S Singer 

et al. EORTC QLQ-THY phase III 24:4 197–207

Research

The EORTC module for quality of life

in patients with thyroid cancer:
phase III

Susanne Singer1,2, Susan Jordan3, Laura D Locati4, Monica Pinto5,

Iwona M Tomaszewska6, Cláudia Araújo7, Eva Hammerlid8, E Vidhubala9,
Olga Husson10, Naomi Kiyota11, Christine Brannan12, Dina Salem13, Eva M Gamper14,
Juan Ignacio Arraras15, Georgios Ioannidis16, Guy Andry17, Johanna Inhestern18,
Vincent Grégoire19, Lisa Licitra4 on behalf of the EORTC Quality of Life Group,
the EORTC Head and Neck Cancer Group, and the EORTC Endocrine Task Force
1Institute of Medical Biostatistics Epidemiology and Informatics (IMBEI), University Medical
Center Mainz, Mainz, Germany
2University Cancer Centre, Mainz, Germany

3QIMR Berghofer Medical Research Institute, Herston, Australia

4Head & Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

5Rehabilitation Unit, Department of Quality of Life, Istituto Nazionale per lo Studio e la Cura dei
Endocrine-Related Cancer

Tumori ‘Fondazione Giovanni Pascale’ – IRCCS, Naples, Italy

6Department of Medical Education, Jagiellonian University Medical College, Krakow, Poland

7Service of Surgical Oncology, Instituto Português do Oncologia do Porto Francisco Gentil, Porto, Portugal

8Department of Otolaryngology and Head and Neck Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden

9Department of Psycho-Oncology, Resource Centre for Tobacco Control, Cancer Institute (WIA),

Chennai, Tamil Nadu, India

10Department of Medical Psychology, Radboud University Medical Center, Nijmegen, The Netherlands

11Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan

12Mount Vernon Cancer Centre, East & North Herts NHS Trust, Northwood, London, UK

13Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

14Department of Nuclear Medicine, Medical University of Innsbruck, Innsbruck Institute of

Patient-Centred Outcome Research, Innsbruck, Austria

15Oncology Departments, Complejo Hospitalario de Navarra, Pamplona, Spain

16Oncology Department, Nicosia General Hospital, Nicosia, Cyprus

17Surgery Department, Jules Bordet Institute, Brussels, Belgium

18Clinic of Otorhinolaryngology, Jena University Hospital, Jena, Germany Correspondence

19Department of Radiation Oncology, Institut de Recherche Experimentale et Clinique, should be addressed
to S Singer
Université Catholique de Louvain, St-Luc University Hospital, Brussels, Belgium
Email
singers@uni-mainz.de

Abstract
The purpose of the study was to pilot-test a questionnaire measuring health- Key Words
related quality of life (QoL) in thyroid cancer patients to be used with the European ff thyroid cancer
Organisation for Research and Treatment of Cancer (EORTC) core questionnaire EORTC ff quality of life
QLQ-C30. A provisional questionnaire with 47 items was administered to patients ff papillary
treated for thyroid cancer within the last 2 years. Patients were interviewed about ff follicular
time and help needed to complete the questionnaire, and whether they found the ff medullary
items understandable, confusing or annoying. Items were kept in the questionnaire ff anaplastic
if they fulfilled pre-defined criteria: relevant to the patients, easy to understand, not ff patient-reported outcomes
confusing, few missing values, neither floor nor ceiling effects, and high variance.
A total of 182 thyroid cancer patients in 15 countries participated (n = 115 with papillary,

