The EORTC module for quality of life in patients with thyroid cancer: phase III

in Endocrine-Related Cancer
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  • 1 Institute of Medical Biostatistics Epidemiology and Informatics (IMBEI), University Medical Center Mainz, Mainz, Germany
  • 2 University Cancer Centre, Mainz, Germany
  • 3 QIMR Berghofer Medical Research Institute, Herston, Australia
  • 4 Head & Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • 5 Rehabilitation Unit, Department of Quality of Life, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’ – IRCCS, Naples, Italy
  • 6 Department of Medical Education, Jagiellonian University Medical College, Krakow, Poland
  • 7 Service of Surgical Oncology, Instituto Português do Oncologia do Porto Francisco Gentil, Porto, Portugal
  • 8 Department of Otolaryngology and Head and Neck Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 9 Department of Psycho-Oncology, Resource Centre for Tobacco Control, Cancer Institute (WIA), Chennai, Tamil Nadu, India
  • 10 Department of Medical Psychology, Radboud University Medical Center, Nijmegen, The Netherlands
  • 11 Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan
  • 12 Mount Vernon Cancer Centre, East & North Herts NHS Trust, Northwood, London, UK
  • 13 Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
  • 14 Department of Nuclear Medicine, Medical University of Innsbruck, Innsbruck Institute of Patient-Centred Outcome Research, Innsbruck, Austria
  • 15 Oncology Departments, Complejo Hospitalario de Navarra, Pamplona, Spain
  • 16 Oncology Department, Nicosia General Hospital, Nicosia, Cyprus
  • 17 Surgery Department, Jules Bordet Institute, Brussels, Belgium
  • 18 Clinic of Otorhinolaryngology, Jena University Hospital, Jena, Germany
  • 19 Department of Radiation Oncology, Institut de Recherche Experimentale et Clinique, Université Catholique de Louvain, St-Luc University Hospital, Brussels, Belgium

The purpose of the study was to pilot-test a questionnaire measuring health-related quality of life (QoL) in thyroid cancer patients to be used with the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire EORTC QLQ-C30. A provisional questionnaire with 47 items was administered to patients treated for thyroid cancer within the last 2 years. Patients were interviewed about time and help needed to complete the questionnaire, and whether they found the items understandable, confusing or annoying. Items were kept in the questionnaire if they fulfilled pre-defined criteria: relevant to the patients, easy to understand, not 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, 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.

Abstract

The purpose of the study was to pilot-test a questionnaire measuring health-related quality of life (QoL) in thyroid cancer patients to be used with the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire EORTC QLQ-C30. A provisional questionnaire with 47 items was administered to patients treated for thyroid cancer within the last 2 years. Patients were interviewed about time and help needed to complete the questionnaire, and whether they found the items understandable, confusing or annoying. Items were kept in the questionnaire if they fulfilled pre-defined criteria: relevant to the patients, easy to understand, not 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, 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) 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 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 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 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, 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.

The pre-defined criteria for keeping an item in the questionnaire (according to the EORTC module development guidelines (Johnson et al. 2011)) were: (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%, respectively), (4) variance (responses range from 1 to 4), (5) acceptance (<5% of patients stated that the item was upsetting), (6) clarity (<5% of patients stated that the items was difficult to understand), (7) compliance (>95% of the patients completed the item), and (8) relevance (>10% of the patients mentioned the item as especially relevant).

The items were grouped into hypothesised scales, and Cronbach’s alpha and scaling error (percentage of items that correlate higher with a different scale than with its own scale, corrected for overlap) were calculated. If items worked well together in a scale, it was another criterion for keeping them in the questionnaire. It should be noted that these psychometric tests are preliminary and that the final psychometric testing will be done in phase IV of this module development.

We tabulated the results per item together with the number of fulfilled criteria. A multi-national multi-professional group of experts then discussed the results and decided on keeping, removing or changing items. An item was kept when most criteria were fulfilled and the patients had assessed it as relevant. An item was removed when few criteria were fulfilled and only few patients had mentioned the item as highly relevant. An item was changed if it was considered relevant by the patients but at the same time difficult to understand or upsetting. According to the EORTC module development guidelines (Johnson et al. 2011), the group of experts could decide to keep an item even if few criteria were fulfilled when they had sound justification, e.g. when the item was highly relevant to a sub-group of patients.

Relevant issues that participants suggested relevant but were lacking from the questionnaire were translated into English (where necessary), similar issues were grouped together and the number of issues was counted. If a new issue was mentioned by at least 5 patients it was added to the module. If items needed to be changed or added, we searched the EORTC item-library and used existing validated items if available.

We calculated the average time it took to complete the questionnaires and how often help was needed to complete the questionnaires.

