The Evaluation of Health-related Quality of Life Issues Experienced by Patients With Desmoid-type Fibromatosis
Conditions: Desmoid Tumor, Desmoid-type Fibromatosis
Sponsor: Erasmus Medical Center

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The evaluation of health-related quality of life 
issues experienced by patients with desmoid-
type fibromatosis 
 
QUALIFIED study 
Version 1.1 
November 26, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

QUALIFIED study 
Version 1.1, November 26, 2019 
 
 
 
 
PROTOCOL TITLE ‘The evaluation of health-related quality of life issues experienced by 
patients with desmoid-type fibromatosis’ 
Protocol ID 
 
Short title 
QUALIFIED study 
EudraCT number  
Not applicable 
Version 
1.1 
Date 
November 26, 2019 
Coordinating investigator 
 
Mw. M.J.M. Timbergen, MD 
Email: m.timbergen@erasmusmc.nl 
010-7041223 
Principal 
investigator(s) 
(in 
Dutch: 
hoofdonderzoeker/ 
uitvoerder) 
 
 
 
 
Multicentre research: per site 
 
prof. dr. C. Verhoef, MD, PhD 
Department of Surgical Oncology 
Erasmus Medical Center (MC) 
Dr. Molewaterplein 40  
3015 GD Rotterdam 
The Netherlands 
Email: c.verhoef@erasmusmc.nl  
 
 
Radboud University Medical Center  
dr. H. Bonenkamp, MD, PhD 
Department of Surgical Oncology 
Geert Grooteplein Zuid 10 
6525 GA Nijmegen, The Netherlands 
Email: h.bonenkamp@radboudumc.nl 
 
Antoni van Leeuwenhoek Ziekenhuis (AVL) / The 
Netherlands Cancer Instituut  
prof. dr. W. van der Graaf, MD, PhD 
Department of Medical Oncology 
Plesmanlaan 121 
1066 CX Amsterdam, The Netherlands 
Email: w.vd.graaf@nki.nl 
Sponsor 
(in 
Dutch: 
verrichter/opdrachtgever) 
Erasmus MC Rotterdam 
prof. dr. J. M. Hendriks 
Head of Department of Surgery 
Dr. Molewaterplein 40  
3015 GD Rotterdam 
The Netherlands 
Subsidising party 
Stichting Coolsingel 
Schiekade 75 
3033 BD Rotterdam 
Reference number: 566 
Independent expert (s) 
Not applicable 
Laboratory sites  
Not applicable  

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Pharmacy  
Not applicable 
Steering 
group 
(intellectual 
input) 
Mw. M.J.M. Timbergen, MD 
Department of Surgical Oncology, Erasmus MC, 
Rotterdam, The Netherlands 
Department of Medical Oncology, Erasmus MC, 
Rotterdam, The Netherlands 
Email: m.timbergen@erasmusmc.nl 
 
prof. dr. S. Sleijfer, MD, PhD 
Department of Medical Oncology, Erasmus MC, 
Rotterdam, The Netherlands 
Email: s.sleijfer@erasmusmc.nl 
 
dr. D.J. Grünhagen, MD, PhD 
Department of Surgical Oncology, Erasmus MC, 
Rotterdam, The Netherlands 
Email: d.grunhagen@erasmusmc.nl  
 
dr. W.J. van Houdt, MD, PhD 
Department of Surgical Oncology, Antoni van 
Leeuwenhoek Ziekenhuis (AVL) / The Netherlands 
Cancer Instituut, Amsterdam, The Netherlands 
Email: w.v.houdt@nki.nl 
 
prof. L.V. van de Poll, MSc, PhD 
Department of Research, Netherlands 
Comprehensive Cancer Organisation (IKNL), 
Eindhoven, the Netherlands 
Division of Psychosocial Research and Epidemiology, 
The Netherlands Cancer Institute, Amsterdam, the 
Netherlands 
Department of Medical and Clinical Psychology, 
Tilburg University, Tilburg, the Netherlands.  
Email: l.vd.poll@nki.nl 
 
dr. O. Husson, MSc, PhD 
Division of Clinical Studies, Institute of Cancer 
Research, London, United Kingdom And Royal 
Marsden NHS Foundation Trust.  
Nederlands Kanker Instituut (NKI), Amsterdam, The 
Netherlands 
Email: o.husson@nki.nl 

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PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Sponsor or legal representative: 
prof. dr. J.M. Hendriks 
Head of the Department of Surgery, 
Erasmus MC 
 
 
 
Principal Investigator: 
prof. dr. C. Verhoef  
Surgical Oncologist,  
Department of Surgical Oncology, 
Erasmus MC  
 
 
 

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TABLE OF CONTENTS 
 
1. 
INTRODUCTION AND RATIONALE .............................................................................10 
2. 
OBJECTIVES ................................................................................................................10 
3. 
STUDY DESIGN ...........................................................................................................11 
4. 
STUDY POPULATION ..................................................................................................11 
4.1 
Population (base) ...................................................................................................11 
4.2 
Inclusion criteria .....................................................................................................11 
4.3 
Exclusion criteria ....................................................................................................11 
4.4 
Sample size calculation ..........................................................................................11 
5. 
TREATMENT OF SUBJECTS .......................................................................................11 
5.1 
Investigational product/treatment ............................................................................12 
5.2 
Use of co-intervention (if applicable) ......................................................................12 
5.3 
Escape medication (if applicable) ...........................................................................12 
6. 
INVESTIGATIONAL PRODUCT ....................................................................................12 
6.1 
Name and description of investigational product(s) ................................................12 
6.2 
Summary of findings from non-clinical studies ........................................................12 
6.3 
Summary of findings from clinical studies ...............................................................12 
6.4 
Summary of known and potential risks and benefits ...............................................12 
6.5 
Description and justification of route of administration and dosage .........................12 
6.6 
Dosages, dosage modifications and method of administration ...............................12 
6.7 
Preparation and labelling of Investigational Medicinal Product ...............................12 
6.8 
Drug accountability .................................................................................................12 
7. 
NON-INVESTIGATIONAL PRODUCT ...........................................................................12 
7.1 
Name and description of non-investigational product(s) .........................................12 
7.2 
Summary of findings from non-clinical studies ........................................................12 
7.3 
Summary of findings from clinical studies ...............................................................12 
7.4 
Summary of known and potential risks and benefits ...............................................12 
7.5 
Description and justification of route of administration and dosage .........................12 
7.6 
Dosages, dosage modifications and method of administration ...............................12 
7.7 
Preparation and labelling of Non Investigational Medicinal Product ........................12 
7.8 
Drug accountability .................................................................................................12 
8. 
METHODS ....................................................................................................................13 
8.1 
Study parameters/endpoints ...................................................................................13 
8.1.1 
Main study parameter/endpoint .......................................................................13 
8.1.2 
Secondary study parameters/endpoints ..........................................................13 
8.1.3 
Other study parameters ...................................................................................13 
8.2 
Randomisation, blinding and treatment allocation ..................................................14 
8.3 
Study procedures ...................................................................................................14 
8.4 
Withdrawal of individual subjects ............................................................................14 
8.4.1 
Specific criteria for withdrawal (if applicable) ...................................................14 
8.5 
Replacement of individual subjects after withdrawal ...............................................15 
8.6 
Follow-up of subjects withdrawn from treatment .....................................................15 
8.7 
Premature termination of the study .........................................................................15 

