The Impact of FoodforCare at Home on Quality of Life of Cancer Patients Undergoing Chemotherapy.
Phase: NA
Conditions: Cancer, Malnutrition
Sponsor: Radboud University Medical Center

 
 
 
 
 
 
 
 
 
 
 
 
TEMPLATE RESEARCH PROTOCOL 
(October 2013) 
The impact of FoodforCare at home on quality of life of advanced 
abdominal cancer patients undergoing chemotherapy. 
- 
May 2015: adaptation section 11.5: text in accordance to old and new Measure 
regarding Compulsory Insurance for Clinical Research in Humans  
 
 

 
 
 
PROTOCOL TITLE ‘The impact of FoodforCare at Home on quality of life of 
advanced abdominal cancer patients undergoing chemotherapy’. 
 
Protocol ID 
<include protocol ID given by sponsor or 
investigator> 
Short title 
The impact of FoodforCare at Home on quality of 
life. 
Version 
1.0 
Date 
 
Coordinating investigator/project 
leader 
 
V.E.  IJmker-Hemink, MSc 
Diëtist-onderzoeker  
Afdeling Maag-, Darm- en 
Leverziekten, Dietetiek en Darmfalen 
Radboudumc, Postbus 9101, HP 455 
6500 HB Nijmegen 
 
Principal investigator(s) (in 
Dutch: hoofdonderzoeker/ 
uitvoerder) 
 
Dr. G.J.A. Wanten, MD, 
Maag-, Darm-, Leverarts 
Afdeling Maag-, Darm – en leverziekten, Diëtetiek en 
Darmfalen 
Radboudumc, Postbus 9101, HP 455 
6500 HB Nijmegen 
 
 
Dr. M.G.A van den Berg 
 
Themaleider voeding/diëtist/wetenschappelijk 
onderzoeker 
 
Afdeling Maag-, Darm – en leverziekten, Diëtetiek en 
Darmfalen 
Radboudumc, Postbus 9101, HP 458 
6500 HB Nijmegen 
 
 
 
Sponsor (in Dutch: 
verrichter/opdrachtgever) 
FoodforCare Foundation 
 
 
Subsidising party 
FoodforCare Foundation 

 
 
 
 
Independent expert (s) 
 
Dr. D.J. de Jong 
 
Maag-, Darm-, Leverarts 
Afdeling Maag-, Darm – en leverziekten, Diëtetiek en 
Darmfalen 
Radboudumc, Postbus 9101, HP 455 
6500 HB Nijmegen 
 
 
 
 
Laboratory sites  
Not applicable 
 
 
Pharmacy  
Not applicable 
 
 
 
PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Head of Department: 
 
 
Prof. Dr. J.P.H. Drenth, MD,  
 
Afdelingshoofd, Maag-, Darm-, 
Leverarts 
 
Afdeling Maag-, Darm – en 
leverziekten, 
Radboudumc, Postbus 9101, 
HP 455 
6500 HB Nijmegen 
 
Principal Investigator: 
 
Dr. G.J.A. Wanten, MD  
 
Maag-, Darm-, Leverarts  
 
Afdeling Maag-, Darm – en 
leverziekten, Diëtetiek en 
Darmfalen 
Radboudumc, Postbus 9101, 
HP 455 
6500 HB Nijmegen 
 
 
 

 
 
