Thyroid Cancer–Specific Quality of Life and Health-Related Quality of Life in Young Adult Thyroid Cancer Survivors

Abstract

Background:

There is a lack of health-related quality of life (HRQOL) research in thyroid cancer (TC) survivors, especially young adults (YAs). This study aims to assess the socio-demographic and clinical factors that most influence TC-specific QOL domains and estimate the impact of different health conditions on HRQOL in a large cohort of YA TC survivors.

Methods:

TC survivors ≥17 years of age were recruited through the thyroid cancer survivor (ThyCa) Web site. Mean scores for the seven domains and six items of THYCA-QoL, MCS and PCS of SF-12v1, and derived SF-6D were compared between factors as well as age groups (YA: 17–39 years, adult ≥40 years), and to the normal population. Regression analyses estimated the relationship between the socio-demographic, clinical, and THYCA-QoL measures and HRQOL in YAs only.

Results:

Of 1028 survivors, 277 (27%) were YAs. Most YAs were female (93.5%), white (86.6%), insured (96.8%), married or in a stable relationship (69%), and listed a comorbidity (43.7%); all reported their entire thyroid had been removed. Average survivorship time was 46.2 months (SD = 51.0). Almost every socio-demographic and clinical factor significantly influenced one or more domain of THYCA-QoL in both YAs and older adults. In both groups, a higher level of education, female sex, unemployment, and having a comorbidity resulted in significantly higher THYCA-QoL scores (more complaints) and lower SF-6D scores (lower HRQOL; p < 0.05). Current YAs had less neuromuscular, voice, sympathetic, and throat/mouth complaints but more grievances involving their scar, headaches, anxiety, and overall psychological state (p < 0.05). The average SF-6D for YAs was 0.70 (SD = 0.13), which was similar to the older adults but significantly different from the normal age-matched population in females (p < 0.01). All THYCA-QoL domains were strongly associated with a lower HRQOL (adj R ² > 0.5) in YAs. The simplest, best regression model (adj R ² = 0.53) in YAs included neuromuscular, concentration, and anxiety complaints, as well as having a comorbidity predicting lower HRQOL.

Conclusion:

TC-specific QOL is significantly influenced by many socio-demographic and clinical factors. HRQOL is lower in female YA TC survivors compared with the normal age-matched population. Neuromuscular, concentration, and anxiety complaints had the greatest impact on HRQOL in YA TC survivors.

Introduction

Thyroid cancer (TC) is the most common cancer in adolescent and young adult (AYA; defined as those aged 15–39 years) females ages 15–29 years and the second most common for females aged 30–39 years. Moreover, TC has the second-highest percent annual change in cancer incidence for the AYA population. Therefore, the prevalence of young TC survivors in the general population will only continue to increase, as the majority of young TC patients experience lifelong survivorship (1). However, there is an overall lack of literature on how a TC diagnosis impacts health-related quality of life (HRQOL) in both the short- and long-term period of TC survivors, especially in younger survivors.

In the general TC population, a handful of smaller studies are conflicting as to whether HRQOL is actually increased or decreased in survivors and what other factors may be potential confounders (2 –9). In younger survivors, the literature is even scarcer. One study on young adult (YA) TC survivors in the early survivorship period reported that their feelings and cancer experience were often downplayed by healthcare providers (10). In another study of 16 adolescents, there was no reported difference in QOL or anxiety in TC survivors (11). Since a TC diagnosis in adolescence or young adulthood has the potential to interrupt “normal life” in unique ways compared with very young or older survivors, it is important to examine HRQOL separately in YAs in addition to the entire population.

The importance of measuring HRQOL in TC survivors is finally being recognized and gaining momentum. This is reflected in the new American Thyroid Association guidelines for adults and has been advocated for by pediatric endocrine experts as well (12,13). The most promising and comprehensive TC-specific HRQOL tool is the THYCA-QoL, a 24-item survey developed in the Netherlands that is meant to be used in conjunction with a preference-based HRQOL tool (14). The questionnaire covers the spectrum of specific mental and physical health problems TC survivors deal with, and is in agreement with the non-validated City of Hope questionnaire but with major additions (15). The purpose of this study is to assess the socio-demographic and clinical factors that most influence TC-specific QOL domains and to estimate the impact of different health conditions on HRQOL in a large cohort of YA TC survivors. It was conducted in the context of larger study of HRQOL in TC survivors of all ages.

Methods

Participants

Online surveys were completed via a link on the Thyroid Cancer Survivor Group ThyCa Web site by 1028 TC survivors aged ≥17 years. Participants had to be able to read and comprehend English to complete the survey. Since no identifying patient data were obtained, the study was exempt from Institutional Review Board approval, and thus participants did not sign an informed consent.

Procedures

Participants were recruited from December 3, 2013, to May 16, 2014, through listserv e-mails (that also include providers and family members) and a direct link on the ThyCa Web site that was easily visible to all ThyCa Web site visitors. Reminder e-mails to complete the survey were sent out on three separate occasions. No incentives or compensation was offered. The survey was conducted and data stored using RedCap (16) with patient anonymity meaning that only the number of completed surveys is known. The data were locked and downloaded for analysis on May 17, 2014.

Measures

A demographic form assessed current age, sex, ethnicity/race, comorbidities, and the following at the time of initial cancer diagnosis: age, employment status, highest level of education, insurance status, relationship status, and geographic region of residence. A treatment form detailed the type of TC, initial treatment (extent of surgery and radioiodine), type of thyroid replacement hormone, and last thyrotropin level if known. Survivors then completed both the SF-12v1 and THYCA-QoL questionnaires.

