Quality-of-life instruments that measure specific functional consequences of mucositis are needed to assess the efficacy of therapeutic interventions targeted against mucositis and to guide patient care. The authors undertook a prospective, multicenter, observational study to assess the validity, reliability, and feasibility of a new instrument, the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer (OMWQ-HN). The OMWQ-HN is a patient-reported outcome questionnaire that measures the symptoms of mucositis, including mouth and throat soreness (MTS), and their impact on patient well-being and function.
The OMWQ-HN, along with the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN), was administered 5 times over an approximately 6-week period to patients with head and neck cancer (HNC) who were receiving radiation therapy with or without chemotherapy. Information on supportive care measures also was collected.
Seventy-five patients were enrolled and completed 93% of scheduled assessments (100% at baseline). The OMWQ-HN demonstrated good test-retest reliability (correlation coefficient, 0.80–0.89). Cross-sectional analyses to assess validity showed that OMWQ-HN scores were different across levels of pain, with those in the worst pain category reporting the highest OMWQ-HN scores. Strong correlations were observed between OMWQ-HN and FACT-HN. Patients experienced increases in MTS, which corresponded with a steady decline in function. MTS scores were highest in the patients who were taking opioid analgesics, suggesting that mucositis pain continued despite standard pain therapy.
Virtually all patients with head and neck cancer (HNC) experience oropharyngeal complications during and after radiation therapy. Among these complications, oral mucositis (OM) is the most debilitating, dose-limiting, and dose-delaying acute toxicity.1–4 Pain from OM can be severe, requiring opioid analgesics for pain management and substantially impairing oropharyngeal function, nutritional intake, and oral medication use. In search of improved cure rates, combined radiotherapy and chemotherapy has become standard therapy for advanced HNC.5, 6 However, aggressive protocols have come at the expense of more frequent and severe complications, with ≥60% of patients experiencing ulcerative OM.7–12
Extensive efforts are being made to prevent or ameliorate OM.3, 13, 14 The first guidelines for the prevention and management of mucositis recently were published.6 The first U.S. Food and Drug Administration-approved agent for reducing the incidence and duration of severe OM, palifermin, was introduced in the United States in 2004.15 The product has been approved for patients with hematologic malignancies who are receiving myeloablative therapy that includes total body irradiation; and, currently, palifermin is under investigation in several solid tumor disease settings. Standardized and validated tools to assess and compare the impact of mucositis interventions on patient well-being and function will be needed as additional indications for palifermin and other agents emerge. There have been no instruments specifically designed to date that measure the acute effects of mucositis.4, 16–23
We conducted a multicenter, longitudinal study to assess the validity, reliability, and feasibility of a new mucositis instrument, the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer (OMWQ-HN). The OMWQ-HN is a patient-reported outcome (PRO) questionnaire that includes domains and questions related to mucositis symptoms, including mouth and throat soreness (MTS), and their impact on patient well-being and function.
MATERIALS AND METHODS
Patients who were receiving radiotherapy with or without chemotherapy for HNC were recruited from 7 centers in the United States. The study protocol was approved by institutional review boards of participating institutions. Eligibility criteria included: 1) histologically confirmed diagnosis of carcinoma of the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx or neck disease (lymph node or soft tissue) of unknown origin; 2) scheduled to receive radiotherapy with or without chemotherapy; 3) age ≥18 years; 4) written informed consent; 5) able to read and complete the questionnaires; and 6) not receiving investigational agent for mucositis.
The OMWQ-HN item content was refined through qualitative research with 30 HNC patients (data on file). In-depth, one-on-one interviews were undertaken to identify missing elements, to eliminate questions that were deemed irrelevant, and to rephrase questions that were judged to be unclear from the patients' perspectives. The question that received the lowest clarity rating was related to the type of diet the patient experienced in the past 24 hours (on a scale from 0 to 10, with 0 indicating no oral intake and 10 indicating solid foods); 23% of patients rated this question unclear or difficult to understand. The effect of OM on the ability to wear dentures and questions related to diarrhea scored low on relevance, with approximately 50% of participants rating the relevance of these questions as 1 or 2, with 1 indicating not at all relevant. The revised OMWQ-HN, which was based on the findings of the qualitative study, was the subject of the current investigation. The revised OMWQ-HN, along with companion instruments, is described below.