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 Research S Singer et al.
n = 31 with follicular, n = 22 with medullary, n = 6 with anaplastic, and n = 8 with other
types of thyroid cancer). Sixty-six percent of the patients needed 15 min or less to
complete the questionnaire. Of the 47 items, 31 fulfilled the predefined criteria and
were kept unchanged, 14 were removed, and 2 were changed. Shoulder dysfunction
was mentioned by 5 patients as missing and an item covering this issue was added. To
conclude, the EORTC quality of life module for thyroid cancer (EORTC QLQ-THY34) is
ready for the final validation phase IV.
Introduction
While thyroid cancer is one of the less common
malignancies with an age-standardised rate in Europe
of 6.3 per 100,000 per year (3.1 in men and 9.3 in
women) (Ferlay  et  al. 2013), the incidence rates have
been rising rapidly in many countries (Amphlett  et  al.
2013, Husson  et  al. 2013b, Radespiel-Troger  et  al. 2014,
Carlberg  et  al. 2016, Morris  et  al. 2016). Papillary and
follicular thyroid cancers have a very good prognosis
with 20-year relative survival rates of 95% (Brenner 2002)
Endocrine-Related Cancer
but the rarer medullary cancers have 10-year survival
rates of 75–85% (Pacini  et  al. 2010, Brown  et  al. 2011,
Wu  et  al. 2012), and patients with (very rare) anaplastic
tumours often do not survive 6  months after diagnosis
(Brown et al. 2011).
The current standard anti-neoplastic treatment
comprises surgery, radioactive iodine (RAI) ablation,
radiotherapy and medical therapy, including thyroxine,
tyrosine kinase inhibitors and chemotherapy, according
to the stage and histological type of the disease. Both
disease and treatment can have profound effects on the
patients’ quality of life (QoL) (Husson et al. 2011, Gamper
& Sztankay 2015, Applewhite et al. 2016).
The most common and significant complications
of total thyroidectomy and neck dissection are long-
term hypoparathyroidism leading to hypocalcaemia
and injury at the laryngeal nerve and its branches
leading to vocal cord paresis and voice changes
(Ryu et al. 2013). Potential long-term side effects of RAI
include xerostomia, nasolacriminal duct stenosis, bone
marrow and gonadal deficiency (Husson  et  al. 2011).
Temporary TSH stimulation along with radioiodine
ablation as a preparation for radioiodine whole-body
imaging and serum thyroglobulin (Tg) measurements
can result in severe fatigue, neurological deficiencies,
reduced appetite, memory problems and depression
(Dow  et  al. 1997, Gamper  et  al. 2015). Potential side
effects of TSH-suppressive doses of levothyroxine are
cardiac tachyarrhythmias, bone demineralisation
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EORTC QLQ-THY phase III 24:4 198
Endocrine-Related Cancer
(2017) 24, 197–207
and symptoms of hyperthyroidism. With the use of
recombinant human thyroid-stimulating hormone
(rhTSH), compared with conventional thyroid hormone
withdrawal, fewer symptoms occur (Taieb  et  al. 2009,
Lee  et  al. 2010). However, this treatment is expensive
compared to hormone withdrawal and is not
administered in all institutions and countries.
Several multi-targeted tyrosine kinase inhibitors (TKI)
are currently available for advanced-stage medullary
thyroid cancer and radioiodine-refractory papillary and
follicular thyroid carcinomas. Their use is commonly
associated with a wide range of toxicities that can
significantly affect QoL, including hypertension, skin
rash and gastrointestinal adverse events (Krajewska et al.
2015, Schlumberger et al. 2015).
Despite this, clinicians sometimes assume that,
due to the good prognosis, thyroid cancer patients
have less distress than other cancer patients, and that
QoL is comparable to the general population as long as
patients do not have to undergo thyroxine withdrawal
(Dow et al. 1997, Borget et al. 2007). Whilst some studies
have found that those with thyroid cancer generally
have a QoL that is comparable to people in the general
population (Crevenna  et  al. 2003, Schroeder  et  al.
2006), others have reported an impaired QoL (Botella-
Carretero et al. 2003, Bianchi et al. 2004, Tagay et al. 2005,
Tan  et  al. 2007, Hoftijzer  et  al. 2008, Singer  et  al. 2012,
Applewhite et al. 2016).
A key weakness of most studies to date has been a lack
of specific questionnaires for thyroid-related problems
and functioning. Assessments have been done largely
using generic instruments. Only few thyroid-specific
QoL questionnaires were developed (Dow  et  al. 1997,
Husson  et  al. 2013a). The European Organisation for
Research and Treatment of Cancer (EORTC) therefore
created a thyroid-cancer-specific module to be used as
a supplement of the quality-of-life core questionnaire
EORTC QLQ-C30 (phase I and II of the EORTC
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 Research S Singer et al.
module development process (Johnson  et  al. 2011)).
This  (provisional) module was developed based on two
systematic reviews and structured interviews with 110
patients and 57 health care professionals (Singer  et  al.
2016). In these previous phases, items were derived from a
longer list of QoL issues that could be relevant for thyroid
cancer patients. The patients and health care professionals
rated these issues for relevance and importance, resulting
in a list of 47 items with the most important and relevant
QoL issues.
The present study was set up to pilot-test this list,
representing phase III of the instrument development
according to the EORTC module development guidelines
(Johnson et al. 2011).
Methods
Study design
The module was pilot-tested in a multi-national cross-
sectional study according to the EORTC module
Endocrine-Related Cancer
development guidelines (Johnson  et  al. 2011). Patients
were eligible if they fulfilled the following criteria:
histologically verified thyroid cancer (International
Classification of Diseases, version 10, code C73), treatment
for thyroid cancer within the last two years, ability to
understand and complete the questionnaire (language
proficiency and cognitive functioning as judged by the
local study coordinator upon inclusion), age 18 years or
above, and written informed consent. Patients could be
on or off treatment.
Consecutive patients attending the collaborating
institutions were screened for eligibility and asked to
participate. The enrolment was monitored monthly
by the principal investigator and fed back to the
collaborators. We tried to maximise the heterogeneity
of the sample in terms of histology, tumour stage
and country. Thus, patients with papillary, follicular,
medullary and anaplastic cancer were included.
Additionally, we aimed to interview at least 15 patients
from each of the following cultural areas: Central
Europe, Southern Europe, Northern Europe, Eastern
Europe, Western Europe, Asia and Australia. As the study
evolved, we monitored whether there were sufficient
patients in each group. Thereafter, additional patients
were enrolled only in groups where patient numbers
had not reached our target. We aimed to include 150
patients, including 60 with papillary, 50 with follicular,
30 with medullary and 10 with anaplastic cancer,
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EORTC QLQ-THY phase III 24:4 199
in order to create a sample with a good representation
of both the rarer and the more frequent types of thyroid
cancer.
Data collection
The provisional questionnaire was completed by the
patients together with the EORTC QLQ-C30. The
questionnaires were administered in the native language
of the individual patient. They had been translated
beforehand via forward and backward translations
according to the EORTC translation guidelines
(Dewolf  et  al. 2009) and coordinated by the EORTC
translation unit.
In a debriefing interview, participants were asked
whether any item was difficult for them to understand or
upsetting, how much time they needed to complete the
questionnaire and whether they required any help with
it. They were requested to name the most important items
they would like to have included in the questionnaire,
and to indicate items they found irrelevant. If the
questionnaire was lacking a certain item, it was written
down using the patients’ wording.
Socio-demographic (age, gender, education) and
clinical characteristics (histology, tumour stage, time
since diagnosis, treatment, Karnofsky performance status,
thyroid hormone status) were documented on case report
forms by the interviewer. All clinical data were obtained
from the patients’ medical charts.
All procedures performed were in accordance with
the ethical standards of the institutional research
committees and with the 1964 Helsinki declaration
and its later amendments of comparable ethical
standards. The study protocol was approved by the
local ethical committees in each country. The approval
of the principal investigator’s institution was granted
on 18 December 2014 (# 837.470.14, 9709). Informed
consent was obtained from all individual participants
included in the study. The study was registered at the
EORTC Quality of Life Group (# EORTC QLQ-THY_
Phase III).
Statistical analysis
We calculated frequencies of all item responses together
with their range and mean and the percentage of missing
values per scale. We counted how often a certain item
was mentioned to be upsetting, difficult to understand,
relevant, or irrelevant.
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 Research S Singer et al. EORTC QLQ-THY phase III 24:4 200