Data entry, cleaning and analysis were conducted using STATA (Stata Statistical Software, release 12; StrataCorp, College Station, TX, USA).

Results

Sample characteristics

A total of 182 patients participated in the study; n = 115 with papillary, n = 31 with follicular, n = 22 with medullary, n = 6 with anaplastic and n = 8 with another type of thyroid cancer (Table 1). They were enrolled from 17 institutions in 15 countries (n = 37 from Italy, n = 25 Australia, n = 17 Poland, n = 14 Portugal, n = 13 Germany, n = 13 India, n = 13 Sweden, n = 11 the Netherlands, n = 9 Japan, n = 9 the United Kingdom, n = 7 Egypt, n = 4 Austria, n = 4 Spain, n = 3 Belgium, and n = 3 Cyprus). The median time since diagnosis was 0.8 years. The majority (96%) had a Karnofsky performance status of 70 or higher.

Table 1

Sample characteristics (n = 182).

NumberPercent (%)
Age (in years)<404123
40–493218
50–593519
60–693921
70–793117
80+32
Unknown11
SexMale6033
Female12267
EducationCompulsory or less5530
Post-compulsory7038
University5329
Unknown42
HistologyPapillary11563
Follicular3117
Medullary2212
Anaplastic63
Other84
Tumour stageT15027
T23821
T34927
T4a2112
T4b63
Tx158
Unknown21
N08547
N1a3016
N1b3318
Nx3117
Unknown32
M012468
M12514
Mx3218

Most of the participants (88%) had had a total thyroidectomy (Table 2), and 55% had been treated with radioactive iodine therapy.

Table 2

Treatment received by the participants.

NumberPercent (%)
SurgeryNone32
Hemithyroidectomy127
Partial thyroidectomy32
Total thyroidectomy16188
Unknown32
Neck dissectionNo9150
Yes7742
Unknown148
Radioactive iodine therapyCurrently receiving this treatment00
Last treatment <6 m before interview3519
Last treatment ≥6 m before interview6536
Never/not yet7943
Unknown32
ChemotherapyCurrently receiving this treatment00
Last treatment <6 m before interview74
Last treatment ≥6 m before interview21
Never/not yet16792
Unknown63
Tyrosine kinase inhibitorsCurrently receiving this treatment95
Last treatment <6 m before interview21
Last treatment ≥6 m before interview11
Never/not yet16490
Unknown63

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 to help them understand the questions, and in 5% no information about help needed was provided (Table 3).

Table 3

Time and help required for completing the questionnaire.

NumberPercent (%)
Duration (min)<105430
11–156737
16–203318
21–30127
>3063
Unknown105
Form of administrationSelf-completed13775
Orally3720
Unknown84
Type of help requiredNo help required10960
Practical help required3016
Supportive help required2112
Help with understanding the questionnaire137
Unknown95

Evaluation of items

Thirty items could be meaningfully combined to scales with Cronbach’s alpha >0.70 and with a decrease of alpha when the item was removed. The hypothesised 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).

