Patient reported outcomes in head and neck cancer: selecting instruments for quality of life integration in clinical protocols

Importance of Health Related-Quality of Life assessment in head and neck cancer patients

Head and neck cancer is undoubtedly related to a decrease in HRQoL. After diagnosis, the treatment most frequently determines a deterioration of basic functions such as breathing, mastication, salivating, swallowing and speaking. Sense's impairment such as hearing, taste and smell along with possible esthetics changes will promote a negative impact in both patients and their relatives HRQoL [1, 4, 7].

HRQoL assessment allows head and neck cancer patients careful monitoring, may recognize risk patient groups being predictive for time to progression suggesting this evaluation as a new prognostic marker for survival [8–10]. HRQoL questionnaires enable patient's clustering according to their most frequent health concerns, ranking its intensity [1, 11]. Also, HRQoL assessment can be considered a stimulating approach for effectiveness and the cost-effectiveness promotion (survival and quality-adjusted survival) contributing thus to the construction of an economical decision model [12–14].

Instruments for HRQoL assessment in head and neck cancer patients

HRQoL instruments must exhibit comproved psychometric characteristics, such as: consistency, reliability, reproducibility, validity and sensibility to change.

Considering the multidimensional approach involved in the HRQoL assessment, instrument applicability and cultural adaptation must be tested for each population.

The instruments that fulfill the minimal requisites for Oncology HRQoL assessment include: Breast Cancer Chemotherapy Questionnaire (BCQ), Cancer Rehabilitation Evaluation Systems (CARES), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ), Functional Assessment of Cancer Therapy Scales (FACT), Functional Living Index Scale (FLIC), Linear Analogue Self-Assessment, Medical Outcome Study Short Form (MOS SF-36), Multidimensional Quality of Life Scale, Quality of Life Index (QL- Index) (Spitzer Index), Rotterdam Symptom Check List (RSCL) [5, 15, 16]. The questionnaires EORTC-QLQ C30, FACT-G, MOS SF-36 and FLIC stand out as the main general in oncology.

There are specific instruments for head and neck cancer patients HRQoL evaluation such as: the EORTC QLQ-H&N35, the FACT H&N, the FLIC, the University of Washington Quality of Life Questionnaire (UW-QOL), the University of Michigan Head and Neck Quality of Life Questionnaire (HNQOL), the Head and Neck Radiotherapy Questionnaire (HNRQ), the Performance Status Scale-Head and Neck-(PSS-H&N), the Obturator Functioning Scale (OFS), the Late Side Effects on Daily Life Scale and the Oral and Pharyngeal Nursing Care Questionnaire (OPNCQ) [17–23].

Clinical trials and clinical practice

HRQoL has been used as a health outcome measure mainly associated to clinical trials. The implementation of routine HRQoL assessment in clinical practice can be used for scientific documentation as well for clinical settings [24–26]. This advance is fundamental to obtain clinical meaningful data that can be a helpful outcome considering patients undergoing cancer treatments and, particularly, when additional supportive services and symptom management are concerned. Moreover, the careful HRQoL monitoring of cancer patients may identify potentially unmet needs and generate the basis of a stepped care model [26–28]. HRQoL information can thus support clinical decisions and promote health gains. However, results obtained either from clinical practice or research must be interpreted, not only in statistical terms, but also considering the clinical importance - it is required then an wide comprehension of the relationship between the patients outcome results and the patients perception of the change [29, 30].

The present study aims to compare the two major HRQoL questionnaires specific for head and neck cancer patients: the EORTC QLQ-C30 and its specific head and neck module QLQ-H&N35 and the Functional Assessment of Cancer Therapy Scales (FACT H&N) in the Portuguese Institute for Oncology, Porto (IPO-Porto). Conceptual differences, psychometric characteristics and scores are analyzed and discussed. A major attention is made on significant differences that can be related to clinical important data.

Patients

From September 2008 to January 2010, 102 outpatients admitted to the Otorhinolaringology service (ORL service) IPO-Porto, Portugal, completed two different HRQoL questionnaires, immediately before consultation as a part of the routine evaluation. The completion order was randomized. Inclusion criteria were a Karnofsky index above 30, age below 90 years, ability to understand written and spoken Portuguese and provision of written consent.