The pre-defined criteria for keeping an item in Data entry, cleaning and analysis were conducted
the questionnaire (according to the EORTC module using STATA (Stata Statistical Software, release 12;
development guidelines (Johnson  et  al. 2011)) were: StrataCorp, College Station, TX, USA).
(1) importance (mean >1.5; items had a response format
1–4), (2) prevalence (scores 3 or 4 >50%), (3) neither
floor nor ceiling effect (responses 1 or 2 and 3 or 4 >10%,
Results
respectively), (4) variance (responses range from 1 to Sample characteristics
4), (5) acceptance (<5% of patients stated that the item
A total of 182 patients participated in the study;
was upsetting), (6) clarity (<5% of patients stated that
n = 115 with papillary, n = 31 with follicular, n = 22 with
the items was difficult to understand), (7) compliance
medullary, n = 6 with anaplastic and n = 8 with another
(>95% of the patients completed the item), and (8)
type of thyroid cancer (Table 1). They were enrolled from
relevance (>10% of the patients mentioned the item as
17 institutions in 15 countries (n = 37 from Italy, n = 25
especially relevant).
Australia, n = 17 Poland, n = 14 Portugal, n = 13 Germany,
The items were grouped into hypothesised scales,
n = 13 India, n = 13 Sweden, n = 11 the Netherlands, n = 9
and Cronbach’s alpha and scaling error (percentage
Japan, n = 9 the United Kingdom, n = 7 Egypt, n = 4 Austria,
of items that correlate higher with a different scale
n = 4 Spain, n = 3 Belgium, and n = 3 Cyprus). The median
than with its own scale, corrected for overlap)
time since diagnosis was 0.8  years. The majority (96%)
were calculated. If items worked well together in
had a Karnofsky performance status of 70 or higher.
a scale, it was another criterion for keeping them
in the questionnaire. It should be noted that these
Table 1  Sample characteristics (n = 182).
psychometric tests are preliminary and that the final
Endocrine-Related Cancer

psychometric testing will be done in phase IV of this Number Percent (%)

module development. Age (in years) <40 41 23

40–49 32 18
We tabulated the results per item together with the
50–59 35 19
number of fulfilled criteria. A multi-national multi- 60–69 39 21
professional group of experts then discussed the results 70–79 31 17
and decided on keeping, removing or changing items. 80+ 3 2
Unknown 1 1
An item was kept when most criteria were fulfilled Sex Male 60 33
and the patients had assessed it as relevant. An item Female 122 67
was removed when few criteria were fulfilled and Education Compulsory or less 55 30
only few patients had mentioned the item as highly Post-compulsory 70 38
University 53 29
relevant. An item was changed if it was considered Unknown 4 2
relevant by the patients but at the same time difficult Histology Papillary 115 63
to understand or upsetting. According to the EORTC Follicular 31 17
Medullary 22 12
module development guidelines (Johnson et al. 2011),
Anaplastic 6 3
the group of experts could decide to keep an item Other 8 4
even if few criteria were fulfilled when they had sound Tumour stage T1 50 27
justification, e.g. when the item was highly relevant to T2 38 21
T3 49 27
a sub-group of patients. T4a 21 12
Relevant issues that participants suggested relevant T4b 6 3
but were lacking from the questionnaire were translated Tx 15 8
Unknown 2 1
into English (where necessary), similar issues were grouped
together and the number of issues was counted. If a new N0 85 47
issue was mentioned by at least 5 patients it was added N1a 30 16
to the module. If items needed to be changed or added, N1b 33 18
Nx 31 17
we searched the EORTC item-library and used existing
Unknown 3 2
validated items if available.
We calculated the average time it took to complete M0 124 68
the questionnaires and how often help was needed to M1 25 14
Mx 32 18
complete the questionnaires.