The OMWQ-HN is a mucositis-specific questionnaire that is similar to a OM daily questionnaire (OMDQ) that was used in a randomized controlled trial (RCT) for patients who were receiving myeloablative therapy and undergoing hematopoietic stem cell transplantation (HSCT).15 In the transplantation setting, MTS-related questions of the OMDQ were valid, reliable, and responsive measures of OM severity that were correlated closely with and predictive of objective assessments of OM using the World Health Organization grading scale.24 The OMWQ-HN consists of 12 items that assess patient well-being and function. The time frame for reference is the past week. All questions use a Likert-type response format. The first 2 questions assess global health and quality of life (QOL) and are taken from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire25; the questions are rated on a 7-point scale, with 1 indicating very poor and 7 indicating excellent: 1) How would you rate your overall health during the past week? 2) How would you rate your overall QOL during the past week?
The third question quantifies MTS the patient is experiencing on a 5-point scale, with 0 indicating no soreness and 4 indicating extreme soreness: 3) How much MOUTH AND THROAT SORENESS did you experience in the past week? If the patient marks 0, then he or she is instructed to stop; and, if soreness is >0, then the remaining 4 questions are completed.
The fourth question, which is made up of 6 items, addresses the impact of MTS on patient function and includes a 5-point scale, with 0 indicating not limited and 4 indicating unable to do: 4) How much did MOUTH AND THROAT SORENESS limit you in each of the following activities during the past week: 1) sleeping, 2) swallowing, 3) drinking, 4) eating, 5) talking, 6) brushing your teeth?
The remaining 3 questions assess the degree of mouth and throat pain and soreness using an 11-point scale, with 0 indicating no pain or soreness and 10 indicating the worst pain or soreness imaginable or possible: 5) On a scale from 0 to 10, how would you rate your OVERALL MOUTH AND THROAT SORENESS during the past week? 6) On a scale from 0 to 10, what number best describes the MOUTH PAIN that you have experienced in the past week? 7) On a scale from 0 to 10, what number best describes the THROAT PAIN that you have experienced in the past week?
The Functional Assessment of Cancer Therapy-Head and Neck Cancer
The Functional Assessment of Cancer Therapy (FACT)-Head and Neck Cancer (FACT-HN) includes the FACT-General (FACT-G) and an HNC-specific additional-concerns subscale (HNCS).26 The FACT-G has 4 subscales: physical well-being (PWB) (7 items), social/family well-being (SWB) (7 items), emotional well-being (EWB) (6 items), and functional well-being (FWB) (7 items). The modified version of the HNCS that was used in this study consisted of 8 of the 9 typically scored HNCS items. The item that was not used (I eat solid foods) was evaluated more thoroughly in the Performance Status Scale for Head and Neck Cancer (PSS-HN). The FACT-HN Symptom Index (FHNSI) is comprised of 10 items from the FACT-HN that have been selected by expert providers as the most important symptom targets when treating patients with advanced HNC.27 A modified 8-item version of the FHNSI that excluded I eat solid foods and I have pain in my mouth, throat, or neck also was administered. All items have a Likert-type response scale (ranging from 0 [not at all] to 4 [very much]). Item responses on negatively worded items were reversed, and subscale and total scores were calculated as described in the FACT-HN scoring guidelines.26–31 A higher score indicates better QOL on all FACT-HN subscales and total scores.
The PSS-HN is a clinician-rated scale that has been validated previously to assess 3 domains of performance status for patients with HNC: Normalcy of Diet, Public Eating, and Understandability of Speech.29 The Normalcy of Diet scale ranges from 0 to 100 and is divided into 10-point increments. A lower score indicates more impairment, with 0 indicating full impairment, nonoral feeding (tube fed), and 100 indicating no impairment, full diet (no restrictions).