The THYCA-QoL is a methodologically developed questionnaire to be used in combination with a more generic QOL instrument to assess all major dimensions of HRQOL in TC survivors (14). The questionnaire consists of 24 items with a time scale of the past week that assess seven scales (neuromuscular, voice, concentration, sympathetic, throat/mouth, psychological, and sensory problems) and six single items (scar, chilly, tingling, weight gain, headache, anxiety). Each item is scored on a four-point response scale ranging from 1 = “not at all” to 4 = “very much,” which are linear transformed to a 0–100 scale. A higher score on this scale means more complaints. After content validation, the THYCA-QoL was successfully employed in >300 Dutch TC survivors in combination with a generic HRQOL questionnaire (EQ-5D) that together appear to cover most issues of concern relevant to TC survivors (17).

The SF-12v1 is a well-validated, self-administered health survey that assesses several domains of HRQOL over the past four weeks (18). It was developed for the Medical Outcomes Study, a multi-year study of patients with chronic conditions, including cancer. Twelve items assess physical functioning, role limitations, bodily pain, health perception, energy level, social functioning, and psychological well-being, resulting in physical (PCS) and mental composite scores (MCS). Higher scores indicate a higher level of functioning.

The SF-6D is a widely used, preference-based generic HRQOL measure derived from a selection of 11/12 SF-12v1 items. A health utility index is calculated from 7/8 health domains covered by the SF-12v1 (all except general health) and a set of preference weights obtained from the general population. In the absence of a U.S. algorithm, the British scoring model based on 836 members of the British general population was used due to the similarities of the two populations (19). Scores range from 0.0 (worst health state) to 1.0 (best health state). The SF-6D was chosen, since it was recently shown to have greater sensitivity for HRQOL in TC survivors than the EQ-5D has (20).

Statistical analysis

Data were examined to make sure there were no duplicate entries so that each set of patient information was unique. All survivors had to complete all questionnaire items for their entry to be valid. Chi-square tests compared the socio-demographic parameters between YAs and older adults, and analysis of variance (ANOVA) tests compared the means of each THYCA-QoL, SF-12v1, and SF-6D domain along with effect size calculations. The remaining analyses were conducted only in the 277 YAs. Independent t-tests and one-way ANOVA tests were used to examine bivariate associations between participants' characteristics and average domain scores for MCS, PCS, SF-6D, as well as all seven domains and six single items of the THYCA-QoL. t-Tests also compared SF-6D values from the TC survivors to that of published U.S. norms both overall and by sex (21). Pearson's correlation was used to examine the association between the THYCA-QoL domains and SF-6D. Multivariate linear regression using a stepwise procedure estimated the relationship between the socio-demographic, clinical, and THYCA-QoL domains and HRQOL. Interaction effects were also tested to examine for any non-linear relationships. However, they did not improve the model fit, and the data are not presented. The model was assessed by its explanatory power (adjusted R ²) and the consistency of the estimated coefficients (sign and parameter estimation). Each model's simplicity was evaluated by the use of the minimum number of predictor variables in the model that did not significantly alter the explanatory power.

Data analyses were performed with IBM SPSS Statistics for Windows v21.0 (IBM Corp., Armonk, NY). All tests were two-sided, and a p-value of <0.05 was considered to be statistically significant.

Results

Of 1028 survivors, 277 were 17–39 years of age at the time of analysis. For both YAs and older survivors, most respondents were female, white, insured, and employed/full-time student or retired, and all survivors that completed the survey reported that their entire thyroid was eventually removed (Table 1). Compared with older adults, the YA respondents were more often female (p = 0.034), single, racially and ethnically diverse (p < 0.001), divorced or widowed (p < 0.001), and without comorbidities. Most survivors had papillary carcinoma and were taking thyroxine or thyroxine/triiodothyronine thyroid replacement, and many received some amount of radioiodine without any significant difference between the two age groups. Average survivorship time for current YAs was 46.3 months compared with 58.38 months for the older age group (p = 0.007).

Table 1.