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 Research S Singer et al. EORTC QLQ-THY phase III 24:4 201

Table 2  Treatment received by the participants. Table 3  Time and help required for completing the
questionnaire.
Percent
Number (%) Percent
Surgery None 3 2 Number (%)
Hemithyroidectomy 12 7 Duration (min) <10 54 30
Partial thyroidectomy 3 2 11–15 67 37
Total thyroidectomy 161 88 16–20 33 18
Unknown 3 2 21–30 12 7
Neck dissection No 91 50 >30 6 3
Yes 77 42 Unknown 10 5
Unknown 14 8 Form of administration Self-completed 137 75
Radioactive Currently receiving this 0 0 Orally 37 20
iodine therapy treatment Unknown 8 4
Last treatment <6 m before 35 19 Type of help required No help required 109 60
interview Practical help 30 16
Last treatment ≥6 m before 65 36 required
interview Supportive help 21 12
Never/not yet 79 43 required
Unknown 3 2 Help with 13 7
Chemotherapy Currently receiving this 0 0 understanding the
treatment questionnaire
Last treatment <6 m before 7 4 Unknown 9 5
interview
Last treatment ≥6 m before 2 1
interview
to help them understand the questions, and in 5% no
Never/not yet 167 92
Endocrine-Related Cancer

Unknown 6 3 information about help needed was provided (Table 3).

Tyrosine kinase Currently receiving this
inhibitors treatment
Last treatment <6 m before
interview
Last treatment ≥6 m before
interview
Never/not yet 164
Unknown
Most of the participants (88%) had had a total
thyroidectomy (Table 2), and 55% had been treated with
radioactive iodine therapy.
In 42 cases (23%), participants had vocal cord
impairment and 29 cases (16%) had parathyroid
insufficiency as a result of treatment, transient
or permanent.
Time and help needed to complete the questionnaire
A total of 121 patients (66%) needed 15 min or less to
complete the questionnaire. Most patients (n = 137, 75%)
completed it on their own while it was administered
orally in 37 (20%) patients, in n = 8 (4%) the method of
administration was not documented.
The majority of patients (n = 109, 60%) required no
help, 16% required practical help (such as reading out loud
if the patient missed his glasses), 12% required supportive
help (such as silently sitting next to the patient while he
completes the questionnaire), 7% needed explanations
9 5
2 1 Evaluation of items
1 1 Thirty items could be meaningfully combined to scales
with Cronbach’s alpha >0.70 and with a decrease of
90
alpha when the item was removed. The hypothesised
6 3
scales were: anxiety, body image, cramps, discomfort in
the head and neck, dry mouth, fatigue, hair, impact on
job or education, joint pain, neuropathological problems,
restlessness, shoulder functioning, social support,
swallowing, temperature tolerance, voice, and worries
about important others.
A total of 34 items fulfilled criterion 1 (mean >1.5).
Only one item satisfied criterion 2 (scores 3 and 4 >50%),
38 items fulfilled criterion 3, i.e. they had neither floor nor
ceiling effects. In all 47 items, the full range of response
categories had been used (criterion 4). All items were well
accepted by the patients both regarding criterion 5 (found
upsetting by less than 5%) and criterion 6 (found difficult
to understand by less than 5%). Nearly all items (n = 45)
were completed by >95% of the patients (criterion 7). A
minimum of 5 out of these 7 criteria were fulfilled by 38
items (Table 4 for details).
Additional items
The patients mentioned 44 issues they felt were missing in
the core questionnaire plus module. Shoulder dysfunction

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 Research S Singer et al. EORTC QLQ-THY phase III 24:4 202

Table 4  Item pilot testing. Results per item, fulfilled criteria and decision by expert group based on the results.

criterion 1
criterion α
hypothesised scale

decreases α if item
Chronbach‘s α of

Chronbach‘s α if
item removed

is removed?

mean > 1.5?

mean
q 31 Have you had sudden attacks of tiredness? 0.85 0.80 1 2.0 1
q 32 Have you felt mentally exhausted? 0.85 0.81 1 1.9 1
q 33 Have you felt physically exhausted? 0.85 0.77 1 2.0 1
q 34 Has your sleep pattern been disrupted? n.a. 0 1.9 1
q 35 Have you felt refreshed when waking up? 0.85 0.87 0 2.9 1
q 36 Have you had pain in your throat? 0.71 0.60 1 1.5 0
q 37 Have you had any discomfort in your neck? 0.71 0.66 1 1.9 1
q 38 Have you had problems breathing? n.a. 0 1.3 0
q 39 Have food and drink tasted different from usual? n.a. 0 1.3 0
q 40 Have you had problems talking to other people because of your voice? 0.91 0.89 1 1.5 1
q 41 Have you had problems with hoarseness? 0.91 0.90 1 1.6 1
q 42 Has your voice sounded different as a result of your disease or treatment? 0.91 0.88 1 1.8 1
q 43 Have you had a tired voice? 0.91 0.90 1 1.7 1
Endocrine-Related Cancer