Questionnaires

The questionnaires under comparison were from the European Organisation for Research and Treatment of Cancer (EORTC) and the Functional Assessment of Cancer Therapy (FACT), both targeted to cancer patients. HRQoL was assessed by general questionnaires, EORTC QLQ-C30 and Functional Assessment of Cancer Therapy - General (FACT-G), and its disease-specific modules for head and neck (FACT H&N) cancer patients was also considered, the QLQ-H&N35 and the FACT H&N, respectively. Scores and conceptual characteristics were compared: between the two core questionnaires - EORTC-QLQC30/FACT-G - and between their disease-specific modules/extensions for H&N patients - QLQ-H&N35/FACT H&N (FACT-G + 12 H&N-specific questions), respectively.

EORTC QLQ-C30 and the disease-specific module QLQ-H&N35

The EORTC QLQ-C30 (version 3.0) is a questionnaire developed to assess the HRQoL of cancer patients. It consists of 30 questions: twenty four form nine multi-item scales presenting various aspects of HRQoL: five functional scales (PF, Physical functioning; SF, Social functioning; EF, Emotional functioning; RF, Role functioning; CF, Cognitive functioning), three symptom scales (fatigue, pain, nausea and vomiting) and a global condition (health and quality of life). The remaining six are single-item scales describing different cancer relevant symptoms. During the scoring procedure, raw EORTC QLQ-C30 scores are linearly transformed into 0 e100 scales. For global health status and the five functioning scales, a score of 100 corresponds to a high HRQoL. For financial difficulties and the eight symptoms, a score of 100 implies maximum difficulty or symptom burden. The additional module - QLQ-H&N35 (version 3.0) - is disease-specific for head and neck patients. It consists of 35 questions organized in seven symptoms multi-item scales (twenty four questions are presented) and eleven are single-item scales describing different specific concerns of these head and neck cancer patients.

FACT-G and the disease-specific FACT H&N

The FACT H&N (version 4) is a multidimensional, self-report HRQoL instrument specifically designed for use with head and neck cancer patients. It consists of 27 core items - FACT-G - assessing patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being (Pwb, Swb, Ewb, and Fwb, respectively). It is further supplemented by 12 site specific items for head and neck related symptoms assessment - FACT - (H&N-G). Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global HRQoL score. Higher scores represent better QoL.

Questionnaire completion

The autonomy expressed for questionnaire completion as well the time patient needed to complete both questionnaires - EORTC QLQ-C30 (version 3)/QLQ H&N35 and FACT H&N - was evaluated.

Sociodemographic and clinical data

Clinical data - such as tumour location, performance status (Karnofsky index), tobacco habits and present symptomatology - as well socio-demographic data - age, gender and schooling years - were collected from the patient's clinical process and complemented, when needed, in semi structured interviews.

Ethics

All patients gave their informed consent. The data were collected for research purposes as part of the routine evaluation. The Committee for Ethics in Medical Research approved the use of these data for research.

Analysis Strategies and Statistics

Completed questionnaires were scored according to the developers' instructions.

For tool comparison, 4 similar domains were always considered in EORTC QLQ-C30 and FACT-G, respectively: PF/Pwb, EF/Ewb, SF/Swb and RF/Fwb.

Descriptive data are presented with means, SDs, medians, ranges, and proportions as appropriate.

Instrument's scores characteristics

In probability theory and statistics, skewness is a measure of the asymmetry of the probability distribution of a real-valued random variable. Qualitatively, a negative skew indicates that the tail on the left side of probability density function is longer than the right side and the bulk of the values (including the median) lie to the right of the mean. A positive skew indicates that the tail on the right side is longer than the left side and the bulk of the values lie to the left of the mean. Kurtosis is a measure of the "peakedness" of the probability distribution of a real-valued random variable. Higher kurtosis means more of the variance is the result of infrequent extreme deviations, as opposed to frequent modestly sized deviations.

Reliability

Reliability expressed as internal consistency is a measure of how well the items in a multi-item scale interrelate. This is usually assessed by computing Cronbach's coefficient (Cronbach's alpha). The score reflects both the number of items and the degree of correlation between items.

