Cochrane · intervention · CD011552
Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy
Riley, P, Glenny, AM, Worthington, HV, et al. · Cochrane Database of Systematic Reviews · 2015 · Cochrane Library
Full textEvery question was extracted from the full review (methods and results), not only its Summary of Findings table.
Questions
39
current version
GRADE rated
26
No studies
6
Included studies
14
as reported
No studies 6 · 15.4%Ungraded 7 · 17.9%Very low 18 · 46.2%Low 4 · 10.3%Moderate 4 · 10.3%High 0 · 0%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | All patients with cancer who are receiving treatment | 1316 participants randomised (1280 analysed) across 14 studies; adults and children (only 1 study, Gori 2007, included children) with a variety of cancers receiving chemotherapy or radiotherapy; majority (1251) adults; solid cancers (8 studies) and haematological cancers (6 studies); no studies involved targeted therapy |
| Intervention | Oral cryotherapy for the prevention of oral mucositis (inclusive of targeted therapy-induced stomatitis); different regimens of oral cryotherapy compared head-to-head | Oral cryotherapy: ice chips, ice-cold water, ice cubes or crushed ice (n=1316 randomised; 1280 analysed) |
| Comparison | Usual care; No treatment; Any other treatment to prevent oral mucositis; another oral cryotherapy regimen | Control: no treatment or standard/usual oral care e.g. saline rinse (n=1280); Chlorhexidine rinse (n=1 study); Low-dose leucovorin rinse (n=1 study); High-dose leucovorin rinse (n=1 study); Oral cryotherapy 60 minutes as comparator (n=1 study) |
| Outcomes | Mucositis incidence of any severity (dichotomised on a 0 to 4 scale as any / moderate to severe / severe); Interruptions to cancer treatment; Oral pain; Quality of life; Normalcy of diet (PEG feeding tubes or total parenteral nutrition, TPN); Adverse events; Number of days in hospital; Number of days of treatment with opioid analgesics; Number of days unable to take medicine orally | Oral mucositis incidence/severity - any, moderate to severe, severe (n=14 studies); Interruptions to cancer treatment (n=80); Oral pain (n=165); Quality of life (n=1 study, data unavailable); Normalcy of diet - days of TPN (n=118); Number of days in hospital (n=163); Number of days of treatment with opioid analgesics (n=118); Adverse events (narrative); Number of days unable to take medicine orally (n=0) |
| Study designs | Randomised controlled trials (RCTs) of parallel design; cross-over studies included using first-period data only | RCT (n=14; 12 parallel design, 2 cross-over analysed as parallel using first-period data) |
| Timing | Not specified | Not specified |
Search date: 2015-06. Databases: Cochrane Oral Health Group Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE via Ovid; EMBASE via Ovid; CANCERLIT via PubMed; CINAHL via EBSCO; US National Institutes of Health Trials Registry (ClinicalTrials.gov); WHO International Clinical Trials Registry Platform
Questions and results
Current version onlyOral cryotherapy (ice chips, ice-cold water, ice cubes or crushed ice held in the mouth during cancer treatment) vs Control (no treatment or standard/usual oral care, e.g. saline rinse)
Population: All patients with cancer who are receiving treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Quality of life High-dose melphalan-based treatment prior to HSCT (haematological cancers) | Summary of findings 2 (melphalan/HSCT): Quality of life - '1 study assessed this outcome but the data are currently unavailable as the study report and analysis have not yet been completed' (Toro 2013; measured with… | 1 study | Ungraded |
Oral pain Fluorouracil (5FU) treatment for solid cancers | MD -1.93 [-2.37, -1.49] Mean oral pain (1 to 5 scale) 3.64 vs 1.93 lower (2.37 to 1.49 lower) | 1 study · 80 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Oral mucositis (any severity) Fluorouracil (5FU) treatment for solid cancers | RR 0.61 [0.52, 0.72] 728 per 1000 vs 444 per 1000 | 5 studies · 444 participants | Moderate Downgraded: risk of bias |
Quality of life Fluorouracil (5FU) treatment for solid cancers | Summary of findings for the main comparison (5FU solid cancers): Quality of life - 'No studies assessed this outcome'. | 0 studies | No studies |
Adverse events High-dose melphalan-based treatment prior to HSCT (haematological cancers) | Adverse events reported narratively: one study did not report adverse events (Askarifar 2015); another reported no serious adverse events (Toro 2013); the remaining two reported low rates of shooting pain from the… | 3 studies | Ungraded |
Oral mucositis (mean severity on WHO 0 to 4 scale) Radiotherapy to the head and neck | MD -0.25 [-0.72, 0.22] | 1 study · 40 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Oral mucositis (any severity) High-dose melphalan-based treatment prior to HSCT (haematological cancers) | RR 0.59 [0.35, 1.01] 824 per 1000 vs 486 per 1000 | 5 studies · 270 participants | Low Downgraded: risk of bias, inconsistency |
Number of days in hospital (duration of hospitalisation) Fluorouracil (5FU) treatment for solid cancers | Summary of findings for the main comparison (5FU solid cancers): Duration of hospitalisation (days) - 'No studies assessed this outcome'. | 0 studies | No studies |