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9. 
SAFETY REPORTING ..................................................................................................15 
9.1 
Temporary halt for reasons of subject safety ..........................................................15 
9.2 
AEs, SAEs and SUSARs ........................................................................................15 
9.2.1 
Adverse events (AEs) ......................................................................................15 
9.2.2 
Serious adverse events (SAEs) .......................................................................15 
9.2.3 
Suspected unexpected serious adverse reactions (SUSARs) .........................15 
9.3 
Annual safety report ...............................................................................................15 
9.4 
Follow-up of adverse events ...................................................................................15 
9.5 
[Data Safety Monitoring Board (DSMB) / Safety Committee] ..................................15 
10. 
STATISTICAL ANALYSIS ..........................................................................................15 
10.1 
Primary study parameter(s) ....................................................................................16 
10.2 
Secondary study parameter(s) ...............................................................................16 
10.3 
Other study parameters ..........................................................................................16 
10.4 
Interim analysis (if applicable) ................................................................................17 
11. 
ETHICAL CONSIDERATIONS ...................................................................................17 
11.1 
Regulation statement .............................................................................................17 
11.2 
Recruitment and consent........................................................................................17 
11.3 
Objection by minors or incapacitated subjects (if applicable) ..................................17 
11.4 
Benefits and risks assessment, group relatedness .................................................17 
11.5 
Compensation for injury .........................................................................................18 
11.6 
Incentives (if applicable) .........................................................................................18 
12. 
ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION .........................18 
12.1 
Handling and storage of data and documents ........................................................18 
12.2 
Monitoring and Quality Assurance ..........................................................................19 
12.3 
Amendments ..........................................................................................................20 
12.4 
Annual progress report ...........................................................................................20 
12.5 
Temporary halt and (prematurely) end of study report ............................................20 
12.6 
Public disclosure and publication policy ..................................................................20 
13. 
STRUCTURED RISK ANALYSIS...............................................................................20 
13.1 
Potential issues of concern .....................................................................................20 
13.2 
Synthesis ...............................................................................................................21 
14. 
REFERENCES ..........................................................................................................22 
Appendix 1. Questionnaires..................................................................................................23 
 
 
 
 
 
 
 
 
 
 
 
 
 

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LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS  
 
AE 
Adverse Event 
CRF 
Case Report Form 
DSMB 
Data Safety Monitoring Board 
DTF 
Desmoid-type fibromatosis 
EORTC 
European Organisation for Research and Treatment of Cancer 
EORTC QLQ-C30 
European Organisation for Research and Treatment of Cancer, Quality of 
Life Questionnaire-Core-30 
EQ-5D-5L 
EuroQoL 5 dimensions, 5 levels 
EudraCT 
European drug regulatory affairs Clinical Trials  
FAP 
Familial Adenomatous Polyposis 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation; in Dutch: Algemene Verordening 
Gegevensbescherming (AVG) 
HRQoL 
Health-related quality of life 
IC 
Informed Consent 
IQR 
Interquartile range 
METC  
Medical research ethics committee (MREC); in Dutch: medisch-ethische 
toetsingscommissie (METC) 
MC 
Medical Center 
PROFILES 
Patient Reported Outcomes Following Initial treatment and Long term 
Evaluation of Survivorship 
QoL 
Quality of Life 
(S)AE 
(Serious) Adverse Event  
SD 
Standard Deviation 
Sponsor 
The sponsor is the party that commissions the organisation or performance 
of the research, for example a pharmaceutical company, academic hospital, 
scientific organisation or investigator. A party that provides funding for a 
study but does not commission it is not regarded as the sponsor, but 
referred to as a subsidising party. 
SUSAR  
Suspected Unexpected Serious Adverse Reaction 
VAS 
Visual Analogue Scale 
WGBO 
Dutch 
Medical 
Treatment 
Contracts 
Act; 
in 
Dutch: 
Wet op 
de 
Geneeskundige Behandelingsovereenkomst 
WMO 
Medical Research Involving Human Subjects Act; in Dutch: Wet Medisch-
wetenschappelijk Onderzoek met Mensen 
 
 

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SUMMARY 
 
Rationale: Desmoid-type fibromatosis (DTF) is a rare, histologically benign soft tissue 
tumour. Although incapable of metastasizing, the clinical course is unpredictable and can be 
aggressive because of local invasive growth. Many invasive treatments (i.e. surgery, 
chemotherapy, radiotherapy) may be considered in patients with symptomatic disease but 
unfortunately, these ‘traditional’ treatment options do not guarantee tumour reduction and/or 
clinical response 1. Local recurrence after surgery remains high 2,3. Active surveillance is now 
recommended as a first line management for most patients with DTF 1,4. Therefore, DTF has 
obtained a more ‘chronic’ status and its impact on patients should be evaluated accordingly. 
 
Health-related quality of life (HRQoL) provides information beyond traditional measures of 
efficacy in oncology such as overall survival, and is increasingly used as an endpoint in 
clinical trials 5,6. Based on previous studies we concluded that there is currently no HRQoL 
measure suitable for DTF patients. Additionally, we concluded that few is known about the 
quality of life of patients living with this rare disease. The previous studies led to the 
development of a DTF-specific HRQoL questionnaire named the ‘DTF-QoL’ 7.  
 
By obtaining data from a relatively large group of patients with this rare disease, we will be 
able to evaluate the prevalence of HRQoL problems in adult DTF patients. The hypothesis is 
that patients with DTF have issues on several HRQoL domains including physical, social and 
emotional well-being. This study aims to evaluate HRQoL issues experienced by DTF 
patients. 
 
Objective:  
The primary objective is to evaluate HRQoL problems in adult DTF patients. 
 
The secondary objectives are:  
1. To compare the level of HRQoL of DTF patients to the general population. 
2. To identify patient subgroups who are at risk for developing certain HRQoL problems, 
3. To evaluate patient preferences regarding their health care needs for DTF. 
 
Study design: Multicentre, cross-sectional, observational, cohort study.  
 
Study population:  
All patients, aged 18 years and above with a histopathological proven DTF and sufficient 
Dutch language skills who have received their last check-up at a medical oncologist or 
surgical oncologist specialized in DTF, in the hospital within the last five years (between 
October 2014 and October 2019).  
 