The FACT-HN and PSS-HN were included alongside the OMWQ-HN as tools to validate the OMWQ-HN. Specifically, the question related to pain from the FACT-HN (I have pain) and the scale related to the ability to eat from the PSS-HN (Normalcy of Diet) served as anchors in the analyses. These anchors were chosen based on previous literature showing that pain is the hallmark symptom of mucositis, and inability to eat is one of the most important mucositis-related functional impairments.
Study Design and Sample
Seventy-five patients were enrolled in this prospective, longitudinal, multicenter, observational study of patients with HNC who were receiving radiotherapy with or without chemotherapy. The questionnaires were administered prior to treatment (Week 0) and at Weeks 2, 4, and 6. During Week 4, the questionnaires were administered twice 24 to 48 hours apart for test-retest reliability evaluation. During Weeks 2, 4, and 6, patients and a physician or nurse separately recorded their perceptions of change, if any, in MTS compared with previous assessments. Patients completed the questionnaires in the physician's office or at the radiation therapy clinic. Upon completion, the study coordinator/nurse reviewed the questionnaires for completeness. Demographic, disease, and treatment data were collected at baseline and are reported in Table 1. Opioid analgesic use and feeding tube use were recorded throughout the study.
Table 1. Patient Demographics and Clinical Characteristics at Baseline (n = 75)
No. of patients (%)
SD indicates standard deviation.
Does not sum to 100%, because some patients >1 tumor location.
Does not sum to 100%, because patients may have received >1 type of treatment.
Cronbach α coefficients were calculated at each assessment to assess internal consistency, and Spearman correlation coefficients (r) were calculated between items of the OMWQ-HN. Removal of items from the OMWQ-HN was considered to balance the desire to maximize α coefficients across assessments and to retain content validity. Based on this analysis, a scoring algorithm was written, and the final scale created from this process was used in all subsequent analyses of the OMWQ-HN. Intraclass correlation coefficients were computed to measure the test-retest reliability of the OMWQ-HN, the FACT-HN, and the PSS-HN using the consecutive Week-4 assessments.29 We also examined the patient and clinician perceptions of change in MTS between the 2 assessments at Week 4 to ensure that substantial clinical change had not occurred during that period, which would distort the test-retest analyses.
Assessment of cross-sectional validity primarily focused on differentiating definable groups according to responses to the pain question from the FACT-HN and the use of opioid analgesics. Differences in mean scores across groups of patients were assessed using analyses of variance (ANOVA) and 2-sample t tests. Effect sizes (difference between means/common standard deviation [SD]) were calculated for these group comparisons to provide an indication of the clinical significance of group differences.30, 31 The associations between the OMWQ-HN, the FACT-HN, and the PSS-HN scales were evaluated at each assessment using Spearman correlation coefficients. To demonstrate the sensitivity of the OMWQ-HN to detect change, changes in the Normalcy of Diet scale of the PSS-HN and the pain item of the FACT-HN were used to form 3 independent groups (better, no change, worse). Mean changes from baseline in the OMWQ-HN were compared between groups using an ANOVA. Both distribution and anchor-based methods were used to identify minimally important differences (MIDs) for the OMWQ-HN and FACT-HN scales. Distribution-based methods included 0.33 and 0.50 SD and the standard error of measurement (SEM = SD*[1-reliability]). The anchor-based approach involved examination of the mean change scores for patients that reported that they were a little better or a little worse compared with their last assessment.
Feasibility was assessed by calculating the percentage of scheduled assessments completed and the percentage of patients who responded to individual items of each questionnaire. SAS software (version 8.02; SAS Institute, Inc. Cary, NC) was used for all analyses.
Ninety-three percent (348 of 375) of scheduled assessments were completed (100% at Week 0). Of a potential 359 assessments for patients who remained on study, 7 assessments (2%) were missed because of administrative error, and another 4 assessments (1%) were missed because of patient refusal. Seven patients (9%) withdrew from the study after completion of the baseline assessment (1 death, 1 hospitalization, and 5 patient refusals).
