Oral cryotherapy reduces oral mucositis

Around 75% of patients receiving chemotherapy, radiotherapy of the head and neck, or targeted therapy suffer from oral mucositis. Ulceration is of varying severity but can lead to difficulties with eating, swallowing, and talking leading to increase need for pain relief and nutritional support. It also has a negative effect on quality of life.

The aim of this Cochrane review was to assess the effects of oral cryotherapy for preventing oral mucositis in patients with cancer who are receiving treatment.

Methods

Searches were conducted in the Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CancerLit, CINHAL, the US National Institutes of Health Trials Registry, and the WHO Clinical Trials Registry Platform databases. No restrictions were placed on the language or date of publication when searching databases. Parallel-design randomised controlled trials (RCTs) assessing the effects of oral cryotherapy in patients with cancer receiving treatment were considered. Standard Cochrane approaches to data collection and analysis were followed.

Results

14 RCTS involving 1280 patients were included.
The majority did not receive head and neck radiotherapy so the review primarily assesses prevention of chemotherapy-induced oral mucositis.
All the included trials were at high risk of bias.
For oral cryotherapy versus control (standard care or no treatment).

Adults receiving fluorouracil-based (5FU) chemotherapy for solid cancers

Oral mucositis severity	No of studies (no patients)	Risk Ratio (95%CI)	Number needed to treat (95%CI)	Quality of evidence
Any severity	5 (444)	0.61 (0.52 to 0.72)	4 (3-5)	Moderate
Moderate to severe	5 (444)	0.52 (0.41 to 0.65)	4 (4-6)	Moderate
Severe	5 (444)	0.40 (0.27 to 0.61)	6 (5-9)	Moderate

In a population where 728 per 1000 would develop oral mucositis of any severity oral cryotherapy would reduce this to 444 (95% CI; 379 to 524).

Adults receiving high-dose melphalan-based chemotherapy before haematopoietic stem cell transplantation (HSCT)

Oral mucositis severity	No of studies (no patients)	Risk Ratio (95%CI)	Number needed to treat (95%CI)	Quality of evidence
Any severity	5 (270)	0.59 (0.35 to 1.01)	3 (2-111)	Low
Moderate to severe	5 (270)	0.43 (0.17 to 1.09)	3 (2-17)	Low
Severe	5 (270)	0.38 (0.20 to 0.72)	6 (5-9)	Moderate

For severe oral mucositis where 427 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 162 (95% CI 85 to 308).

Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, numbness/taste disturbance, and tooth pain. This appears to contribute to the high rates of compliance seen in the included studies.
There was limited or no evidence on the secondary outcomes of this review, or on patients undergoing other chemotherapies, radiotherapy, targeted therapy, or on comparisons of oral cryotherapy with other interventions or different oral cryotherapy regimens.
There was also no evidence on the effects of oral cryotherapy in children undergoing cancer treatment.

Conclusions

The authors concluded:

We are confident that oral cryotherapy leads to large reductions in oral mucositis of all severities in adults receiving 5FU for solid cancers. We are less confident in the ability of oral cryotherapy to reduce oral mucositis in adults receiving high-dose melphalan before 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 review includes some very recent and currently unpublished data, and strengthens international guideline statements for adults receiving the above cancer treatments.

Comments

Cryotherapy involves the use of ice chips in the mouth. This is thought to reduce the blood flow so decreasing the amount of chemotherapeutic agent delivered to the tissue. This Cochrane review is clear that oral cryotherapy is beneficial for adults receiving 5FU chemotherapy and the authors suggest that further RCTs should compare cryotherapy with new promising treatment. They are clear that further studies are required to clarify the effects of cryotherapy in patients receiving high-dose melphalan before HSCT.

This Cochrane review is the first of a series replacing previous Cochrane reviews covering interventions for the prevention of oral mucositis in patients with cancer receiving treatment. These reviews are being developed in liaison with the Mucositis Study Group (MSG) of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The reviews will cover the following areas.

basic oral care/good clinical practice;
growth factors and cytokines;
anti-inflammatory agents;
antimicrobials, mucosal coating agents, anaesthetics, and analgesics;
laser and other light therapy;
cryotherapy;
natural and miscellaneous agents;
amifostine.

Links

Primary paper

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.