Intervention (if applicable): Eligible patients will be asked to fill out a set of questionnaires 
consisting of 173 questions in total. Patients will only have to fill out these questionnaires 
once. 
 
Main study parameters/endpoints:  
To evaluate HRQoL problems in adult DTF patients, regardless of their disease stage or 
treatment course, using the DTF-QoL, the EORTC QLQ-C30, and the EQ-5D-5L 
questionnaires. 
 
Secondary objectives: 
a) Comparison of EORTC QLQ-C30 scores (describing symptoms, single items, 
functioning and global health) between DTF patients and the general population (age- 
and sex-matched). 
b) Identification of DTF patients who are at risk for impaired HRQoL (risk factors). 
c) Evaluating patient preferences for the health care for DTF. 

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Nature and extent of the burden and risks associated with participation, benefit and 
group relatedness:  
The total number of questions is 173. 
 
Completing all the questionnaires will take about 30-60 minutes. Our experience of high 
response in previous large-scale cancer survivorship studies using the PROFILES (Patient 
Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship) 
registry indicates that this number of questionnaires and its content is feasible and well 
accepted by patients. However some patients might find this burdensome. Risks are 
considered to be negligible and the burden is considered to be minimal. Because patients will 
complete these questionnaire in their own time, they will have the time and space to think 
about HRQoL issues which are important to them. 
 
 
 
 
 
 
 
 
 
 
 

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1. INTRODUCTION AND RATIONALE 
Desmoid-type fibromatosis (DTF) is a benign soft tissue tumour which can cause significant 
morbidity by local aggressive growth behaviour 8. Due to its local aggressive behaviour, and 
its known tendency of local recurrence after initial surgical resection, it is categorized as a 
borderline tumour in clinical guidelines 8.This tumour is rare with an estimated incidence of 5 
patients per million persons per year in the Dutch population 9. The biological behaviour is 
variable with phases of progressive growth, growth stabilization and even regression of the 
tumour without any treatment 10. Most patients are females, aged between 20 and 40 years 
at primary diagnosis 9. 
 
 
Sporadic DTF arises in musculoaponeurotic structures with the most common sites being 
the abdominal wall and the extremities 11. Symptoms vary, depending on tumour site, size 
and infiltration of adjacent structures, resulting in pain and/or functional impairment. DTF 
does not metastasize, and rarely has fatal outcomes. Surgical resection, radiotherapy, non-
cytotoxic and cytotoxic systemic therapies may be considered in patients with symptomatic 
disease but unfortunately, these ‘traditional’ treatment options do not guarantee tumour 
reduction and/or clinical response 1. Local recurrence after surgery remains high 2,3, leading 
to a reduction in surgical treatments for DTF over recent decades 9,11. Additionally, ‘active’ 
forms of treatment can be debilitating, causing greater morbidity than the tumour itself. For 
these reasons, active surveillance is now recommended as a first line management for most 
patients with DTF 1,4. Therefore, DTF has obtained a ‘chronic’ status and its impact on 
patients should be evaluated accordingly.  
 
 
 
Health-related quality of life (HRQoL) provides information beyond traditional measures of 
efficacy in oncology such as overall survival, and is increasingly used as an endpoint in 
clinical trials 5,6. We previously performed a systematic literature review to evaluate which 
HRQoL-measures were used in research to assess HRQoL in DTF 12. Studies used generic 
HRQoL-measures (e.g. the cancer specific core questionnaire from European Organisation 
for Research and Treatment of Cancer; the EORTC quality of life core questionnaire 
(EORTC QLQ-C30)), which may not consider disease-specific issues in DTF patients. Also, 
site-specific tools (e.g. Toronto Extremity Salvage Score), were used, which may not be 
relevant to certain groups (e.g. those with an abdominal wall, or head and neck tumours). 
 
 
At present, there is no validated DTF-specific HRQoL-tool. In order to gain greater insight 
into the issues that patients with DTF experience in their daily lives, and to evaluate their 
experiences with the current health care and supportive system for DTF, we previously 
organised focus groups and semi-structured interviews, in the United Kingdom and in the 
Netherlands 7,12. These studies identified issues covering various domains including; the 
diagnostic pathway, the treatment pathway, daily limitations (e.g. physical and psychological 
symptoms), and experiences with the current health care system. Additionally, issues were 
ranked according to their relevance by patients and health care providers (Timbergen et al., 
2019, submitted). A DTF-specific HRQoL tool, named the DTF-QoL, was developed based 
on the results of these studies. 
 
 
With the current study we would like to assess the HRQoL problems experienced by DTF 
patients. The DTF-specific tool, the (DTF-QoL), combined with additional HRQoL-tools will 
be used to gain more insight into the problems that DTF patients face on a daily basis. This 
study functions as an exploratory study which may generate new hypotheses for future 
studies. 
 
2. OBJECTIVES 
Primary objective: To evaluate HRQoL problems in adult DTF patients, regardless of their 
disease stage or treatment course, using the DTF-QoL, the EORTC QLQ-C30, and the EQ-
5D-5L questionnaires. 
 

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Secondary objectives: 
1. To compare the level of HRQoL of DTF patients to that of the general population (age- 
and sex-matched), using the EORTC QLQ-C30 (version 3.0). 
2. To identify DTF patients who are at risk for late effects and/or impaired HRQoL (risk 
factors), using the baseline questionnaire, the DTF-QoL (version 1.0), the EORTC QLQ-
C30 (version 3.0), and the EQ-5D-5L (version 1.0). 
3. To evaluate patient preferences regarding their health care for DTF, using the healthcare 
utility and decision making questionnaires (both version 1.0). 
. 
3. STUDY DESIGN 
Multicentre, cross-sectional, observational, cohort study. 
 
4. STUDY POPULATION 
4.1 Population (base)  
Patients, aged ≥18 years, diagnosed with a histopathological proven DTF, regardless of 
disease stage and received treatment(s) who have received their last check-up of their DTF 
in one of the participating hospitals the hospital between October 2014 and October 2019.  
 