Oral mucositis (moderate to severe) High-dose melphalan-based treatment prior to HSCT (haematological cancers) | RR 0.43 [0.17, 1.09] 679 per 1000 vs 292 per 1000 | 5 studies · 270 participants | Low Downgraded: risk of bias, inconsistency |
Interruptions to cancer treatment (incidence) High-dose melphalan-based treatment prior to HSCT (haematological cancers) | Summary of findings 2 (melphalan/HSCT): Interruptions to cancer treatment - 'No studies assessed this outcome'. | 0 studies | No studies |
Number of days of treatment with opioid analgesics Fluorouracil (5FU) treatment for solid cancers | No studies in the 5FU subgroup assessed the number of days of treatment with opioid analgesics. | 0 studies | No studies |
Oral mucositis (severe) High-dose melphalan-based treatment prior to HSCT (haematological cancers) | RR 0.38 [0.20, 0.72] 427 per 1000 vs 162 per 1000 | 5 studies · 270 participants | Moderate Downgraded: risk of bias |
Oral pain Radiotherapy to the head and neck | Oral pain was assessed in this subgroup but the study (Kakoei 2013) did not report details of the scale used, so the data could not be used (no usable estimate). | 1 study | Ungraded |
Oral mucositis (any severity) Low-dose methotrexate for GVHD prophylaxis after allogeneic HSCT | RR 0.98 [0.90, 1.07] | 1 study · 122 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Oral mucositis (severe) Low-dose methotrexate for GVHD prophylaxis after allogeneic HSCT | RR 0.88 [0.61, 1.25] | 1 study · 122 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Normalcy of diet (days of total parenteral nutrition, TPN) High-dose melphalan-based treatment prior to HSCT (haematological cancers) | MD -2.18 [-4.33, -0.03] Mean number of days of TPN 7 vs 2.18 days fewer (4.33 to 0.03 fewer) | 1 study · 78 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Number of days of treatment with opioid analgesics High-dose melphalan-based treatment prior to HSCT (haematological cancers) | MD -2.28 [-5.33, 0.77] | 1 study · 78 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Oral mucositis (severe) Fluorouracil (5FU) treatment for solid cancers | RR 0.40 [0.27, 0.61] 300 per 1000 vs 120 per 1000 | 5 studies · 444 participants | Moderate Downgraded: risk of bias |
Normalcy of diet (days of total parenteral nutrition, TPN) Fluorouracil (5FU) treatment for solid cancers | Summary of findings for the main comparison (5FU solid cancers): Normalcy of diet (days of total parenteral nutrition) - 'No studies assessed this outcome'. | 0 studies | No studies |
Number of days unable to take medicine orally Fluorouracil (5FU) treatment for solid cancers | No studies reported the number of days unable to take medicine orally (whole review). | 0 studies | No studies |
Number of days in hospital (duration of hospitalisation) High-dose melphalan-based treatment prior to HSCT (haematological cancers) | MD -1.39 [-2.97, 0.19] Mean duration of hospitalisation (days) 0 vs 1.39 fewer (2.97 fewer to 0.19 more) | 2 studies · 123 participants | Low Downgraded: risk of bias, imprecision |
Oral pain High-dose melphalan-based treatment prior to HSCT (haematological cancers) | MD -1.5 [-2.11, -0.89] Weighted mean oral pain (0 to 10 scale) 2.13 vs 1.5 lower (2.11 to 0.89 lower) | 2 studies · 85 participants | Low Downgraded: risk of bias, imprecision |
Duration of interruptions to cancer treatment Fluorouracil (5FU) treatment for solid cancers | MD -8 [-9.26, -6.74] | 1 study · 80 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Interruptions to cancer treatment (incidence) Fluorouracil (5FU) treatment for solid cancers | RR 0.44 [0.20, 0.95] 400 per 1000 vs 176 per 1000 | 1 study · 80 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Oral mucositis (moderate to severe) Fluorouracil (5FU) treatment for solid cancers | RR 0.52 [0.41, 0.65] 530 per 1000 vs 276 per 1000 | 5 studies · 444 participants | Moderate Downgraded: risk of bias |
Oral mucositis (moderate to severe) Low-dose methotrexate for GVHD prophylaxis after allogeneic HSCT | RR 1.01 [0.85, 1.20] | 1 study · 122 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Adverse events Fluorouracil (5FU) treatment for solid cancers | Adverse events reported narratively (not meta-analysed): one study reported no adverse effects (Katranci 2012); the other four 5FU studies reported low rates of very minor adverse events (headache, chills,… | 5 studies · 444 participants | Ungraded |
Oral cryotherapy for 30 minutes vs Oral cryotherapy for 60 minutes
Population: Adults with solid cancers receiving fluorouracil (5FU) and leucovorin
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (moderate to severe) | RR 0.68 [0.36, 1.30] | 1 study · 178 participants | Very low Downgraded: risk of bias, imprecision |
Oral mucositis (severe) | RR 0.60 [0.23, 1.58] | 1 study · 178 participants | Very low Downgraded: risk of bias, imprecision |
Oral mucositis (any severity) | RR 0.89 [0.62, 1.29] | 1 study · 178 participants | Very low Downgraded: risk of bias, imprecision |