 
TABLE OF CONTENTS 
 
1. 
INTRODUCTION AND RATIONALE .............................................................................. 8 
2. 
OBJECTIVES ................................................................................................................10 
3. 
STUDY DESIGN ...........................................................................................................11 
4. 
STUDY POPULATION ..................................................................................................13 
4.1 
Population (base) ...................................................................................................13 
4.2 
Inclusion criteria .....................................................................................................13 
4.3 
Exclusion criteria ....................................................................................................13 
4.4 
Sample size calculation ..........................................................................................14 
5. 
INVESTIGATIONAL PRODUCT ....................................................................................15 
5.1 
Name and description of investigational  product(s) ...............................................15 
5.2 
Summary of findings from clinical studies ...............................................................15 
5.3 
Summary of known and potential risks and benefits ...............................................15 
5.4 
Dosages, dosage modifications and method of administration ...............................16 
6. 
METHODS ....................................................................................................................17 
6.1 
Study parameters/endpoints ...................................................................................17 
6.1.1 
Main study parameter/endpoint .......................................................................17 
6.1.2 
Secondary study parameters/endpoints ..........................................................17 
6.1.3 
Other study parameters ...................................................................................18 
6.2 
Study procedures ...................................................................................................19 
6.3 
Randomisation, blinding and treatment allocation ..................................................19 
6.4 
Withdrawal of individual subjects ............................................................................20 
6.4.1 
Specific criteria for withdrawal .........................................................................20 
6.5 
Replacement of individual subjects after withdrawal ...............................................20 
6.6 
Follow-up of subjects withdrawn from treatment .....................................................20 
6.7 
Premature termination of the study .........................................................................20 
7. 
SAFETY REPORTING ..................................................................................................21 
7.1 
Section 10 WMO event ..........................................................................................21 
7.2 
AEs, SAEs and SUSARs ........................................................................................21 
7.2.1 
Adverse events (AEs) ......................................................................................21 
7.2.2 
Serious adverse events (SAEs) .......................................................................21 
7.2.3 
Suspected unexpected serious adverse reactions (SUSARs) .........................21 
7.3 
Follow-up of adverse events ...................................................................................22 
8. 
STASTICAL ANALYSIS ................................................................................................23 
8.1 
Descriptive statistics ...............................................................................................23 
8.2 
Primary study parameter ........................................................................................23 
8.3 
Secondary study parameter(s) ...............................................................................23 
8.4 
Interim analysis ......................................................................................................23 
9. 
ETHICAL CONSIDERATIONS ......................................................................................24 
9.1 
Regulation statement .............................................................................................24 
9.2 
Recruitment and consent........................................................................................24 
9.3 
Objection by minors or incapacitated subjects ........................................................24 

 
 
 
9.4 
Compensation for injury .........................................................................................24 
9.5 
Incentives ...............................................................................................................24 
10. 
ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION .........................25 
10.1 
Handling and storage of data and documents ........................................................25 
10.2 
Monitoring and Quality Assurance ..........................................................................25 
10.3 
Amendments ..........................................................................................................25 
10.4 
Annual progress report ...........................................................................................25 
10.5 
End of study report .................................................................................................25 
10.6 
Public disclosure and publication policy ..................................................................26 
11. 
STRUCTURED RISK ANALYSIS...............................................................................27 
11.1 
Potential issues of concern .....................................................................................27 
11.2 
Synthesis ...............................................................................................................27 
12. 
REFERENCES ..........................................................................................................28 

Version 3.0, 09-10-17 
 
6 of 30 
LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS  
 
ABR 
ABR form, General Assessment and Registration form, is the application 
form that is required for submission to the accredited Ethics Committee (In 
Dutch, ABR = Algemene Beoordeling en Registratie) 
AE 
Adverse Event 
AR 
Adverse Reaction 
CA 
Competent Authority 
CCMO 
Central Committee on Research Involving Human Subjects; in Dutch: 
Centrale Commissie Mensgebonden Onderzoek 
CV 
Curriculum Vitae 
DSMB 
Data Safety Monitoring Board 
EU 
European Union 
EudraCT European drug regulatory affairs Clinical Trials  
GCP 
Good Clinical Practice 
IB 
Investigator’s Brochure 
IC 
Informed Consent 
IMP 
Investigational Medicinal Product  
IMPD 
Investigational Medicinal Product Dossier  
METC  
Medical research ethics committee (MREC); in Dutch: medisch ethische 
toetsing commissie (METC) 
(S)AE 
(Serious) Adverse Event  
SPC 
Summary of Product Characteristics (in Dutch: officiële productinfomatie 
IB1-tekst) 
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 
Wbp 
Personal Data Protection Act (in Dutch: Wet Bescherming Persoonsgevens) 
WMO 
Medical Research Involving Human Subjects Act (in Dutch: Wet Medisch-
wetenschappelijk Onderzoek met Mensen 
 
 

Version 3.0, 09-10-17 
 
7 of 30 
SUMMARY 
 
Rationale: Cancer patients receiving treatment such as chemotherapy experience a variety 
of symptoms that interfere with their appetite and their ability to eat and enjoy meals. Several 
studies suggest that nutritional intake increases when the patient is satisfied about the quality 
of the meals. Therefore, adapting meals in a way that responds to these symptoms might be 
a good strategy to improve patient satisfaction, nutritional status and hence, quality of life. In 
this vein, we hypothesize that meals from FoodforCare at Home will contribute to the quality 
of life of advanced abdominal cancer patients undergoing chemotherapy when compared to 
usual care. Also, we expect that this strategy will have a positive effect on patient 
satisfaction, other nutrition-related issues, including nausea and vomiting, on nutritional 
intake per se and hence, on the nutritional status. Additional benefits might include reduced 
use of medication, especially anti-emetics. 
 