Demographics of Questionnaire Respondents

	AYA now (n = 277), n	(%)	>40 years now (n = 751), n	(%)	p-Value
Survivorship time (years)					0.386
<1	73	26.4%	168	22.4%
1–5	125	45.1%	335	44.6%
6–10	54	19.5%	160	21.3%
>10	25	9.0%	88	11.7%
Current age (years)
17–25	27	9.7%
26–30	52	18.8%
31–35	96	34.7%
36–40	127	45.8%
Age at diagnosis (years)
<15	13		23
15–24	54		10
25–39	210		78
40–49			280
50–59			266
≥60			94
Sex					0.034
Male	18	6.5%	82	10.9%
Female	259	93.5%	669	89.1%
Race/ethnicity					<0.001
White	240	86.6%	712	94.8%
Black	3	1.1%	8	1.1%
Asian	14	5.1%	11	1.5%
American Indian or Pacific Islander	4	1.4%	7	0.9%
Other	16	5.8%	13	1.7%
Ethnicity					0.040
Hispanic	23	8.3%	37	4.9%
Non-Hispanic	254	91.7%	714	95.1%
Relationship status					<0.001
Single, divorced, or widowed	86	31.0%	149	19.8%
Married or long-term relationship	191	69.0%	602	80.2%
Insurance status					0.789
Insured	9	3.2%	27	3.6%
Uninsured	268	96.8%	724	96.4%
Highest level of education					0.164
High school	36	13.0%	121	16.1%
Associates/trade degree	49	17.7%	166	22.1%
College	103	37.2%	256	34.1%
Masters or doctorate	89	32.1%	208	27.7%
Current employment status					<0.001
Employed or full-time student	237	85.6%	486	64.7%
Unemployed	40	14.4%	139	18.5%
Retired	0	0	126	16.8%
Place of current residence					0.597
U.S. Northeast	67		150
U.S. Midwest	49		146
U.S. South	49		122
U.S. Northwest	16		42
U.S. Mid-Atlantic	15		70
U.S. West	56		157
Canada	11		23
Non-North America	14		32
Type of thyroid cancer					0.578
Papillary or follicular	270	97.5%	727	96.8%
Medullary	7	2.5%	24	3.2%
Type of hormone replacement					0.479
T4	246	88.8%	656	87.4%
T3	5	1.8%	8	1.1%
T4/T3	14	5.1%	55	7.3%
Natural (armor)	12	4.3%	32	4.3%
Generic replacement					0.961
Yes	103	37.2%	278	37.0%
No	174	62.8%	473	63.0%
RAI					0.795
Yes	232	83.8%	634	84.4%
No	45	16.2%	117	15.6%
RAI dose					0.663
0–30 mCi	13	7.0%	25	5.0%
31–75 mCi	20	10.8%	58	11.6%
76–150 mCi	91	49.2%	262	52.6%
>150 mCi	61	33.0%	153	30.7%
Comorbidities (yes; can have >1)
None	121	43.7%	158	21.0%	<0.001
Diabetes	9	3.2%	55	7.3%	0.016
Hypertension	22	7.9%	248	33.0%	<0.001
Hyperlipidemia	23	8.3%	171	22.8%	<0.001
Coronary artery disease	1	0.4%	12	1.6%	0.155
Other cancer	3	1.1%	73	9.7%	<0.001
Mental health problems	77	27.8%	176	23.4%	0.150
Arthritis, muscle/joint, fibromyalgia	18	6.5%	182	24.2%	<0.001
Other	65	23.5%	177	23.6%	0.451
Hypoparathyroidism					0.541
Yes	3	1.1%	12	1.6%
No	274	98.9%	739	98.4%
Menopause (females only)					<0.001
Yes	4	1.5%	406	60.6%
No	255	98.5%	264	39.4%

AYA, adolescent and young adult; T4, thyroxine; T3, triiodothyronine; RAI, radioiodine.

Most THYCA-QoL domains measured were significantly different between the two age groups, though the effect size was small, and the SF-6D means did not differ between the two age groups (Table 2). YAs reported significantly more psychological, scar, chilly, headache, and anxiety complaints and less neuromuscular, voice, sympathetic, and throat/mouth complaints.

Table 2.

Comparison of THYCA-QoL Scores in AYAs Versus Older Patients

	AYA now, M (SD)	>40 years now, M (SD)	p-Value	Partial eta²
Neuromuscular	44.60 (27.70)	49.90 (27.19)	0.006	0.01
Voice	19.61 (20.47)	24.48 (20.84)	0.001	0.01
Concentration	46.63 (31.13)	42.57 (29.19)	0.052
Sympathetic	36.34 (31.51)	41.83 (30.12)	0.011	0.01
Throat/mouth	25.27 (22.11)	29.01 (22.27)	0.017	0.01
Psychological	40.88 (19.24)	35.41 (16.93)	<0.001	0.02
Sensory	31.11 (27.58)	32.51 (25.83)	0.448
Scar	30.57 (29.43)	18.11 (24.41)	<0.001	0.05
Chilly	47.17 (34.71)	40.99 (33.21)	0.009	0.01
Tingling	36.58 (32.50)	36.09 (33.66)	0.832
Weight gain	43.92 (34.52)	43.45 (33.39)	0.843
Headache	41.28 (33.35)	32.53 (30.20)	<0.001	0.02
Anxiety	81.47 (31.87)	75.68 (27.86)	0.005	0.01
PCS12	45.89 (10.29)	43.01 (10.89)	<0.001	0.01
MCS12	39.36 (10.21)	40.75 (10.33)	0.057
SF-6D^a/HUI	0.70 (0.14)	0.69 (0.14)	0.558

Norm SF-6D for ages 35–44 = 0.80.

Almost every socio-demographic and clinical factor significantly influenced one or more domain of THYCA-QoL in YAs. In general, significantly lower THYCA-QoL scores (fewer complaints) were experienced in males, those with employment or a full-time student status, those with a higher education level, and those without comorbidities (p < 0.05; Tables 3 and 4). Only education and the presence of a comorbidity affected both MCS and PCS in YAs, whereas sex (p = 0.004), race/ethnicity (p = 0.043), employment (p < 0.001), education (p < 0.001), relationship status (p = 0.023), and the presence of a comorbidity (p < 0.001) all significantly affected HRQOL; survivorship time and age were not important (Table 5) (22).

Table 3.

