Support Care Cancer DOI 10.1007/s00520-014-2438-2
ORIGINAL ARTICLE
Assessment of radiation-induced xerostomia: validation of the Italian version of the xerostomia questionnaire in head and neck cancer patients Federica Pellegrino & Elena Groff & Luca Bastiani & Bruno Fattori & Guido Sotti
Received: 31 March 2014 / Accepted: 9 September 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Xerostomia is the most common acute and late side effect of radiation treatment for head and neck cancer. Affecting taste perception, chewing, swallowing and speech, xerostomia is also the major cause of decreased quality of life. The aims of this study were to validate the Italian translation of the self-reported eight-item xerostomia questionnaire (XQ) and determine its psychometric properties in patients treated with radiotherapy for head and neck cancer. Methods An observational cross-sectional study was conducted in the Radiotherapy Unit of the Veneto Institute of Oncology – IOV in Padua. The XQ was translated according to international guidelines and filled out by 102 patients. Construct validity was assessed using principal component analysis, internal consistency using Cronbach’s α coefficient and test-retest reliability at 1-month interval using the intraclass correlation coefficient (ICC). Criterion-related validity was evaluated to compare the Italian version of XQ with the European Organization for Research and Treatment of F. Pellegrino (*) : E. Groff : G. Sotti Radiotherapy Unit, Veneto Institute of Oncology IOV - IRCCS, Via Gattamelata, 64, 35128 Padova, Italy e-mail: [email protected] E. Groff e-mail: [email protected] G. Sotti e-mail: [email protected] L. Bastiani Institute of Clinical Physiology of the Italian National Research Council (IFC-CNR), Via Moruzzi 1, 56124 Pisa, Italy e-mail: [email protected] B. Fattori ENT, Audiology and Phoniatrics Unit, University of Pisa, Via Paradisa, 2, 56100 Pisa, Italy e-mail: [email protected]
Cancer (EORTC) Core Quality-of-Life Questionnaire (QLQC30) and its Head and Neck Cancer Module (QLQ-H&N35). Results Cronbach’s α for the Italian version of XQ was strong at α=0.93, test-retest reliability was also strong (0.79) and factor analysis confirmed that the questionnaire was one-dimensional. Criterion-related validity was excellent with high association with the EORTC QLQ-H&N35 xerostomia and sticky saliva scales. Conclusions The Italian version of XQ has excellent psychometric properties and can be used to evaluate the impact of emerging radiation delivery techniques aiming at preventing xerostomia. Keywords Xerostomia . Radiotherapy . Quality of life . Head and neck cancer . Dysphagia
Introduction Head and neck cancer (HNC) accounts for approximately 5 % of the overall prevalence of cancer in Italy and has a relative survival rate of 57 % after 5 years from diagnosis [1]. Radiation therapy has an essential role in the management of HNC as it is the main non-surgical option. However, a substantial percentage of survivors suffer from significant longterm treatment-related adverse effects [2]. Xerostomia is the most common early and late sequela of head and neck radiation, and it is frequently permanent. It includes the objective reduction in the salivary output, the changes in its composition and the subjective symptoms reported by the patients [3]. The changes in quantity and composition of saliva that occur shortly after radiotherapy relate to the extreme radiosensitivity of the gland tissue. Studies of patients receiving definitive radiation therapy have shown a rapid diminution of salivary flow during the first
Support Care Cancer
week of radiotherapy. Minimal gland function reduction occurs at 40 Gy [4]. Saliva is important in daily living because it is responsible for moistening and softening food during ingestion, protecting oral mucosa and teeth. When salivary function is compromised, the resulting effects include alteration of taste, difficulty with chewing, swallowing and speaking. Furthermore, oral mucosal dryness can also change the oral pH level and predispose to oral infections, dental caries and contribute to osteoradionecrosis. Such changes can lead to nutritional deficits that can be difficult to reverse. The development of xerostomia in HNC patients, therefore, is of serious consequence to their nutritional status, their ability to interact socially and their overall quality of life [5]. In a recent study, Kakoei et al. [24] explored the associations of quality of life (QoL), xerostomia and saliva production in HNC patients after radiotherapy and found that the feeling of xerostomia more strongly affected QoL compared to actual salivary flow. In addition, patients began to suffer from