The Influence of Stochastic Modulated Vibrations on the Autonomic Nervous System of Breast Cancer Patients During Radiotherapy: a Randomized Clinical Trial
Phase: NA
Conditions: Autonomic Nervous System Imbalance, Psychological Distress, Cancer-related Pain, Breast Cancer Lymphedema, Quality of Life
Sponsor: Universitair Ziekenhuis Brussel

Protocol versie 1.1, gedateerd op 19/12/2018 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The influence of stochastic modulated vibrations on the autonomic 
nervous system of breast cancer patients during radiation therapy: 
A randomised clinical trial. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol of the VUB chair 'Andullation Care Research' 
 
 
November 2018 
 
 
Chair promotor: Prof. Dr. N. Adriaenssens 
Chair coordinator: Prof. Em. Dr. P. Lievens 
Chair researcher: Ellen Vandyck 
 
 
 
                                                                                                                    
 

Protocol versie 1.1, gedateerd op 19/12/2018 
1) Title of the project: 
 
The influence of stochastic modulated vibrations on the autonomic nervous system of breast cancer 
patients during radiation therapy. 
 
2) Objective of the study: 
 
The aim of this research is to study the influence of stochastic modulated vibrations (Andullation® 
technology) on the autonomic nervous system of breast cancer patients during radiation therapy.  
 
Since it is well known that breast cancer patients experience an important load of stress from 
diagnosis through treatment and throughout cancer survivorship (fear of cancer recurrence), this 
study focusses on activating the parasympathetic nervous system and making patients as 
comfortable as possible during treatment. The scope of this study is based on previous research, that 
has shown that controlling physical and psychological complications during treatment, may have a 
positive (preventive) effect on late term and long-term quality of life and survival outcomes. (Basch 
E et al., 2017) 
 
Our choice for the intervention, the application of Andullation® technology, is twofold. First and 
foremost, this technique has shown positive effects on the use of analgesics and an increase of the 
pain threshold in chronic pain patients. Furthermore, an increase of the lymphatic and arterio-
venous flow was found following the application of this technique, which makes it promising in the 
frame of this study. (www.iaat.eu/science) Based on these results, our hypothesis is that 
Andullation® technology has an influence on the autonomic nervous system and thereby may 
influence commonly experienced complications of breast cancer (treatment) that are related to the 
autonomic nervous system.  
 
The primary outcome measure of the autonomic nervous system is vagal nerve activity, a modulator 
of the parasympathetic nervous system. Vagal nerve activity plays an important role in subjective 
(patient reported) sensations of pain, (di)stress and edema (Koenig J et al., 2016; De Couck et al., 
2014; Adriaenssens et al., article in progress) (secondary outcome measures), three common 
complications of breast cancer and its treatment. These three negative side effects may be risk 
factors for sleeping disorders in this population. Our hypothesis is that vagal nerve activity may 
directly influence sleeping disorders in this population without the presence of stress, pain and/or 
edema as well. (Werner et al., 2015) The relations between the parameters are shown in Figure 1. 
 
The second reason for choosing this intervention, the application of Andullation® technology, is 
socio-economically. The whole western world is searching for self management strategies to help 
this big growing population of chronic patients, that can no longer be followed up close in the long 
run in standard hospital care.  
 
 
 
 

Protocol versie 1.1, gedateerd op 19/12/2018 
 
Figure 1: Hypothesis of the relations between the intervention and the outcome measures. 
 
 
3) Investigator(s): 
 
Promotor: Prof. Dr. N. Adriaenssens 
 
Universitair Ziekenhuis Brussel; Laarbeeklaan 101, 1090 Jette  
- Oncologisch centrum: coördinator Oncological Rehabilitation and responsible for Cancer 
Survivorship at the UZ B  
- Lymfekliniek: responsible of conservative treatment, consultant 
 
Vrije Universiteit Brussel; Laarbeeklaan 103, 1090 Jette – Faculteit Lichamelijke Opvoeding en 
Kinesitherapie  
- vakgroep KIMA, unit KINE – docent Revalidatiewetenschappen en Kinesitherapie  
- research group Rehabilitation Research – Head of research line 'vascular pathology and oncology' 
President of the Postgraduate course 'Vascular Pathology and Oncology' at VUB 
General Secretary of the Belgian Society of Lymphology 
 