THYCA-QoL Scores in AYAs—The Seven Domains

	Neuromuscular p-value/M (SD)	Voice p-value/M (SD)	Concentration p-value/M (SD)	Sympathetic p-value/M (SD)	Throat/mouth p-value/M (SD)	Psychological p-value/M (SD)	Sensory p-value/M (SD)
Survivorship time (years)	0.77	0.12	0.49	0.74	0.01	0.06	0.06
<1	45.66 (26.03)	21.69 (19.58)	49.54 (30.04)	33.11 (27.71)	21.46 (18.17)	36.53 (18.19)	25.34 (26.22)
1–5	45.69 (26.45)	20.80 (21.34)	47.60 (32.15)	36.80 (33.28)	27.47 (22.65)	43.20 (18.97)	31.20 (26.68)
6–10	42.39 (31.58)	13.58 (18.05)	43.52 (29.75)	37.96 (32.12)	20.78 (22.02)	39.20 (20.52)	33.64 (29.93)
>10	40.89 (24.99)	20.67 (22.19)	40.00 (32.27)	40.00 (32.63)	35.11 (26.38)	45.67 (18.96)	42.00 (28.10)
Age (years)	0.82	0.39	0.50	0.42	0.42	0.73	0.90
17–25	46.09 (31.08)	20.37 (22.33)	38.27 (30.94)	27.78 (31.35)	26.34 (26.17)	38.89 (25.84)	28.40 (30.60)
26–30	41.88 (27.54)	16.67 (19.80)	46.47 (30.49)	35.90 (32.06)	24.36 (20.05)	41.51 (16.54)	30.13 (24.71)
31–35	44.10 (26.81)	22.22 (20.76)	48.61 (31.31)	39.24 (32.62)	28.01 (22.97)	42.36 (20.68)	30.90 (28.92)
36–40	46.08 (26.60)	18.46 (20.03)	47.06 (31.41)	36.11 (30.22)	22.88 (21.14)	39.71 (17.16)	32.52 (27.19)
Sex	0.01	0.97	0.14	0.01	0.09	0.08	0.01
Male	27.78 (15.83)	19.44 (19.17)	36.11 (20.81)	17.59 (27.10)	16.67 (14.38)	33.33 (14.85)	15.74 (19.36)
Female	45.77 (27.45)	19.63 (20.59)	47.36 (31.62)	37.64 (31.43)	25.87 (22.45)	41.41 (19.42)	32.18 (27.78)
Race/ethnicity	0.30	0.90	0.04	0.27	0.30	0.02	0.28
White	43.89 (27.04)	19.58 (20.47)	46.94 (31.06)	35.90 (31.12)	25.69 (22.31)	40.97 (18.77)	30.56 (27.00)
Black	44.44 (33.33)	27.78 (25.46)	61.11 (34.69)	55.56 (50.92)	18.52 (23.13)	36.11 (25.46)	33.33 (16.67)
Asian	41.27 (27.02)	16.67 (22.65)	30.95 (27.63)	35.71 (32.59)	15.08 (14.19)	35.71 (17.73)	26.19 (28.28)
American Indian or Pacific Islander	69.44 (30.59)	16.67 (0.000)	33.33 (16.67)	66.67 (40.83)	38.89 (23.13)	70.83 (19.84)	58.33 (44.10)
Other	52.08 (27.43)	21.88 (21.70)	27.81 (6.951)	32.29 (30.10)	25.69 (23.56)	37.50 (21.94)	36.46(31.75)
Ethnicity	0.62	0.59	0.33	0.80	0.61	0.52	0.35
Hispanic	47.34 (26.43)	17.39 (17.75)	40.58 (26.98)	34.78 (25.58)	27.54 (24.5)	38.41 (19.90)	36.23 (27.36)
Non-Hispanic	44.36 (27.31)	19.82 (20.72)	47.18 (31.46)	36.48 (32.04)	41.11 (19.21)	41.11 (19.21)	30.64 (27.61)
Relationship status	0.23	0.85	0.18	<0.01	0.18	0.01	0.08
Single, divorced, widowed	47.559 (28.75)	19.96 (21.66)	50.39 (32.24)	44.38 (33.39)	27.91 (23.60)	45.06 (21.21	35.47 (28.45)
Married, long relationship	43.28 (26.44)	19.46 (19.96)	44.94 (30.55)	32.72 (30.03)	24.08 (21.37)	39.01 (18.03)	29.14 (27.04)
