Quality of Life in Thyroid Cancer Patients

Thyroid cancer ranks as the ninth most common cancer worldwide and third in Saudi Arabia. Given thyroid cancer's high incidence, thyroid cancer patients' quality of life (QoL) has been a concern for many years. However, no study has been dedicated to assessing thyroid cancer patients' QoL in Saudi Arabia. Thus, we aimed to fill this gap by assessing thyroid cancer patients' QoL in Saudi Arabia. This cross-sectional study was conducted among thyroid cancer patients attending outpatient clinics at the Diabetes and Endocrinology Centre, King Fahad Specialist Hospital, Qassim region, Saudi Arabia, from 2017 to 2023. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) assessed the patients' QoL through an individual interviewer-administered technique. We used RStudio to perform statistical analysis. Statistical differences between groups based on QoL scores were assessed using the Wilcoxon and Kruskal-Wallis rank-sum tests. Our results showed that for QoL scores of functional domains, the lowest was in social functioning, and the highest was in cognitive functioning. Regarding the subscales of symptoms, the highest scores were fatigue and insomnia. In conclusion, numerous factors affect thyroid cancer patients' QoL. Recognition and appropriate management of these factors will improve the overall QoL; there is a need to understand what is driving these factors in further clinical studies.


Introduction
The World Health Organization (WHO) defines quality of life (QoL) as "individuals' perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards, and concerns" [1].The literature interchangeably uses the terms healthrelated quality of life (HRQoL) and QoL.However, several attempts exist to differentiate between these terms to create one general definition and another specific one focusing more on health-related QoL [2].Moreover, QoL is a multidimensional construct that includes physical, social, psychological, disease, and treatment-related symptoms.One of the proposed and widely accepted definitions of QoL in cancer studies defines it as "a state of well-being which is a composite of two components: 1) the ability to perform everyday activities that reflect physical, psychological, and social well-being and 2) patient satisfaction with levels of functioning and the control of disease and/or treatment-related symptoms" [3].The first component of the state of well-being indicates a more objective aspect of the QoL.By contrast, the second component is more subjective and relies on the patient's reported satisfaction.The Centers for Disease Control and Prevention (CDC) has defined HRQoL as "an individual's or group's perceived physical and mental health over time."Measuring the HRQoL proved its importance and usefulness for assessing the efficacy of treatments.Measuring the HRQoL helps reveal the burden of diseases and explore the relationships between HRQoL and different risk factors.Tracking the HRQoL can also help in monitoring the progress/regress of a country in achieving its health objectives [4].Measuring the HRQoL is a method that can reflect multiple clinical indicators of the patients' health.In addition, the goal of healthcare services should be addressing more than just the results of labs and imaging studies.Instead, it must also address the patients' general well-being and assess their satisfaction level.
Thyroid cancer is one of the most common cancers globally.According to the latest Global Cancer Observatory (GLOBOCAN) estimates, thyroid cancer was the ninth most commonly diagnosed worldwide, with an incidence of 586,202 cases [5].In the United States and other industrialized countries, the incidence of thyroid cancer has been increasing for the past 30 years [6][7][8][9].The leading causes behind the increase in the incidence of thyroid cancer are the improvement of medical imaging and ionizing radiation, environmental and genetic factors, and better accessibility of the population to healthcare services [10].In Saudi Arabia, the latest cancer incidence report was issued by the Saudi Health Council in 2018, showing that thyroid cancer is the third most common cancer among Saudi nationals after breast and colorectal cancers.Thyroid cancer in Saudi Arabia ranked second among women and 10th among men.Furthermore, the report showed that the annual incidence of thyroid cancer among Saudi nationals is 1,323 cases.In Saudi Arabia, thyroid cancer's age-standardized incidence rate (ASR) was 10.6/100,000 for women and 2.9/100,000 for men [11].The high incidence of thyroid cancer patients necessitated building infrastructure to meet the needs of affected patients.Among the infrastructure that has been built is the center we collected data from for this study, the Diabetes and Endocrinology Centre at King Fahad Specialist Hospital in Qassim region.Most thyroid cancers fall into these categories: papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), both of which are further classified as differentiated thyroid carcinoma (DTC), undifferentiated thyroid carcinoma (UTC), and medullary thyroid carcinoma (MTC) [12].Given thyroid cancer's high incidence worldwide, the QoL of thyroid cancer patients has been an area of concern for many years [10].

