Impact of Radiation-Induced Xerostomia on Quality of Life After Primary Radiotherapy Among Patients With Head and Neck Cancer

Purpose

To investigate the impact of xerostomia on overall quality of life (QoL) outcome and related dimensions among head and neck cancer patients treated with primary radiotherapy.

Methods and Materials

A total of 288 patients with Stage I–IV disease without distant metastases were included. Late xerostomia according to the Radiation Therapy Oncology Group (RTOG-xerostomia) and QoL (European Organization for Research and Treatment of Cancer QLC-C30) were assessed at baseline and every 6th month from 6 months to 24 months after radiotherapy.

Results

A significant association was found between RTOG-xerostomia and overall QoL outcome (effect size [ES] 0.07, p < 0.001). A significant relationship with global QoL, all functioning scales, and fatigue and insomnia was observed. A significant interaction term was present between RTOG-xerostomia and gender and between RTOG-xerostomia and age. In terms of gender, RTOG-xerostomia had a larger impact on overall QoL outcome in women (ES 0.13 for women vs. 0.07 for men). Furthermore, in women ES on individual scales were larger, and a marked worsening was observed with increasing RTOG-xerostomia. No different ES according to age was seen (ES 0.10 for 18–65 years vs. 0.08 for >65 years). An analysis of the impact of RTOG-xerostomia on overall QoL outcome over time showed an increase from 0.09 at 6 months to 0.22 at 24 months. With elapsing time, a worsening was found for these individual scales with increasing RTOG-xerostomia.

Conclusions

The results of this prospective study are the first to show a significant impact of radiation-induced xerostomia on QoL. Although the incidence of Grade ≥2 RTOG-xerostomia decreases with time, its impact on QoL increases. This finding emphasizes the importance of prevention of xerostomia.

Introduction

Radiotherapy is an important treatment modality for head and neck cancer. Radiotherapy as a single modality is generally considered standard in early stages (e.g., T1N0M0 glottic cancer), whereas in the more advanced cases radiotherapy is combined with surgery and/or chemotherapy 1, 2, 3. The most frequently reported late side effect of radiation by patients is xerostomia, which, depending on tumor location, they also reported as the most serious problem after radiation by patients 4, 5, 6. There is an increasing interest in the prevention of radiation-induced xerostomia because reduced salivary output may result in problems with mastication, digestion, swallowing, and speech, and an increased risk of caries and oral infections 7, 8, 9, 10, 11.

In general, a distinction is made between early and late radiation-induced morbidity. Early side effects occur during or immediately after completion of radiotherapy and subsequently decrease with time. In contrast, late side effects are generally considered irreversible and progressive and are, therefore, probably more relevant for patients with respect to their quality of life (QoL).

A number of toxicity grading systems have been developed for classifying late radiation-induced toxicity, in which grading is ranked according to the severity of a given side effect. These classification systems include the Subjective, Objective, Management, Analytic/Late Effects Normal Tissue system (12), the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer system (RTOG/EORTC) (13), and more recently, the Common Terminology for Adverse Events version 3.0 (14). The latter toxicity grading system not only takes into account toxicity induced by radiotherapy but also adverse effects induced by other treatment modalities, such as surgery and chemotherapy. It is often assumed that because of the ranking depending on the severity of late toxicity, QoL of patients will decrease with increasing rates of morbidity. However, information with regard to the clinical relevance of radiation-induced toxicity in terms of QoL is scarce.

Therefore, the aim of the present study was to investigate the impact of xerostomia on QoL among head and neck cancer patients treated with primary radiotherapy. The hypothesis to be tested was that higher grades of radiation-induced toxicity, as assessed by the RTOG Late Radiation Morbidity Scoring System, should be associated with worse QoL.

In addition, because the profile of side effects may change over time, we investigated whether the impact of xerostomia on QoL changed over time. Because a number of studies indicated a gradual reduction of radiation-induced xerostomia over time 15, 16, 17, the hypothesis was tested that the impact of radiation-induced xerostomia on overall QoL would decrease over time as well.