Changes and predictors of radiation-induced oral mucositis in patients with oral cavity cancer during active treatment
Introduction
In 2012, the incidence rate of oral cavity cancer was 300 per 1000 worldwide (Ferlay et al., 2013). Oral cavity cancer is associated with a high prevalence of cancer risk factors (betel nut chewing, smoking, and drinking) (International Agency for Research on Cancer, 2004, Ko et al., 1995). Approximately 6300 cases of oral cavity cancer were diagnosed in Taiwan during 2010, with many patients diagnosed with Stage III or IV disease (Taiwan cancer registry, 2010). The evidence suggests that radical excision and radiation therapy (RT) and surgery with concurrent chemoradiation therapy (CCRT) are the most important modalities for successful advanced oral cavity cancer treatment (Shah and Gil, 2009). Radiation-induced oral mucositis (OM) is the most debilitating side effect of radiation treatment in oral cavity cancer.
Radiation-induced oral mucositis (OM) is one of the most severe morbidities in patients with oral cavity cancer receiving RT or CCRT and may adversely affect vital oral functions (Chen et al., 2010). OM refers to inflammation of the oral mucosa due to radiation in head and neck cancer patients, and is characterized by atrophy of squamous epithelial tissue, vascular damage, and evidence of concentrated inflammatory infiltrate (Peterson et al., 2011). Radiation-induced oral mucositis begins at cumulative doses of 15 Gy (after around 10 days) and severity at 30 Gy, lasts for weeks or even months (Raber-Durlacher et al., 2010). More than 60% of cancer patients continue to experience severe OM during aggressive RT or CCRT to the head and neck region (Airoldi et al., 2004, Bernier et al., 2004, Cooper et al., 2004). The presence of OM has a significant impact on vital oral function, including the processes of eating, drinking, and speaking resulting in malnutrition, dehydration, treatment interruptions, which may create an inability to cope with the disease (Scully et al., 2003, Putwatana et al., 2009).
Mucositis is a five-phase process: (1) initiation, (2) upregulation and message generation, (3) signaling and amplification, (4) ulceration, and (5) healing (Sonis, 2004). OM may develop at any time from 2 days to 3 weeks after initiation of RT and improves within 2–4 weeks after completion of RT (Cooper, 1994). Epstein et al. (2007) found that head and neck cancer patients reported mouth and throat soreness across radiation therapy, peaking at week 6 after treatment initiation, with a corresponding decline in oral function (eating, swallowing, drinking, and talking). In a study of 52 patients in Ireland receiving a chemoradiation regimen for head and neck squamous cell carcinoma, Grades 3 and 4 oral mucositis were reported by 22 (43.3%) and 6 patients (12%), respectively (Osman et al., 2013). Mitsudo et al. (2014) surveyed 112 advanced oral cancer patients treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy and found Grade 3 or 4 toxicities in patients that included mucositis in 92.0%, neutropenia in 30.4%, dermatitis in 28.6%, anemia in 26.8%, and thrombocytopenia in 7.1% correlating with dysphagia, nausea, vomiting, and fever related symptoms.
Numerous studies have reported increased levels of OM-related symptoms in head and neck cancer patients during active treatment associated with oral vital dysfunction (e.g., pain, difficulty swallowing, difficulty drinking, difficulty talking, change in taste, xerostomia, thick secretions, and mucosal sensitivity) (Ganzer et al., 2013, Murphy et al., 2009) and generalized problems (e.g., fatigue, poor oral intake, and weight loss) (Chen et al., 2010, Ganzer et al., 2013) with greater oral mucositis symptoms more often associated with higher depression (Chen et al., 2010, Haddad, 2006).
Studies showed that treatment-related factors during radiation therapy, including higher cumulative dose of RT and concurrent use of chemotherapy, can increase the risk of developing oral mucositis (Machtay et al., 2012, Vera-Llonch et al., 2006, Kazemian et al., 2009). Most studies indicate that smoking status (Wuketich et al., 2012), low BMI (Meyerhardt et al., 2004, Rose-Ped et al., 2002), and high levels of depression or emotional distress (Chen et al., 2010, Rose-Ped et al., 2002) may coexist with OM.
Longitudinal studies are needed to demonstrate the trajectory of the prevalence of OM-related symptoms during active treatment. Understanding the relationships between radiation-induced OM and disease/treatment-related variables can assist healthcare providers in developing strategies to palliate symptoms. Purposes of the study were to investigate the longitudinal changes in the prevalence of severe OM and OM-related symptoms and to identify factors that contribute to predicting the development of OM in oral cavity cancer patients during active treatment.
Section snippets
Design
The study was a longitudinal survey of radiation-induced OM using repeated measures.
Participants and setting
A convenience sampling method was used to recruit 77 oral cavity cancer patients between August 2011 between March 2013 who were being treated in the head and neck outpatient radiation department of a medical center in northern Taiwan. Inclusion criteria were as follows: (1) 20 years or older; (2) definitive histopathological diagnosis of oral cavity squamous cell carcinoma (OSCC); and (3) receiving active
Demographic and clinical characteristics of patients
The mean age of the sample was 51.64 years (SD = 10.05) (range, 31–82 years) and the majority were male (90.9%). Most of the patients were unemployed (59.3%), married (70.1%), had junior high (26.0%) and senior high (37.7%) education, and had a Buddhism or Taoism religious affiliation (80.5%). Of these patients, 26.0% were smoking, most of the patients (89.6%) were diagnosed with advanced-stage oral cavity cancer (stages III and IV) and the most common sites of cancer were the buccal mucosa
Discussion
This study investigated the longitudinal change in radiation-induced OM in oral cavity cancer patients during active treatment. Overall prevalence of severe OM and OM-related symptoms were moderate. The peak for prevalence of severe OM was at T5 and T6. OM-related symptoms peaked at T8. The prevalence of severe OM and OM-related symptoms were strongly associated with type of treatment, cumulative RT dose, and smoking.
Our study found that patients reported the highest prevalence of severe OM at
Conflict of interest
None declared.
Acknowledgment
This study was supported by grants by the National Science Council (NSC100-2314-B-255-003) and Chang Gung Memorial Hospital (NMRPF3A0051) of Taiwan. The authors thank all the study participants for sharing their experiences. The authors also thank Patricia Stanfill Edens, PhD, RN, LFACHE (Life Fellow in the American College of Healthcare Executives) for English editing.
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