q 44 Have you had thin or lifeless hair as a result of your disease or treatment? 0.90 0.83 1 1.6 1
q 45 Have you lost any hair? 0.90 0.84 1 1.6 1
q 46 If you have lost any hair: Have you been upset by the loss of your hair? 0.90 0.89 1 2.0 1
q 47 Have you had problems swallowing liquids? 0.82 0.73 1 1.3 0
q 48 Have you had problems swallowing pureed food? 0.82 0.71 1 1.2 0
q 49 Have you had problems swallowing solid food? 0.82 0.85 0 1.4 0
q 50 Have you had a dry mouth? n.a. 0 1.8 1
q 51 Have you had problems tolerating heat or cold? n.a. 0 1.8 1
q 52 Have you felt physically less attractive as a result of your disease or treatment? n.a. 0 1.6 1
q 53 Have you felt restless or agitated? 0.66 1 1.8 1
q 54 Have you had a rapid heartbeat? 0.66 1 1.5 0
q 55 Have you worried about your ability to have children? n.a. 0 1.2 0
q 56 Have you had pain in your shoulder? n.a. 0 1.8 1
q 57 Have you felt as though there was a knot in your throat? 0.71 0.62 1 1.6 1
q 58 Have you worried about a possible recurrence of the disease? 0.53 0.59 0 2.3 1
q 59 Have you worried about having to come off your thyroid hormone tablets? 0.53 0.34 1 1.4 0
q 60 Have you worried about having to take drugs for the rest of your life? 0.53 0.36 1 1.6 1
q 61 Has weight gain been a problem for you? n.a. 0 1.8 1
q 62 Has weight loss been a problem for you? 0.75 1 1.2 0
q 63 Have you worried about losing weight? 0.75 1 1.3 0
q 64 Have you had pain in your joints? n.a. 0 2.0 1
q 65 Have you had problems with your teeth? n.a. 0 1.5 1
q 66 Have you had tingling or numbness in your fingers or toes? 0.66 1 1.6 1
q 67 Have you had tingling or numbness around your mouth? 0.66 1 1.2 0
q 68 Have you had any muscle cramps? n.a. 0 1.6 1
q 69 Have you found it upsetting to see those close to you distressed as a result of your disease or treatment? 0.91 0.90 1 1.9 1
q 70 Have you worried about the future of people who are important to you? 0.91 0.90 1 2.3 1
q 71 Have you worried about disrupting the lives of those close to you? 0.91 0.87 1 2.2 1
q 72 Have you worried how those close to you will cope with your illness and treatment? 0.91 0.88 1 2.1 1
q 73 Have you worried that you will be a burden to others? 0.91 0.90 1 2.1 1
q 74 Have you had any problems with your job or your education because of your disease or treatment? n.a. 0 1.7 1
q 75 Have you felt supported by your doctors? 0.84 0.70 1 1.8 1
q 76 Have you felt supported by other health care professionals (e.g. nurse)? 0.84 0.71 1 1.9 1
q 77 Have you felt supported by your family members or friends? 0.84 0.87 0 1.5 0

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 Research S Singer et al. EORTC QLQ-THY phase III 24:4 203

criterion 4

criterion 6
criterion 2

criterion 3

criterion 5

criterion 7

criterion 8

Decision
relevant or criterion 1–7 and
relevant and criterion 1–7
relevant or criterion 1–7

 
criterion α
prevalence of scores

min. 5 of crit 1 to 7?
scores 3/4 >50%?

neither floor nor

>95% complete?
<5% upsetting

≥10% relevant
sum crit 1 to 7
non-missing
<5% difficult

% irrelevant
% upsetting

proportion

% relevant
% difficult
scores 1/2

ceiling

range

range
3/4

0.27 0 0.73 1 1–4 1 0.00 1 0.01 1 1.00 1 6 1 0.14 0.01 1 1 1 1 keep

0.23 0 0.76 1 1–4 1 0.00 1 0.01 1 0.99 1 6 1 0.16 0.02 1 1 1 1 keep
0.29 0 0.71 1 1–4 1 0.00 1 0.01 1 0.99 1 6 1 0.15 0.01 1 1 1 1 keep
0.26 0 0.74 1 1–4 1 0.00 1 0.00 1 1.00 1 6 1 0.08 0.00 0 1 0 0 remove
0.64 1 0.35 1 1–4 1 0.01 1 0.03 1 0.99 1 7 1 0.05 0.00 0 1 0 0 remove
0.12 0 0.88 1 1–4 1 0.00 1 0.01 1 1.00 1 5 1 0.05 0.01 0 1 0 1 keep
0.24 0 0.76 1 1–4 1 0.00 1 0.00 1 1.00 1 6 1 0.10 0.01 0 1 0 1 keep
0.05 0 0.95 0 1–4 1 0.00 1 0.01 1 1.00 1 4 0 0.05 0.01 0 0 0 0 remove
0.09 0 0.91 0 1–4 1 0.00 1 0.00 1 1.00 1 4 0 0.04 0.03 0 0 0 0 remove
0.14 0 0.86 1 1–4 1 0.00 1 0.00 1 1.00 1 6 1 0.08 0.02 0 1 0 1 remove
0.17 0 0.83 1 1–4 1 0.00 1 0.02 1 1.00 1 6 1 0.08 0.01 0 1 0 1 keep
0.20 0 0.79 1 1–4 1 0.00 1 0.00 1 0.99 1 6 1 0.10 0.01 0 1 0 1 keep
0.20 0 0.79 1 1–4 1 0.00 1 0.01 1 0.99 1 6 1 0.09 0.01 0 1 0 1 keep
Endocrine-Related Cancer

