Abstract

Patients with head and neck cancer (HNC) experience serious pain related to tumour, surgery, chemotherapy, and radiotherapy treatment (RT). Oral mucositis, a painful complication of RT, may require opioid analgesics to control pain.This longitudinal study, during RT but also four weeks post-RT, examines the relationships between oral mucositis, pain, and opioid doses in in HNC patients. The aim was to evaluate the clinical effectiveness of an opioid treatment strategy. Sixty-three patients with HNC undergoing radiotherapy answered self-reported questionnaires on pain intensity on a 0-10 numerical rating scale (NRS) three times a week. Oral mucositis signs were evaluated using the WHO mucositis index score, ranging from 0 (normal) to 4 (severe), and pharmacological treatment with opioids was registered prospectively once a week. All data were related to given radiation dose, and all outcome measures at each time point therefore relate to the same radiation dose (i.e.,not to when the patient was included in the study). Opioids were used by 78% of the patients. Most of the patients experienced only mild pain (NRS 0-4), although the majority developed mucositis grade 2-4 according to WHO mucositis index. Function-related pain intensity and opioid doses were highest during the sixth week of RT, with 3.67 (0-9) in NRS and 84 (0-430)mg oral morphine equivalents per day (median, range). At that same time point, significant positive correlations were found between the grade of mucositis and pain intensities. Patients with mucositis grade 2-4 were investigated further; in this subgroup, we found that opioid doses did not differ between patients with mild pain and patients with moderate to severe pain. Our multivariate data analysis defined a cluster of patients characterized by the presence of mucositis, cancer site in pharynx, concomitant chemotherapy, and the absence of surgery. In HNC patients who were followed closely by pain care personnel during and after RT, pain was often satisfactorily alleviated with a structured use of opioids, including stepwise increases of fentanyl patches and oral morphine as needed. However, some patients with oral mucositis grade 2-4 experienced severe pain. Strong opioids, i.e. the third step of the WHO pain ladder, remain the mainstay of analgesic therapy in treating moderate to severe cancer-related pain, including patients with HNC. This real-life study indicates that RT-related pain is not a fatality. A proactive stance, monitoring these patients closely and regularly, is probably crucial in order to achieve good treatment results. Further studies are needed to develop better pain treatment strategies for those patients who develop severe oral mucositis-related pain despite intensive opioid treatment.

Highlights

  • Worldwide, head and neck cancer (HNC) affects more than 500,000 people, representing about 6% of all cancer diagnoses, and causes 350,000 deaths yearly [1, 2]

  • The Multivariate data analysis (MVDA) analysis showed that not undergoing surgery was associated with higher degree of mucositis, but this was only apparent in the MVDA model and not by additional inferential statistics (19/26 vs. 20/35, p=0.2). This real-life study evaluated the effectiveness of our local guidelines in clinical practice, investigating the relationships between opioid doses, oral mucositis and pain during HNC-related radiotherapy treatment (RT)

  • We studied the temporal dynamics involved, but we focused on measurement point (MP) 51–60, which was the time point of highest opioid doses, highest grade of mucositis and highest pain intensities

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Summary

Introduction

Head and neck cancer (HNC) affects more than 500,000 people, representing about 6% of all cancer diagnoses, and causes 350,000 deaths yearly [1, 2]. Head and neck cancer is a heterogenous group of diseases concerning incidence, treatment, and prognosis [3]. Treatment of HNC may include surgery, chemotherapy, and radiotherapy (RT) in various combinations [1, 4]. Patients treated for HNC suffer from several psychological and physical symptoms that negatively impact daily life, including depression and a sense of lack of meaning, pain, xerostomia and swallowing disorders [5]. According to the National Comprehensive Cancer Network Task Force, nausea, vomiting and mucositis are the most physical common adverse events in connection with cancer treatment [6]. Oral mucositis is an inflammation of the oral and oropharyngeal mucous membrane resulting from the toxic effects of RT and chemotherapy [7]

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