Insurance status	0.07	<0.01	0.61	0.34	0.20	0.11	0.20
Insured	44.07 (27.32)	18.97 (20.24)	46.46 (31.28)	36.01 (31.80)	24.96 (21.93)	40.55 (19.25)	30.72 (27.47)
Uninsured	60.49 (17.66)	38.89 (18.63)	51.85 (26.93)	46.30 (20.03)	34.57 (26.90)	50.93 (16.89)	42.59 (30.17)
Highest level of education	<0.001	0.86	<0.001	0.01	0.06	<0.001	0.02
High school	48.46 (31.44)	22.22 (24.56)	49.07 (35.62)	41.20 (31.49)	30.25 (25.69)	49.07 (24.13)	34.72 (29.65)
Associates degree	59.18 (25.60)	19.73 (17.24)	63.61 (27.15)	48.30 (31.04)	27.66 (21.77)	47.96 (18.52)	39.12 (30.34)
College	43.58 (25.59)	19.42 (21.53)	45.47 (30.80)	34.95 (31.44)	26.65 (22.78)	39.40 (18.67)	31.39 (26.84)
Masters or doctorate	36.20 (24.76)	18.73 (19.27)	37.64 (28.04)	29.40 (30.15)	20.35 (19.26)	35.39 (15.81)	24.91 (24.89)
Current employment	<0.01	0.05	0.001	0.04	0.12	<0.001	0.01
Employed, full-time student	42.66 (27.04)	18.64 (20.26)	44.02 (30.07)	34.74 (31.60)	24.43 (21.55)	39.21 (18.78)	29.47 (26.97)
Unemployed	56.11 (25.53)	25.42 (21.01)	62.08 (33.12)	45.83 (29.66)	30.28 (24.91)	50.83 (19.13)	40.83 (29.46)
Type of hormone replacement	0.18	0.13	0.03	0.44	0.83	0.10	0.14
T4 brand	43.54 (27.24)	19.44 (20.71)	44.92 (31.30)	36.38 (31.85)	25.16 (22.22)	40.18 (19.26)	19.44 (20.71)
T3 brand	53.33 (26.53)	40.00 (19.00)	46.67 (29.81)	23.33 (34.56)	33.33 (17.57)	45.00 (15.14)	40.00 (19.00)
T4/T3 brand	46.83 (23.14)	15.48 (15.28)	57.14 (28.28)	30.95 (24.34)	23.02 (18.72)	40.48 (19.57)	40.48 (19.57)
Natural (armor)	60.19 (28.61)	19.44 (18.57)	69.44 (21.12)	47.22 (30.84)	26.85 (26.57)	54.17 (16.85)	54.17 (16.85)
Generic replacement	0.56	<0.01	0.89	0.14	0.10	0.93	0.17
No	45.34 (27.15)	16.76 (19.99)	46.84 (31.21)	38.51 (32.04)	23.63 (20.33)	40.80 (19.07)	32.85 (27.84)
Yes	43.37 (27.37)	24.43 (20.45)	46.28 (31.13)	32.69 (30.42)	28.05 (24.69)	41.02 (19.62)	28.16 (27.02)
RAI	0.33	0.43	0.67	0.34	0.01	0.41	<0.01
No	40.99 (26.15)	17.41 (20.40)	44.81 (31.35)	32.22 (25.47)	17.53 (19.17)	38.70 (18.39)	20.74 (23.61)
Yes	45.31 (27.40)	20.04 (20.50)	46.98 (31.14)	37.14 (32.55)	26.77 (22.36)	41.31 (19.41)	33.12 (27.89)
Comorbidities	<0.001	0.36	<0.01	<0.01	<0.01	<0.001	<0.001
None	37.47 (25.71)	18.32 (21.13)	40.50 (29.48)	30.03 (30.70)	21.12 (18.11)	34.44 (16.94)	24.38 (23.57)
≥1	50.14 (27.11)	20.62 (19.95)	51.39 (31.62)	41.24 (31.36)	28.49 (24.35)	45.89 (19.48)	36.32 (29.36)
Hypoparathyroidism	0.05	0.77	0.48	0.02	0.67	0.19	0.06
No	45.36 (27.28)	19.67 (20.59)	47.19 (31.82)	37.06 (31.24)	25.80 (22.52)	41.21 (19.49)	31.76 (27.46)
Yes	72.22 (29.40)	16.67 (23.57)	58.33 (9.62)	75.00 (21.52)	30.56 (18.98)	54.17 (8.33)	58.33 (39.67)

