The M. D. Anderson Symptom Inventory–Head and Neck Module, a Patient-Reported Outcome Instrument, Accurately Predicts the Severity of Radiation-Induced Mucositis

Purpose

To compare the M. D. Anderson Symptom Inventory–Head and Neck (MDASI-HN) module, a symptom burden instrument, with the Functional Assessment of Cancer Therapy–Head and Neck (FACT-HN) module, a quality-of-life instrument, for the assessment of mucositis in patients with head-and-neck cancer treated with radiotherapy and to identify the most distressing symptoms from the patient's perspective.

Methods and Materials

Consecutive patients with head-and-neck cancer (n = 134) completed the MDASI-HN and FACT-HN before radiotherapy (time 1) and after 6 weeks of radiotherapy or chemoradiotherapy (time 2). The mean global and subscale scores for each instrument were compared with the objective mucositis scores determined from the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0.

Results

The global and subscale scores for each instrument showed highly significant changes from time 1 to time 2 and a significant correlation with the objective mucositis scores at time 2. Only the MDASI scores, however, were significant predictors of objective Common Terminology Criteria for Adverse Events mucositis scores on multivariate regression analysis (standardized regression coefficient, 0.355 for the global score and 0.310 for the head-and-neck cancer-specific score). Most of the moderate and severe symptoms associated with mucositis as identified on the MDASI-HN are not present on the FACT-HN.

Conclusion

Both the MDASI-HN and FACT-HN modules can predict the mucositis scores. However, the MDASI-HN, a symptom burden instrument, was more closely associated with the severity of radiation-induced mucositis than the FACT-HN on multivariate regression analysis. This greater association was most likely related to the inclusion of a greater number of face-valid mucositis-related items in the MDASI-HN compared with the FACT-HN.

Introduction

Radiotherapy (RT) for head and neck cancer (HNC) leads to mucositis in virtually all patients. Although intensive treatment regimens, altered fractionation schedules, and chemoradiotherapy (CRT) can improve tumor control, they also lead to mucositis that is more severe and longer lasting. Patients with high-grade mucositis affecting large oropharyngeal volumes have a variety of symptoms, including pain, dysphagia/odynophagia, weight loss, oropharyngeal mucus and associated gagging/regurgitation, and aspiration, that have not been captured effectively during toxicity reporting in cancer therapeutic clinical trials. The severity of the acute symptoms or the fear that higher grade mucositis might progress to necrosis can lead to unplanned RT interruptions or reduced chemotherapy compliance, resulting in poorer outcomes (1). Acute mucositis has thus come to be identified as the dose-limiting toxicity for intensive RT fractionation and CRT regimens in the acute setting, and it is a surrogate risk marker for long-term dysphagia, aspiration, and feeding tube dependency (2).

The true incidence of mucositis might not be fully appreciated. A review of 33 therapeutic HNC studies by Trotti et al.(3) suggested an overall incidence of 80%, with severe mucositis (Grade 3-4) occurring in at least one-third of patients with HNC given conventional RT and one-half or more of patients given altered fractionation RT or concurrent CRT. Moreover, the reported results of many aggressive cancer therapeutic trials have underestimated the incidence of mucositis; thus, it has been estimated that the real incidence of mucositis in these patients was >90%, with ≥60% experiencing severe mucositis 4, 5.

In the United States, mucositis is typically assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCI CTCAE) (6). This clinician-completed instrument grades mucositis on the basis of either clinical or functional criteria. The clinical criteria include observation of erythema, ulcerative or pseudomembranous lesions, and tissue necrosis. The functional criteria rate the patient reports of difficulties in eating/swallowing and/or respiratory symptoms. Significant inter-rater variability exists in the scoring of mucositis, however, especially among those not specifically trained (7).

Although clinician-completed instruments such as the NCI CTCAE can provide a reasonable estimate of the frequency and severity of mucositis and its associated symptoms, patient-reported outcome (PRO) instruments are increasingly being used to measure symptom burden, functionality, and quality of life (QOL) 8, 9. The U.S. Food and Drug Administration now recognizes patient self-reported symptoms as legitimate outcome variables for clinical trials leading to the registration of new drugs or devices (10). The PRO instruments have the advantage of avoiding inter-rater variability and of directly capturing the patient's perception of symptom severity without the interpretation of a third party. Because patient-reported symptoms tend to be more severe than those recorded by physicians, PRO instruments might give a more accurate representation of symptom burden 11, 12.

Many HNC PRO instruments lack important features. Instruments that focus on measurements of functionality might not address the patient's perceptions about these outcomes or the symptom distress experienced (13). However, instruments that focus on QOL might overlook specific symptoms and the distress that they cause. In addition, the relationship between functionality and QOL is not yet fully understood. For example, Vokes et al.(14) demonstrated that a common residual side effect of aggressive CRT in HNC survivors, the inability to eat solid food, was not related to measures of QOL. Because of these shortcomings, new instruments have been designed to measure specifically both the severity of symptoms and the extent to which they interfere with aspects of daily function.

The M. D. Anderson Symptom Inventory–Head and Neck (MDASI-HN) module is a validated PRO instrument that provides a brief measure of the symptom distress experienced by HNC patients as a result of their disease and/or treatment (15). The MDASI-HN includes questions that measure general cancer symptom burden, symptom burden specific to HNC, and the degree to which symptoms interfere with everyday life. The MDASI-HN is patient-administered, using the 0–10 response scale recommended by the Food and Drug Administration and Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials 8, 9, and has been adapted for use with interactive voice response systems.

The purpose of this study was to evaluate the sensitivity of the MDASI-HN, a symptom distress tool, compared with another widely used PRO instrument, the Functional Assessment of Cancer Therapy–Head and Neck (FACT-HN), a QOL instrument, for the assessment of mucositis and its symptoms in HNC patients treated with RT or CRT. In addition, we sought to identify the most common and distressing symptoms.