacteria enter the body through the ulcer, which is an open wound. This can lead to sepsis (a dangerous inflammatory reaction of the body to infection), which requires antibiotics and hospitalisation, and can cause death.
Oral cryotherapy is the cooling of the mouth using ice, ice-cold water, ice cream or ice lollies/popsicles. It is thought to help prevent oral mucositis in people receiving certain types of chemotherapy because the coldness makes the blood vessels in the mouth narrower, and this reduces the amount of blood containing chemotherapy drugs from reaching the mouth and causing oral mucositis. It is a low-cost, natural treatment without serious side effects.
What was the research?
A systematic review of the evidence to find out whether or not keeping the mouth cold during cancer treatment, by using ice, ice-cold water, ice cream or ice lollies/popsicles, can help prevent mouth soreness and ulcers in children and adults
Who conducted the research?
The research was conducted by a team led by Philip Riley from the University of Manchester on behalf of the Cochrane Oral Health Group. Anne-Marie Glenny, Helen V. Worthington, Anne Littlewood, Jan E. Clarkson and Martin G. McCabe were also on the team.
What evidence was included in the review?
Data was extracted from 14 randomised controlled trials. A total of 1,316 cancer patients participated in the trials, and were randomly assigned to receive oral cryotherapy versus standard care (usually saline mouthrinses) or no treatment or a different treatment or a different method of oral cryotherapy. Nearly all the evidence was on adults receiving oral cryotherapy versus standard care or no treatment. This evidence fell into two main groups: 1) adults receiving fluorouracil-based (5FU) treatment for solid cancers; or 2) adults receiving high-dose melphalan-based cancer treatment before haematopoietic stem cell transplantation (HSCT). HSCT is given to help the body to produce all types of blood cells, which are destroyed during cancer treatment.
What did the evidence say?
There is evidence showing that oral cryotherapy can lead to large reductions in the numbers of adults who get oral mucositis of all severities after receiving 5FU-based treatment for solid cancers. There is less certain evidence to suggest that oral cryotherapy may reduce the numbers of adults who get oral mucositis after receiving high-dose melphalan-based cancer treatment prior to HSCT. The evidence suggests that it does reduce oral mucositis in these adults, but the size of the reduction is much less certain. Oral cryotherapy did not cause any serious side effects in any of the participants of these studies, and most people seemed able to carry it out properly and complete it.
How good was the evidence?
The evidence presented, on the main outcome of whether or not people developed oral mucositis of all severities, is of moderate (because the nature of the oral cryotherapy treatment meant that the studies could not be ‘blinded’ which is a desirable characteristic of these studies) to low quality (because in addition to the above problem, the results of the individual studies were too different to give a precise result when they were combined).
What are the implications for dentists and the general public?
We are confident that oral cryotherapy leads to large reductions in the incidence of oral mucositis of all severities in adults receiving fluorouracil-based (5FU) treatment for solid cancers. We are less confident in the ability of oral cryotherapy to reduce the incidence of oral mucositis in adults receiving high-dose melphalan-based cancer treatment prior to haematopoietic stem cell transplantation (HSCT). Evidence suggests that it does reduce oral mucositis in these adults, but we are less certain about the size of the reduction, which could be large or small. However, we are confident that there is an appreciable reduction in severe oral mucositis in these adults. This Cochrane systematic review has included some very recent and currently unpublished data, and strengthens international guideline statements for adults receiving the above cancer treatments.
What should researchers look at in the future?
It is fairly clear that oral cryotherapy is beneficial for adults receiving 5FU chemotherapy, and therefore further randomised controlled trials (RCTs) are probably not warranted. Instead, it may be better to conduct new head-to-head RCTs comparing oral cryotherapy with other promising preventive treatments such as lasers, growth factors and cytokines, and other interventions. We need more studies assessing oral cryotherapy in people receiving high-dose melphalan-based cancer treatment prior to HSCT in order to further strengthen the body of evidence reported in this review. Further investigation of the optimum cryotherapy regimen may be warranted in these patients and, as mentioned above, more head-to-head studies.
Riley P, Glenny AM, Worthington HV, Littlewood A, Clarkson JE, McCabe MG. Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy. Cochrane Database of Systematic Reviews 2015, Issue 12. Art. No.: CD011552. DOI: 10.1002/14651858.CD011552.pub2.