The Cronbach α coefficient for all 12 OMWQ-HN items was 0.912 at Week 4; however, the overall health and overall QOL items and the brushing teeth item had low item-total correlations at all assessments (generally <0.5) relative to the other OMWQ-HN items (generally >0.7). The overall health and overall QOL items were correlated highly with each other (r = 0.72–0.81) but were correlated only moderately with the other MTS-related items (r = 0.2–0.5). There were strong correlations (>0.7) among the MTS-related items, including mouth pain and throat pain. Based on these findings, a summary OMWQ-HN score was calculated as the sum of the responses of the items excluding overall health, overall QOL, and limits brushing teeth. That score was used in the remaining analyses and is referred to as the OMWQ-HN scale.
Descriptive statistics are shown in Table 2 for the OMWQ-HN, FACT-HN, and PSS-HN Normalcy of Diet scales at baseline and at subsequent assessments. Test-retest reliabilities of most scales ranged from 0.80 to 0.89. Results of the cross-sectional analyses to assess validity, using Week 4 data, are shown in Table 3. Week 4 was chosen, because it captures a time by which there has been onset of mucositis, and the data quality still was excellent. Results from other time points did not differ significantly. The OMWQ-HN scores clearly were different across levels of pain at Week 4, with patients in the worst pain category exhibiting the highest OMWQ-HN scores. Effect sizes in the range from 0.2 to 0.5 are considered MIDs in the measurement of health-related QOL; the observed effect sizes exceeded these criteria. Patients who were taking opioid analgesics had significantly worse OMWQ-HN scores than patients who were not taking opioid analgesics at Week 4, and the observed effect sizes exceeded 0.5.
Table 2. Descriptive Statistics at Weeks 0, 2, 4, and 6
SD indicates standard deviation; ICC, intraclass correlation coefficients; OMWQ-HN, Oral Mucositis Weekly Questionnaire-Head and Neck; MTS, mouth and throat soreness; FACT-G, Functional Assessment of Cancer Treatment-General; NA, not available; HNCS, Head and Neck Cancer-specific Subscale; FACT-HN, FACT-Head and Neck; FHNSI, FACT-HN Symptom Index; PSS-HN, Performance Status Scale for Head and Neck Cancer.
All analyses were statistically significant (P < .001; test-retest reliability ICC between 2 Week-4 assessments).
OMWQ-HN, 9 item
MTS, 1 item
FACT-G, 27 items
HNCS, 8 items
FACT-HN total, 35 items
FHNSI, 8 items
PSS-HN Normalcy of Diet, 1 item
Table 3. Oral Mucositis Weekly Questionnaire-Head and Neck and Functional Assessment of Cancer Treatment-Head and Neck Scores for Groups Defined by Pain and Opioid Analgesic Use at Week 4
OMWQ-HN indicates the Oral Mucositis Weekly Questionnaire-Head and Neck; MTS, mouth and throat soreness; FACT-G, Functional Assessment of Cancer Treatment-General; HNCS, Head and Neck Cancer-specific Subscale; FACT-HN, FACT-Head and Neck; FHNSI, FACT-HN Symptom Index; SD, standard deviation; t(60), t statistic (degrees of freedom).
“I have pain”
1. Not at all/a little bit (n = 21)
2. Somewhat (n = 19)
3. Quite a bit/very much (n = 25)
Effect size (mean difference/common SD)
1 vs 2
2 vs 3
Opioid analgesic use
Yes (n = 44)
No (n = 18)
The associations between the OMWQ-HN, FACT-HN, and PSS-HN scales were assessed using Spearman correlation coefficients at Week 4. There were strong correlations, as expected, between the OMWQ-HN and the FACT-HNCS (η = −0.57), the FHNSI (ρ = −0.63), the FACT PWB (η = −0.66), and the FACT FWB (η = −0.48). The OMWQ-HN was correlated weakly with the FACT SWB (η = −0.16) but was correlated rather highly with the FACT EWB (η = −0.52). Correlations between the OMWQ-HN and the PSS-HN scales were lower than expected (η range = −0.09 for Understandability of Speech to −0.37 for Public Eating). Figure 1 shows the strikingly similar longitudinal patterns for the OMWQ-HN and the 2 symptom-focused, validated endpoints from the FACT-HN: HNCS and FHNSI.