xerostomia after the start of treatment but the amount of saliva secreted did not significantly change during therapy. A significant correlation between xerostomia and QoL scores in HNC undergoing radiotherapy was found even by Lin et al. [9]. A variety of methods are currently available for the evaluation of radiation-induced xerostomia. They can be grouped into (1) morphological assessment methods (i.e. histological evaluation, CT, MRI and ultrasonography), (2) functional assessment methods (i.e. sialometry, MR sialography and scintigraphy) and (3) clinical and quality-of-life grading (i.e. observer-assessed toxicity grading and patient-reporting evaluation). The technical complexity of the first two groups of methods actually precludes their use in the routine clinical assessment, where the clinical and quality-of-life grading is prevalent [3, 6]. Clinical grading systems, as Common Terminology Criteria for Adverse Events (CTCAE), provide a standard for the description of the toxicity profiles of cancer therapies. However, as xerostomia is primarily a subjective experience, its assessment should rely on patient self-reports. In addition, it has been found that observer-based systems tend to underestimate the severity of xerostomia compared with that reported by the patients [7]. To best define xerostomia, Deasy et al. [4] suggested that an observer-based system be supplemented by a validated quality-of-life tool that describes the symptom from the patient’s perspective. For this purpose, they proposed the xerostomia questionnaire (XQ), a patient-reported xerostomia-specific tool, which has been tested for its validity and reliability at the University of Michigan and has been widely used in several clinical trials [8]. The original version
of this tool is in English. Recently, it has been validated a Taiwanese version [9]. Currently, there is not in Italy a validated tool for selfassessment of radiotherapy-induced xerostomia and this might be the reason why research in this field is lacking. In the last 10 years, just one Italian study on xerostomia has been published and it adopted a questionnaire whose translation had not been previously validated [10]. To determine health-related quality of life after irradiation of HNC, the European Organization for Research and Treatment of Cancer (EORTC) developed a Core Quality-ofLife Questionnaire (QLQ-C30) and its Head and Neck Cancer Module (QLQ-H&N35). These questionnaires are widely used both in clinical trials and clinical practice. They address many domains and have to be used together, requiring a time of administration of about 10–15 min. The EORTC QLQ-H&N35 module contains 35 questions concerning treatment-related symptoms frequently reported by HNC patients. This module includesone item on xerostomia and one item on sticky saliva (both representing two different scales) that are not probably sensitive enough to score even subtle changes of patient-reported dryness. For example, patients may experience dryness at rest or in different oral functions, while speaking or swallowing. For these functions, the EORTC module has other symptom scales, which had not been validated separately and could not be used unless the administration of both QLQ-C30 and QLQH&N35, which means 65 items totally. XQ, instead, appears to be sufficiently complete to measure patient-rated xerostomia and can be used in different settings as it has only eight items and it is easy to administer. The aims of this study were to validate the Italian version of the XQ and determine its psychometric properties in a population of HNC patients treated with radiotherapy. In this text, the abbreviation XQ-I will be adopted to refer to the Italian version of the XQ.
Materials and methods Design and setting This observational cross-sectional single-centre study was conducted in the Radiotherapy Unit of the Veneto Oncology Institute-IOV in Padua. The study was approved by the local ethics committee (ethical code EC-IOV 2014/14/NOTIFICA), and patients had to provide informed consent. Participants Participants were patients with head and neck cancer, treated with 3D conformational radiotherapy at the Radiotherapy Unit of the Veneto Institute of Oncology from 2007 to 2013.
Support Care Cancer
Recruitment took place during follow-up visits. Mailed questionnaires were not used. Inclusion criteria were the following: 1. Histological diagnosis of primary tumor of the head and neck; 2. Radiotherapy follow-up 0–60 months; 3. Age 18 years or older; 4. Absence of recurrence in areas previously treated; 5. Cognitively able to self-administer patient-reported outcomes; 6. Written informed consent. Exclusion criteria were the following: 1. 2. 3. 4.