Table 4.

THYCA-QoL Scores in AYAs—The 6 Items

	Scar, p-value/M (SD)	Chilly, p-value/M (SD)	Tingling, p-Value/M (SD)	Weight gain, p-value/M (SD)	Headache, p-value/M (SD)	Anxiety, p-value/M (SD)
Survivorship time (years)	0.03	0.82	0.99	0.20	0.01	0.01
<1	36.99 (31.21)	48.40 (36.02)	35.62 (33.48)	37.44 (34.67)	34.25 (29.38)	72.15 (27.22)
1–5	31.47 (30.32)	45.33 (35.01)	36.80 (32.19)	48.27 (33.72)	38.67 (33.17)	86.40 (31.71)
6–10	21.60 (21.63)	47.53 (34.63)	37.65 (36.08)	42.59 (33.91)	49.38 (34.71)	79.01 (33.83)
>10	26.67 (30.43)	52.00 (30.55)	36.00 (23.41)	44.00 (38.15)	57.33 (35.38)	89.33 (35.64)
Age (years)	0.39	0.94	0.77	0.02	0.82	0.59
17–25	35.80 (33.24)	49.38 (39.62)	39.51 (37.02)	30.86 (29.12)	41.98 (34.08)	85.19 (32.47)
26–30	33.33 (33.01)	48.08 (36.99)	32.69 (31.99)	36.54 (31.83)	39/74 (33.68)	85.90 (33.88)
31–35	26.74 (26.76)	45.49 (35.58)	36.46 (34.23)	45.14 (36.83)	43.75 (32.91)	79.86 (32.97)
36–40	31.37 (28.85)	47.71 (31.64)	37.91 (30.05)	50.00 (33.74)	39.54 (33.74)	79.42 (29.72)
Sex	0.04	0.08	0.01	0.04	0.13	0.13
Male	16.67 (20.61)	33.33 (28.01)	18.52 (26.13)	27.78 (30.78)	29.63 (32.11)	70.37 (30.01)
Female	31.53 (29.73)	48.13 (34.97)	37.84 (32.57)	45.05 (34.54)	42.08 (33.34)	82.24 (31.91)
Race/ethnicity	0.27	0.95	0.01	0.74	0.90	0.37
White	29.17 (28.13)	46.67 (35.01)	35.28 (31.33)	43.75 (35.00)	41.11 (33.19)	81.67 (31.49)
Black	55.56 (38.49)	55.56 (38.49)	11.11 (19.25)	44.44 (19.23)	44.44 (19.25)	66.67 (33.33)
Asian	38.10 (28.81)	50.00 (36.39)	33.33 (29.24)	45.24 (33.61)	35.71 (44.27)	73.81 (39.61)
American Indian or Pacific Islander	33.33 (47.14)	41.67 (16.67)	75.00 (50.00)	66.67 (27.22)	41.67 (31.91)	108.33 (31.91)
Other	39.58 (40.77)	52.08 (34.36)	54.17 (40.14)	39.58 (32.70)	47.92 (29.74)	81.25 (29.74)
Ethnicity	0.98	0.46	0.20	0.72	0.33	0.68
Hispanic	30.43 (37.48)	42.03 (22.96)	44.93 (34.24)	46.38 (31.36)	47.83 (29.86)	84.06 (31.57)
Non-Hispanic	30.58 (28.68)	47.64 (35.58)	35.83 (32.30)	43.70 (34.84)	40.68 (33.64)	81.23 (31.95)
Relationship status	0.04	0.74	<0.01	0.28	0.84	0.01
Single, divorced, or widowed	36.05 (31.19)	46.12 (36.57)	44.19 (34.08)	47.29 (34.85)	41.86 (34.75)	88.76 (32.98)
Married or long-term relationship	28.10 (28.33)	47.64 (33.92)	33.16 (31.25)	42.41 (34.36)	41.01 (32.79)	78.18 (30.89)
Insurance status	0.29	0.93	0.15	0.02	0.96	0.29
Insured	30.22 (28.75)	47.14 (34.80)	36.07 (32.39)	43.03 (34.46)	41.29 (33.56)	81.09 (31.98)
Uninsured	40.74 (46.48)	48.15 (33.79)	51.85 (33.79)	70.37 (26.06)	40.74 (27.78)	92.59 (27.78)
Highest level of education	0.09	0.06	<0.001	0.04	0.01	0.03
High school	25.93 (32.96)	57.41 (40.33)	43.52 (32.68)	48.15 (39.39)	49.07 (33.32)	89.81 (31.69)
Associates degree	24.49 (26.15)	53.74 (31.78)	53.74 (35.24)	54.42 (32.41)	52.38 (31.18)	89.12 (25.81)
College	35.92 (30.85)	44.98 (34.52)	32.04 (30.93)	42.72 (32.81)	38.19 (33.46)	80.58 (33.18)
Masters or doctorate	29.59 (27.26)	41.95 (33.15)	29.59 (29.06)	37.83 (34.52)	35.58 (32.87)	74.91 (32.28)
Current employment	0.40	<0.01	0.59	0.12	<0.01	0.45
Employed, full-time student	29.96 (29.07)	44.59 (34.10)	36.15 (32.93)	42.62 (34.28)	38.96 (32.71)	80.87 (32.18)
Unemployed	34.17 (31.56)	62.50 (34.75)	39.17 (30.08)	51.67 (35.36)	55.00 (34.22)	85.00 (30.15)
Type of hormone replacement	0.20	0.56	0.71	0.18	0.96	0.82
T4 brand	30.49 (28.98)	46.88 (34.56)	36.18 (33.07)	42.82 (33.67)	41.46 (33.36)	81.17 (32.18)
T3 brand	46.67 (29.81)	33.33 (40.83)	26.67 (27.88)	33.33 (47.14)	46.67 (44.72)	86.67 (38.01)
T4/T3 brand	19.05 (28.38)	47.62 (36.31)	40.48 (26.73)	61.90 (36.65)	38.10 (28.82)	78.57 (24.83)
Natural (armor)	38.89 (37.15)	58.33 (35.17)	44.44 (29.58)	50.00 (41.44)	38.89 (37.15)	88.89 (32.82)
Generic replacement	0.84	0.42	0.52	0.24	0.95	0.72
No	30.84 (28.89)	48.47 (35.76)	37.55 (33.35)	45.79 (34.82)	41.38 (33.42)	81.99 (31.78)
Yes	30.10 (30.43)	44.98 (32.91)	34.95 (31.09)	40.78 (33.96)	41.10 (33.40)	80.58 (32.18)
RAI	0.04	0.13	0.66	0.96	0.35	0.09
No	38.52 (33.30)	40.00 (36.65)	38.52 (34.78)	43.70 (36.11)	37.04 (30.34)	74.07 (30.88)
Yes	29.02 (28.44)	48.56 (34.23)	36.21 (32.10)	43.97 (34.28)	42.10 (33.90)	82.90 (31.93)
Comorbidities	0.17	0.06	0.09	<0.01	<0.01	<0.001
≥1	32.69 (30.40)	50.64 (34.80)	39.53 (32.08)	49.15 (33.11)	45.94 (34.15)	88.03 (31.21)
None	27.82 (28.00)	42.70 (34.22)	32.78 (32.50)	37.19 (35.27)	35.26 (31.41)	73.00 (30.83)
Hypoparathyroidism	0.66	0.59	0.45	0.21	0.04	0.26
No	30.78 (29.47)	46.96 (34.72)	36.01 (32.17)	43.92 (34.67)	40.75 (33.11)	81.27 (31.86)
Yes	11.11 (19.24)	66.67 (33.33)	88.89 (19.24)	44.44 (19.25)	88.89 (19.25)	100.00 (33.33)

Table 5.