Table 4

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

criterion α criterion 1criterion 2criterion 3 criterion 4criterion 5criterion 6criterion 7criterion 8 relevant or criterion 1–7relevant and criterion 1–7 relevant or criterion 1–7 and criterion αDecision
Chronbach‘s α of hypothesised scaleChronbach‘s α if item removeddecreases α if item is removed?meanmean > 1.5?prevalence of scores 3/4scores 3/4 >50%?scores 1/2neither floor nor ceilingrangerange% upsetting<5% upsetting% difficult<5% difficultproportion non-missing>95% complete?sum crit 1 to 7min. 5 of crit 1 to 7?% relevant% irrelevant≥10% relevant
q 31Have you had sudden attacks of tiredness?0.850.8012.010.2700.7311–410.0010.0111.001610.140.011111keep
q 32Have you felt mentally exhausted?0.850.8111.910.2300.7611–410.0010.0110.991610.160.021111keep
q 33Have you felt physically exhausted?0.850.7712.010.2900.7111–410.0010.0110.991610.150.011111keep
q 34Has your sleep pattern been disrupted?n.a.01.910.2600.7411–410.0010.0011.001610.080.000100remove
q 35Have you felt refreshed when waking up?0.850.8702.910.6410.3511–410.0110.0310.991710.050.000100remove
q 36Have you had pain in your throat?0.710.6011.500.1200.8811–410.0010.0111.001510.050.010101keep
q 37Have you had any discomfort in your neck?0.710.6611.910.2400.7611–410.0010.0011.001610.100.010101keep
q 38Have you had problems breathing?n.a.01.300.0500.9501–410.0010.0111.001400.050.010000remove
q 39Have food and drink tasted different from usual?n.a.01.300.0900.9101–410.0010.0011.001400.040.030000remove
q 40Have you had problems talking to other people because of your voice?0.910.8911.510.1400.8611–410.0010.0011.001610.080.020101remove
q 41Have you had problems with hoarseness?0.910.9011.610.1700.8311–410.0010.0211.001610.080.010101keep
q 42Has your voice sounded different as a result of your disease or treatment?0.910.8811.810.2000.7911–410.0010.0010.991610.100.010101keep
q 43Have you had a tired voice?0.910.9011.710.2000.7911–410.0010.0110.991610.090.010101keep
q 44Have you had thin or lifeless hair as a result of your disease or treatment?0.900.8311.610.2000.8011–410.0010.0111.001610.070.080101keep
q 45Have you lost any hair?0.900.8411.610.1500.8511–410.0010.0111.001610.050.070101keep
q 46If you have lost any hair: Have you been upset by the loss of your hair?0.900.8912.010.2800.7211–410.0110.0010.430510.060.040101remove
q 47Have you had problems swallowing liquids?0.820.7311.300.0700.9201–410.0010.0010.991400.050.020000remove
q 48Have you had problems swallowing pureed food?0.820.7111.200.0300.9501–410.0010.0010.981400.050.020000remove
q 49Have you had problems swallowing solid food?0.820.8501.400.1000.8901–410.0010.0010.991400.080.010000keepa
q 50Have you had a dry mouth?n.a.01.810.2000.7811–410.0010.0010.981610.070.010100keep
q 51Have you had problems tolerating heat or cold?n.a.01.810.2400.7511–410.0010.0010.991610.100.000100keep
q 52Have you felt physically less attractive as a result of your disease or treatment?n.a.01.610.1500.8411–410.0110.0110.991610.070.020100keep
q 53Have you felt restless or agitated?0.6611.810.2200.7711–410.0010.0010.991610.070.010101keep
q 54Have you had a rapid heartbeat?0.6611.500.1000.8911–410.0010.0010.991510.070.020101keep
q 55Have you worried about your ability to have children?n.a.01.200.0600.8801–410.0010.0110.950300.030.060000remove
q 56Have you had pain in your shoulder?n.a.01.810.2300.7711–410.0010.0111.001610.040.030100changeb
q 57Have you felt as though there was a knot in your throat?0.710.6211.610.1500.8511–410.0010.0110.991610.090.010101keep
q 58Have you worried about a possible recurrence of the disease?0.530.5902.310.3800.6111–410.0210.0110.991610.150.001110keep
q 59Have you worried about having to come off your thyroid hormone tablets?0.530.3411.400.1000.8511–410.0110.0410.951510.030.030101change
q 60Have you worried about having to take drugs for the rest of your life?0.530.3611.610.1500.8511–410.0010.0111.001610.060.030101keep
q 61Has weight gain been a problem for you?n.a.01.810.2100.7611–410.0010.0310.971610.070.030100remove
q 62Has weight loss been a problem for you?0.7511.200.0500.9301–410.0010.0310.981400.040.030000remove
q 63Have you worried about losing weight?0.7511.300.0800.9101–410.0010.0010.991400.030.030000remove
q 64Have you had pain in your joints?n.a.02.010.2800.7211–410.0010.0111.001610.060.020100keepc
q 65Have you had problems with your teeth?n.a.01.510.1200.8711–410.0010.0010.991610.030.030100remove
q 66Have you had tingling or numbness in your fingers or toes?0.6611.610.1400.8511–410.0010.0110.991610.060.070101keep
q 67Have you had tingling or numbness around your mouth?0.6611.200.0400.9601–410.0010.0110.991400.030.060000keep
q 68Have you had any muscle cramps?n.a.01.610.1900.8011–410.0010.0110.991610.040.040100keepd
q 69Have you found it upsetting to see those close to you distressed as a result of your disease or treatment?0.910.9011.910.2600.7311–410.0310.0110.991610.120.021111keep
q 70Have you worried about the future of people who are important to you?0.910.9012.310.3600.6211–410.0310.0210.971610.110.021111keep
q 71Have you worried about disrupting the lives of those close to you?0.910.8712.210.3700.6111–410.0410.0210.981610.100.011111removee
q 72Have you worried how those close to you will cope with your illness and treatment?0.910.8812.110.3200.6611–410.0310.0110.981610.120.011111keep
q 73Have you worried that you will be a burden to others?0.910.9012.110.3200.6611–410.0210.0110.991610.100.011111keep
q 74Have you had any problems with your job or your education because of your disease or treatment?n.a.01.710.1800.8011–410.0010.0110.971610.090.020100keep
q 75Have you felt supported by your doctors?0.840.7011.810.1900.7911–410.0110.0210.981610.180.011111keep
q 76Have you felt supported by other health care professionals (e.g. nurse)?0.840.7111.910.2100.7511–410.0110.0210.961610.120.011111keep
q 77Have you felt supported by your family members or friends?0.840.8701.500.1200.8611–410.0010.0110.981510.140.001110keep

keep because 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

Additional items

The patients mentioned 44 issues they felt were missing in the core questionnaire plus module. Shoulder dysfunction was mentioned 5 times, face and neck sensitivity 3 times, and menstruation problems 2 times (Table 5).

