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We would like to provide a point-wise clarification to the concerns raised in the letter to editor manuscript number: EAOR-D-20-00971. A query was raised in the letter to editor to clarify if the meta-analysis included only early glottic cancers or had included all laryngeal cancers. The present meta-analysis tested hypofractionation versus conventional fractionation in early laryngeal cancer including glottic and supraglottic cancer. The idea of hypofractionation was initially tested in only early glottic cancer with subsequent studies including supraglottic larynx as well. Due to lack of data, subset analysis on each sub-site as well as volume of radiotherapy was not done. We acknowledge the inadvertent error in the abstract. Another clarification sought by the author was whether Embase search was conducted. We would like to state that a comprehensive systematic search of Embase was done and no additional studies were found. We acknowledge that writing ‘Embase = 0 articles’ was missed in the PRISMA chart [1]. The third query raised was regarding the analysis of dichotomous variables. Dichotomous variables can be described in terms of odds ratio or risk ratio. Often interpreting risk ratio is easier for clinicians; therefore, is more commonly used [2]. We would like to state that both odds ratio and risk ratio were calculated in the present meta-analysis. The risk ratio using random effects model for acute mucositis was 1.17 (95% CI 1.043–1.312); p value 0.007; I2 = 0%. The interpretation of this result remains that hypofractionation is associated with increased mucositis compared with conventional fractionation in early laryngeal cancers as described in our article. Another query raised by our fellow researcher is whether the number of patients in the intervention (hypofractionation) arm from the Yamazaki article was 91 or 92. The original article by Yamazaki et al. actually creates this confusion, where in it is stated in the abstract that there were 91 patients while in the tables in the article proper, it is stated as 92 [3]. So, we had to run the statistical analysis considering both 91 or 92 patients in the intervention arm and 88 or 89 patients in the control arm. The results in any combination showed that the hypofractionation arm is associated with a higher mucositis.
References
Benson R, Prashanth G, Mallick S (2020) Moderate hypofractionation for early laryngeal cancer improves local control: a systematic review and meta-analysis. Eur Arch Otorhinolaryngol. https://doi.org/10.1007/s00405-020-06012-9(published online ahead of print, 2020 May 6)
Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ et al (2019) Cochrane handbook for systematic reviews of interventions, 2nd edn, pp 246–8
Yamazaki H, Nishiyama K, Tanaka E, Koizumi M, Chatani M (2006) Radiotherapy for early glottic carcinoma (T1N0M0): results of prospective randomized study of radiation fraction size and overall treatment time. Int J Radiat Oncol Biol Phys 64(1):77–82
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Benson, R., Giridhar, P. & Mallick, S. Moderate hypofractionation for early laryngeal cancer improves local control with increased risk of mucositis: clarification. Eur Arch Otorhinolaryngol 277, 2945 (2020). https://doi.org/10.1007/s00405-020-06257-4
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DOI: https://doi.org/10.1007/s00405-020-06257-4