Diabetes mellitus; Parkinson’s disease; Sjögren syndrome and any other cause of xerostomia; Use of any medication known to affect salivary function.
Patients recruited were asked to fill out the self-reported eight-item XQ-I and the EORTC QLQ-C30 and QLQH&N35. To confirm test-retest reliability of the XQ-I, patients were invited to complete the questionnaire for a second time, approximately 1 month after the first administration. Medical data were collected by review of medical care records. The researcher checked for absent responses after receiving the questionnaire and asked patients to answer to the missing items.
Translation procedure of the XQ The eight items of the XQ were translated according to international guidelines [13] as follows: (1) two independent Italian translations were obtained from two independent translators who were native Italian speakers with proficiency in English. Cross-cultural adaptation was achieved during a consensus meeting. (2) The back-translation from Italian to English was carried out by a native English mother tongue who was not involved in developing the initial version. (3) The original and the back-translated English versions were compared to assure that there were no differences in the meaning of the questions in the questionnaire; inconsistencies were discussed and resolved among the translators until a final version was reconciled. Most items in the questionnaire were translated without difficulty. Agreement was generally reached with little discussion and just few phrases required more extensive discussion. For example, “Ha difficoltà a” was chosen instead of “Valuti la sua difficoltà a” for “Rate your difficulty in” because the former was thought to represent an expression with a higher frequency of use in the Italian language and therefore more understandable. For the same reason, “Ha difficoltà a dormire” was preferred instead of “Valuti la frequenza di disturbi del sonno” for “Rate the frequency of your sleeping problems”. A pilot test was performed in an Italian population (n=10) aimed at clarifying the exact wording for every item. The average time necessary to complete the XQ-I was less than 5 min, and the questionnaire was well understandable and acceptable in most patients.
Xerostomia questionnaire EORTC QLQ-C30 and QLQ-H&N35 The XQ has been developed and validated at the University of Michigan. It gives a measure of the severity of radiationinduced xerostomia that affects patients’ quality of life [8]. It consists of eight questions, four of which relate to patientreported dryness while eating or chewing and the other four relate to dryness while not eating or chewing. The XQ does not include questions related to taste or to oral pain, which usually improve over time after therapy. As the XQ is a selfadministered tool, subjects are asked to rate each symptom on an 11-point ordinal Likert scale from “0” to “10”, with higher scores indicating greater dryness or discomfort due to dryness. Each item score is added, and the sum is transformed linearly to produce the final summary score ranging from 0 to 100, with higher scores representing greater levels of xerostomia. The validity and reproducibility of this instrument have been documented after radiation therapy (RT) for HNC both at the University of Michigan and Florida, and the results with this questionnaire correlate with more global quality-of-life parameters [11, 12].
The EORTC Quality-of-Life Questionnaire (QLQ) is an integrated system for assessing the health-related quality of life (QoL) of cancer patients participating in international clinical trials [14, 15]. The core questionnaire is the EORTC QLQ-C30 whose content areas reflect the multi-dimensionality of the QoL construct. This questionnaire incorporates five functional scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea and vomiting), a global health status/QoL scale and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. The HNC module (QLQ-H&N35) is meant for use among a wide range of patients with HNC, varying in disease stage and treatment modality (i.e. surgery, radiotherapy and chemotherapy). The module incorporates seven multi-item scales that assess pain, swallowing, senses (taste and smell), speech,
Support Care Cancer