4.2 Inclusion criteria 
In order to be eligible to participate in this study, a subject must meet all of the following 
criteria: 
 
• 
Patients, aged ≥18 years 
• 
Patients with histopathological proven DTF, regardless of disease stage or treatment. 
• 
Patients diagnosed between January 1990 and October 2019, with a visit to the 
hospital for their DTF (between October 2014 and October 2019) 
• 
Patients with sufficient Dutch language skills 
• 
Patients competent to complete a questionnaire 
• 
Patients with a written informed consent 
 
4.3 Exclusion criteria 
A potential subject who meets any of the following criteria will be excluded from 
participation in this study: 
• 
Patients diagnosed with familial adenomatous polyposis (FAP) 
 
4.4 Sample size calculation 
The incidence of DTF is 5.4 patients per million per year 9. However, a sample size 
calculation is challenging due to rarity of the disease and lack of published data regarding 
this subject. In our previous study, the response rate of the Dutch patients was 41.5%. The 
Erasmus MC pathology database from 1990 until 2019 contains roughly 250 patients. Since 
we are a tertiary academic centre, about one third of these patients are pathology 
consultations from other centres. A small fraction of the remaining patients will be excluded 
because they are younger than 18 years old (about 5%) and because their desmoid tumour 
is part of the genetic syndrome Familial Adenomatous Polyposis (FAP) (about 5%). Because 
of the high incidence of malignant colorectal tumours in FAP patients, these patients might 
experience different HRQoL problems compared to patients with “sporadic” DTF. Currently, 
there are about 80 patients who are under follow-up at our institution. With the participation 
of two other centres with similar patient numbers we hope to approach a total of 250 patients. 
Based on the previous response rate we expect to obtain data from 100 DTF patients. 
  
5. TREATMENT OF SUBJECTS 
Not applicable, as this study does not involve an investigational product. 

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5.1 Investigational product/treatment 
Not applicable, as this study does not involve an investigational product. 
5.2 Use of co-intervention (if applicable) 
 
Not applicable, as this study does not involve an investigational product. 
5.3 Escape medication (if applicable) 
Not applicable, as this study does not involve an investigational product. 
 
6. INVESTIGATIONAL PRODUCT  
Not applicable, as this study does not involve an investigational product. 
6.1 Name and description of investigational product(s) 
 
Not applicable, as this study does not involve an investigational product. 
6.2 Summary of findings from non-clinical studies 
 
Not applicable, as this study does not involve an investigational product. 
6.3 Summary of findings from clinical studies 
 
Not applicable, as this study does not involve an investigational product. 
6.4 Summary of known and potential risks and benefits 
 
Not applicable, as this study does not involve an investigational product. 
6.5 Description and justification of route of administration and dosage 
 
Not applicable, as this study does not involve an investigational product. 
6.6 Dosages, dosage modifications and method of administration 
 
Not applicable, as this study does not involve an investigational product. 
6.7 Preparation and labelling of Investigational Medicinal Product 
 
Not applicable, as this study does not involve an investigational product. 
6.8 Drug accountability 
 
Not applicable, as this study does not involve an investigational product. 
 
 
7. NON-INVESTIGATIONAL PRODUCT 
Not applicable, as this study does not involve a non-investigational product. 
7.1 Name and description of non-investigational product(s) 
 
Not applicable, as this study does not involve a non-investigational product 
7.2 Summary of findings from non-clinical studies 
 
Not applicable, as this study does not involve a non-investigational product 
7.3 Summary of findings from clinical studies 
Not applicable, as this study does not involve a non-investigational product 
7.4 Summary of known and potential risks and benefits 
 
Not applicable, as this study does not involve a non-investigational product 
7.5 Description and justification of route of administration and dosage 
Not applicable, as this study does not involve a non-investigational product 
7.6 Dosages, dosage modifications and method of administration 
Not applicable, as this study does not involve a non-investigational product 
7.7 Preparation and labelling of Non Investigational Medicinal Product 
Not applicable, as this study does not involve a non-investigational product 
7.8 Drug accountability 
Not applicable, as this study does not involve a non-investigational product 

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8. METHODS 
8.1 Study parameters/endpoints 
8.1.1 Main study parameter/endpoint 
 
The EORTC QLQ-C30 (version 3.0) questionnaire, the DTF-QoL questionnaire, and 
the EQ-5D-5L questionnaire will be used. More information about these 
questionnaires can be found in Appendix 1.  
 
The mean score or median score per scale of the EORTC QLQ-C30 questionnaire 
(symptom scales, single item scales, global health scale, and functioning scales) will 
be calculated with the standard deviation (SD) or interquartile range (IQR). 
Additionally, a summary score will be calculated based on all scales except financial 
difficulties and the global quality of life score, to reflect overall quality of life. 
 
A mean score per item with an SD or a median score with a IQR will be calculated for 
the DTF-QoL questionnaire. 
 
The outcomes of the EQ-5D-5L will be reported as frequency (proportion) of reported 
problems for each level and for each dimension 
8.1.2 Secondary study parameters/endpoints  
Patients with DTF will be matched to the general Dutch population using age and sex. 
The data from the general population in the Netherlands was obtained from the 
EORTC 13. The median or mean values for each scale (symptom scales, single items 
scales, global health scale, and functioning scales) of the EORTC QLQ-C30 (version 
3.0) from DTF patients will be compared to the median or mean scores per scale of 
the general population. 
 
Subgroups will be created based on the information of the baseline questionnaire and 
will encompass: sex (male, female), age groups (categorized based by the median 
age and/or quartiles), primary treatment type (surgical resection, systemic treatment, 
radiotherapy, local treatment (e.g. cryoablation), ethnicity, educational level, 
relationship status, job demands, comorbidities, tumour location, and tumour 
recurrences.  
 
Mean or median scores of each scale (EORTC QLQ-C30, version 3.0), items (DTF-
QoL, version 1,0) or frequency scores (EQ-5D-5L, version 1,0) will be calculated for 
each relevant subgroup. More information about these questionnaires can be found in 
Appendix 1. 
 
The outcomes of the health care utilization and the decision making questionnaires 
will be descriptive and reported in numbers and corresponding frequencies per 
answer option. More information about these questionnaires can be found in 
Appendix 1. 
8.1.3 Other study parameters 
 
The following variables will be collected from the medical records: 
- 
Date of first histological diagnosis 
- 
Details about treatment 
o Treatment start date 
o Type of treatments, including medication doses 
o Radiation dose 

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o Date of surgery 
o Sequence of treatments 
- 
Response to treatment 
o Progression, stable disease, regression based on imaging 
o Tumour sizes on imaging (magnetic resonance imaging, 
computed tomography or ultrasound) 
o Recurrence (based on imaging), recurrence based on 
pathology 
o Date of recurrence 
o Treatment type of recurrent tumour, date of treatment of 
recurrence 
 
8.2 Randomisation, blinding and treatment allocation 
 
Not applicable, as this study is no intervention study. 
 
8.3 Study procedures 
Selected patients will receive an invitation package by mail from their (former) treating 
health care professional (surgical oncologist, or medical oncologist). Data collection is 
done via PROFILES. Chapter 12 describes the use of PROFILES in more detail. 
 