Coordinator: Prof. Em. Dr. P. Lievens 
 
Vrije Universiteit Brussel; Laarbeeklaan 103, 1090 Jette – Faculteit Lichamelijke Opvoeding en 
Kinesitherapie  
- vakgroep KIMA, unit KINE – Gewoon Hoogleraar emeritus Revalidatiewetenschappen en 
Kinesitherapie 
- co-founder of the European Society of Lymphology 

Protocol versie 1.1, gedateerd op 19/12/2018 
- winner of the Europa Donna award by Queen Mathilde of Belgium 
- winner of the Hilde Breurs award by the Vrije Universiteit Brussel 
 
Research collaborator (Master of Science - Rehabilitation Sciences and Physical Therapy): 
Ellen Vandyck 
 
Vrije Universiteit Brussel; Laarbeeklaan 103, 1090 Jette – Faculteit Lichamelijke Opvoeding en 
Kinesitherapie. 
 
4) Sponsor:  
 
This research is financed by the VUB Chair ‘Andullation Care Research’, represented by the 
investigators (cfr. point 3) and  
 
- 
International Association of Andullation Technology (IAAT) - Avenue Louise 65 Box 11, 
1050 Brussel (president dr. Guy Declerck) 
- 
Home Health Product bvba (HHP) – Ambachtstraat 1, 9700 Oudenaarde (CEO Bruno 
Nuyttens) 
 
5) Departments/laboratories involved in the study: 
 
Universitair Ziekenhuis Brussel; Laarbeeklaan 101, 1090 Jette  
 
- Medical Oncology (Prof. Dr. Jacques De Grève) 
- Radiotherapy (Prof. dr. Mark De Ridder) 
- Breast Clinic (Prof. dr. Jan Lamote) 
 
6) Introduction: 
 
The (breast) cancer population in Belgium is growing due to increasing prevalence and decreased 
mortality, thanks to evolutions in diagnostics and treatment of cancer. More breast cancer patients 
survive and live with the complications of cancer and its treatment. That is why quality of life of 
this big group of chronic patients has become more important in the past decade(s). Bio-psycho-
socially as well as economically and financially, the whole Western World is struggling with a lack 
of options to monitor these patients with long-term effects and late effects of breast cancer and its 
treatment. Therefore, there is an active search for ways to prevent complications and facilitate self-
management for these cancer survivors with negative side effects.   
 
With this study, we address the breast cancer patient and not the breast cancer survivor in the first 
place. Our hypothesis is that a lot of complications can be prevented when acting proactively at the 
start of treatment. From recent research, we know that monitoring complications during 
chemotherapy results in higher survival rates for example. (Basch E. et al., 2017) The comfort of 
the patient during treatment will result in a more positive outcome, for example because there is a 
better therapy adherence and compliance. This will lead to faster rehabilitation and reintegration, 
less work absenteeism and other psycho-socio-economical disadvantages.  
 
Physical and mental comfort of the patient during treatment is co-determined by (di)stress of 
diagnosis and treatment with its consequences like f.e. pain. From previous research, we know that 
the autonomic nervous system and more specifically the vagal nerve plays an important role in 

Protocol versie 1.1, gedateerd op 19/12/2018 
(di)stress and pain. These two symptoms can be mediated by vagal nerve activity. The vagus nerve 
is the tenth of twelve cranial nerves and the main nerve of the parasympathetic nervous system. 
Several hypotheses emerged and theorized that vagal nerve activity may moderate and inhibit the 
pathophysiological mechanism and risk factors in predicting cancer. (Gidron et al., 2005; De Couck 
et al., 2012) Three mechanisms might play an important role in tumorigenesis: oxidative stress, 
inflammation and excessive sympathetic nervous system activity, all of which are inhibited by vagal 
nerve activity. (De Couck et al., 2012) These mechanisms can also be found in the pathophysiology 
of pain and stress.  
 