Objective: To study whether FoodforCare at Home is superior to usual care with respect to 
quality of life in advanced abdominal cancer patients undergoing chemotherapy.  
 
Study design: Randomized controlled trial  
 
Study population: Advanced abdominal cancer patients undergoing chemotherapy, 18 
years and older. 
 
Intervention and procedure: Inclusion will take place at the department of Medical 
Oncology at the start of palliative chemotherapy. Patients will be randomly assigned to one of 
two groups before the start of the second cycle of chemotherapy. The intervention group will 
receive meals from FoodforCare at Home and the control group will continue their regular 
diet for 3 weeks between the 2nd and 3rd cycle of chemotherapy. The FoodforCare at Home 
meals will be delivered at the patient’s home by research assistants or AYA’s. These are 
Adolescents and Young Adults with cancer who are also trained to perform the 
measurements.    
 
Main study parameters/endpoints: The main study parameter is quality of life of patients 
receiving FoodforCare at Home compared with patients receiving their usual diet. This will be 
evaluated by the EORTC-QLQ-c30 at all time points. The secondary endpoints are patient 
satisfaction, nutritional status, nutritional intake, performance scale, medication use, 
symptoms and quality of life of the partner/caregiver.  
 
Nature and extent of the burden and risks associated with participation, benefit and 
group relatedness: There are no additional tests or hospital tests necessary for the patient. 
This study will not confer any no additional risks. Food will be delivered within the expiration 
dates and the meals will be prepared according to the regular hygienic and food safety 
criteria that are valid. Possible serious reactions to the meals will be noted as SAE’s.  

Version 3.0, 09-10-17 
 
8 of 30 
 
1. INTRODUCTION AND RATIONALE 
 
Cancer patients receiving treatment such as chemotherapy often experience a variety of 
symptoms that interfere with their ability to eat and enjoy meals. These symptoms like loss of 
appetite, nausea and pain are referred to as nutrition impact symptoms [1]. Patients with 
several of these symptoms are more likely to experience a decline in nutritional intake [2]. 
Thus, reducing symptoms might lead to an improved nutritional intake. Furthermore, several 
studies suggest that nutritional intake increases when the patient is satisfied about the quality 
of the meals [3]. Therefore, adapting meals in a way that responds to these symptoms might 
be a good strategy to improve patient satisfaction and nutritional status. 
 
Abdominal malignancies constitute a considerable proportion of all cancer types. Worldwide, 
the incidence of this type of tumors is 7.2 million and in the Netherlands alone this comprised  
more than 30.000 cases in 2015 [4]. Colon cancer is the most prevalent type of cancer within 
this group with an incidence of more than 15.500 in 2015 [5]. Furthermore, not unexpected, 
patients with abdominal cancer most frequently seem to experience symptoms that can 
interfere with eating [6]. For example, patients with gynecological tumors indicate to have 
some form of gastro-intestinal complaints in 70% of cases during hospitalization with loss of 
appetite, nausea and reduced taste being the most prominent features [7]. Gastro-intestinal 
side effects in colorectal cancer concern primarily abdominal fullness, nausea and vomiting 
[6, 8]. Besides, taste and smell alterations are well-known side effects of chemotherapy [9]. 
In the palliative stage, 70% of the patients experiences four or more diet-related symptoms 
[10]. It is important that special attention goes to symptom management in this stage 
because of the association between symptoms and quality of life [11, 12]. Accordingly, the 
main focus of palliative care is alleviating symptoms and increasing quality of life [10]. 
 
As a result of the symptoms caused by the disease and the treatment, palliative patients 
have a high risk for the development of malnutrition. This is due to decreased nutritional 
intake and disease-related metabolic changes resulting in a disturbed carbohydrate, fat and 
protein metabolism [10]. These metabolic disturbances are further exaggerated by the loss of 
appetite that is a common symptom in palliative patients [13, 14]. This interaction is called 
the anorexia-cachexia syndrome and can lead to cachexia [10]. Prevalence of cachexia 
varies between cancer types but the gastrointestinal tract has one of the highest rates with 
over half of all patients being affected [15]. In addition, cachexia is associated with reduced 
survival and decreased quality of life [16]. Therefore, maintaining and improving nutritional 
status is important during palliative treatment in order to improve quality of life. However, 
maintaining or improving nutritional status is only possible depending on the state of the 
disease [10].  
 