Patients are asked to complete the following questionnaires once. More information 
about these questionnaires can be found in Appendix 1. 
Questionnaire A: Baseline questionnaire, version 1.0 (21 questions 
Questionnaire B: Health care utilization, version 1.0 (7 questions) 
Questionnaire C: Decision-making, version 1.0 (6 questions)  
Questionnaire D: EORTC QLQ-C30, version 3.0 (30 questions) 
Questionnaire E: DTF-QoL, version 1.0 (102 questions) 
Questionnaire F: EQ-5D-5L, version 1.0 (7 questions) 
 
 
Clinical characteristics (8.1.3) will be collected from the medical records. 
 
Patients are assured that non-participation has no consequences for their treatment or 
follow-up care. If the patient does not have access to internet, or prefers written rather 
than digital communication, (s)he will receive a paper version of the questionnaire 
package. The informed consent form and questionnaires are then sent by post.  
 
The questionnaire will be available at www.profielstudie.nl for a total of three months. 
Patients only have to fill out the questionnaire once but are able to stop at any given time 
point and are able to continue the questionnaire at any given time point. In case only a 
part of the questionnaire is filled out, the patient will receive a reminder (via PROFILES) 
to fill out the remaining questionnaire. Patients will receive a reminder 4 weeks after the 
first invitation. 
 
Patients will be made aware of the fact that additional data will be obtained from their 
electronic patients files in the patient information file and will sign informed consent for 
this on the informed consent form. 
 
8.4 Withdrawal of individual subjects 
Subjects can leave the study at any time for any reason if they wish to do so without 
any consequences.  
8.4.1 Specific criteria for withdrawal (if applicable) 
 
 
Not applicable, as this is not an interventional study 

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8.5 Replacement of individual subjects after withdrawal 
 
 
Not applicable, as this is not an interventional study. 
8.6 Follow-up of subjects withdrawn from treatment 
 
Not applicable, as this is not an interventional study. 
8.7 Premature termination of the study 
 
Not applicable, as this is not an interventional study. 
 
 
9. SAFETY REPORTING 
As this is not an interventional study and patients are not subjected to treatment in this study, 
this does not apply. 
9.1 Temporary halt for reasons of subject safety 
As patients are not subjected to treatment in this study, this does not apply. 
 
9.2 AEs, SAEs and SUSARs 
9.2.1 Adverse events (AEs) 
 
As patients are not subjected to treatment in this study, this does not apply. 
9.2.2 Serious adverse events (SAEs) 
 
As patients are not subjected to treatment in this study, this does not apply. 
9.2.3 Suspected unexpected serious adverse reactions (SUSARs) 
As patients are not subjected to treatment in this study and the study does not 
involve an investigational medicinal product, this does not apply. 
9.3 Annual safety report 
As patients are not subjected to treatment in this study and the study does not 
involve an investigational medicinal product, this does not apply. 
9.4 Follow-up of adverse events 
As patients are not subjected to treatment in this study and the study does not 
involve an investigational medicinal product, this does not apply.  
9.5 [Data Safety Monitoring Board (DSMB) / Safety Committee] 
As patients are not subjected to treatment in this study and the study does not 
involve an investigational nor a non-investigational medicinal product, this does not 
apply. No DSMB will be installed for this study. No safety measures are involved 
since there are no risks involved in administering questionnaires to the patients. 
 
10. STATISTICAL ANALYSIS 
Rstudio (RStudio, version 1.0.153, Boston, MA, USA) and SPSS Statistics (version 24, IBM, 
Armonk, New York, USA) will be used for the statistical analysis. 
 
The following questionnaires are descriptive outcomes and will be expressed as numbers 
and corresponding percentages:  
Questionnaire A: Baseline questionnaire, version 1.0 
Questionnaire B: Health care utilization, version 1.0 
Questionnaire C: Decision-making, version 1.0 
Questionnaire E: DTF-QoL, version 1.0 
More information about these questionnaires can be found in Appendix 1. 

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10.1 Primary study parameter(s) 
The scores for each item of the DTF-QoL will be calculated using a Likert scale from 1-4. 
The scores of each item will be calculated as mean ± SD, or as median (IQR). These 
scores (median or mean) will be reported per item.  
 
The scores of the EORTC-QLQ30 (version .3.0) will be calculated using a Likert scale 
from 1-4. The scoring manual of the EORTC will be followed. After linear transformation, 
all scales and single item measures range in score from 0-10014. Scores for each scale 
will be reported as mean (SD), or as median (IQR).The EORTC QLQ-C30 summary 
score will be calculated using the mean scores of the function scales and the reversed 
mean scores of the symptom scales and represented as the mean of the combined 13 
QLQ-C30 scale scores (financial impact and global health status excluded) 15,16.  
 
Each of the five dimensions of the EQ-5D-5L (version 1.0) can be divided into five levels 
of perceived problem (1-5). Health states can be converted into single index values. The 
outcomes will be reported as frequency (proportion) of reported problems for each level 
and for each dimension. The Visual Analogue Scale (VAS) data will be presented as a 
mean value (SD). In case of skewed data, median values and IQR will be used. 
 
10.2 Secondary study parameter(s)  
 
Using the baseline values (reported in the baseline questionnaire) for age and sex, 
patients will be matched, using a 1:10 nearest-neighbour match method, with the general 
population13 based on age, and sex using Rstudio (RStudio, version 1.0.153, Boston, 
MA, package MatchIt).  
 
Differences in scores (of the EORTC QLQ-C30 scales between groups will be tested for 
their significance using the Mann-Whitney U test or the t-test, depending on the 
distribution. SPSS Statistics (IBM, Armonk, New York, USA, version 24) will be used for 
these tests. A two-sided p<0.05 will be considered statistically significant. 
 
The outcomes of the health care utilization and the decision making questionnaire will be 
reported in numbers and corresponding percentages per answer option.  
10.3 Other study parameters 
Information extracted from medical files will be used as follows: 
- 
Date of first histological diagnosis: this variable will be used to 
calculate age at diagnosis using date of birth and date of first 
histological diagnosis, 
- 
Details about treatment 
o Treatment start date: this variable will be used to calculate age 
at the start of treatment using date of birth and the date of the 
start of the treatment. Additionally this variable can be used to 
calculate the time between the diagnosis and the start of 
treatment. 
o Type of treatments, including medication doses: this variable 
will be used as numbers with corresponding percentages 
o Radiation dose: this variable will be used in case a patient 
received surgery. This variable will be used descriptively 
o Date of surgery: this variable will be used to calculate the age 
at the time of surgery. Additionally this variable can be used to 
calculate the time between the diagnosis or the first treatment 
and surgery. 
o Sequence of treatments will be used descriptive 
- 
Response to treatment 

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o Progression, stable disease, regression based on imaging: 
these variables will be used in a descriptive manner 
o Tumour sizes on imaging (magnetic resonance imaging, 
computed tomography or ultrasound): these variables will be 
used to calculate mean size with standard deviation or median 
with interquartile range. Additionally this variable can be used to 
evaluate treatment outcome. 
10.4 Interim analysis (if applicable) 
Not applicable, no interim analysis will be done. 
 