0.20 0 0.80 1 1–4 1 0.00 1 0.01 1 1.00 1 6 1 0.07 0.08 0 1 0 1 keep

0.15 0 0.85 1 1–4 1 0.00 1 0.01 1 1.00 1 6 1 0.05 0.07 0 1 0 1 keep
0.28 0 0.72 1 1–4 1 0.01 1 0.00 1 0.43 0 5 1 0.06 0.04 0 1 0 1 remove
0.07 0 0.92 0 1–4 1 0.00 1 0.00 1 0.99 1 4 0 0.05 0.02 0 0 0 0 remove
0.03 0 0.95 0 1–4 1 0.00 1 0.00 1 0.98 1 4 0 0.05 0.02 0 0 0 0 remove
0.10 0 0.89 0 1–4 1 0.00 1 0.00 1 0.99 1 4 0 0.08 0.01 0 0 0 0 keepa
0.20 0 0.78 1 1–4 1 0.00 1 0.00 1 0.98 1 6 1 0.07 0.01 0 1 0 0 keep
0.24 0 0.75 1 1–4 1 0.00 1 0.00 1 0.99 1 6 1 0.10 0.00 0 1 0 0 keep
0.15 0 0.84 1 1–4 1 0.01 1 0.01 1 0.99 1 6 1 0.07 0.02 0 1 0 0 keep
0.22 0 0.77 1 1–4 1 0.00 1 0.00 1 0.99 1 6 1 0.07 0.01 0 1 0 1 keep
0.10 0 0.89 1 1–4 1 0.00 1 0.00 1 0.99 1 5 1 0.07 0.02 0 1 0 1 keep
0.06 0 0.88 0 1–4 1 0.00 1 0.01 1 0.95 0 3 0 0.03 0.06 0 0 0 0 remove
0.23 0 0.77 1 1–4 1 0.00 1 0.01 1 1.00 1 6 1 0.04 0.03 0 1 0 0 changeb
0.15 0 0.85 1 1–4 1 0.00 1 0.01 1 0.99 1 6 1 0.09 0.01 0 1 0 1 keep
0.38 0 0.61 1 1–4 1 0.02 1 0.01 1 0.99 1 6 1 0.15 0.00 1 1 1 0 keep
0.10 0 0.85 1 1–4 1 0.01 1 0.04 1 0.95 1 5 1 0.03 0.03 0 1 0 1 change
0.15 0 0.85 1 1–4 1 0.00 1 0.01 1 1.00 1 6 1 0.06 0.03 0 1 0 1 keep
0.21 0 0.76 1 1–4 1 0.00 1 0.03 1 0.97 1 6 1 0.07 0.03 0 1 0 0 remove
0.05 0 0.93 0 1–4 1 0.00 1 0.03 1 0.98 1 4 0 0.04 0.03 0 0 0 0 remove
0.08 0 0.91 0 1–4 1 0.00 1 0.00 1 0.99 1 4 0 0.03 0.03 0 0 0 0 remove
0.28 0 0.72 1 1–4 1 0.00 1 0.01 1 1.00 1 6 1 0.06 0.02 0 1 0 0 keepc
0.12 0 0.87 1 1–4 1 0.00 1 0.00 1 0.99 1 6 1 0.03 0.03 0 1 0 0 remove
0.14 0 0.85 1 1–4 1 0.00 1 0.01 1 0.99 1 6 1 0.06 0.07 0 1 0 1 keep
0.04 0 0.96 0 1–4 1 0.00 1 0.01 1 0.99 1 4 0 0.03 0.06 0 0 0 0 keep
0.19 0 0.80 1 1–4 1 0.00 1 0.01 1 0.99 1 6 1 0.04 0.04 0 1 0 0 keepd
0.26 0 0.73 1 1–4 1 0.03 1 0.01 1 0.99 1 6 1 0.12 0.02 1 1 1 1 keep
0.36 0 0.62 1 1–4 1 0.03 1 0.02 1 0.97 1 6 1 0.11 0.02 1 1 1 1 keep
0.37 0 0.61 1 1–4 1 0.04 1 0.02 1 0.98 1 6 1 0.10 0.01 1 1 1 1 removee
0.32 0 0.66 1 1–4 1 0.03 1 0.01 1 0.98 1 6 1 0.12 0.01 1 1 1 1 keep
0.32 0 0.66 1 1–4 1 0.02 1 0.01 1 0.99 1 6 1 0.10 0.01 1 1 1 1 keep
0.18 0 0.80 1 1–4 1 0.00 1 0.01 1 0.97 1 6 1 0.09 0.02 0 1 0 0 keep
0.19 0 0.79 1 1–4 1 0.01 1 0.02 1 0.98 1 6 1 0.18 0.01 1 1 1 1 keep
0.21 0 0.75 1 1–4 1 0.01 1 0.02 1 0.96 1 6 1 0.12 0.01 1 1 1 1 keep
0.12 0 0.86 1 1–4 1 0.00 1 0.01 1 0.98 1 5 1 0.14 0.00 1 1 1 0 keep