Literature review
Multiple instruments have been developed to measure QoL among cancer patients [13].The European Organization for the Research and Treatment of Cancer (EORTC) developed one commonly used instrument named the Core Quality-of-Life Questionnaire (QLQ-C30).It was developed to assess the QoL of cancer patients, and due to the comprehensiveness of this instrument and the fact that it has been translated and validated into over 100 languages, this instrument was widely used by thousands of studies [14].The QLQ-C30 was used in many studies to assess the QoL in thyroid cancer patients [15][16][17].A group of researchers analyzed the HRQoL among patients with DTC at the Medical University of Innsbruck using the QLQ-C30; they found that the patients' HRQoL was worse than the general population in all domains except the cognitive functioning, diarrhea, and financial impacts.Differences between DTC patients and the general population in HRQoL were particularly significant for role functioning and fatigue [15].In Shandong Provincial Qianfoshan Hospital, patients with DTC undergoing radioactive iodine-131 treatment were recruited.Their QoL was measured using QLQ-C30, and after one year of psychological and behavioral interventions, the patients' QoL was significantly improved [16].
Interestingly, a South Korean study showed that even disease-free survivors of DTC had lower HRQoL when compared to the general population [17].A UK-based study assessing the QoL among DTC patients using the European Quality of Life 5 Dimensions revealed that thyroid cancer patients had lower QoL than colorectal cancer patients.Studying patients with a type of thyroid cancer more invasive than DTC could yield worse QoL results [18].However, it is worth mentioning that thyroid cancer patients have better survival compared to colorectal cancer patients [19].
In Saudi Arabia, multiple studies have been conducted to assess the QoL among cancer patients attending the outpatient clinics of various tertiary hospitals [20][21][22].However, no study is dedicated to assessing the QoL among thyroid cancer patients despite the previously discussed significance of assessing the QoL [4].We believe that assessing the QoL among thyroid cancer patients can give an insight into the quality of healthcare provided them.We aimed to fill this gap by assessing the QoL among thyroid cancer patients attending outpatient clinics at the Diabetes and Endocrinology Centre, King Fahad Specialist Hospital, Qassim region, Saudi Arabia.

Study design, area, population, and duration
This cross-sectional study was conducted at the Diabetes and Endocrinology Centre, King Fahad Specialist Hospital, Qassim region, Saudi Arabia.All thyroid cancer patients attending outpatient clinics from 2017 to 2023 who agreed to participate in the study were included.

Sample size and selection of samples
We reached a total of 129 patients.Our required minimal sample size was 124 patients calculated using Cochran's equation together with a population correction, where the population size is 181 patients based on the number of thyroid cancer patients seen at the Diabetes and Endocrinology Centre, King Fahad Specialist Hospital, Qassim region, Saudi Arabia, from 2017 to 2023, the confidence level is 95%, the precision level is ±5%, and the estimated proportion is 0.5.
The sampling technique is a non-probability convenient sampling technique.All thyroid cancer patients attending the outpatient clinics from 2017 to 2023 who agreed to participate in the study were included.

Tools and data collection methods
A retrospective chart review of thyroid cancer patients seen at the Diabetes and Endocrinology Centre, King Fahad Specialist Hospital, Qassim region, Saudi Arabia, from 2017 to 2023 was done.Contact information was obtained from the center's inpatient medical files.The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) [23] was used to assess the QoL through an individual interviewer-administered technique.Data collection was done from November 2022 to April 2023.The survey consisted of 30 items, which assess five functional subscales (physical, cognitive, role, social, and emotional) and nine symptomatic subscales (fatigue, nausea/vomiting, dyspnea, insomnia, pain, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status (GHS) subscale.All the subscales (except the GHS subscale) were collected on a four-point Likert scale ranging between 1 = "not at all" to 4 = "very much."Items of the GHS subscale were recorded on a seven-point scale from 1 = "very poor" to 7 = "excellent."The scores of the symptoms' subscales were reversed, and an overall QoL score was computed by summing up the items of the functional subscales and symptomatic subscales (except financial difficulties) [24].Therefore, a higher QoL score indicated a higher QoL indicator.All the scores were converted to their percentage counterparts to be easily interpreted.The questionnaire used was the Arabic version of the EORTC QLQ-C30 developed, translated, and validated by the EORTC.