social eating, social contact and sexuality. There are also 11 single items, each representing a specific scale. The saliva domain is assessed by two single-item scales, i.e. dry mouth (HNDR) and sticky saliva (HNSS). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology or problems. EORTC QLQ-H&N35 has already been used to validate a patient-rated xerostomia questionnaire [22] and used to assess salivary function in several studies, as instance, a multi-centre one aimed to investigate the significance of the radiation dose to major and minor salivary glands [25]. Statistical analysis Descriptive statistics was performed to present demographic and clinical characteristics of the patients. Reproducibility of the scale was estimated through a testretest reliability after 1 month. The strength of agreement between the repeated measures was examined using the intraclass correlation coefficient (ICC). An ICC0.75 as excellent agreement [16]. To investigate the internal validity, principal component analysis (PCA) was performed. This statistical technique examines the assumed construct validity and uni-dimensionality of the scale. The number of dimensions and the item loading structure of PCA with orthogonal rotation (varimax method) were conducted on the correlation matrix of XQ-I. Two classical criteria from PCA were used, eigenvalue rule (number of factor with eigenvalue >1) and factor loading rule (item-factor correlations >0.32, suggested for behavioral phenotypes interpretation). Cronbach’s alpha was used to assess internal consistency with values above 0.7 indicating desirable levels [17]. Additionally, to investigate the association explained by the first dimension, inter-item association and Cronbach’s alpha when item deleted were also computed. Criterion-related validity was investigated by multiple regression model evaluating the relation between the total score at XQ-I (dependent variable) and the scales of the EORTC QLQ-H&N35 questionnaire assessing saliva domain and deglutition: HNDR (dry mouth), HNSS (sticky saliva) and HNSW (swallowing). Before multiple regression model analysis, covariates (HNDR; HNSS; HNSW) were individually tested with a univariate linear regression model. Furthermore, Spearman’s rho correlation analysis was carried out in order to
compare XQ-I score with the global quality-of-life scale (QL2) and the physical (PF2), role (RF2), emotional (EF) and social (SF) scales of the EORTC QLQ C-30. Statistical analysis was performed using the Statistical Analysis System (SPSS version 20.0).
Results Patients Demographic and clinical characteristics of the 102 head and neck cancer patients included in this study are shown in Table 1. Most patients were male (81.4 %), male/female ratio 4.3/1. Age of subjects ranged from 24 to 85 years; mean age was 62.5 for men and 64.4 for women. The sites of cancer represented in the study population were the following: nasopharynx, oropharynx (including tonsil region), oral cavity (tongue and floor of mouth), larynx and vocal cords. The targets covered by the radiation treatment were represented by the primary tumor and lymph nodes of the neck at risk of being compromised. The protocol adopted was following the administration of therapeutic doses, delivered at 2.0 Gy fraction: (a) 70 Gy to the primary tumor resected, (b) 55 to 60 Gy to the tumor bed after resection of primary tumor and (c) 50 Gy on subclinical areas at risk. The average dose in Gy delivered on the primary tumor was 66.3. The median time from completion of radiation treatment to questionnaire administration was 11 months (mean 15.4 months) with a range from 1 to 60 months. The mean and standard deviation of XQ-I scores was respectively 42.6 and 27.4 (median=41.2; range=0–97.5). Test-retest reliability and dimensionality analysis XQ-I scores between first and second visits were used to assess the test-retest reliability, which was good with ICC value of 0.79 (confidence interval (CI) 95 %; 0.67–0.87). Among the XQ-I items, the ICC varied between 0.62 and 0.88. The eight items of the XQ-I were all included in the principal component analysis (PCA) as they were all highly correlated to each other. For XQ-I items, the PCA identified one principal component (PC) with eigenvalue >1 (5.44) that explained for 68.0 % of the observed total variance. Under typical conditions, this means that the first component will be correlated with at least some of the observed variables; thus, PCA confirmed that the XQ-I is one-dimensional. Cronbach’s alpha was 0.93 (CI 95 %; 0.91–0.95), showing good internal consistency of the questionnaire. The psychometric properties examined show a good level of correlation of the items with the principal component. The
Support Care Cancer Table 1 Socio-demographic and clinical characteristics of the study subjects (n=102)
Association analysis
Patient, tumor and treatment characteristics
Criterion-related validity was investigated by evaluating the relationship between the total score at XQ-I and the score at the scales of the EORTC QLQ-H&N35 module assessing saliva domain and deglutition. In the questionnaire, these domains are assessed by the two single-item scales HNSS and HNDR and the four-item scale HNSW. The results of a univariate linear regression model indicated that XQ-I is significantly correlated with each the three scales HNSS, HNDR and HNSW (p