Several studies show that patients often receive too little nutritional care which causes 
symptoms to worsen and frequently leads to hospitalization [17, 18]. Proper nutritional care 
and food provision contribute beneficially to maintaining nutritional status and quality of life of 
patients [3, 18]. Next to the fact that the meals should meet the nutritional requirements of 
the patients, other factors such as food quality and patients’ satisfaction are important as 
well. In general, hospital food has a negative connotation due to the unfavorable contrast 
with homemade food [3, 19]. Patients value food quality and service quality the most and 
therefore, these are important predictors for patient satisfaction and quality of life [19, 20]. 

Version 3.0, 09-10-17 
 
9 of 30 
Furthermore, there is evidence of a positive association between patient satisfaction and 
energy intake [20].  
 
There are various types of meal services that are used in the hospital setting and in the past 
years these have been optimized to the preferences and needs of hospitalized patients [21-
24]. However, research has mainly focused on foodservice satisfaction in hospitals while this 
phenomenon might also be relevant for palliative patients at home, also in terms of time 
management. Studies on home delivered meal services mostly have been carried out in 
elderly people. In this population, improvements were seen in nutritional and functional status 
although most studies were cross-sectional with small sample sizes [25]. Few studies 
focused on patient satisfaction and quality of life [26, 27]. Frongillo et al. reported an overall 
satisfaction of 77% of the elderly who received home-delivered meals [26]. 
 
In the Netherlands, an innovative hospital food formula, FoodforCare, was recently 
developed and implemented hospital-wide in the academic hospital (Radboudumc) in 
Nijmegen. This formula consists of dishes with high nutritional values that aim at improving 
appetite and contributing to patients’ wellbeing. FoodforCare makes use of small, frequent 
meals in order to reduce the risk of gastro-intestinal complaints and to reduce plate waste. 
There are studies stating that smaller portions are related to reductions in plate waste and an 
increase in energy intake [28-30]. In a recent pilot, so-called onco-proof products were 
offered to cancer patients. These products take account of the special consequences of the 
presence and treatment of the underlying condition for taste and smell and are rich in energy 
and protein. Patients who were submitted to this service described that they experienced 
lower levels of nausea when using these products compared to usual hospital meals. A 
tentative conclusion was formulated that this concept has a positive effect on the wellbeing 
and status of the patients. 
  
It takes robust and well-designed studies to assess determine whether any meal service at 
home positively contributes to symptom management and quality of life in advanced 
abdominal cancer patients. The hypothesis of the present study is that FoodforCare at Home 
will be superior to usual care with respect to quality of life of advanced abdominal cancer 
patients undergoing chemotherapy. Furthermore, we expect that this meal service will have a 
beneficial effect on symptoms, patient satisfaction, performance scale, on nutritional intake 
and therefore, on the nutritional status of the patients. Another positive effect might result 
from a reduction in medication use (e.g. anti-emetics) and an improved quality of life of the 
partner/caregiver. 
 
 
 
 
 
 
 
 
 

Version 3.0, 09-10-17 
 
10 of 30 
 
 
2. OBJECTIVES 
 
Primary objective: 
 
To study whether FoodforCare at Home is superior to usual care with respect to quality of life 
in advanced abdominal cancer patients undergoing chemotherapy. 
 
Secondary objectives:  
1. To reduce diet-related symptoms in these patients by using FoodforCare at Home 
compared to usual care. 
2. To improve nutritional intake (adequate protein and energy intake) in these patients 
by using FoodforCare at Home compared to usual care. 
3. To improve the nutritional status of these patients by using FoodforCare at Home 
compared to usual care. 
4. To improve the functional status of these patients by using FoodforCare at Home 
compared to usual care. 
5. To reduce medication use for the purpose of treating diet-related symptoms in these 
patients by using FoodforCare at Home compared to usual care.  
6. To improve quality of life of the partners/caregivers of these patients by using 
FoodforCare at Home compared to usual care. 
7. To improve patient satisfaction towards nutrition in these patients by using 
FoodforCare at Home compared to usual care. 
 