Table 5

Issues mentioned as missing by the participants.

TopicMissing issueFrequency of mentioning
ShoulderShoulder dysfunction5
Upper limb pain and function1
EyesEyesight impaired1
Dry eyes1
Bilateral lacrimation1
Problems with light1
Painful and dry eyes1
HearingUnderstanding surroundings and doctors1
Deafness1
CognitionExecutive/cognitive functioning1
Memory loss1
Problems with finding words1
SensitivityFace and neck sensitivity3
MenstruationMenstruation problems2
PainHeadaches/migraine1
Muscle pain1
Joint pain1
EmotionalNeed to defend oneself against the opinion that thyroid cancer is not a serious disease1
Pressures of work1
Need for further treatment1
Dependent on thyroid medication1
Stress1
Positive lifestyle change after cancer1
InformationInformation tends to be mainly for women, not men1
To understand information given before operation1
Financial problemsCost of expensive investigations, how to solve financial problems1
Effect of disease on financial situation1
Body imageAesthetics1
Scars left by treatment1
FatigueStamina1
OtherSexual functioning, relationship with the husband1
Skin problems (dry, psoriasis)1
Stomach and intestine problems1
Metastatic disease questions missing1
Over-reactive mucosa1
Satisfaction with treatment plan1
Timing of diagnosis and stay of treatment1

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 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?’.

Table 6

The items of the EORTC QLQ-THY34.

q 31Have you had sudden attacks of tiredness?
q 32Have you felt mentally exhausted?
q 33Have you felt physically exhausted?
q 34Have you had pain in your throat?
q 35Have you had any discomfort in your neck?
q 36Have you had problems with hoarseness?
q 37Has your voice sounded different as a result of your disease or treatment?
q 38Have you had a tired voice?
q 39Have you had thin or lifeless hair as a result of your disease or treatment?
q 40Have you lost any hair?
q 41Have you had problems swallowing solid food?
q 42Have you choked when swallowing?
q 43Have you had a dry mouth?
q 44Have you had problems tolerating heat or cold?
q 45Have you felt physically less attractive as a result of your disease or treatment?
q 46Have you felt restless or agitated?
q 47Have you had a rapid heartbeat?
q 48Have you had problems raising your arm or moving it sideways?
q 49Have you felt as though there was a knot in your throat?
q 50Have you worried about a possible recurrence of the disease?
q 51Have you worried about having to come off your thyroid hormone replacement tablets to prepare for a radioiodine body scan or radioiodine treatment?
q 52Have you worried about having to take drugs for the rest of your life?
q 53Have you had pain in your joints?
q 54Have you had tingling or numbness in your fingers or toes?
q 55Have you had tingling or numbness around your mouth?
q 56Have you had any muscle cramps?
q 57Have you found it upsetting to see those close to you distressed as a result of your disease or treatment?
q 58Have you worried about the future of people who are important to you?
q 59Have you worried how those close to you will cope with your illness and treatment?
q 60Have you worried that you will be a burden to others?
q 61Have you had any problems with your job or your education because of your disease or treatment?
q 62Have you felt supported by your doctors?
q 63Have you felt supported by other health care professionals (e.g. nurse)?
q 64Have you felt supported by your family members or friends?

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 (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 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 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).

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.

References

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    • Search Google Scholar
    • Export Citation
  • Applewhite MK, James BC, Kaplan SP, Angelos P, Kaplan EL, Grogan RH & schebrook-Kilfoy B 2016 Quality of life in thyroid cancer is similar to that of other cancers with worse survival. World Journal of Surgery 40 551561. (doi:10.1007/s00268-015-3300-5)

    • Search Google Scholar
    • Export Citation
  • Bianchi GP, Zaccheroni V, Solaroli E, Vescini F, Cerutti R, Zoli M & Marchesini G 2004 Health-related quality of life in patients with thyroid disorders – a study based on Short-Form 36 and Nottingham Health Profile Questionnaires. Quality of Life Research 13 4554. (doi:10.1023/B:QURE.0000015315.35184.66)

    • Search Google Scholar
    • Export Citation
  • Borget I, Corone C, Nocaudie M, Allyn M, Iacobelli S, Schlumberger M & De Pouvourville G 2007 Sick leave for follow-up control in thyroid cancer patients: comparison between stimulation with Thyrogen and thyroid hormone withdrawal. European Journal of Endocrinology 156 531538. (doi:10.1530/EJE-06-0724)