ORIGINAL ARTICLE
Assessment of radiation-induced xerostomia: validation of the Italian version of the xerostomia questionnaire in head and neck cancer patients Federica Pellegrino & Elena Groff & Luca Bastiani & Bruno Fattori & Guido Sotti
Received: 31 March 2014 / Accepted: 9 September 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Xerostomia is the most common acute and late side effect of radiation treatment for head and neck cancer. Affecting taste perception, chewing, swallowing and speech, xerostomia is also the major cause of decreased quality of life. The aims of this study were to validate the Italian translation of the self-reported eight-item xerostomia questionnaire (XQ) and determine its psychometric properties in patients treated with radiotherapy for head and neck cancer. Methods An observational cross-sectional study was conducted in the Radiotherapy Unit of the Veneto Institute of Oncology – IOV in Padua. The XQ was translated according to international guidelines and filled out by 102 patients. Construct validity was assessed using principal component analysis, internal consistency using Cronbach’s α coefficient and test-retest reliability at 1-month interval using the intraclass correlation coefficient (ICC). Criterion-related validity was evaluated to compare the Italian version of XQ with the European Organization for Research and Treatment of F. Pellegrino (*) : E. Groff : G. Sotti Radiotherapy Unit, Veneto Institute of Oncology IOV - IRCCS, Via Gattamelata, 64, 35128 Padova, Italy e-mail: [email protected] E. Groff e-mail: [email protected] G. Sotti e-mail: [email protected] L. Bastiani Institute of Clinical Physiology of the Italian National Research Council (IFC-CNR), Via Moruzzi 1, 56124 Pisa, Italy e-mail: [email protected] B. Fattori ENT, Audiology and Phoniatrics Unit, University of Pisa, Via Paradisa, 2, 56100 Pisa, Italy e-mail: [email protected]
Cancer (EORTC) Core Quality-of-Life Questionnaire (QLQC30) and its Head and Neck Cancer Module (QLQ-H&N35). Results Cronbach’s α for the Italian version of XQ was strong at α=0.93, test-retest reliability was also strong (0.79) and factor analysis confirmed that the questionnaire was one-dimensional. Criterion-related validity was excellent with high association with the EORTC QLQ-H&N35 xerostomia and sticky saliva scales. Conclusions The Italian version of XQ has excellent psychometric properties and can be used to evaluate the impact of emerging radiation delivery techniques aiming at preventing xerostomia. Keywords Xerostomia . Radiotherapy . Quality of life . Head and neck cancer . Dysphagia
Introduction Head and neck cancer (HNC) accounts for approximately 5 % of the overall prevalence of cancer in Italy and has a relative survival rate of 57 % after 5 years from diagnosis [1]. Radiation therapy has an essential role in the management of HNC as it is the main non-surgical option. However, a substantial percentage of survivors suffer from significant longterm treatment-related adverse effects [2]. Xerostomia is the most common early and late sequela of head and neck radiation, and it is frequently permanent. It includes the objective reduction in the salivary output, the changes in its composition and the subjective symptoms reported by the patients [3]. The changes in quantity and composition of saliva that occur shortly after radiotherapy relate to the extreme radiosensitivity of the gland tissue. Studies of patients receiving definitive radiation therapy have shown a rapid diminution of salivary flow during the first
Support Care Cancer
week of radiotherapy. Minimal gland function reduction occurs at 40 Gy [4]. Saliva is important in daily living because it is responsible for moistening and softening food during ingestion, protecting oral mucosa and teeth. When salivary function is compromised, the resulting effects include alteration of taste, difficulty with chewing, swallowing and speaking. Furthermore, oral mucosal dryness can also change the oral pH level and predispose to oral infections, dental caries and contribute to osteoradionecrosis. Such changes can lead to nutritional deficits that can be difficult to reverse. The development of xerostomia in HNC patients, therefore, is of serious consequence to their nutritional status, their ability to interact socially and their overall quality of life [5]. In a recent study, Kakoei et al. [24] explored the associations of quality of life (QoL), xerostomia and saliva production in HNC patients after radiotherapy and found that the feeling of xerostomia more strongly affected QoL compared to actual salivary flow. In