akeepbecause of anaplastic patients, add “choked when swallowing”; bchange in: dysfunction in the shoulder; cbecause of TKI; dbecause of TKI; etoo
many items on the same issue

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 Research S Singer et al. EORTC QLQ-THY phase III 24:4 204

Table 5  Issues mentioned as missing by the participants. Table 6  The items of the EORTC QLQ-THY34.

Frequency of q 31 Have you had sudden attacks of tiredness?

Topic Missing issue mentioning q 32 Have you felt mentally exhausted?
Shoulder Shoulder dysfunction 5 q 33 Have you felt physically exhausted?
Upper limb pain and function 1 q 34 Have you had pain in your throat?
Eyes Eyesight impaired 1 q 35 Have you had any discomfort in your neck?
Dry eyes 1 q 36 Have you had problems with hoarseness?
Bilateral lacrimation 1 q 37 Has your voice sounded different as a result of your
Problems with light 1 disease or treatment?
Painful and dry eyes 1 q 38 Have you had a tired voice?
Hearing Understanding surroundings and 1 q 39 Have you had thin or lifeless hair as a result of your
doctors disease or treatment?
Deafness 1 q 40 Have you lost any hair?
Cognition Executive/cognitive functioning 1 q 41 Have you had problems swallowing solid food?
Memory loss 1 q 42 Have you choked when swallowing?
Problems with finding words 1 q 43 Have you had a dry mouth?
Sensitivity Face and neck sensitivity 3 q 44 Have you had problems tolerating heat or cold?
Menstruation Menstruation problems 2 q 45 Have you felt physically less attractive as a result of your
Pain Headaches/migraine 1 disease or treatment?
Muscle pain 1 q 46 Have you felt restless or agitated?
Joint pain 1 q 47 Have you had a rapid heartbeat?
Emotional Need to defend oneself against 1 q 48 Have you had problems raising your arm or moving it
the opinion that thyroid cancer sideways?
is not a serious disease q 49 Have you felt as though there was a knot in your
Pressures of work 1 throat?
Need for further treatment 1 q 50 Have you worried about a possible recurrence of the
Endocrine-Related Cancer

Dependent on thyroid 1 disease?

medication q 51 Have you worried about having to come off your
Stress 1 thyroid hormone replacement tablets to prepare for a
radioiodine body scan or radioiodine treatment?
Positive lifestyle change after 1
cancer q 52 Have you worried about having to take drugs for the
rest of your life?
Information Information tends to be mainly 1
for women, not men q 53 Have you had pain in your joints?
To understand information given 1 q 54 Have you had tingling or numbness in your fingers or
before operation toes?
Financial Cost of expensive investigations, 1 q 55 Have you had tingling or numbness around your
problems how to solve financial problems mouth?
Effect of disease on financial 1 q 56 Have you had any muscle cramps?
situation q 57 Have you found it upsetting to see those close to you
Body image Aesthetics 1 distressed as a result of your disease or treatment?
Scars left by treatment 1 q 58 Have you worried about the future of people who are
important to you?
Fatigue Stamina 1
q 59 Have you worried how those close to you will cope with
Other Sexual functioning, relationship 1
your illness and treatment?
with the husband
q 60 Have you worried that you will be a burden to others?
Skin problems (dry, psoriasis) 1
q 61 Have you had any problems with your job or your
Stomach and intestine problems 1
education because of your disease or treatment?
Metastatic disease questions 1
q 62 Have you felt supported by your doctors?
missing
q 63 Have you felt supported by other health care
Over-reactive mucosa 1
professionals (e.g. nurse)?
Satisfaction with treatment plan 1
q 64 Have you felt supported by your family members or
Timing of diagnosis and stay of 1
friends?
treatment

was mentioned 5 times, face and neck sensitivity 3 times,

and menstruation problems 2 times (Table 5).
Decision on items
The multi-professional group of experts decided, based
on the pre-defined criteria and on clinical experience, to
remove 14 items, keep 31, change 2 and add 1, resulting
in 34 items (Table 6). Two of these new items were taken
from the EORTC item-library, one item was re-worded.
This item was discussed in detail in the group and was
changed because patients found it important, but
difficult to understand. The experts decided to add more
information so that patients would better understand the