11. ETHICAL CONSIDERATIONS 
11.1 Regulation statement 
The study will be conducted according to the principles of the Declaration of Helsinki (64th 
World Medical Association General Assembly, Fortaleza, Brazil, October 2013). This 
study has been exempted by the medical research ethics committee (MREC); in Dutch: 
Medisch Ethische Toetsings Commissie (METC). Following review of the protocol, the 
MREC concluded that this study is not subject to the Medical Research Involving Human 
Subjects Act (WMO). They concluded that the study is a medical/scientific research, but 
no patients are subjected to procedures or are required to follow rules of behaviour. The 
study will be conducted according to the rules of the Dutch Medical Treatment Contracts 
Act (WGBO) and the Dutch General Data Protection Regulation (AVG) and in accordance 
with 
the 
Code 
of 
Conduct 
for 
Health 
Research 
(in 
Dutch: 
Gedragscode 
Gezondheidsonderzoek). 
 
11.2 Recruitment and consent 
Patients will be selected (based on their diagnosis) by the responsible treating Surgical 
Oncology or Medical Oncology Consultant who will check the patient for eligibility criteria 
from the electronic patient records. The treating healthcare professional or specialist 
nurse will introduce the study to the patient in the outpatient clinic and provide an 
invitation package. In case that the patient does not visit the outpatient clinic within two 
months of the start of the study, the treating healthcare professional or specialist nurse 
will invite the patient with the invitation package per post. The patients’ address data will 
be checked with the national administration (in Dutch: gemeentelijke basis administratie) 
to assure its correctness.  
 
The invitation package consists of a letter, a patient information sheet, an informed 
consent form and a prepaid return envelope. The patient information sheet explains the 
goals and procedure of the study. It includes a link to a secure website 
(www.profielstudie.nl), a login name, and a password. If patients have read the 
information sheet and have no further questions, they can login to the website. Informed 
consent is obtained both written and online. After providing written and online informed 
consent, they will be able to complete the questionnaires online.  
 
11.3 Objection by minors or incapacitated subjects (if applicable) 
Not applicable. No minors or incapacitated subjects will participate in this study. 
 
11.4 Benefits and risks assessment, group relatedness 
The study involves completing questionnaires and therefore risks are considered to be 
negligible and the burden is considered to be minimal. For the patient there is no direct 
advantage with participating in this study, as the answers to the questionnaire will not 
impact their current treatment plan. As the study is used to gain insight into HRQoL 
problems of DTF patients, it can potentially benefit their health care in the future. 

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Because patients will complete these questionnaire in their own time, they will have the 
time and space to think about HRQoL issues which are important to them. It is possible 
that a patient will become upset when thinking about how their DTF has impact on their 
HRQoL. Researchers will need to be aware of this and provide support if participants 
become upset.  
 
11.5 Compensation for injury 
As the study is not subjected to the Medical Research Involving Human Subjects Act 
(WMO), the statutory obligation to provide insurance for subjects participating in medical 
research (article 7 of the WMO) also does not apply. 
 
11.6 Incentives (if applicable) 
There is no compensation offered to participants. 
 
12. ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 
12.1 Handling and storage of data and documents 
Questionnaire administration will be done within the PROFILES registry (Patient Reported 
Outcomes Following Initial treatment and Long term Evaluation of Survivorship; 
www.profilesregistry.nl). PROFILES is a data management system set up in 2009 in The 
Netherlands for the study of the physical and psychosocial impact of cancer and its 
treatment. PROFILES is currently used in the Erasmus MC for the QUEST study (MEC-
2018-1037) and the HOLISTIC study (MEC-2018-1101) investigating HRQoL in sarcoma 
patients. PROFILES uses an audit trail. 
 
The local research coordinator at each study site will have access to a password 
protected file which links patients study ID number to their PROFILES online login 
username.  
 
All answers that are entered by each individual patient are linked to their study ID 
number and do not contain overt identifiers (i.e. names or date of birth). Only after written 
informed consent from the patient, answers can be collected and linked to data collected 
from the medical records on case report forms in Open Clinica. All case report forms are 
completed with the patient’s study number and do not contain person-identifiable 
information such as name or date of birth.  
 
PROFILES 
The PROFILES management system is hosted in The Netherlands on multi-processor 
servers for which infrastructure, configuration, license, security and patching are 
established in accordance with current norms (Dutch Data Protection Act (in Dutch: 
‘Algemene Verordening Gegevensbescherming (AVG)). Participants log in with their own 
user name and password into a PHP web application that communicates with a MySQL 
database located on a different server. This database server is shielded through a firewall 
from the internet. Both PHP and MySQL database servers run Linux as Operating 
System. Participants fill in their questionnaire on a separate server cluster, consisting of 
Windows 2008 R2 Servers running BlaiseIS questionnaire software (Statistics 
Netherlands). The answers to the questions are stored on a dedicated data storage 
server, shielded through firewalls from the internet. All servers are located in a secured 
room with access only for authorized personnel. The PROFILES infrastructure and 
software is updated regularly to optimize system operations and security. In addition, 
PROFILES has been awarded with the international data seal of approval for trusted data 
repository (http://www.datasealofapproval.org/en/). Questionnaire data will be stored on 
this secure Dutch system for 15 years.  
 

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Questionnaires on paper 
Paper copies of the questionnaires will be entered by the research coordinator using the 
data entry option of PROFILES, after which a control check takes place on the eventually 
generated dataset. Paper versions of the questionnaires will be stored for 15 years in a 
according to legal requirements at the study site. 
 
Completion of the study 
The questionnaire data will be linked with the case report form (CRF) database (Open 
Clinica) (containing coded clinical data). Data linkage will be done by an epidemiologist 
involved in this project. Data linkage will take place using non-identifiable study numbers 
generated by PROFILES, allowing us to analyse the data pseudonymously.  
 
In order to retrieve the data, the coordinating investigator at each study site who is 
authorised to login, can download the data in SPSS or Microsoft excel format. The 
FileSender server software allows authenticated users to securely send large files to other 
uses. This application has been developed to the requirements of the higher education 
and research community and allows end to end encryption. The combined dataset will be 
stored on computers within the Erasmus MC and will be under appropriate password 
protection. 
 
Confidentiality and pseudo-anonymity of patients 
Confidentiality and pseudo-anonymity of patients will be guaranteed with the assignation 
of a study number to each patient. Only a delegated research study member from each 
study team (site) will have access to a record that links the patient study numbers and 
their PROFILES login details to identifiable information. A study number is auto-generated 
by the PROFILES system. An example of the study number is: RNEMC0001 
(RN[centre][number]). 
 