PCS, MCS, and SF-6D Scores in AYAs

	n (%)	Sf-12 MCS, M (SD)	p-Value	Sf-12 PCS, M (SD)	p-Value	SF-6D, M (SD)	p-Value
Survivorship time (years)			0.28		0.80		0.78
<1	73	39.40		44.49		0.692 (0.130)
15	125	38.82		45.59		0.692 (0.135)
6–10	54	39.93		47.83		0.703 (0.148)
>10	25	40.77		47.34		0.719 (0.124)
Age (years)			0.60		0.31		0.77
17–25	27	38.31		46.26		0.67
2630	52	38.10		48.01		0.70
31–35	96	39.41		44.68		0.69
36–40	102	40.25		45.87		0.70
Sex			0.010		0.362		0.004
Male	18	45.25		48.04		0.782 (0.128)
Female	259	38.95		45.74		0.691 (0.134)
Race/ethnicity			0.57		0.069		0.043
White	240	39.53		46.07		0.700 (0.136)
Black	3	41.74		50.02		0.773 (0.104)
Asian	14	41.34		39.76		0.677 (0.132)
American Indian or Pacific Islander	4	24.90		39.97		0.502 (0.136)
Other	16	38.25		49.35		0.696 (0.077)
Ethnicity			0.647		0.708		0.709
Hispanic	23	38.44		46.67		0.686 (0.102)
Non-Hispanic	254	39.45		45.83		0.697 (0.137)
Relationship status			0.362		0.000		0.029
Single, divorced, or widowed	86	36.18		46.74		0.670 (0.117)
Married or long-term relationship	191	40.80		45.51		0.708 (0.141)
Insurance status			0.717		0.372		0.407
Insured	268	39.33		46.00		0.698 (0.136)
Uninsured	9	40.57		42.88		0.659 (0.103)
Highest level of education			0.008		0.000		<0.001
High school	36	37.11		44.41		0.677 (0.151)
Associates/trade degree	49	36.42		41.05		0.637 (0.135)
College	103	39.33		45.75		0.692 (0.123)
Masters or doctorate	89	41.94		49.34		0.742 (0.127)
Current employment status			0.076		0.000		<0.001
Employed or full-time student		39.81		47.25		0.709 (0.130)
Unemployed		36.74		37.90		0.619 (0.137)
Type of hormone replacement			0.427		0.331		0.316
T4	246	39.47		46.28		0.701 (0.138)
T3	5	41.00		40.57		0.642 (0.147)
T4/T3	14	40.73		42.98		0.683 (0.086)
Natural (armor)	12	34.86		43.65		0.637 (0.094)
Generic replacement			0.816		0.565		0.403
Yes	103	39.18		45.43		0.694 (0.136)
No	174	39.47		46.17		0.707 (0.132)
RAI			0.709		0.830		0.578
Yes	232	39.26		45.95		0.694 (0.44)
No	45	39.88		45.59		0.702 (0.129)
Comorbidities			0.000		0.000		<0.001
None	121	41.76		48.99		0.740 (0.129)
Yes (≥1)	156	37.51		43.50		0.663 (0.130)
Hypoparathyroidism			0.909		0.019		0.334
Yes	3	40.03		32.06		0.621 (0.116)
No	274	39.36		46.05		0.697 (0.135)
Menopause (females only)			0.366		0.051		0.052
Yes	4	34.66		35.74		45.36 (27.28)
No	255	39.03		45.91		72.22 (29.39)

Norm SF-6D for ages 35–44 years = 0.80; norm PCS for ages 35–44 years = 52.0, for ages 25–34 years = 53.3; norm MCS for ages 35–44 and 25–34 years = 48.8.

The average SF-6D score was 0.70 (SD = 0.13) in YAs and approximated a normal curve (skewness 0.07). This differed significantly from the normative SF-6D value of 0.80 for those 35–44 years of age (p < 0.001) (21); when stratified by sex, the SF-6D for YA TC male survivors was not different from the norm (norm: 0.81, p = NS) but remained significantly lower for YA TC females compared to the norm (norm: 0.80, p < 0.001). The same overall and sex-specific differences existed for survivors >40 years old (data not shown).

All THYCA-QoL domains correlated with HRQOL. Neuromuscular, concentration, and psychological complaints had the strongest correlation with worsening health status (r = −0.23 to −0.62; Supplementary Appendix. Supplementary Data are available online at www.liebertpub.com/thy). The simplest, best multivariate regression model included neuromuscular, concentration, and anxiety complaints along with the presence of a comorbidity for predicting lower HRQOL (Table 6). No other clinical or socio-demographic variable contributed significantly to the regression model, and they were therefore dropped for simplicity. When males were excluded from the analysis (due to low numbers), the same THYCA-QoL factors remained significant, together with comorbidities, employment, and relationship status (R ² = 0.54; data not shown). The simplest regression model for survivors currently >40 years of age included the same THYCA-QoL elements but substituted employment for lack of comorbidities (R ² = 0.48; data not shown).

Table 6.

