Riley, P., Glenny, A.M., Worthington, H.V., Littlewood, A., Fernandez Mauleffinch, L.M., Clarkson, J.E., & McCabe, M.G. (2017). Interventions for preventing oral mucositis in patients with cancer receiving treatment: cytokines and growth factors. Cochrane Database of Systematic Reviews, 11, CD011990.

• STUDY PURPOSE: To assess the effects of cytokines and growth factors for preventing oral mucositis in patients with cancer who are receiving treatment.
• TYPE OF STUDY: Systematic review

• DATABASES USED: Cochrane Oral Health’s information specialist searched the following databases: Cochrane Oral Health’s Trials Register (searched May 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 4) in the Cochrane Library (searched May 2017); MEDLINE Ovid (1946 to May 2017); Embase Ovid (December 2015 to May 2017); CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to May 2017); and CANCERLIT PubMed (1950 to May 2017). The U.S. National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. 
• YEARS INCLUDED: Through May 2017 
• INCLUSION CRITERIA: RCTs
• EXCLUSION CRITERIA:Not a RCT or unclear; stomatitis incidence reported in adverse events table; unclear if mucositis was oral or gastrointestinal; study stopped early with very few participants enrolled; oral mucositis not mentioned and unknown if measured; some participants had oral mucositis at baseline; crossover study with no reporting of first-period data; results reported by cycle assuming independence; survival/cure was primary outcome with mucositis (unclear if oral or gastrointestinal) as a toxicity

• TOTAL REFERENCES RETRIEVED: 3,145
• EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two review authors independently screened the results of electronic searches, extracted data, and assessed risk of bias. For dichotomous outcomes, they reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, they reported mean differences (MD) and 95% CIs. They pooled similar studies in random-effects meta-analyses. 

• FINAL NUMBER STUDIES INCLUDED: 35 (published from 1993 to 2017) 
• TOTAL PATIENTS INCLUDED IN REVIEW: 3,102 
• SAMPLE RANGE ACROSS STUDIES: Fourteen studies enrolled participants with hematological cancers. Eighteen studies enrolled participants with solid cancers: head and neck, colorectal, breast, and sarcoma. The remaining three studies enrolled a mixture of participants with solid cancers and participants with hematological cancers, two of which were 80%-90% solid, and the other study only 3% solid.
• KEY SAMPLE CHARACTERISTICS: All patients being treated for cancer, aged 1 to 87 years old

PHASE OF CARE: Active anti-tumor treatment

• There might be a reduction in the risk of moderate to severe oral mucositis in adults receiving bone marrow/stem cell transplantation after conditioning therapy for hematological cancers (RR = 0.89, 95% CI [0.8, 0.99]; 6 studies; 852 participants; low-quality evidence).
• A possible reduction in the risk of severe oral mucositis in bone marrow/stem cell transplantation after conditioning therapy for hematological cancers, but there is also some possibility of an increase in risk (RR = 0.85, 95% CI [0.65, 1.11]; 6 studies; 852 participants; low-quality evidence).  
• Probably a reduction in the risk of moderate to severe oral mucositis in adults receiving radiotherapy to the head and neck with cisplatin or fluorouracil (RR = 0.91, 95% CI [0.83, 1]; 3 studies; 471 participants; moderate-quality evidence). 
• Likely that there is a reduction in the risk of severe oral mucositis in adults receiving radiotherapy to the head and neck (RR = 0.79, 95% CI [0.69, 0.9]; 3 studies; 471 participants; high-quality evidence)
• Likely that there is a reduction in the risk of moderate to severe oral mucositis in adults receiving chemotherapy alone for mixed solid and hematologic cancers (RR = 0.56, 95% CI [0.45, 0.7]; 4 studies; 344 participants; moderate-quality evidence)
• Might be a reduction in the risk of severe oral mucositis in this population (RR = 0.3, 95% CI [0.14, 0.65]; 3 studies; 263 participants; low-quality evidence)

Although authors concluded that KGF is beneficial in the prevention of oral mucositis in adults who are receiving (a) radiotherapy to the head and neck with cisplatin or fluorouracil, or (b) chemotherapy alone for mixed solid and hematologic cancers, the results are not conclusive. Could conclude likely effective but not established

• Low sample sizes
• 13 studies (37%) were at low overall risk of bias
• 12 studies (34%) were at unclear overall risk of bias.
• 10 studies (29%) were at high overall risk of bias

The analysis showed inconsistent effect of KGF (keratinocyte growth factor). Because of the concern of cost and benefit, this is not strong evidence enough to recommend.