Clinical data 
Clinical data will be collected from the medical files of patients and maintained according 
to GCP standards and entered into the study password protected database where it will 
be stored. The patient records will not leave the hospital where the patient is treated. The 
research data will be stored in a password protected, database and will be handled 
confidentially. Research data that can be traced to individual persons can only be viewed 
by the on-site researcher. From a legal point of view; members of the health care 
inspection and members of the Medical Research Ethics Committee of the participating 
hospital also have access to this data. Data review may be necessary in order to ensure 
the reliability and quality of the research. The handling of personal data is in compliance 
with 
the 
Dutch 
Data 
Protection 
Act 
(in 
Dutch: 
‘Algemene 
Verordening 
Gegevensbescherming (AVG)). 
 
Data will be saved and stored for a period of 15 years, conform Erasmus MC’s 
agreements for studies that are not subject to the Medical Research Involving Human 
Subjects Act (WMO).  
 
12.2 Monitoring and Quality Assurance  
The principal investigator or a project leader, will monitor quality of the data in the 
database by checking correctness and completeness of data (e.g. the answers from the 
DTF-QoL and EORTC QLQ-C30 questionnaires) for a random selection of 10% of 
patients, with a minimum of 10 patients per participating hospital. The data sources are 
the answers of the questionnaires completed by the patients and stored at the PROFILES 
server (in Dutch: Profiel). 

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12.3 Amendments  
Amendments are changes made to the research after a favourable opinion by the 
accredited METC has been given. All amendments will be notified to the METC that gave 
a favourable opinion.  
12.4 Annual progress report 
Not applicable, as this study will not be subject to the Medical Research Involving Human 
Subjects Act (WMO). 
12.5 Temporary halt and (prematurely) end of study report 
Within one year after the end of the study, the investigator/sponsor will submit a final 
study report with the results of the study, including any publications/abstracts of the 
study, to the accredited METC. 
12.6 Public disclosure and publication policy 
The results of this cross-sectional study will be reported using the STROBE guidelines 17. 
The results of this study will be presented (orally or poster presentations) at conferences 
and the final results will be published into relevant journals. Patients’ anonymity will be 
ensured throughout every publication. 
 
This study is funded by Stichting Coolsingel (reference number: 566), which will be 
mentioned during any oral or poster presentations. Additionally they will be mentioned in 
the acknowledgement section of each published paper.  
 
Patients will be informed about the results of the study in case they specifically asked to 
be informed. 
 
Agreements on authorship: 
The current study is a multicentre study; therefore, any publication based on the results 
obtained during this study will not be made before the first multicentre presentation. This 
will be coordinated by the coordinating investigator and/or the epidemiologist.  
 
All authors, mentioned under steering group (intellectual input), who provided significant 
input to the study and/or publication will receive an authorship position. The principal 
investigator of each participating centre will receive an authorship position. 
 
Milea J.M. Timbergen, PhD candidate will be first author of the first publication. Olga 
Husson will be the final author of the first publication. The remaining authorships will be 
allocated in mutual agreement according to the final contribution to the paper. Additional 
publications will include persons from the steering group and the PI’s from every including 
centre as authors. The order of authors will be determined in mutual agreement. 
This study will be registered at clinicaltrials.gov (https:/clinicaltrials.gov)  
 
13. STRUCTURED RISK ANALYSIS  
Not applicable, as this study does not involve an experimental investigational or non-
investigational product (see chapters 6 and 7). 
 
13.1 Potential issues of concern 
Not applicable, as this study does not involve an experimental investigational or non-
investigational product. 
a. Level of knowledge about mechanism of action 
Not applicable. 
 
b. Previous exposure of human beings with the test product(s) and/or products with a 
similar biological mechanism 

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Not applicable. 
 
c. Can the primary or secondary mechanism be induced in animals and/or in ex-vivo 
human cell material? 
Not applicable. 
 
d. Selectivity of the mechanism to target tissue in animals and/or human beings 
Not applicable. 
 
e. Analysis of potential effect 
Not applicable. 
 
f. Pharmacokinetic considerations 
Not applicable. 
 
g. Study population 
Not applicable. 
 
h. Interaction with other products 
Not applicable. 
 
i. Predictability of effect 
Not applicable. 
 
j. Can effects be managed? 
Not applicable. 
 
13.2 Synthesis 
Not applicable since this study does not involve an investigational or non-investigational 
product. 
 
 
 
 

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14. REFERENCES 
 
 
1. 
Kasper B, Baumgarten C, Garcia J, et al: An update on the management of 
sporadic desmoid-type fibromatosis: A European Consensus Initiative between Sarcoma 
PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of 
Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG). Ann Oncol 28:2399-2408, 
2017 
 
2. 
Posner MC, Shiu MH, Newsome JL, et al: The desmoid tumor. Not a 
benign disease. Arch Surg 124:191-6, 1989 
 
3. 
Crago AM, Denton B, Salas S, et al: A prognostic nomogram for prediction 
of recurrence in desmoid fibromatosis. Ann Surg 258:347-53, 2013 
 
4. 
Gronchi A, Colombo C, Le Pechoux C, et al: Sporadic desmoid-type 
fibromatosis: a stepwise approach to a non-metastasising neoplasm--a position paper from 
the Italian and the French Sarcoma Group. Ann Oncol 25:578-83, 2014 
 
5. 
Gundle KR, Cizik AM, Jones RL, et al: Quality of life measures in soft tissue 
sarcoma. Expert Review of Anticancer Therapy 15:95-100, 2015 
 
6. 
Gounder MM, Mahoney MR, Van Tine BA, et al: Sorafenib for Advanced 
and Refractory Desmoid Tumors. N Engl J Med 379:2417-2428, 2018 
 
7. 
Husson O, Younger E, Dunlop A, et al: Desmoid fibromatosis through the 
patients' eyes: time to change the focus and organisation of care? Support Care Cancer, 
2018 
 
8. 
Landelijke Richtlijn Wekedelen Tumoren, versie 2.0 (2011), Oncoline, 
richtlijnen oncologische zorg, 2011 
 
9. 
van Broekhoven DL, Grunhagen DJ, den Bakker MA, et al: Time trends in 
the incidence and treatment of extra-abdominal and abdominal aggressive fibromatosis: a 
population-based study. Ann Surg Oncol 22:2817-23, 2015 
 
10. 
Bonvalot S, Ternes N, Fiore M, et al: Spontaneous regression of primary 
abdominal wall desmoid tumors: more common than previously thought. Ann Surg Oncol 
20:4096-102, 2013 
 
11. 
Penel N, Le Cesne A, Bonvalot S, et al: Surgical versus non-surgical 
approach in primary desmoid-type fibromatosis patients: A nationwide prospective cohort 
from the French Sarcoma Group. Eur J Cancer 83:125-131, 2017 
 