Version 3.0, 09-10-17 
 
11 of 30 
3. STUDY DESIGN 
A randomized controlled trial will be performed in palliative abdominal oncology patients at 
home. Inclusion will take place at the department of Medical Oncology at the start of 
palliative chemotherapy. The study is intended to be performed from March 2017 to July 
2018. Patients will be randomly assigned to one of two groups before the start of the second 
cycle of chemotherapy because it is expected that FoodforCare at Home will make the 
largest difference during this cycle. The intervention group will receive meals from 
FoodforCare at Home and the control group will continue their regular diet for three weeks 
from the second cycle of chemotherapy until the next cycle of chemotherapy. Before the start 
of this study, a pilot study will be performed to determine whether the intervention is feasible 
in terms of logistics and delivery of the meals for example. 
 
Measurements will take place at four time points during the study period i.e. before the start 
of chemotherapy, at the 2nd cycle of chemotherapy, at the 3rd cycle of chemotherapy and 
three month after T3 (figure 1). These measurements will be performed by AYA’s/research 
assistants who will visit the patients at home. Time point 1, before the start of chemotherapy, 
will serve as the baseline measurement. At this moment, informed consent will be obtained 
and signed by the patient and the MUST score will be determined. Quality of life of patient 
and caregiver, nutritional intake, nutritional status, functional status and medication use will 
be assessed at all time points. For quality of life, the EORTC-QoL-C30 questionnaire will be 
filled in by the patients and the Caregiver Reaction Assessment by their caregivers. 
Nutritional status will be assessed using the handgrip strength measurement, the PG-SGA 
and performance scale by means of the Karnofsky score and the SPPB. Data on nutritional 
intake will be recorded using a 3-day food diary, which the patients will fill in by themselves. 
Medication use will be obtained from the patient’s medical file. Additionally, during the 
intervention period, patients will record their symptoms using ‘Utrecht Symptoom Dagboek’ 
and medication use will be assessed by using a diary. At time point 3, patient satisfaction in 
the intervention group will be assessed by the Net Promoter Score with additional questions. 
An overview of the measurements can be found in table 1.   
 
Figure 1. Flowchart of the study design of the FoodforCare at Home study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
T2 
at chemotherapy 
cycle 2 
FoodforCare at Home
Usual care 
T1 
before start of 
chemotherapy 
T3 
at chemotherapy 
cycle 3 
T3 
at chemotherapy 
cycle 3 
T4 
3 months after 
cycle 3 
T4 
3 months after 
cycle 3 

Version 3.0, 09-10-17 
 
12 of 30 
 
 
 
 
 
Table 1. Measurements performed at each time point during the FoodforCare at Home study 
 
 
Before 
chemotherapy 
2nd cycle 
chemotherapy 
3rd cycle 
chemotherapy 
3 months after 
T3 
Informed consent  
MUST score 
QoL patient  
QoL caregiver 
Nutritional intake    
X 
X 
X 
X 
X 
 
 
X 
X 
X 
 
 
X 
X 
X 
 
 
X 
X 
X 
PG-SGA  
X 
X 
X 
X 
Handgrip strength 
Performance scale 
Medication use 
Patient satisfaction 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 

Version 3.0, 09-10-17 
 
13 of 30 
  
4. STUDY POPULATION 
4.1 Population (base)  
 
The study population comprises advanced abdominal cancer patients with gynecological 
malignancies or tumors in the colon. All patients scheduled for receiving palliative 
chemotherapy at the department of medical oncology (E30) at the Radboud University 
Medical Centre, Nijmegen (UMCN) will be recruited. In total, we expect approximately 
200 palliative patients, with gynecological malignancies or tumors in the colon, to be 
scheduled for palliative chemotherapy at the UMCN annually. Taking a radius of 40 km 
from the UMCN into account, we expect that 40% will be outside this radius. This means 
that we expect approximately 120 patients to be able to be included in the study in a year. 
 
Eligible patients will be requested to take part in the study after obtaining permission from 
the treating physician. This request will then be discussed with the patient, whenever 
possible in the presence of the caregiver, by the nurse or by one of the researchers. 
Additionally, the patient will receive a written leaflet with further information. The nurse or 
one of the researchers will ask the patient whether he/she has read the leaflet, whether 
the information is clear and whether he/she would like to participate in the study. After 
that, the informed consent form will be signed by the patient and the researcher will 
register the patient. Our intention is to consider an inclusion period of up to one and a half 
year. 
 