addition, patients began to suffer from xerostomia after the start of treatment but the amount of saliva secreted did not significantly change during therapy. A significant correlation between xerostomia and QoL scores in HNC undergoing radiotherapy was found even by Lin et al. [9]. A variety of methods are currently available for the evaluation of radiation-induced xerostomia. They can be grouped into (1) morphological assessment methods (i.e. histological evaluation, CT, MRI and ultrasonography), (2) functional assessment methods (i.e. sialometry, MR sialography and scintigraphy) and (3) clinical and quality-of-life grading (i.e. observer-assessed toxicity grading and patient-reporting evaluation). The technical complexity of the first two groups of methods actually precludes their use in the routine clinical assessment, where the clinical and quality-of-life grading is prevalent [3, 6]. Clinical grading systems, as Common Terminology Criteria for Adverse Events (CTCAE), provide a standard for the description of the toxicity profiles of cancer therapies. However, as xerostomia is primarily a subjective experience, its assessment should rely on patient self-reports. In addition, it has been found that observer-based systems tend to underestimate the severity of xerostomia compared with that reported by the patients [7]. To best define xerostomia, Deasy et al. [4] suggested that an observer-based system be supplemented by a validated quality-of-life tool that describes the symptom from the patient’s perspective. For this purpose, they proposed the xerostomia questionnaire (XQ), a patient-reported xerostomia-specific tool, which has been tested for its validity and reliability at the University of Michigan and has been widely used in several clinical trials [8]. The original version
of this tool is in English. Recently, it has been validated a Taiwanese version [9]. Currently, there is not in Italy a validated tool for selfassessment of radiotherapy-induced xerostomia and this might be the reason why research in this field is lacking. In the last 10 years, just one Italian study on xerostomia has been published and it adopted a questionnaire whose translation had not been previously validated [10]. To determine health-related quality of life after irradiation of HNC, the European Organization for Research and Treatment of Cancer (EORTC) developed a Core Quality-ofLife Questionnaire (QLQ-C30) and its Head and Neck Cancer Module (QLQ-H&N35). These questionnaires are widely used both in clinical trials and clinical practice. They address many domains and have to be used together, requiring a time of administration of about 10–15 min. The EORTC QLQ-H&N35 module contains 35 questions concerning treatment-related symptoms frequently reported by HNC patients. This module includesone item on xerostomia and one item on sticky saliva (both representing two different scales) that are not probably sensitive enough to score even subtle changes of patient-reported dryness. For example, patients may experience dryness at rest or in different oral functions, while speaking or swallowing. For these functions, the EORTC module has other symptom scales, which had not been validated separately and could not be used unless the administration of both QLQ-C30 and QLQH&N35, which means 65 items totally. XQ, instead, appears to be sufficiently complete to measure patient-rated xerostomia and can be used in different settings as it has only eight items and it is easy to administer. The aims of this study were to validate the Italian version of the XQ and determine its psychometric properties in a population of HNC patients treated with radiotherapy. In this text, the abbreviation XQ-I will be adopted to refer to the Italian version of the XQ.
Materials and methods Design and setting This observational cross-sectional single-centre study was conducted in the Radiotherapy Unit of the Veneto Oncology Institute-IOV in Padua. The study was approved by the local ethics committee (ethical code EC-IOV 2014/14/NOTIFICA), and patients had to provide informed consent. Participants Participants were patients with head and neck cancer, treated with 3D conformational radiotherapy at the Radiotherapy Unit of the Veneto Institute of Oncology from 2007 to 2013.
Support Care Cancer
Recruitment took place during follow-up visits. Mailed questionnaires were not used. Inclusion criteria were the following: 1. Histological diagnosis of primary tumor of the head and neck; 2. Radiotherapy follow-up 0–60 months; 3. Age 18 years or older; 4. Absence of recurrence in areas previously treated; 5. Cognitively able to self-administer patient-reported outcomes; 6. Written informed consent. Exclusion criteria were the following: 1. 2. 3. 4.
