Abstract 4860: Association between timing of radiotherapy and severity of oral mucositis in head-neck cancer patients
Authors: Gu Fangyi , Duncan William D. , Feng YingDong , Miller Austin , Schlecht Nicolas , Hutson Alan , Singh Anurag K. 
Published: August 2019

Abstract
Background: Oral mucositis is a very painful and debilitating complication of radiotherapy, occurring in nearly all head and neck cancer patients. It can severely affect quality of life and lead to treatment interruptions that subsequently impact clinical outcomes. With limited treatment options, there is an urgent need to develop new strategies for mucositis prevention.
Animal studies have shown that sensitivity to genotoxic stress strongly depends on the time of a day therapy is administered. Therefore, radiotherapy could be conducted at optimal times of a day associated with best tolerability, to reduce mucosal damage. This hypothesis is partially supported by two clinical trials that reported less severe oral mucositis in head and neck cancer patients treated in the morning vs. late afternoon; but results were not significant and times of a day not fully covered.
Methods: This study examined the associations between timing of radiotherapy and development of oral mucositis in 219 head neck cancer patients treated at Roswell Park Comprehensive Cancer Center, using data from Electronic Medical Records. Patients’ treatment time was consistent throughout a 6/7-week course, and mucositis survey was self-reported weekly during treatment, providing a unique resource for this study. The primary endpoint is “soreness quality score” (SQS), a five-level score “0-no, 1-a little, 2-moderate, 3-quite a lot, and 4-extreme” in assessing patients’ soreness severity for mouth and throat in the past 24 hours. We used a generalized linear model approach to assess the association between radiotherapy time and the maximum SQS (MSQS) reported during treatment, adjusting for age, smoking, treatment type, survey week and cancer site.
Results: Multivariate analyses revealed treatment time to be significantly associated with MSQS (p-value=0.025), with lowest MSQS (lsmean=2.26, ste=0.18) seen for patients treated in the early morning (8:30-&lt;9:30am). MSQS increased in patients treated at later times, peaking in the early afternoon (lsmean=2.92 (ste 0.21) and 2.84 (ste 0.18) for patients treated at 12:00-&lt;13:30pm and 13:30-&lt;15:00pm, respectively), then decreased for patients treated in late afternoon (lsmean=2.37, ste=0.25). Among patients treated between 8:30-&lt;9:30am, 43.2% developed severe oral mucositis (SQS grade 3 or 4), compared to 69.2% among those treated between 13:30-&lt;15:00pm.
Conclusion: To our knowledge, this is the first study to find a significant variation of oral mucositis severity by treatment hour of radiotherapy; the variation shows an arc shape with the peak in the early afternoon. Our results suggest that identifying an optimal time of a day for radiotherapy may substantially prevent severe oral mucositis in head and neck cancer patients. Further studies are worthwhile to confirm our findings, and to find optimal treatment times for individual patients.
Citation Format: Fangyi Gu, William D. Duncan, YingDong Feng, Austin Miller, Nicolas Schlecht, Alan Hutson, Anurag K. Singh. Association between timing of radiotherapy and severity of oral mucositis in head-neck cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4860.