    • Search Google Scholar
    • Export Citation
  • Botella-Carretero JI, Galan JM, Caballero C, Sancho J & Escobar-Morreale HF 2003 Quality of life and psychometric functionality in patients with differentiated thyroid carcinoma. Endocrine-Related Cancer 10 601610. (doi:10.1677/erc.0.0100601)

    • Search Google Scholar
    • Export Citation
  • Bottomley A, Tridello G, Coens C, Rolland F, Tesselaar MET, Leemans CR, Hupperets P, Licitra L, Vermorken JB & van den Weyngaert D 2014 An international phase 3 trial in head and neck cancer: quality of life and symptom results. Cancer 120 390398. (doi:10.1002/cncr.28392)

    • Search Google Scholar
    • Export Citation
  • Brenner H 2002 Long-term survival rates of cancer patients achieved by the end of the 20th century: a period analysis. Lancet 360 11311135. (doi:10.1016/S0140-6736(02)11199-8)

    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
    • Export Citation
  • Crevenna R, Zettinig G, Keilani M, Posch M, Schmidinger M, Pirich C, Nuhr M, Wolzt M, Quittan M & Fialka-Moser V 2003 Quality of life in patients with non-metastatic differentiated thyroid cancer under thyroxine supplementation therapy. Supportive Care in Cancer 11 597603. (doi:10.1007/s00520-003-0474-4)

    • Search Google Scholar
    • Export Citation
  • Dewolf L, Koller M, Velikova G, Johnson C, Scott N, Bottomley A, on behalf of the EORTC Quality of Life Group 2009 EORTC Translation Procedure. Brussels, Belgium: EORTC.

    • Search Google Scholar
    • Export Citation
  • Dow KH, Ferrell BR & Anello C 1997 Quality-of-life changes in patients with thyroid cancer after withdrawal of thyroid hormone therapy. Thyroid 7 613619. (doi:10.1089/thy.1997.7.613)

    • Search Google Scholar
    • Export Citation
  • Ediebah DE, Coens C, Maringwa JT, Quinten C, Zikos E, Ringash J, King M, Gotay C, Flechtner HH & von Koch JS 2013 Effect of completion-time windows in the analysis of health-related quality of life outcomes in cancer patients. Annals of Oncology 24 231237. (doi:10.1093/annonc/mds220)

    • Search Google Scholar
    • Export Citation
  • Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JWW, Comber H, Forman D & Bray F 2013 Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. European Journal of Cancer 49 13741403. (doi:10.1016/j.ejca.2012.12.027)

    • Search Google Scholar
    • Export Citation
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  • Gamper EM, Wintner LM, Rodrigues M, Buxbaum S, Nilica B, Singer S, Giesinger JM, Holzner B & Virgolini I 2015 Persistent quality of life impairments in differentiated thyroid cancer patients: results from a monitoring programme. European Journal of Nuclear Medicine and Molecular Imaging 42 11791188. (doi:10.1007/s00259-015-3022-9)

    • Search Google Scholar
    • Export Citation
  • Hoftijzer HC, Heemstra KA, Corssmit EPM, van der Klaauw AA, Romijn JA & Smit JWA 2008 Quality of life in cured patients with differentiated thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism 93 200203. (doi:10.1210/jc.2007-1203)

    • Search Google Scholar
    • Export Citation
  • Husson O, Haak HR, Oranje WA, Mols F, Reemst PHM & van de Poll-Franse L 2011 Health-related quality of life among thyroid cancer survivors: a systematic review. Clinical Endocrinology 75 544554. (doi:10.1111/j.1365-2265.2011.04114.x)

    • Search Google Scholar
    • Export Citation
  • Husson O, Haak HR, Mols F, Nieuwenhuijzen GA, Nieuwlaat WA, Reemst PH, Huysmans DA, Toorians AW & van de Poll-Franse L 2013a Development of a disease-specific health-related quality of life questionnaire (THYCA-QoL) for thyroid cancer survivors. Acta Oncologica 52 447454. (doi:10.3109/0284186X.2012.718445)

    • Search Google Scholar
    • Export Citation
  • Husson O, Haak HR, van Steenbergen LN, Nieuwlaat WA, van Dijk BAC, Nieuwenhuijzen GAP, Karim-Kos H, Kuijpens JL, van de Poll-Franse L & Coebergh JWW 2013b Rising incidence, no change in survival and decreasing mortality from thyroid cancer in The Netherlands since 1989. Endocrine-Related Cancer 20 263271. (doi:10.1530/ERC-12-0336)

    • Search Google Scholar
    • Export Citation
  • Johnson C, Aaronson N, Blazeby JM, Bottomley A, Fayers P, Koller M, Kulis D, Ramage J, Sprangers MAG & Velikova G 2011 EORTC Guidelines for Developing Questionnaire Modules. Brussels, Belgium: EORTC.