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 Research S Singer et al.
item, even though it resulted in a rather lengthy question:
‘Have you worried about having to come off your thyroid
hormone replacement tablets to prepare for a radioiodine
body scan or radioiodine treatment?’. This new item was
subsequently translated into the several languages used
in this study. This process was coordinated by the EORTC
translation unit. The item mentioned as missing by the
patient (‘shoulder dysfunction’) was taken from the item-
library, the wording is ‘Have you had problems raising
your arm or moving it sideways?’.
Patients treated with tyrosine kinase inhibitors (TKI)
In the sample, there were 9 patients who received TKIs
at the time of the study and 3 had received it previously.
Hence, 12 patients (7%) had received TKI treatment.
Since they are often treated for long periods of time, we
did some additional analyses for this group. We found
that the ranking of the mean was similar in patients with
and without TKI. However, the TKI patients reported
more frequently problems with thin or lifeless hair
Endocrine-Related Cancer
(mean 1.9). Hair loss was rated as relevant by 2 of the
patients. Compliance rates per item were similar to the
entire sample. When asked for what items they missed
from the questionnaire, the majority (n = 11) said nothing
was missing. One patient said the only problem for her
was that she always ruminates about being dependent
on medication.
Discussion
The purpose of this study was to pilot-test the newly
developed EORTC module measuring QoL in thyroid
cancer patients. We wanted to check whether patients
understood and accepted the wording of the items,
whether they found the content relevant and whether
anything important was missing from the questionnaire.
The second aim was to shorten the module without
compromising its comprehensiveness.
The patient responses confirmed that the QoL
issues identified in phase I of this module development
(Singer et al. 2016) are relevant and important to patients.
Most of the items were well accepted by the patients.
Only one item (‘Have you worried about having to come
off your thyroid hormone tablets?’) was considered
relevant but difficult to understand by some patients. Its
wording was changed to ‘Have you worried about having
to come off your thyroid hormone replacement tablets
to prepare for a radioiodine body scan or radioiodine
treatment?’. Our expert group discussed this new
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EORTC QLQ-THY phase III 24:4 205
wording extensively. While it is now a relatively lengthy
item and we usually try to keep items as short as possible,
we found that the old item was difficult to understand.
This was not because of ‘difficult words’ but because of
the complex treatment captured by it. Patients need to
understand what is meant by an item in a questionnaire
without needing to ask a study nurse or clinician for help
in completing it. It was therefore decided to add more
information to this item.
Further, compliance in completing the items was
high. This is especially important as low completion
rates of QoL tools are a major challenge in clinical trials
(Kopp et al. 2003, Ediebah et al. 2013, Johnston et al. 2013,
Bottomley et al. 2014). In order to increase the likelihood
of high completion rates, we shortened the module
to 34 items, in accordance with the EORTC module
development guidelines (Johnson et al. 2011).
Interestingly, a considerable number of patients
said they felt there should be more items on shoulder
functioning which was why we added another item on
this issue. This is in line with a recent study (Roerink et al.
2017) which found that more than half of the thyroid
cancer survivors suffer from shoulder problems.
A limitation of our study was that we were able to
include only a few patients with anaplastic thyroid cancer.
This type of disease is very rare and its prognosis is poor
(Brown  et  al. 2011, Amphlett  et  al. 2013, Husson  et  al.
2013b), making it difficult to enrol patients. Our aim
had been to include at least 10 patients but we managed
to include only 6. Hence, the perspective of this patient
group may be under-represented in our module. Although
we assume that the type of disease has no major effect
on how well patients can understand an item or whether
they find it upsetting or annoying, it is possible that the
relevance and completion rates might differ as patients
with different disease experience different side effects.
Few patients had received chemotherapy as this
type of treatment is rarely given to patients with thyroid
cancer. The treatment received by the patients in this
study reflects therefore the usual situation in this
patient group.
Patients who had received tyrosine kinase inhibitors
responded similarly to the module than the patients who
had received different treatments. However, they reported
more problems with lifeless and thin hair and rated hair
loss as relevant. Moreover, one of the patients highlighted
the problem of having to take medication for a longer
period of time.
A strength of this study was that we included patients
from Europe, Asia, Australia and Africa. This allowed us
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 Research S Singer et al.
to ensure that the module is well accepted in patients
with different cultural backgrounds and languages.
The heterogeneity of the sample in terms of histology,
treatment and stage of disease enables the use of this
module in different settings and treatment lines.
In summary, the EORTC quality of life module for
thyroid cancer consisting of 34 items is now pilot-tested
and ready for the final international field validation
in phase IV. It is available in the following languages:
Arabic, Chinese, Dutch, English, French, German, Greek,
Hebrew, Hindi, Japanese, Italian, Polish, Portuguese,
Spanish and Tamil.
Declaration of interest
The authors declare that there is no conflict of interest that could be
perceived as prejudicing the impartiality of the research reported.
Funding
This study was generously funded by the European Organisation for
Research and Treatment of Cancer, Quality of Life Group (# THY III).
Endocrine-Related Cancer
Acknowledgements
The authors would like to acknowledge the work of the anonymous
colleagues who reviewed the grant proposal and the study report. They
are grateful to the EORTC QLG Executive Committee for reviewing the
study report and this paper.
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Received in final form 31 January 2017
Accepted 21 February 2017
Accepted Preprint published online 21 February 2017
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