When the patient has a lot of discomfort, mentally (due to stress) or physically (due to pain), vagal 
nerve activity decreases and melatonine concentration decreases (while adrenaline levels are 
elevated). Melatonine is necessary for a good sleep-awake cycle (circadian rhythm) (Werner et al., 
2015) and therefore, sleep deprivation is also a frequently registered complication during cancer 
treatment. Besides stress, pain and sleeping disorders, lymphedema (and/or vascular edema) is also 
a common complication of breast cancer treatment. (Lymph)edema may develop due to damage of 
the lymphatic (and/or vascular) system, but can be triggered by a disbalance of its innervation (by 
the autonomic nervous system) as well. (Yulan et al., 2018; Földi M) 
 
Vagal nerve activity can be stimulated by f.e. relaxation therapy and biofeedback of heart rate 
variability (HRV). (van Dixhoorn et al., 2005) Since the application of Andullation® technology has 
shown positive effects on the use of analgesics and an increase of the pain threshold in chronic pain 
patients, as well as an increase of the lymphatic and arterio-venous flow, (www.iaat.eu/science) N 
our hypothesis is that Andullation® technology has an influence on the autonomic nervous system 
and thereby may influence commonly experienced complications of breast cancer (treatment) that 
are related to the autonomic nervous system.  
 
 
7) Study design: 
 
The design of the study is a randomised clinical trial (that will be registered at clinicaltrials.gov). 
Breast cancer patients will be randomised into two groups (group 1: intervention or group 2: 
control). The patients will be randomized using the Efron's biased coin design. (Efron, 1971) 
Patients are stratified by duration of radiation therapy/intervention (3 weeks vs. 5 weeks), type of 
surgery (mastectomy vs. breast conserving surgery and axillary lymph node dissection vs. sentinel 
node biopsy), and chemotherapy sequence (none vs. sequential vs. concomitant chemotherapy).  
Randomisation occurs when the informed consent is signed by the patient. Patients need to be 
referred as eligible candidates by an MD and can give consent only following an intake 
conversation, giving all information concerning the trial by going through the informed consent 
with the patient. This design is shown in figure 2. 

Protocol versie 1.1, gedateerd op 19/12/2018 
 
Figure 2: Design of the study. 
Details concerning the 
measurements, the timing 
of the measurements and 
the instruments that will be 
used are described in table 
1. 

Protocol versie 1.1, gedateerd op 19/12/2018 
 
8) Medical device 
 
Andullation® technology is a horizontal vibration technique, with stochastically modulated 
vibrations. Lievens (2007) described Andullation® as “a new vibration therapy introduced for 
medical application approved by the TÜV Rheinland Belgium N.V. and FDA massage mattress 
VM9100RM”. The technology is build-in in a massage mattress. Several studies show that vibration 
(Prisby et al., 2008) and horizontal position (Nepal et al., 2012) in general have a positive influence 
on relaxation, without side effects. References concerning the technology can be found at 
http://www.iaat.eu/science/  
The medical device has a CE-mark in classification Pc IIa, type bf with certificate number Z-18-
051-P and identification No. 0633. 
 
Composition and dosing 
Group 1 (intervention group): 3 to 5-week Andullation® intervention* (depending on and as long as 
the duration of the radiation therapy) will be performed, 3 times a week for 20 minutes. Patients 
wear comfortable clothing. The position of the medical device is adapted to the body contours of 
the patient for an ergonomic position. The patient is lying in a relaxed position with hands posed 
next to the body on the lateral side of the mattress.  
 
* https://www.hhp.be/nl/producten/andumedic-3-professional  
Medical device: Andumedic® 3 Professional 
Settings of the medical device: a combination of program 3, 8 and 18 (standardized)  
 
Group 2 (control group) will follow the same intervention protocol as group 1, but without the 
application of the Andullation® technology. Environmental parameters will be equal to those of 
group 1. 
 
Producer/distributor 
Producer: 
International Association of Andullation® Technology (IAAT) - Avenue Louise 65 Box 11, 1050 
Brussel (president dr. Guy Declerck) www.iaat.eu  
 
Official dealer: 
Home Health Product bvba (HHP) – Ambachtstraat 1, 9700 Oudenaarde (CEO Bruno Nuyttens) 
www.hhp.be  
 
Packaging/storage conditions 
Normal packaging, transport and storage conditions. 
 