    • Search Google Scholar
    • Export Citation
  • Johnston DL, Nagarajan R, Caparas M, Schulte F, Cullen P, Aplenc R & Sung LL 2013 Reasons for non-completion of health related quality of life evaluations in pediatric acute myeloid leukemia: a report from the Children’s Oncology Group. PLoS ONE 8 e74549. (doi:10.1371/journal.pone.0074549)

    • Search Google Scholar
    • Export Citation
  • Kopp I, Lorenz W, Rothmund M & Koller M 2003 Relation between severe illness and non-completion of quality-of-life questionnaires by patients with rectal cancer. Journal of the Royal Society of Medicine 96 442448. (doi:10.1258/jrsm.96.9.442)

    • Search Google Scholar
    • Export Citation
  • Krajewska J, Handkiewicz-Junak D & Jarzab B 2015 Sorafenib for the treatment of thyroid cancer: an updated review. Expert Opinion on Pharmacotherapy 16 573583. (doi:10.1517/14656566.2015.1005601)

    • Search Google Scholar
    • Export Citation
  • Lee J, Yun MJ, Nam KH, Chung WY, Soh EY & Park CS 2010 Quality of life and effectiveness comparisons of thyroxine withdrawal, triiodothyronine withdrawal, and recombinant thyroid-stimulating hormone administration for low-dose radioiodine remnant ablation of differentiated thyroid carcinoma. Thyroid 20 173179. (doi:10.1089/thy.2009.0187)

    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
    • Export Citation
  • Singer S, Lincke Th, Gamper E, Schreiber S, Hinz A, Bhaskaran K & Schulte Th 2012 Quality of life in patients with thyroid cancer compared with the general population. Thyroid 22 117124. (doi:10.1089/thy.2011.0139)

    • Search Google Scholar
    • Export Citation
  • Singer S, Husson O, Tomaszewska IM, Locati L, Kiyota N, Scheidemann-Wesp U, Hofmeister D, Winterbotham M, Brannan C & Araújo C 2016 Quality of life priorities in patients with thyroid cancer – results from a multi-national EORTC phase I study. Thyroid 26 16051613 (doi:10.1089/thy.2015.0640)

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    • Export Citation
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  • Amphlett B, Lawson Z, Abdulrahman GO, White C, Bailey R, Premawardhana LD & Okosieme OE 2013 Recent trends in the incidence, geographical distribution, and survival from thyroid cancer in Wales, 1985–2010. Thyroid 23 14701478. (doi:10.1089/thy.2012.0573)

    • Search Google Scholar
    • Export Citation
  • Applewhite MK, James BC, Kaplan SP, Angelos P, Kaplan EL, Grogan RH & schebrook-Kilfoy B 2016 Quality of life in thyroid cancer is similar to that of other cancers with worse survival. World Journal of Surgery 40 551561. (doi:10.1007/s00268-015-3300-5)

    • Search Google Scholar
    • Export Citation
  • Bianchi GP, Zaccheroni V, Solaroli E, Vescini F, Cerutti R, Zoli M & Marchesini G 2004 Health-related quality of life in patients with thyroid disorders – a study based on Short-Form 36 and Nottingham Health Profile Questionnaires. Quality of Life Research 13 4554. (doi:10.1023/B:QURE.0000015315.35184.66)

    • Search Google Scholar
    • Export Citation
  • Borget I, Corone C, Nocaudie M, Allyn M, Iacobelli S, Schlumberger M & De Pouvourville G 2007 Sick leave for follow-up control in thyroid cancer patients: comparison between stimulation with Thyrogen and thyroid hormone withdrawal. European Journal of Endocrinology 156 531538. (doi:10.1530/EJE-06-0724)

    • Search Google Scholar
    • Export Citation
  • Botella-Carretero JI, Galan JM, Caballero C, Sancho J & Escobar-Morreale HF 2003 Quality of life and psychometric functionality in patients with differentiated thyroid carcinoma. Endocrine-Related Cancer 10 601610. (doi:10.1677/erc.0.0100601)

    • Search Google Scholar
    • Export Citation
  • Bottomley A, Tridello G, Coens C, Rolland F, Tesselaar MET, Leemans CR, Hupperets P, Licitra L, Vermorken JB & van den Weyngaert D 2014 An international phase 3 trial in head and neck cancer: quality of life and symptom results. Cancer 120 390398. (doi:10.1002/cncr.28392)