12. 
Timbergen MJM, van de Poll-Franse LV, Grunhagen DJ, et al: Identification 
and assessment of health-related quality of life issues in patients with sporadic desmoid-type 
fibromatosis: a literature review and focus group study. Qual Life Res, 2018 
 
13. 
Nolte S, Liegl G, Petersen MA, et al: General population normative data for 
the EORTC QLQ-C30 health-related quality of life questionnaire based on 15,386 persons 
across 13 European countries, Canada and the Unites States. Eur J Cancer 107:153-163, 
2018 
 
14. 
Center QCQoLUED: EORTC QLQ-C30 Scoring Manual Third edition, 
European Organisation for Research and Treatment of Cancer  2001 
 
15. 
Giesinger JM, Kieffer JM, Fayers PM, et al: Replication and validation of 
higher order models demonstrated that a summary score for the EORTC QLQ-C30 is robust. 
J Clin Epidemiol 69:79-88, 2016 
 
16. 
Gundy CM, Fayers PM, Groenvold M, et al: Comparing higher order 
models for the EORTC QLQ-C30. Qual Life Res 21:1607-17, 2012 
 
17. 
von Elm E, Altman DG, Egger M, et al: The Strengthening the Reporting of 
Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting 
observational studies. Lancet 370:1453-7, 2007 
 
18. 
The European Organisation for Research and Treatment of Cancer 
(EORTC) QLQ-C30 Scoring Manual, 2001 
 
19. 
Herdman M, Gudex C, Lloyd A, et al: Development and preliminary testing 
of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res 20:1727-36, 2011 
 
 
 
 
 

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Appendix 1. Questionnaires 
 
Baseline questionnaire, version 1.0, October 29 2019, (Dutch) 
Self-reported demographic data include age, sex, ethnicity, relationship status, family 
composition, educational level, employment status, physical and mental demands of current 
job, comorbidities will be collected using this baseline questionnaire. Additionally, clinical 
data regarding the DTF will be collected: tumour location, multiple DTF locations, received 
treatments, current treatment, recurrences. Health literacy will be assessed by one single 
item question (question 14). The baseline questionnaire (A) will be used to identify relevant 
subgroups (e.g. sex or age).  
 
Outcomes of this questionnaire will be descriptive and are expressed as numbers with 
corresponding percentages. 
 
Information regarding the pathology, treatment and outcome will be extracted from the 
(electronic) medical patient records by the researcher on the case report form (CRF). Details 
about which information is extracted from the (electronic) medical patient records can be 
found in paragraph 8.1.3. Patients will be made aware of this in the patient information file 
and will sign informed consent for this on the informed consent form.  
 
Health care utilization, version 1.0, October 29 2019, (Dutch) 
Health care utilization will be assessed by the health care utilization questionnaire. Patients 
will be asked about the following topics: satisfaction with received care, frequency of visits to 
the general practitioner / specialist, satisfaction with the follow-up schedule, preferences and 
needs for receiving care in a DTF expert centre, receiving additional care of support from 
professionals (medical and non-medical). 
 
Outcomes of this questionnaire will be descriptive and expressed as numbers with 
corresponding percentages to explore health care utilization. 
 
Decision-making, version 1.0, October 29 2019, (Dutch) 
Six questions were designed to obtain information on how patients make medical decisions, 
what their current role is and what their preferred role, and one question regarding their 
awareness of their choices, the benefits and risks of certain treatment and whether they 
received support an advice are designed. Two questions were designed to gain insight into 
the reasons for choosing an active form of treatment. 
 
Outcomes of this questionnaire will be descriptive and expressed as numbers with 
corresponding percentages. 
 
EORTC QLQ-C30, version 3.0, (Dutch) 
Health-related quality of life will be assessed with the EORTC QLQ-C30, version 3.0. This 
30-item HRQoL questionnaire consists of five functional scales (physical, role, cognitive, 
emotional and social), a global quality of life scale, 3 symptom scales (fatigue, pain, nausea 
and vomiting) and a number of single items assessing common symptoms (dyspnoea, loss of 
appetite, sleep disturbance, constipation and diarrhoea) and perceived financial impact of the 
disease.  
 
For the interpretation of the Global health related quality of life score (EORTC-QLQ-C30), the 
manuals of the European Organisation for Research and Treatment of Cancer (EORTC) will 
be used 18. Each question will be scored: not at all (1), a little (2), quite a bit (3), very much 
(4). After linear transformation, all scales and single item measures range in score from 0-
100. A higher score on the functional scales and global quality of life means better 
functioning and HRQoL, whereas a higher score on the symptom scales means more 
complaints 14. The EORTC QLQ-C30 summary score will be calculated using the mean 

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scores of the function scales and the reversed mean scores of the symptom scales and 
represented as the mean of the combined 13 QLQ-C30 scale scores (financial impact and 
global health status excluded). A higher summary score represented a better outcome 15,16.  
 
DTF-QoL, version 1.0, October 29 2019, (Dutch) 
This topic is of particular interest for DTF patients because of the rarity of the disease with an 
incidence of 5.4 patients per million persons per year 9. Even doctors sometimes do not know 
what the best approach for a particular patient is. Therefore we would like to know what the 
issues are that patients are dealing with in daily life. 
 
We designed a 102-items questionnaire encompassing HRQoL issues that DTF patients 
might experience. The questions were designed based on the previous studies were the 
issues were identified and ranked by DTF patients and health care professionals (manuscript 
submitted to Quality of Life and Health Outcomes) 7,12. Topics covered regard issues in 
several domains including: diagnosis, treatment, living with DTF, health care facilities for 
DTF. These questions have not been validated but serve as patient reported experience 
measure rather than patient reported outcome measure. The scores will be calculated using 
a Likert scale from 1-4. The mean scores will be calculated with standard deviation (SD), or 
median scores with an interquartile range (IQR). De prevalence will be calculated using the 
percentages of patients reporting this problem compared to the total population.  
 
EQ-5D-5L, version 1.0, September 1, 2014, (Dutch) 
The EuroQol five-dimensional questionnaire (EQ-5D-5L) is a descriptive system for the 
measurement of health. It measures health-related quality of life on five dimensions of health: 
mobility, self-care, usual activities, pain-discomfort, and anxiety/depression.19 Additionally 
two questions aim to rank a patients’ health (scale 0-100, with 100 representing a better 
health). 
 
Each of the five dimension of the EQ-5D-5L can be divided into five levels of perceived 
problems; no problems (level 1), slight problems (level 2), moderate problems (level 3), 
severe problems (level 4) and extreme problems (level). Health states can be converted into 
single index values. The outcomes will be reported as frequency (proportion) of reported 
problems for each level and for each dimension. EQ- Visual Analogue Scale (VAS) data will 
be presented as a mean value with standard deviation. In case of skewed data, median 
values and IQR will be used.