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LETTERS TO THE EDITOR

Co-ordinating editor and editors, Cochrane Oral Health Group, The Cochrane Suite, Manchester Dental Education Centre, School of Dentistry, University of Manchester, Higher Cambridge Street, Manchester M15 6FH, UK

To the Editor:

We were disappointed to see that the systematic review on "Preventive Intervention Possibilities in Radiotherapy- and Chemotherapy-induced Oral Mucositis: Results of Meta-analyses" [JDR 85(8):690–700, 2006] did not acknowledge the Cochrane review on this topic. We undertook the Cochrane review, "The prevention of oral mucositis in patients receiving treatment for cancer", initially in 1999 and have updated this review every 2 years since then. The current version was published in May this year, and the reference is given below. In the process of these updates, we even contacted two of the authors of this JDR review, M.A. Stokman (in 2004) and F.K.L. Spijkervet (in 2001), for information about their trials, explaining that we were updating this Cochrane review. We received an e-mail response from Monique Stokman (dated 5/11/2004).

Even if the authors were unaware of the Cochrane review, it is surprising that they did not include The Cochrane Library in their search strategy. It is widely acknowledged that The Cochrane Library is the best single source when searching for evidence (both from systematic reviews and clinical trials) on the effectiveness of healthcare interventions. One of the primary goals of the Cochrane Collaboration is to avoid duplication. Whilst the existence of a Cochrane review clearly does not preclude another review of the same topic being undertaken, it is not unreasonable to expect previous reviews to be referenced and any differences in results and conclusions explored. We are disappointed that the authors of the recent review were either unaware of the Cochrane review, or chose not to comment on it. We are also surprised that none of the editors or referees for JDR was familiar with the Cochrane review.

Comparing the Stokman review with the Cochrane review, there are 36 trials (pre-December, 2004) included in the Cochrane review that are missing from this review. Three trials included in the Stokman review do not appear in the Cochrane review; however, two of these are included in the Cochrane review on the treatment of mucositis, and we have also put the reference for this below.

Yours sincerely,

REFERENCES

Worthington HV, Clarkson JE, Eden OB (2004). Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev (2):CD001973.

Worthington HV, Clarkson JE, Eden OB (2006). Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev (2):CD000978.

The authors reply

We appreciate the comments of colleagues Worthington, Clarkson, and Glenny on our article, "Preventive Intervention Possibilities in Radiotherapy- and Chemotherapy-induced Oral Mucositis: Results of Meta-analyses" (Stokman et al., 2006), and realize that they were disappointed not to be quoted in our paper. The results of their review were not included in our paper since Worthington and co-workers used, in comparison with our approach, a much wider search strategy for their review. Their search was not limited to mucositis, but also included, amongst others, amount of analgesia, dysphagia, systemic infection, length of hospitalization, cost, and patient quality of life. Because of the dissimilar approach, the outcomes of the 2001, 2003, and 2006 Cochrane Collaboration reviews (Clarkson et al., 2001, 2003; Worthington et al., 2006) and our review are in some respects different.

In the 2001 Cochrane Collaboration review (Clarkson et al., 2001), prevention of oral mucositis was studied in chemotherapy patients only. In their 2003 review (Clarkson et al., 2003), oral care in head and neck cancer patients was included as well. However, this review was not limited to prevention of mucositis, but also reported on pain, amount of analgesia, dysphagia, systemic infection, length of hospitalization, cost, and patient quality of life as outcome criteria. By contrast, in our publication, only randomized clinical trials with prevention of mucositis as primary endpoint were included. Finally, the 2006 review (Worthington et al., 2006) was not available to us, since our paper was already in press in the Journal of Dental Research. Moreover, our study aimed to evaluate the effectiveness of interventions for the prevention of oral mucositis in cancer patients treated with head and neck radiotherapy and/or chemotherapy, with a focus on randomized clinical trials. The difference of 36 articles mentioned in the Cochrane review, but not included in our review, is due to the inclusion differences. While we limited our search to the English literature, the Cochrane Group also included in their reference list some non-English papers (Japanese, German, Spanish, etc.), but, more importantly, they included a number of abstracts, non-randomized clinical trials, and studies not using prevention of oral mucositis as a primary study endpoint. In addition, many of these studies are referenced, but not included in their analyses or conclusions. Finally, in the Cochrane reviews, studies were included in which, according to expert criteria, it was at least questionable whether mucositis was assessed or scored using a reliable (controlled) method. We omitted such studies from our analyses.

Summarizing, it is indeed a pity that we have not commented on the outcomes of the Cochrane Collaboration studies (Clarkson et al., 2001, 2003) in the discussion of our paper. It would have been appropriate to discuss the (dis)similar conclusions from both studies. With regard to the 8 interventions that were included in our meta-analyses, 4 interventions (amifostine, PTA [antibiotic lozenges], GM-CSF, and oral cooling) showed a significant preventive effect on the development or severity of oral mucositis. Concerning amifostine, the outcomes of the Cochrane Group (Worthington et al., 2006) and our analysis (Stokman et al., 2006) were comparable, although the Cochrane Group did not mention the differences between the dosages of amifostine used. Moreover, the Cochrane Group (Worthington et al., 2006) concluded that amifostine may prevent or reduce the severity of oral mucositis in adults with head and neck cancer treated with radiotherapy, but the Cochrane Group (Clarkson et al., 2001, 2003) also included chemoradiation treatments in their analyses. In addition, the Cochrane Group concluded that there is currently insufficient evidence to support or refute the efficacy of GM-CSF (Worthington et al., 2006). In our analyses, however, we found a significant effect of systemic, but not local, administration of GM-CSF on prevention of oral mucositis (Stokman et al., 2006). The Cochrane Group did not state such a difference, which is of interest, however, because of the different pharmacodynamics of local and systemic GM-CSF. Finally, the results for PTA, oral cooling/ice chips, chlorhexidine, sucralfate, iseganan, and glutamine on prevention of mucositis were comparable between both reviews (Stokman et al., 2006; Worthington et al., 2006).

Sincerely yours,

REFERENCES

Clarkson JE, Worthington HV, Eden OB (2001). Interventions for preventing oral mucositis or oral candidiasis for patients with cancer receiving chemotherapy (excluding head and neck cancer) (Cochrane review). In: The Cochrane Library, Issue 2. Oxford: Update software.

Clarkson JE, Worthington HV, Eden OB (2003). Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev (3):CD000978.

Stokman MA, Spijkervet FKL, Boezen HM, Schouten JP, Roodenburg JLN, de Vries EGE (2006). Preventive intervention possibilities in radiotherapy- and chemotherapy-induced oral mucositis: results of meta-analyses. J Dent Res 85:690–700.[Abstract/Free Full Text]

Worthington HV, Clarkson JE, Eden OB (2006). Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev (2):CD000978.

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