    • Search Google Scholar
    • Export Citation
  • Brenner H 2002 Long-term survival rates of cancer patients achieved by the end of the 20th century: a period analysis. Lancet 360 11311135. (doi:10.1016/S0140-6736(02)11199-8)

    • Search Google Scholar
    • Export Citation
  • Brown RL, de Souza JA & Cohen EE 2011 Thyroid cancer: burden of illness and management of disease. Journal of Cancer 2 193199. (doi:10.7150/jca.2.193)

    • Search Google Scholar
    • Export Citation
  • Carlberg M, Hedendahl L, Ahonen M, Koppel T & Hardell L 2016 Increasing incidence of thyroid cancer in the Nordic countries with main focus on Swedish data. BMC Cancer 16 426. (doi:10.1186/s12885-016-2429-4)

    • Search Google Scholar
    • Export Citation
  • Crevenna R, Zettinig G, Keilani M, Posch M, Schmidinger M, Pirich C, Nuhr M, Wolzt M, Quittan M & Fialka-Moser V 2003 Quality of life in patients with non-metastatic differentiated thyroid cancer under thyroxine supplementation therapy. Supportive Care in Cancer 11 597603. (doi:10.1007/s00520-003-0474-4)

    • Search Google Scholar
    • Export Citation
  • Dewolf L, Koller M, Velikova G, Johnson C, Scott N, Bottomley A, on behalf of the EORTC Quality of Life Group 2009 EORTC Translation Procedure. Brussels, Belgium: EORTC.

    • Search Google Scholar
    • Export Citation
  • Dow KH, Ferrell BR & Anello C 1997 Quality-of-life changes in patients with thyroid cancer after withdrawal of thyroid hormone therapy. Thyroid 7 613619. (doi:10.1089/thy.1997.7.613)

    • Search Google Scholar
    • Export Citation
  • Ediebah DE, Coens C, Maringwa JT, Quinten C, Zikos E, Ringash J, King M, Gotay C, Flechtner HH & von Koch JS 2013 Effect of completion-time windows in the analysis of health-related quality of life outcomes in cancer patients. Annals of Oncology 24 231237. (doi:10.1093/annonc/mds220)

    • Search Google Scholar
    • Export Citation
  • Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JWW, Comber H, Forman D & Bray F 2013 Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. European Journal of Cancer 49 13741403. (doi:10.1016/j.ejca.2012.12.027)

    • Search Google Scholar
    • Export Citation
  • Gamper EM & Sztankay M 2015 Quality of life and distress of patients with thyroid cancer. Onkologe 21 625629. (doi:10.1007/s00761-015-2918-0)

  • Gamper EM, Wintner LM, Rodrigues M, Buxbaum S, Nilica B, Singer S, Giesinger JM, Holzner B & Virgolini I 2015 Persistent quality of life impairments in differentiated thyroid cancer patients: results from a monitoring programme. European Journal of Nuclear Medicine and Molecular Imaging 42 11791188. (doi:10.1007/s00259-015-3022-9)

    • Search Google Scholar
    • Export Citation
  • Hoftijzer HC, Heemstra KA, Corssmit EPM, van der Klaauw AA, Romijn JA & Smit JWA 2008 Quality of life in cured patients with differentiated thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism 93 200203. (doi:10.1210/jc.2007-1203)

    • Search Google Scholar
    • Export Citation
  • Husson O, Haak HR, Oranje WA, Mols F, Reemst PHM & van de Poll-Franse L 2011 Health-related quality of life among thyroid cancer survivors: a systematic review. Clinical Endocrinology 75 544554. (doi:10.1111/j.1365-2265.2011.04114.x)

    • Search Google Scholar
    • Export Citation
  • Husson O, Haak HR, Mols F, Nieuwenhuijzen GA, Nieuwlaat WA, Reemst PH, Huysmans DA, Toorians AW & van de Poll-Franse L 2013a Development of a disease-specific health-related quality of life questionnaire (THYCA-QoL) for thyroid cancer survivors. Acta Oncologica 52 447454. (doi:10.3109/0284186X.2012.718445)

    • Search Google Scholar
    • Export Citation
  • Husson O, Haak HR, van Steenbergen LN, Nieuwlaat WA, van Dijk BAC, Nieuwenhuijzen GAP, Karim-Kos H, Kuijpens JL, van de Poll-Franse L & Coebergh JWW 2013b Rising incidence, no change in survival and decreasing mortality from thyroid cancer in The Netherlands since 1989. Endocrine-Related Cancer 20 263271. (doi:10.1530/ERC-12-0336)

    • Search Google Scholar
    • Export Citation
  • Johnson C, Aaronson N, Blazeby JM, Bottomley A, Fayers P, Koller M, Kulis D, Ramage J, Sprangers MAG & Velikova G 2011 EORTC Guidelines for Developing Questionnaire Modules. Brussels, Belgium: EORTC.