4.2 Inclusion criteria 
In order to be eligible to participate in the study, the patient must meet all of the following 
criteria: 
 
 
age 18 years or older  
 
diagnosed with advanced colon or gynecological cancer  
 
receiving primary or secondary palliative chemotherapy according to a 
three weekly schedule  
 
living within a 40 km radius around the Radboud University Nijmegen 
Medical Centre 
 
written informed consent 
 
4.3 Exclusion criteria 
Patients will be excluded from participation in the study according to any of the following 
criteria: 
 
 
renal insufficiency (MDRD-GFR < 60ml/min and/or proteinuria)* 
 
dementia or any other condition which makes it impossible to fill out 
questionnaires correctly 
 
unable to understand or speak Dutch 

Version 3.0, 09-10-17 
 
14 of 30 
 
depending on artificial nutrition in the form of Oral Nutritional Supplements,  
tube feeding or total parenteral nutrition 
 
*proteinuria is defined in case of a protein creatinine ratio > 0.5g/10mmol or an albuminuria > 
300mg/day. This is checked by default before the start of chemotherapy by the treating 
physician to decide whether or not the patient is eligible for receiving chemotherapy. 
4.4 Sample size calculation 
The sample size calculation is based on the primary outcome of this study: the EORTC-QoL-
C30 questionnaire for quality of life. The primary outcome of this study is the difference in 
quality of life between the 2 groups at the start of the 3rd cycle of chemotherapy. Based on 
literature, advanced cancer patients with gynecological tumors and tumors of the colon have 
a mean score of approximately 60 points with a standard deviation of 22 points on the 
EORTC-QoL-C30 questionnaire. Assuming a difference of 10 points, on a scale of 0-100 
points, is a clinically relevant difference in favor of FoodforCare at Home, we estimate that 76 
patients are needed in each group in order to obtain a power of 80% (two-tailed t-test, 
alpha=0.05). Assuming a drop-out rate of 20%, this means a total of 180 patients. In order to 
improve the power significantly, we will make use of the ANCOVA test [31]. By multiplying 
the number of patients with (1-(ρ²)) a total of 164 patients will be needed. The correlation 
between the baseline and follow-up outcome T2 (ρ) is estimated at 0.3. 
 

Version 3.0, 09-10-17 
 
15 of 30 
 
5. INVESTIGATIONAL PRODUCT  
5.1 Name and description of investigational  product(s) 
In a period of 1.5 year, 164 patients will be randomized into two groups. The intervention 
group will receive meals from FoodforCare at Home and the control group will continue their 
usual diet for 3 weeks. The FoodforCare at Home concept consists of five to six small protein 
and energy enriched meals that will be delivered twice a week. After an individual intake, the 
composition of the dishes will be tailored to the needs of the patient in terms of composition, 
diet, taste, flavor and portion size. Besides the meals, patients in the intervention group will 
also receive an information leaflet about the importance of protein during treatment and how 
to reach their protein requirements. The control group has no restrictions to their diet. The 
dishes are prepared every day by Maison van den Boer. 
 
5.2 Summary of findings from clinical studies 
The relevance of a good nutritional status in cancer patients undergoing chemotherapy has 
been described in several studies. Observational studies have shown that low nutritional 
status is associated with reduced survival and quality of life [12, 32]. Not many trials have 
been done into the effect of nutritional interventions on advanced cancer patients undergoing 
chemotherapy. Furthermore, the nutritional intervention mostly consists of Oral Nutritional 
Supplements (ONS), nutritional counselling or parenteral nutrition.  
 
One trial in patients with gastrointestinal tumours undergoing palliative chemotherapy 
showed no effect of nutritional advice or nutritional supplements on quality of life. However, 
this study was small (N=68) and compliance to the supplements was low [33]. Another study 
from 2009 in advanced colorectal cancer patients undergoing chemotherapy found that 
supplementation with parenteral nutrition slows weight loss and improves quality of life. 
Patients in this study reached their energy and protein requirements 95-100% of all times 
[34].  
 
To our knowledge, there is one other study that used regular foods and drinks as a nutritional 
intervention. The conclusion was that the products increased protein intake but no 
improvements in physical performance was seen. However, this study was performed in 
elderly people at home after hospital admission [35]. 
 
5.3 Summary of known and potential risks and benefits 
The food products of Maison van den Boer meet the highest standards of nutrition and 
quality and has therefore, no additional risk compared to usual products. All products will be 
served according to the regular hygienic and food safety criteria that are valid. Possible 
serious reactions to the products will be noted as SAE’s. There are no additional tests or 
hospital visits necessary for the patient. Therefore, we do not expect any potential risk. 
 