Diabetes mellitus; Parkinson’s disease; Sjögren syndrome and any other cause of xerostomia; Use of any medication known to affect salivary function.
Patients recruited were asked to fill out the self-reported eight-item XQ-I and the EORTC QLQ-C30 and QLQH&N35. To confirm test-retest reliability of the XQ-I, patients were invited to complete the questionnaire for a second time, approximately 1 month after the first administration. Medical data were collected by review of medical care records. The researcher checked for absent responses after receiving the questionnaire and asked patients to answer to the missing items.
Translation procedure of the XQ The eight items of the XQ were translated according to international guidelines [13] as follows: (1) two independent Italian translations were obtained from two independent translators who were native Italian speakers with proficiency in English. Cross-cultural adaptation was achieved during a consensus meeting. (2) The back-translation from Italian to English was carried out by a native English mother tongue who was not involved in developing the initial version. (3) The original and the back-translated English versions were compared to assure that there were no differences in the meaning of the questions in the questionnaire; inconsistencies were discussed and resolved among the translators until a final version was reconciled. Most items in the questionnaire were translated without difficulty. Agreement was generally reached with little discussion and just few phrases required more extensive discussion. For example, “Ha difficoltà a” was chosen instead of “Valuti la sua difficoltà a” for “Rate your difficulty in” because the former was thought to represent an expression with a higher frequency of use in the Italian language and therefore more understandable. For the same reason, “Ha difficoltà a dormire” was preferred instead of “Valuti la frequenza di disturbi del sonno” for “Rate the frequency of your sleeping problems”. A pilot test was performed in an Italian population (n=10) aimed at clarifying the exact wording for every item. The average time necessary to complete the XQ-I was less than 5 min, and the questionnaire was well understandable and acceptable in most patients.
Xerostomia questionnaire EORTC QLQ-C30 and QLQ-H&N35 The XQ has been developed and validated at the University of Michigan. It gives a measure of the severity of radiationinduced xerostomia that affects patients’ quality of life [8]. It consists of eight questions, four of which relate to patientreported dryness while eating or chewing and the other four relate to dryness while not eating or chewing. The XQ does not include questions related to taste or to oral pain, which usually improve over time after therapy. As the XQ is a selfadministered tool, subjects are asked to rate each symptom on an 11-point ordinal Likert scale from “0” to “10”, with higher scores indicating greater dryness or discomfort due to dryness. Each item score is added, and the sum is transformed linearly to produce the final summary score ranging from 0 to 100, with higher scores representing greater levels of xerostomia. The validity and reproducibility of this instrument have been documented after radiation therapy (RT) for HNC both at the University of Michigan and Florida, and the results with this questionnaire correlate with more global quality-of-life parameters [11, 12].
The EORTC Quality-of-Life Questionnaire (QLQ) is an integrated system for assessing the health-related quality of life (QoL) of cancer patients participating in international clinical trials [14, 15]. The core questionnaire is the EORTC QLQ-C30 whose content areas reflect the multi-dimensionality of the QoL construct. This questionnaire incorporates five functional scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea and vomiting), a global health status/QoL scale and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. The HNC module (QLQ-H&N35) is meant for use among a wide range of patients with HNC, varying in disease stage and treatment modality (i.e. surgery, radiotherapy and chemotherapy). The module incorporates seven multi-item scales that assess pain, swallowing, senses (taste and smell), speech,
Support Care Cancer