    • Search Google Scholar
    • Export Citation
  • Johnston DL, Nagarajan R, Caparas M, Schulte F, Cullen P, Aplenc R & Sung LL 2013 Reasons for non-completion of health related quality of life evaluations in pediatric acute myeloid leukemia: a report from the Children’s Oncology Group. PLoS ONE 8 e74549. (doi:10.1371/journal.pone.0074549)

    • Search Google Scholar
    • Export Citation
  • Kopp I, Lorenz W, Rothmund M & Koller M 2003 Relation between severe illness and non-completion of quality-of-life questionnaires by patients with rectal cancer. Journal of the Royal Society of Medicine 96 442448. (doi:10.1258/jrsm.96.9.442)

    • Search Google Scholar
    • Export Citation
  • Krajewska J, Handkiewicz-Junak D & Jarzab B 2015 Sorafenib for the treatment of thyroid cancer: an updated review. Expert Opinion on Pharmacotherapy 16 573583. (doi:10.1517/14656566.2015.1005601)

    • Search Google Scholar
    • Export Citation
  • Lee J, Yun MJ, Nam KH, Chung WY, Soh EY & Park CS 2010 Quality of life and effectiveness comparisons of thyroxine withdrawal, triiodothyronine withdrawal, and recombinant thyroid-stimulating hormone administration for low-dose radioiodine remnant ablation of differentiated thyroid carcinoma. Thyroid 20 173179. (doi:10.1089/thy.2009.0187)

    • Search Google Scholar
    • Export Citation
  • Morris LGT, Tuttle RM & Davies L 2016 Changing trends in the incidence of thyroid cancer in the United States. JAMA Otolaryngology-Head and Neck Surgery 142 709711. (doi:10.1001/jamaoto.2016.0230)

    • Search Google Scholar
    • Export Citation
  • Pacini F, Castagna MG, Cipri C & Schlumberger M 2010 Medullary thyroid carcinoma. Clinical Oncology 22 475485. (doi:10.1016/j.clon.2010.05.002)

  • Radespiel-Troger M, Batzler WU, Holleczek B, Luttmann S, Pritzkuleit R, Stabenow R, Urbschat I, Zeissig SR & Meyer M 2014 Rising incidence of papillary thyroid carcinoma in Germany. Bundesgesundheitsblatt-Gesundheitsforschung-Gesundheitsschutz 57 8492. (doi:10.1007/s00103-013-1884-1)

    • Search Google Scholar
    • Export Citation
  • Roerink SH, Coolen L, Schenning ME, Husson O, Smit JW, Marres HA, de Wilt JH & Netea-Maier RT 2017 High prevalence of self-reported shoulder complaints after thyroid carcinoma surgery. Head and Neck 39 260268. (doi:10.1002/hed.24579)

    • Search Google Scholar
    • Export Citation
  • Ryu J, Ryu YM, Jung YS, Kim S, Lee YJ, Lee EK, Kim SK, Kim TS, Kim TH & Lee CY 2013 Extent of thyroidectomy affects vocal and throat functions: a prospective observational study of lobectomy versus total thyroidectomy. Surgery 154 611620. (doi:10.1016/j.surg.2013.03.011)

    • Search Google Scholar
    • Export Citation
  • Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH & Hoff AO 2015 Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. New England Journal of Medicine 372 621630. (doi:10.1056/NEJMoa1406470)

    • Search Google Scholar
    • Export Citation
  • Schroeder PR, Haugen BR, Pacini F, Reiners C, Schlumberger M, Sherman SI, Cooper DS, Schuff KG, Braverman LE & Skarulis MC 2006 A comparison of short-term changes in health-related quality of life in thyroid carcinoma patients undergoing diagnostic evaluation with recombinant human thyrotropin compared with thyroid hormone withdrawal. Journal of Clinical Endocrinology and Metabolism 91 878884. (doi:10.1210/jc.2005-2064)

    • Search Google Scholar
    • Export Citation
  • Singer S, Lincke Th, Gamper E, Schreiber S, Hinz A, Bhaskaran K & Schulte Th 2012 Quality of life in patients with thyroid cancer compared with the general population. Thyroid 22 117124. (doi:10.1089/thy.2011.0139)

    • Search Google Scholar
    • Export Citation
  • Singer S, Husson O, Tomaszewska IM, Locati L, Kiyota N, Scheidemann-Wesp U, Hofmeister D, Winterbotham M, Brannan C & Araújo C 2016 Quality of life priorities in patients with thyroid cancer – results from a multi-national EORTC phase I study. Thyroid 26 16051613 (doi:10.1089/thy.2015.0640)

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