Known side effects 
Up to now, there are no negative side effects reported about 20 minutes of Andullation® technology 
in literature or clinical experience. The Andullation® application is approved as a medical device by 
TÜV Rheinland Belgium N.V. and FDA massage mattress VM9100RM. 
Pregnancy, epilepsy and a recent orthopaedic implant are contra indications reported by the 
producer and dealer. 
 
Side effects will be registered during the trial. 
 

Protocol versie 1.1, gedateerd op 19/12/2018 
9) The subjects: 
 
 
Number of subjects 
At the Department of Radiation Therapy of the UZ Brussel, an average of 8 breast cancer patients 
starts radiation therapy for about 3 to 5 weeks every week. Taking into account the sample size 
estimation/calculation, the duration of the project (Chair ‘Andullation Care Research’ of the VUB) 
and the availability of the medical device(s), we have constructed the inclusion schedule below 
(table 1). 
The schedule is based on a 5-week intervention (and control) over a duration of 14 months to 
include 118 patients for the two study arms. If patients who have only 3 weeks of intervention are 
included, even more patients can be included. Therefore, insurance is based on the inclusion of 
maximum 130 patients, taking into account extra (3-week intervention) patients and a drop-out of 
10%.  
 
 
Table 1: Inclusion schedule of the study. 
 
Inclusion criteria  
- Histological proven breast cancer, following breast cancer surgery  
- Starting with adjuvant radiation therapy (with or without concomitant chemotherapy) for 3 to 5 
weeks 
- Age: older than 18 years 
- Medical report (possibly for another hospital) is required with: 
diagnosis: tumor type and time of 1st biopsy (if relevant) 
proposed therapy (start and end dates of each treatment and treatment type) 
- Patients have to be able to perform the intervention (laying supine on the mattress for 30’, of 
which 20’ intervention)  
- A written informed consent has to be signed in the spoken language of the patient. (French, Dutch 
or English as well as the questionnaires) 
 
Exclusion criteria  
- Severe neurological, orthopaedic or rheumatic disorders of the lower or upper limbs which makes 
it impossible to lay on the mattress in supine position 
- Cardiac disorders  
start/2M N = (op M14)
W1
W2
W3
W4
W5
W6
W7
W8
W9
1st week intervention
2
2
2
2
2
2
2
2
2
18
118
2nd week intervention
2
2
2
2
2
2
2
2
3rd week intervention
2
2
2
2
2
2
2
4th week intervention
2
2
2
2
2
2
5th week intervention
2
2
2
2
2
interventions/day
2
4
6
8
10
10
10
10
10
W53
W54
W55
W56
W57
W58
W59
W60
W61
1st week intervention
2
2
2
2
2
2nd week intervention
2
2
2
2
2
2
3rd week intervention
2
2
2
2
2
2
2
4th week intervention
2
2
2
2
2
2
2
2
5th week intervention
2
2
2
2
2
2
2
2
2
interventions/day
10
10
10
10
10
8
6
4
2
M1/M2
M13/M14

Protocol versie 1.1, gedateerd op 19/12/2018 
- Early or synchronous malignancy  
- Pregnancy or lactation 
- Persons suffering from depression or illnesses who influence the mental health or wellbeing 
 
Replacement of subjects 
A drop-out of 10% was taken into account in the sample size calculation and inclusion schedule. 
Since we can prolong the intervention with a few weeks (the Chair is assigned for 24 months), we 
can have an extra medical device of the distributor during the study, we can include more than two 
patients a week at the UZ Brussel, because there are on average 8 patients starting radiation therapy 
every week, … we will be able to anticipate for a bigger drop out. 
 
 
Restrictions and prohibitions for the subjects 
Provocation of vagal nerve activity minimal 24 hours before intervention will be registered prior to 
every intervention. The use of medication that influences pain sensation, fluid homeostasis, sleep 
hygiene and stress will be registered. 
 
10) Procedures: 
 
The measurements will be obtained and results will be analysed at the PR4 building of the 
Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Jette. 
 