Sensitivity

Sensitivity measures how well the instrument identifies differences between groups. An instrument with a high sensitivity is able to detect a relatively small difference with a modest sample size. Sensitivity is measured by comparing the scores of different groups of patients. In this study the patient population was divided: i) in two groups according to the expressed symptomatology (symptomatic and asymptomatic) ii) into five broad groups according tumour location (vocal cord neoformation, laryngeal neoformation, pharynx neoformation, pharynxlaryngeal neoformation, and tongue neoplasia), iii) into four broad groups according tumour size (T1, T2 T3 and T4) and iv) into four broad groups according age (less than 45 year old, 46-55 years old, 56-65 years old and older than 65). The scores were compared using the Mann-Whitney or Kruskal-Wallis tests. Based on clinical experience, significant differences between these patient groups were expected.

Construct Validity

Construct validation evaluates how well an instrument measures the construct it is intended to measure. Convergence between instruments (external convergent validity) is an assessment of the correlation between EORTC and FACT measures of the same concept. This is included in the multi-trait multi-method (MTMM) analysis where Pearson's correlations are used to compute the degree of correlation. A correlation above 0.70 between scales measuring the same concept is considered to be an indication of the same underlying concept. Discriminant validity was analysed to verify if the HRQoL operationalization does not correlate with other operationalizations that theoretically should not be correlated with.

Patients Characteristics

Patients presented 59.4 ± 12.1 years and revealed a low educational level presenting 5 ± 3 schooling years and long tobacco habits being the majority (60.6%) exposed for more than 31 years.

The Karnofsky performance status scale revealed that all patients performed above 50% and 57% of head and neck cancer patients were mainly ascribed to high Karnofsky Index (90-100%).

Questionnaire completion

The time response varied between 3 and 20 minutes (9,3 ± 3,1) for EORTC QLQ-C30 (version 3)/QLQ H&N35 and 3 to 23 minutes (7,3 ± 2,7) for FACT-H&N. Most head and neck cancer patients (79,4%) required some kind of help to answer the questionnaires.

Questionnaire's conceptual characteristics

Instrument's scores characteristics

Concerning SF and Swb, the most evident difference was the extent of the flattening where FACT-G showed a leptokurtic distribution (-0.67) and EORTC QLQ- C30 a platikurtic one (-0.84). The EF and Ewb domain presented similar measurement's distribution and may be considered as normal; RF and Fwb revealed a similar distribution in shape. The Cognitive domain exhibited a distribution very skewed to the right (-1.78).

Reliability

When internal consistency was compared by measuring how well the items interrelate, EORTC demonstrated a higher total consistency, both in the core questionnaire EORTC QLQ-C30 (α = 0.87 versus 0.76 for FACT-G) as well in the disease specific module H&N35 (α = 0.90 versus 0.79 for FACT - (H&N-G)). Most values observed (Table 3, 4) were above 0.7 although the EF scale was found below in both questionnaires, EORTC QLQ-C30 and FACT-G (α = 0.46 and 0.69, respectively). Cognitive functioning scale revealed a low reliability (0.27).

The disease-specific module H&N35 revealed an internal consistency in all scales (α = 0.72 to 0.99) except in Speech problems (α = 0.46).

Patient symptoms Sensitivity

Disease specific module EORTC QLQ-H&N35 was also able to discriminate in all scales except Senses problems nor three simple item questions considering Dry mouth, Weight loss and Weight loss. FACT - (H&N-G) was found to be sensitive when total score was considered and statistical significant differences were found in 5 single items (questions 1, 5, 7, 10 and 11).

Tumour location sensitivity

EORTC QLQ-C30 revealed no sensitivity to tumour location being Fatigue in the discrimination boundary for Vocal cord neoformation (p = 0.05). The Pwb in FACT-G is sensitive to Vocal cord neoformation location (p = 0.008) presenting higer HRQoL score.

Tumour size sensitivity

Patients with different tumour size are not depicted by the FACT-G assessment and EORTC QLC-C30 is only able to discriminate T3 and T4 when SF or the 2 simple items Diarrhea and Financial difficulties are considered.

Construct Validity