Version 3.0, 09-10-17 
 
16 of 30 
5.4 Dosages, dosage modifications and method of administration 
The composition of the FoodforCare at Home dishes are developed to enable maintenance 
and if possible improvement of the nutritional status of the patient. Therefore, a number of 
basic principles are chosen which are described below. 
 
The aim is to stimulate protein intake as much as possible in order to maximize protein 
synthesis during treatment. Protein intake of at least 1.2 g/kg body weight is recommended 
for cancer patients [36]. On average, this is equivalent to an intake of 90-95 grams of protein 
per person per day (assuming an average weight of 75-80 kg). Protein intake of 20-25 grams 
per meal would ensure optimal postprandial protein synthesis in the muscles [37]. This and 
other information about the protein content of the FoodforCare products will be spread to the 
patients in order for them to make decisions that contribute to their protein requirements. 
 

Version 3.0, 09-10-17 
 
17 of 30 
6. METHODS 
6.1 Study parameters/endpoints 
 
6.1.1 
 
Main study parameter/endpoint 
Quality of life: 
The main study parameter is the quality of life of advanced cancer patients using 
FoodforCare at Home. Quality of life will be evaluated using the EORTC-QoL-C30 at 
every time point. This is a validated questionnaire for measuring quality of life in 
palliative patients [38]. The global quality of life and the functional scales will be 
included as the main items in determining the quality of life of the patients. The 
symptom scales will be analyzed as secondary endpoint. Questionnaires will be 
scored according to the procedures specified by the EORTC [39].  
6.1.2 
Secondary study parameters/endpoints 
  
For this study there are multiple secondary study parameters: 
 
QoL caregiver:  
The quality of life of the caregiver will be evaluated at every time point using the 
Caregiver Reaction Assessment (CRA). The CRA is a feasible and reliable instrument 
for determining the burden of caregivers of cancer patients which includes both 
negative and positive aspects [40].  
 
Nutritional intake: 
Nutritional intake will be evaluated at every time point based on a 3-day food diary 
filled in by the patient. The food diary will be cross checked by a dietician and, if 
necessary, the patient will be called for clarification. The food items will be coded and 
calculated according to the Dutch Food Composition Table (NEVO, RIVM).  
 
Nutritional status: 
Nutritional status will be assessed using the handgrip method with the JAMAR 
handgrip measurer at every time point. Hand grip strength serves as a predictor for 
the overall muscle strength and functional status [41, 42] For reliable results, two 
consecutive measurements alternating both hands will be recorded with patients 
sitting in an upward position and the arm in a 90-degree angle. The validated Patient 
Generated- Subjective Global Assessment (PG-SGA) will also be used to determine 
the nutritional status and will be filled in by the AYA’s/research assistants in 
consultation with the patient at every time point [43].  
 
Performance scale: 
The Karnofsky Performance Status Scale is used to summarize the ability of patients 
to perform daily activities and the degree of dependence on help to do so. This status 
is based on 11 levels and ranges from 0, indicating death, to 100, indicating no 
complaints or evidence of disease [44]. This score will be determined in consultation 
with the patient at every time point. Physical performance will also be assessed by 
the Short Physical Performance Battery (SPPB). This is a frequently used test to 
measure functional status and physical performance. It consists of three lower 

Version 3.0, 09-10-17 
 
18 of 30 
extremity physical performance measures: standing balance, gait speed and chair 
rises (sit-to-stand) [45].                                                                  
 
Medication use: 
Medication use will be evaluated at every time point by obtaining information from the 
medical file of the patients. Information will be cross-checked by the researcher on 
doses and frequency of medication use. During the intervention period, medication 
use will be assessed by asking patients to log on a diary when they used which 
medication including dosage. 
 
Symptoms: 
To assess the number and the severity of symptoms experienced by the patients, 
they are asked to fill in the ‘Utrecht Symptoom Dagboek' every day for 3 weeks during 
the intervention period. This is a diary based on the ESAS which consists of 12 
symptoms which are frequently experienced by palliative cancer patients [46]. On a 
scale from 0 to 10, patients can score the severity of the symptoms with 0 indicating 
no symptom and 10 indicating the worst possible symptom.  
 