To demonstrate sensitivity to detect change in QOL during treatment, changes in the pain item of the FACT-HN and Normalcy of Diet scale of the PSS-HN were used to form 3 independent groups (better, no change, worse). Because the numbers of patients that improved were quite small for both pain and Normalcy of Diet, the better and no change categories were combined. Means, SDs, t statistics, and P values for the OMWQ-HN and MTS are shown in Table 4. For both grouping criteria, the better/no change and worse groups differed significantly on both scale scores.
Table 4. Change from Baseline to Week 4 by Changes in Pain and Normalcy of Diet
OMWQ-HN indicates the Oral Mucositis Weekly Questionnaire-Head and Neck; MTS, mouth and throat soreness; SD, standard deviation; PSS-HN, Performance Status Scale for Head and Neck Cancer; t(63), t statistic (degrees of freedom).
“I have pain”
No change/improved (n = 26)
Worsened (n = 39)
PSS-HN Normalcy of Diet
No change/improved (n = 13)
Worsened (n = 52)
MID estimates focused primarily on the groups of patients who worsened, because very few patients reported being a little better, and effect sizes for this group were small (0.06–0.17). The mean OMWQ-HN change score for the patients who reported being a little worse ranged from 4.3 to 9.5 for Weeks 2, 4, and 6. Across 4 assessments, 0.33 SD units of the OMWQ-HN (possible score range, 0–54) ranged from 3.6 to 4.8, and 0.50 SD units of the OMWQ-HN ranged from 5.4 to 7.2. Combining the distribution-based and anchor-based information on OMWQ-HN performance, it is reasonable to estimate an MID range from 4 to 7. For group comparisons, the lower bound of the MID range may be applied; and, for individual classification, the higher end may be used. Thus, a group difference over time of 4 points (approximately 0.33 SD) likely would reflect a meaningful treatment effect, and a 7-point change (approximately 0.5 SD) would provide reasonable confidence in classifying an individual as having changed from baseline.
Across the study period, patients experienced increases in MTS that corresponded with a steady decline in function (Fig. 2). Eighteen patients had a feeding tube placed postbaseline (6 patients by Week 2, 5 patients by Week 4, and 7 patients by Week 6).
The current results indicate that the OMWQ-HN is a valid, reliable, and feasible instrument for measuring the impact of mucositis in patients who are receiving radiation therapy, with or without chemotherapy for HNC. The OMWQ-HN captured dramatic changes throughout the course of radiation therapy.
The final OMWQ-HN scale included 9 items. Three items were removed from the initial questionnaire (overall health, overall QOL, and the effects of MTS on brushing teeth) because of low item-total correlations at all assessments. The finding that overall health and QOL were correlated poorly with items related to mucositis is consistent with some studies, which showed that changes in specific patient morbidities or symptoms were not reflected in global measures of health or QOL.16, 17, 32 Brushing teeth also had the highest level of nonresponse in the OMWQ-HN scale. We did not control for the use of prostheses or the presence or absence of teeth, which may have affected this variable.
The measurement properties of the OMWQ-HN scale were strong with internal-consistency reliability coefficients that exceeded acceptable standards at all time points. The OMWQ-HN scale successfully differentiated patients who had different levels of pain, and patients who reported more pain also had worse OMWQ-HN scores. Furthermore, patients who were taking opioid analgesics also had significantly worse OMWQ-HN scores than patients who were not taking opioid analgesics. The OMWQ-HN demonstrated responsiveness to change in clinical status over time, successfully differentiating patients who reported worsening versus no change or improvement in their status across levels of pain and the Normalcy of Diet scale of the PSS-HN. Convergent validity of the OMWQ-HN, FACT-HN, and FHNSI scales also was demonstrated. Coefficients were high, suggesting the OMWQ-HN measures a similar construct, but not too high, indicating that the OMWQ-HN is not redundant with the other tools.
Greater than 90% of scheduled assessments were completed. There were few missed assessments because of administrative error, and those that were missed were distributed evenly throughout the study, minimizing potential for missing bias. For completed questionnaires, patients provided responses to nearly all items. These compliance figures are particularly noteworthy, because the questionnaires were administered 5 times over a 6-week treatment period, the majority of patients received aggressive therapy, and the number of items at each assessment totaled >50.