social eating, social contact and sexuality. There are also 11 single items, each representing a specific scale. The saliva domain is assessed by two single-item scales, i.e. dry mouth (HNDR) and sticky saliva (HNSS). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology or problems. EORTC QLQ-H&N35 has already been used to validate a patient-rated xerostomia questionnaire [22] and used to assess salivary function in several studies, as instance, a multi-centre one aimed to investigate the significance of the radiation dose to major and minor salivary glands [25]. Statistical analysis Descriptive statistics was performed to present demographic and clinical characteristics of the patients. Reproducibility of the scale was estimated through a testretest reliability after 1 month. The strength of agreement between the repeated measures was examined using the intraclass correlation coefficient (ICC). An ICC0.75 as excellent agreement [16]. To investigate the internal validity, principal component analysis (PCA) was performed. This statistical technique examines the assumed construct validity and uni-dimensionality of the scale. The number of dimensions and the item loading structure of PCA with orthogonal rotation (varimax method) were conducted on the correlation matrix of XQ-I. Two classical criteria from PCA were used, eigenvalue rule (number of factor with eigenvalue >1) and factor loading rule (item-factor correlations >0.32, suggested for behavioral phenotypes interpretation). Cronbach’s alpha was used to assess internal consistency with values above 0.7 indicating desirable levels [17]. Additionally, to investigate the association explained by the first dimension, inter-item association and Cronbach’s alpha when item deleted were also computed. Criterion-related validity was investigated by multiple regression model evaluating the relation between the total score at XQ-I (dependent variable) and the scales of the EORTC QLQ-H&N35 questionnaire assessing saliva domain and deglutition: HNDR (dry mouth), HNSS (sticky saliva) and HNSW (swallowing). Before multiple regression model analysis, covariates (HNDR; HNSS; HNSW) were individually tested with a univariate linear regression model. Furthermore, Spearman’s rho correlation analysis was carried out in order to
compare XQ-I score with the global quality-of-life scale (QL2) and the physical (PF2), role (RF2), emotional (EF) and social (SF) scales of the EORTC QLQ C-30. Statistical analysis was performed using the Statistical Analysis System (SPSS version 20.0).
Results Patients Demographic and clinical characteristics of the 102 head and neck cancer patients included in this study are shown in Table 1. Most patients were male (81.4 %), male/female ratio 4.3/1. Age of subjects ranged from 24 to 85 years; mean age was 62.5 for men and 64.4 for women. The sites of cancer represented in the study population were the following: nasopharynx, oropharynx (including tonsil region), oral cavity (tongue and floor of mouth), larynx and vocal cords. The targets covered by the radiation treatment were represented by the primary tumor and lymph nodes of the neck at risk of being compromised. The protocol adopted was following the administration of therapeutic doses, delivered at 2.0 Gy fraction: (a) 70 Gy to the primary tumor resected, (b) 55 to 60 Gy to the tumor bed after resection of primary tumor and (c) 50 Gy on subclinical areas at risk. The average dose in Gy delivered on the primary tumor was 66.3. The median time from completion of radiation treatment to questionnaire administration was 11 months (mean 15.4 months) with a range from 1 to 60 months. The mean and standard deviation of XQ-I scores was respectively 42.6 and 27.4 (median=41.2; range=0–97.5). Test-retest reliability and dimensionality analysis XQ-I scores between first and second visits were used to assess the test-retest reliability, which was good with ICC value of 0.79 (confidence interval (CI) 95 %; 0.67–0.87). Among the XQ-I items, the ICC varied between 0.62 and 0.88. The eight items of the XQ-I were all included in the principal component analysis (PCA) as they were all highly correlated to each other. For XQ-I items, the PCA identified one principal component (PC) with eigenvalue >1 (5.44) that explained for 68.0 % of the observed total variance. Under typical conditions, this means that the first component will be correlated with at least some of the observed variables; thus, PCA confirmed that the XQ-I is one-dimensional. Cronbach’s alpha was 0.93 (CI 95 %; 0.91–0.95), showing good internal consistency of the questionnaire. The psychometric properties examined show a good level of correlation of the items with the principal component. The
Support Care Cancer Table 1 Socio-demographic and clinical characteristics of the study subjects (n=102)
Association analysis
Patient, tumor and treatment characteristics
Criterion-related validity was investigated by evaluating the relationship between the total score at XQ-I and the score at the scales of the EORTC QLQ-H&N35 module assessing saliva domain and deglutition. In the questionnaire, these domains are assessed by the two single-item scales HNSS and HNDR and the four-item scale HNSW. The results of a univariate linear regression model indicated that XQ-I is significantly correlated with each the three scales HNSS, HNDR and HNSW (p