Simplest, Best Regression Model for Predicting Lower Overall HRQOL in AYA Thyroid Cancer Survivors

	B coefficient	CI	R²
Neuromuscular	−0.466	−0.003 to −0.002	0.53
Concentration	−0.233	−0.001 to −0.001
Anxiety	−0.125	−0.001 to 0.000
No comorbidity	0.110	0.007 to 0.053

HRQOL, health-related quality of life; CI, confidence interval.

Discussion

In this large study of YA TC survivors, there was a significant difference in most TC-specific QOL domains measured by the THYCA-QoL questionnaire between the younger and older age groups. Compared with older survivors, YAs had more complaints that related to general psychological issues and anxiety, as well as headaches, chilliness, and their scar. They reported fewer complaints related to neuromuscular, voice, sympathetic, or throat/mouth symptoms. Although a number of clinical and socio-demographic variables affected HRQOL on univariate analysis, only neuromuscular, concentration, and anxiety complaints along with the presence of a comorbidity were important predictors of a lower overall HRQOL in YAs. Moreover, in YA females, overall HRQOL differed significantly from the U.S. norm.

Although TC is a disease with low disease-specific mortality, there is a small but significant risk of both short- and long-term complications from surgery, radioiodine, and medical therapy, and all survivors must undergo lifelong surveillance for disease recurrence. These issues likely form the backbone of the increased complaints seen with regard to psychological issues and anxiety in the present cohort's YAs, and are consistent with a recent study that reported emotional and psychological concerns are largely unmet in this population (23). They are also in line with other YA cancer patient surveys that describe negative emotions related to body image and perceived stigma, as well as struggles and fears related to the cancer experience (24). A recent study from Korea showed that within the first year post thyroidectomy, an adverse scar negatively affected QOL of TC survivors, independent of socio-demographic characteristics (25). Therefore, the negative impact on QOL of a TC diagnosis in YAs should not be discounted. The current study is added proof that the interruptions to family planning, career advancement, and intimate relationship building that happens in older YAs leaves a similar impact on QOL across all cancer types (26,27).

Although the present study did not use a specific distress screening tool, the domains measured by the THYCA-QoL are similar to specific distress domains. Distress has been called the sixth vital sign in cancer patients, and there is increasing evidence that increased levels of distress in cancer patients can negatively impact treatment, follow-up adherence, and QOL (28). Analogous to a Dutch study where a third of almost 200 TC survivors seen in the outpatient setting reported clinically significant levels of physical distress, neuromuscular complaints had the greatest impact on overall HRQOL (29). Additionally, a Korean study used the same distress assessment tool and their version of the mini-mental scale to show that anxiety and helplessness were the only factors that increased distress in TC survivors, which could correspond to the anxiety and psychological domains highlighted in the present cohort (30). No significance was found with distress and any clinical or demographic factors in either article, whereas the presence of comorbidities was found to impact HRQOL significantly in the YA respondents of the current study.

No studies have explored HRQOL specifically in YAs, and few have incorporated cancer-specific QOL domains into their preference-based models. In the few that have examined HRQOL across all ages in specific cancers, there are differing reports as to the influence of various clinical and socio-demographic factors (31 –33). Most of these studies used the EQ-5D, a similar but different preference-based health assessment tool that has been shown to be inferior to the SF-6D for use in predictions for cancer-specific QOL measures (34). Age, sex, cancer stage, and QOL domain scores were important for determining HRQOL in at least one study (34,35). This is in contrast to our regression model that is comprised mainly of TC-specific QOL domains and not clinical or demographic factors.

There are inherent limitations to the current study. There is the potential of selection bias regarding which patients and survivors knew about the study and additionally opted to participate. Participants had to know about the TC survivor group ThyCa and either be registered on their listserv or check the Web site during the enrollment period. Therefore, all participants had to have knowledge about the support group, which would come either from their physicians or from being Internet-savvy. Although one might hypothesize that these survivors had worse cancer treatment experiences or came only from large academic or cancer centers, previous work with this population has shown this not to be true (36). Additionally, although this study was able to capture >1000 survivors from a wide range of demographic backgrounds and TC treatments, and should therefore be fairly representative of the larger TC patient and survivor population, the authors acknowledge that the population is skewed toward more short-term (within 10 years) survivors and that the self-reported permanent hypoparathyroidism rate is a little lower then reported in the literature (36).

An important next step in research would be a longitudinal assessment of individual THYCA-QoL scores over time with corresponding information of interventions, changes in lifestyle, or socio-demographic parameters that influence the THYCA-QoL scores. This study was a one-time self-report, and therefore no triangulation of data could be performed. Additionally, since the predictive performance of the regression model was on the lower end of the range for R ² goodness-of-fit values for other survey predictors of the SF-6D, it needs to be validated in another cohort of young TC survivors to assess its ultimate usefulness in cost and utility studies (34,35,37 –39).

Conclusion

TC-specific QOL is significantly influenced by many socio-demographic and clinical factors. In YA TC survivors, neuromuscular, concentration, and anxiety complaints, along with the presence of a comorbidity, had the greatest impact on HRQOL. Clinicians should be more aware of how these complaints can influence overall health. Interventions should be designed to identify which survivors are suffering from these complaints during annual survivorship visits so that these survivors can be referred for appropriate counseling and intervention.

Footnotes

Acknowledgments

We would like to thank Dr. Olga Husson for providing the scoring system and statistical syntax for converting the THYCA-QOL into scales. We would also like to thank Stephanie Morley for her help in acquiring statistical scoring syntax for the SF-12v1.

Author Disclosure Statement

No competing financial interests exist.

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