 
Autonomic 
nervous system  
Stress 
Pain 
Edema 
Sleep 
Quality of life 
Outcome 
measure 
Primary 
Secondary 
Secondary 
Secondary 
Secondary 
Secondary 
Measurement 
  
 
Heart rate 
variability 
through skin 
sensor 
(ANSWatch®) 
 
 
Volume 
measurement of 
the arms 
(Perometer®) for 
the evaluation of 
lymphedema 
Body 
composition  
(bioimpedance) 
for the 
evaluation of 
vascular edema 
  
 
 
Questionnaire 
 
- Distress 
Thermometer 
- Brief Pain 
Inventory (BPI) 
- Numeric Pain 
Rating Scale 
(NRS) 
 
- Pittsburgh 
Sleep Quality 
Index (PSQI) 
- Insomnia 
Severity Index 
(ISI) 
- EORTC QLQ 
BR23  

Protocol versie 1.1, gedateerd op 19/12/2018 
Table 2: Procedures of the study. 
 
 
 
 
Questionnaires 
 
Distress Thermometer 
A questionnaire to evaluate in what extent the patient experiences complaints like distress 
and anxiety, on a visual thermometer. (Mitchell et al., 2007) 
  
Measurement 
moment 
Before, during 
and after each 
intervention  
Baseline 
After each 
3rd intervention 
Follow-up 
NRS: Before and 
after each interve
ntion, Follow-
up   
BPI: baseline, 
after each 
3rd intervention 
and follow-up 
 
Baseline  
After 3 weeks  
After 5 weeks (if 
radiation lasts 5 
weeks)  
Follow-up 
 
Baseline  
After 3 weeks  
After 5 weeks (if 
radiation lasts 5 
weeks)  
Follow-up 
 
Baseline  
After 3 weeks  
After 5 weeks (if 
radiation lasts 5 
weeks)  
Follow-up 
 
Week schedule of the 
intervention during the 
duration of the radiation 
therapy 
Intervention 1: 
vibrations or control 
•Supine 
•On an ergonomic 
bedding 
•Immediately after 
radiation therapy 
•During 20 minutes 
Intervention 2: 
vibrations or control 
•Supine 
•On an ergonomic 
bedding 
•Immediately after 
radiation therapy 
•During 20 minutes 
Intervention 3: 
vibrations or control 
•Supine 
•On an ergonomic 
bedding 
•Immediately after 
radiation therapy 
•During 20 minutes 
Figure 1: These measurements will be repeated in week 3 and if your radiation therapy has a duration of more than 3 weeks, these measurements 
will also be repeated in week 5.  

Protocol versie 1.1, gedateerd op 19/12/2018 
 
EORTC QLQ BR23 
A questionnaire designed to investigate the quality of life in breast cancer patients. (Michels 
et al., 2013) 
  
 
Brief Pain Inventory 
This questionnaire was designed to investigate the extent of pain and the influence of it on 
quality of life. (Abahussin et al., 2018) 
 
 
Pittsburgh Sleep Quality Index (PSQI) 
This questionnaire was designed to assess sleep quality, quantity and disturbance. (Beck et 
al., 2004) 
 
 
Insomnia Severity Index (ISI) 
This questionnaire was designed to assess the severity, nature and impact of insomnia over 
the past two to four weeks. (Morin et al., 2011) 
  
Body parameters 
 
ANSWatch® 
A device measuring heart rate through skin sensors. With the information withdrawn, the 
device calculates heart rate variability. (Sun et al., 2011) 
  
 
Perometer® 
A device measuring arm contours with the use of infrared light. It is an efficient, safe, 
painless and reliable method to examine arm volumes. (Adriaenssens et al., 2013) 
   
 
Bioimpedance 
By using bioimpedance, body composition will be estimated. Patients have to stand on scale 
and hold on to a handgrip that is connected with the scale. A small current will determine 
the body composition and especially extracellular fluid. This is a painless and innocuous 
examination. (Seward et al., 2016) 
 
11) Flowchart 
 
Inclusion (and intervention) will start from the moment we receive a positive advice of the Medical 
Ethical Comité and will last for 14 months. The project (VUB Chair) is assigned for 24 months in 
total. An MD will refer patients as potential candidates for the trial after screening of the inclusion 
criteria and during the intervention, there will always be at least one MD in the PR4 building. (cfr 
table 1 and figure 2) 
 
12) Randomisation/blinding: 
 
The patients will be randomized using the Efron's biased coin design. (Efron, 1971) Patients are 
stratified by duration of radiation therapy (3 weeks vs. 5 weeks), type of surgery (mastectomy vs. 