Oral cryotherapy (ice chips, ice-cold water, ice cubes or crushed ice held in the mouth during cancer treatment) vs Chlorhexidine rinse
Population: Adults with solid cancers receiving fluorouracil (5FU) and leucovorin
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (any severity) | RR 0.97 [0.71, 1.32] | 1 study · 133 participants | Very low Downgraded: risk of bias, imprecision |
Oral mucositis (severe) | RR 0.86 [0.34, 2.18] | 1 study · 133 participants | Very low Downgraded: risk of bias, imprecision |
Oral mucositis (moderate to severe) | RR 0.89 [0.51, 1.56] | 1 study · 133 participants | Very low Downgraded: risk of bias, imprecision |
Oral cryotherapy (ice chips, ice-cold water, ice cubes or crushed ice held in the mouth during cancer treatment) vs Low-dose leucovorin rinse
Population: Patients with osteosarcoma (bone cancer) receiving high-dose methotrexate, vincristine and leucovorin
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (severe) | Oral mucositis (severe). Not estimable - no participants had developed severe oral mucositis by the fourth day after chemotherapy when the data were reported (Zhang 2011, Analysis 4.3, subgroup 3.1); 118 participants… | 1 study · 118 participants | Ungraded |
Oral mucositis (any severity) | RR 0.67 [0.50, 0.90] | 1 study · 118 participants | Very low Downgraded: risk of bias, imprecision |
Oral mucositis (moderate to severe) | RR 0.18 [0.01, 3.42] | 1 study · 118 participants | Very low Downgraded: risk of bias, imprecision |
Oral cryotherapy (ice chips, ice-cold water, ice cubes or crushed ice held in the mouth during cancer treatment) vs High-dose leucovorin rinse
Population: Patients with osteosarcoma (bone cancer) receiving high-dose methotrexate, vincristine and leucovorin
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (severe) | Oral mucositis (severe). Not estimable - no participants had developed severe oral mucositis by the fourth day after chemotherapy when the data were reported (Zhang 2011, Analysis 4.3, subgroup 3.2); 81 participants in… | 1 study · 81 participants | Ungraded |
Oral mucositis (any severity) | RR 0.65 [0.47, 0.90] | 1 study · 81 participants | Very low Downgraded: risk of bias, imprecision |
Oral mucositis (moderate to severe) | Oral mucositis (moderate to severe). Not estimable - no participants had developed moderate or severe oral mucositis by the fourth day after chemotherapy when the data were reported (Zhang 2011, Analysis 4.2, subgroup… | 1 study · 81 participants | Ungraded |
Oral cryotherapy (e.g. ice chips held in the mouth during cancer treatment) vs Placebo, no treatment, or any other treatment to prevent oral mucositis
Population: All patients with cancer who are receiving treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Adverse events | Protocol stage (published 24 February 2015): planned outcome; no studies included and no results reported at the protocol stage (results first reported in PUB2). | 0 studies | No studies |
Number of days of treatment with opioid analgesics | Protocol stage (published 24 February 2015): planned outcome; no studies included and no results reported at the protocol stage (results first reported in PUB2). | 0 studies | No studies |
Oral pain | Protocol stage (published 24 February 2015): planned outcome; no studies included and no results reported at the protocol stage (results first reported in PUB2). | 0 studies | No studies |
Normalcy of diet (days of total parenteral nutrition, TPN) | Protocol stage (published 24 February 2015): planned outcome; no studies included and no results reported at the protocol stage (results first reported in PUB2). | 0 studies | No studies |
Oral mucositis (moderate to severe) | Protocol stage (published 24 February 2015): planned outcome; no studies included and no results reported at the protocol stage (results first reported in PUB2). | 0 studies | No studies |
Quality of life | Protocol stage (published 24 February 2015): planned outcome; no studies included and no results reported at the protocol stage (results first reported in PUB2). | 0 studies | No studies |
Oral mucositis (any severity) | Protocol stage (published 24 February 2015): planned outcome; no studies included and no results reported at the protocol stage (results first reported in PUB2). | 0 studies | No studies |
Number of days unable to take medicine orally | Protocol stage (published 24 February 2015): planned outcome; no studies included and no results reported at the protocol stage (results first reported in PUB2). | 0 studies | No studies |
Number of days in hospital (duration of hospitalisation) | Protocol stage (published 24 February 2015): planned outcome; no studies included and no results reported at the protocol stage (results first reported in PUB2). | 0 studies | No studies |
Interruptions to cancer treatment (incidence) | Protocol stage (published 24 February 2015): planned outcome; no studies included and no results reported at the protocol stage (results first reported in PUB2). | 0 studies | No studies |
Oral mucositis (severe) | Protocol stage (published 24 February 2015): planned outcome; no studies included and no results reported at the protocol stage (results first reported in PUB2). | 0 studies | No studies |