Our study reflects the morbidity associated with mucositis in patients who are receiving radiation with or without chemotherapy for HNC. Mean MTS increased throughout the course of study and approached a score of 3 or 4 (extreme soreness) in the last weeks of treatment (Fig. 2, top). A doubling of patient symptoms occurred in the first 2 weeks of treatment, and almost a tripling was observed at 4 weeks. The impact of MTS was greatest with eating, swallowing, and drinking (Fig. 2, bottom). It is noteworthy that patients who had worse OMWQ-HN scores also were prescribed opioid analgesics. These results suggest that, despite the use of potent pain medications, patients with HNC still suffer from symptoms of mucositis. There were no significant differences in OMWQ-HN scores or single-item ratings of mouth and throat soreness between patients with and without a feeding tube. Although the current study was not powered to test differences between patient treatment groups, we did compare patients who received radiotherapy alone (n = 24 patients) versus patients who received radiotherapy plus concurrent chemotherapy (n = 41) and patients who received radiotherapy plus concurrent and induction chemotherapy (n = 10 patients), and we observed no significant differences between groups, although the sample sizes were small. Patients with tumors of the larynx were compared with all other patients, and no significant differences were observed. Men were affected disproportionately in the population by the tumor sites under study (81% vs 19%); however, there were no significant differences between men and women.
We undertook the current study because of the lack of a specific and parsimonious PRO tool to measure the impact of mucositis symptoms on patients with HNC. Such a simple and specific tool may be useful not only for assessing and comparing the effects of mucositis interventions in an RCT setting but also in clinical practice to communicate with patients about what they are experiencing and to identify additional supportive care or treatment changes that may be required.
In results that were published from a pivotal RCT in patients who underwent HSCT in which the daily version of the OMWQ-HN instrument was used, patients reported onset, peak, and resolution of oral pain/soreness earlier by an average 1 to 3 days than the respective changes observed by clinicians.33 Because observer assessments often are made during a visit to the clinic or during hospitalization, the observations may not be sensitive enough to capture accurately daily changes in the severity of OM and its accompanying consequences. Further studies of time to onset of patient-reported MTS scores compared with observer-graded mucositis assessments in HNC currently are under investigation.
Noteworthy in this study was the greater sensitivity to change of the OMWQ-HN from baseline to Week 2 (Fig. 1) compared with FACT-HN and FHNSI scores. The OMWQ-HN and MTS scores more than double during the first 2 weeks, as opposed to a much more modest change among the other QOL scores (Table 1). These results suggest that the OMWQ-HN is more responsive than less symptom-focused QOL instruments in detecting early changes in symptoms related to OM.
A limitation of this study was that we did not include a standardized clinical anchor, such as an objective, clinician-rated assessment of OM. We chose to use a patient assessment alone based on recent reports that symptoms associated with mucositis, including oropharyngeal pain and pain on swallowing, were relevant clinically and were correlated highly with objective assessments.34–36 Some clinicians also recently argued that a patient assessment of the impact of mucositis may be more useful than objective findings upon oral examination.35 Nevertheless, the relation between objective and subjective findings is an important step in the validation of the OMWQ-HN scale and is being assessed in an ongoing RCT.
The results from this study show that the OMWQ-HN is valid, reliable, readily applied in a multicenter trial to assess acute changes associated with treatment, and responsive to change throughout treatment. This study adds to the prior experience of QOL evaluation and specific oral function/symptom scales in patients with HNC.
We are indebted to the study coordinators for their high-quality assistance with the study: Yvonne Agee, Helene Levi, Donna Malveau, Deirdre Mooring, Neeta Nair, Tina Peters, Mary Ann Rubio, Kristin Shade, Kristina Sinclair, Susan Suter, and Priscilla Wong. We acknowledge the leadership of Lisa Bellm in this project. We also acknowledge Tricia Cheney and Rebecca Cheng for their help with study conduct and data management.