Protocol versie 1.1, gedateerd op 19/12/2018 
breast conserving surgery and axillary lymph node dissection vs. sentinel node biopsy), and 
chemotherapy sequence (none vs. sequential vs. concomitant chemotherapy).  
 
Blinding is not possible. 
 
 
13) Prior and concomitant therapy: 
 
The patients are allowed to use every medication needed for their treatment before, during and after 
the intervention. 
Any medication that has an influence on HRV activity, sleep, stress, edema and pain are reported 
before intake in the trial and monitored throughout the study. 
 
14) Study analysis: 
 
Sample size calculation 
 
Based on our calculation in G*Power (with a medium effect size of 0.5 and with a power = 0.8), the 
total sample size is 128.  
 
   
 
Figure 5: Sample size calculation 
 
 
Analysis of the samples and statistical analysis 
The promotor and researcher of the VUB Chair will analyze the samples and do the statistical 
analysis. 
 

Protocol versie 1.1, gedateerd op 19/12/2018 
For all statistical analyses, superiority will be based on a two-sided p-value < .05. All statistical 
computations use SPSS v. 20.0 (IBM Corporation, Somers, NY, 10589, USA). Descriptive statistics 
will be used to describe medical and demographic characteristics of the population. Normality and 
homogeneity for both groups will be calculated. The repeated measures ANOVA design will be 
used to evaluate the changes over time and between groups. Correlations between outcome 
measures will be calculated as well. 
 
15) Quality control and quality assurance: 
 
The researcher will be present when the intervention is given to install the patient, to start the 
intervention and to make sure that everything runs according to plan. 
The researcher will also make sure that all settings are properly programmed and placed as 
indicated in the protocol prior to welcoming the patient. The researcher will use the same checklist 
before starting each intervention. 
 
Related to the quality control and assurance of the outcome measures: 
- 
Each participant will have a form fill to list every data. 
- 
All measurements are conducted by the same investigator and the same validated 
measurement instruments. 
- 
All interventions are performed with the same medical device. 
 
16) Publication policy: 
 
Scientific and marginal publications will be possible within the academic freedom of the 
researchers and there are no restrictions concerning the other (industrial) partners of the VUB Chair. 
 
A signed agreement of the Chair can be obtained at VUB TechTransfer (Sophie Cammaerts) 
Contracts Administration Building M - Room 409 Pleinlaan 2, 1050 Brussels. 
 
17) All documents are confidential. These documents are only accessible to the treating doctor 
and to the persons concerned in the execution and control of this clinical study. The name 
and every information that could reveal patients’ identity will not be used in publications 
arising from this study and will not be shared with third parties The data will be processed 
according the principles imposed by the new European General Data Protection Regulation 
(GDPR), that is operative since May 25th 2018. In the context of the study certain personal 
data will be collected. We, Adriaenssens Nele and Vandyck Ellen, are responsible for the 
correct processing and the information duty that is required. 
 
Of course, we are only allowed to use personal data for the scientific purposes described in 
the information consent document. It is possible that the data are seen by persons in 
countries that do not use the same norms in the field of legal protection of data as in the EU. 
In that case, we commit to ensure that the requirements of the European and Belgian 
legislation about the protection of personal data are respected. 
Thereafter we would like to announce that, conform the relevant legislation, the data 
obtained in this study will be saved during at least 4 years. According to the GDPR there are 

Protocol versie 1.1, gedateerd op 19/12/2018 
certain rights in the processing of the data. The data protection officer of the VUB can be 
contacted: dpo@vub.be 
 
 
References: 
 
All references related to Andullation® technology: http://www.iaat.eu/science/  
 
 
Abahussin AA, West RM, Wong DC, Ziegler LE (2018) PROMs for Pain in Adult Cancer Patients: 
A Systematic Review of Measurement Properties. Pain Pract. doi: 10.1111/papr.12711 
 
Adriaenssens N, Buyl R, Lievens P, Fontaine C, Lamote J (2013) Comparative study between 
mobile infrared optoelectronic volumetry with a Perometer and two commonly used methods for 
the evaluation of arm volume in patients with breast cancer related lymphedema of the arm.  
Lymphology 46 (3): 132-43. 
 