Data management and analysis plan
We used RStudio (R version 4.3.0) to perform statistical analysis.We used frequencies and percentages to express categorical variables, whereas continuous variables were presented as the median and interquartile range (IQR).Statistical differences between different groups based on QoL scores were assessed using a Wilcoxon rank-sum test for variables with two groups and a Kruskal-Wallis rank sum test for variables with three or more categories.Statistical significance was considered at p-value < 0.05.

Ethical considerations
An informed consent explaining the aim of the study and how the data will be managed was obtained from each participant.Only the researchers can access the collected data.We obtained ethical approval from the Regional Research Ethics Committee (NCBE, No. H-04-Q-001) for the application and publication of the study (protocol code 607-44-3752; date of approval: October 10, 2022).

Demographic characteristics of patients
Data from 129 patients with thyroid cancer were analyzed in the current study.The majority of patients were women (86.8%), unemployed/housewives (70.5%), married (79.8%), and aged more than 35 years (80.6%)(Table 1).

Description of the QoL scores
Descriptive statistics for the QoL scores are provided in Table 2.For the QoL scores of functional domains, the lowest score was relevant to social functioning (median = 25.0,IQR = 25.0 to 50.0), whereas the highest score was related to cognitive functioning (median = 50.0,IQR = 37.5 to 62.5).Regarding the subscales of symptoms, the highest scores (indicating more discomfort and suffering) were reported for fatigue (median = 50.0,IQR = 33.3 to 75.0) and insomnia (median = 50.0,IQR = 25.0 to 100.0;Table 2).

Discussion
To the best of our knowledge, this study is the first study dedicated to assessing the QoL among thyroid cancer patients in Saudi Arabia.Studies that assessed thyroid cancer patients' QoL are limited.Our sample's demographics align with the demographics of thyroid cancer patients in Saudi Arabia.Women constitute 78.9% of all the new cases of thyroid cancer in Saudi Arabia; in our study, they constitute 86.6% of the sample.We believe that this alignment between the percentage of women with thyroid cancer in Saudi Arabia and the proportion of women in our sample enhances the applicability of this study [11].Patients with cancer often experience psychological burdens due to heightened stress experienced in different functional domains [24].In our study, the lowest score was in social functioning, unlike a study conducted in Korea, which showed significantly lower scores in all functional domains among disease-free survivors of DTC, including physical, role, cognitive, emotional, and social.This discrepancy could be explained by different contextual or cultural factors open for research [17].
Moreover, our study showed that the pain scores were higher among women than men, which is consistent with the finding of the paper published by Alshehri et al. [20].According to their study, women tended to score worse in all domains.However, we acknowledge the potential for sample bias since most of our patients were women.Women, in general, tend to score lower than men in HRQoL scores.Different sociodemographic characteristics could explain the gender differences, most importantly individual income, which was found by a study conducted in the USA to be one of the most impactful factors in creating a difference between men's and women's HRQoL scores [25].Previous multivariate analyses of the patients' age prove a negative relationship between age and global QoL scores [20,21].By contrast, our study did not show significant differences in QoL scores based on age categories.However, this could be due to the smaller size of our sample.
Interestingly, regarding patients' marital status, our results showed that single participants had significantly higher levels of QoL impairment due to appetite loss than married participants, which contradicts the study published by Alshehri et al. [20] that showed no significant differences in QoL scores based on patients'

TABLE 2 : Descriptive analysis of the QoL scores
IQR: interquartile range, SD: standard deviation, Min: minimum, Max: maximum