Basch E., Deal A.M., Dueck A.C., Scher H.I., Kris M.G., Hudis C., Schrag D. 2017. Overall 
survival results of a trial assessing patient-reported outcomes for symptom monitoring during 
routine cancer treatment. JAMA, Jul 11; 318(2): 197-198. 
Beck, S. L., Schwartz, A. L., Towsley, G., Dudley, W., & Barsevick, A. (2004). Psychometric 
evaluation of the Pittsburgh Sleep Quality Index in cancer patients. Journal of pain and symptom 
management, 27(2), 140-148. 
De Couck M., Mravec B., Gidron Y. 2012. You may need the vagus nerve to understand 
pathophysiology and to treat disease. Clin Sci (Lond) Apr; 122(7): 323-8. 
De Couck M., Nijs J., Gidron Y. 2014. You may need a nerve to treat pain: the neurobiological 
rationale for vagal nerve activation in pain management. Clin J Pain Dec; 30(12): 1099-105. 
Efron B: Forcing a sequential experiment to be balanced. Biometrika 1971, 58:403–417. 
Földi M, Földi E. 3rd edition. Földi’s Textbook of Lymphology for physicians and lymphedema 
therapists. 
 
Gidron Y., Perry H., Glennie M. 2005. Does the vagus nerve inform the brain about preclinical 
tumours and modulate them? Lancet Oncol. Apr; 6(4): 245-8. 
 
Koenig J., Falvay D., Clamor A., Wagner J., Jarczok M.N., Ellis R.J., Weber C., Thayer J.F. 2016. 
Vagus Nerve activity indexed by heart rate variability in chronic pain patients compared to healthy 
controls: a systematic review and meta-analysis. Pain Physician Jan; 19(1): E55-78. 
 

Protocol versie 1.1, gedateerd op 19/12/2018 
Michels, F. A. S., Latorre, M. do R. D. de O. and Maciel, M. do S. (2013) ‘Validity , reliability and 
understanding of the EORTC-C30 and EORTC-BR23 , quality of life questionnaires specific for 
breast cancer’, Rev Bras Epidemiol, 16(2), pp. 352–363. 
 
Mitchell A, (2007) Pooled results from 38 analyses of the accuracy of distress thermometer and 
other ultra-short methods of detecting cancer-relate mood disorders. J Clin Oncol 25: 4670-4681. 
 
Morin, C. M., Belleville, G., Bélanger, L., & Ivers, H. (2011). The Insomnia Severity Index: 
psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep, 34(5), 
601-608. 
 
Nepal G.B., Paudel B.H., 2012. Effect of posture on heart rate variability in school children. Nepal 
Med Coll J., Dec;14(4):298-302. 
 
Prisby R.D., Lafage-Proust M.H., Malaval L., Belli A., Vico L., 2008. Effects of whole body 
vibration on the skeleton and other organ systems in man and animal models: what we know and 
what we need to know. Ageing Res Rev, Dec;7(4):319-29.  
 
Seward C, Skolny M, Brunelle C, Asdourian M, Salama L, Taghian AG (2016) A comprehensive 
review of bioimpedance spectroscopy as a diagnostic tool for the detection and measurement of 
breast cancer related lymphedema. J Surg Oncol 114 (5): 537-42. 
 
Sun, D.C. et al. (2011), ANSWatch– a Novel Portable Multi-functional Wrist Monitor System for 
Clinical Applications in Integrated and Preventive Medicine. 116-126. 
 
van Dixhoorn J., White A. 2005. Relaxation therapy for rehabilitation and prevention in ischaemic 
heart disease: a systematic review and meta-analysis. Eur J Cardiovasc Prev Rehabil. Jun; 12(3): 
193-202. 
 
Werner G.G., Ford B.Q., Mauss I.B., Schabus M., Blechert J., Wilhelm F.H. 2015. High cardiac 
vagal control is related to better subjective and objective sleep quality. Biol Psychol Mar; 106: 79-
85. 
 
Yulan Sheng, Li Zhu, 2018. The crosstalk between autonomic nervous system and blood vessels. 
Int J Physiol Pathophysiol Pharmacol, 10 (1): 17-28.