Patient satisfaction: 
The Net Promoter Score (NPS) with additional questions will be used to assess 
patient satisfaction in the intervention group at time point 3. The NPS is determined 
by asking the question: ‘How likely is it that you would recommend FoodforCare to a 
friend or colleague?’. The score ranges from 1-10 and patients can be grouped in 
‘promoters’ (9-10 grading), ‘passively satisfied’ (7-8 grading) and ‘criticasters’ (0-6 
grading). The NPS is finally calculated by subtracting the percentage of criticasters 
from the percentage of promoters [47]. Additional questions about satisfaction with 
respect to the food supply and logistics of FoodforCare at Home will be answered by 
the patients to explain their score. The control group will also receive a questionnaire 
about their wellbeing and way of shopping and cooking. Both questionnaires are self-
composed and based on validated questionnaires because there is no Dutch 
validated questionnaire available about a home-delivered meal service. 
 
During the pilot study, participants in the intervention group are asked to participate in 
an in-depth interview instead of the questionnaire. This interview will be leaded by 
one of the researchers. It will generate information about the home-delivered meal 
service so it can be improved when implemented in the RCT.   
6.1.3 
Other study parameters 
Body weight: 
Each patient’s body weight will be determined at every time point. Relative weight 
changes will be presented as the percent weight change relative to the weight at 
baseline. 
 
Height: 
Each patient’s height will be measured with a SECA ruler at the start of the study. 
From the measured body weight and height, BMI will be calculated by dividing body 
weight (kg) by the square of height (m). 

Version 3.0, 09-10-17 
 
19 of 30 
 
Age, gender, type and doses of cytostatics, the number of chemotherapy cycles, 
education level, smoking and alcohol consumption: 
Data on these variables will be determined at baseline by a questionnaire or from the 
medical files. The doses of the cytostatics will be determined at every time point.  
 
Treatment toxicity: 
Treatment toxicity will be monitored by the treating physician according to the 
Common Toxicity Criteria during the entire study period [48].  
 
MUST: 
The Malnutrition Universal Screening Tool (MUST) will be used at baseline to 
determine the risk of malnutrition.  
 
6.2 Study procedures 
A number of things will be set in motion after the patient signs the informed consent. As 
described earlier, the researcher will register the patient. If the patient is allocated to the 
intervention group, FoodforCare will be informed by the researcher. FoodforCare will take 
care of the delivering of the products and will have contact with the AYA’s/research 
assistants about the measurements. Before the start of the intervention, an individual intake 
will take place with the patient by FoodforCare. During this intake, the composition of the 
dishes will be tailored to the needs of the patient in terms of composition, diet, taste, flavor 
and portion size. These dishes will be delivered to the patients by the AYA’s/research 
assistants every three days. Depending on the patient’s wishes, the partner or caregiver of 
the patient can receive the same dishes. In case the patient is allocated to the control group, 
the AYA’s/research assistants are informed to perform the measurements at home at the 
given time points. 
 
6.3 Randomisation, blinding and treatment allocation 
Patients will be randomized into two groups at the department of medical oncology in the 
Radboudumc. This will be performed by using the randomization program which is part of the 
clinical data management system ‘Research Manager’. This validated web based data 
management system will be used during the entire study. The researcher will have a 
password to the randomization program. After randomization, a study number will be 
assigned to the patient. The researcher documents the patient information and study number 
in a designated source document. The study number and birth date will be listed on all study 
documents. The randomization will be stratified on tumor type and type of chemotherapy 
because of the possible effect on the primary outcome. This stratification reduces the risk of 
an uneven distribution of prognostic factors. We will not stratify for other characteristics; the 
exclusion criteria will contribute sufficiently to a homogenous patient population.  
 
Blinding is not possible for the coordinating researcher, since one group will receive 
FoodforCare at Home and the other group will receive no additional products. Patients have 
to be aware of in which group they are in. Whether blinding is possible for the AYA’s/ 

Version 3.0, 09-10-17 
 
20 of 30 
research assistants will be examined during the pilot study. In that case, patients will be 
asked not to tell the AYA’s/research assistants in which group they are allocated. 
 
6.4 Withdrawal of individual subjects 
6.4.1 
 
Specific criteria for withdrawal 
Subjects can end their participation in the study at any time for any reason if they wish to 
do so without any consequences. The investigator can decide to withdraw a subject from 
the study for urgent medical reasons. 
 
6.5 Replacement of individual subjects after withdrawal 
During the inclusion period, additional patients will be included to be able to achieve the 
necessary number of patients in case of withdrawal of patients during the study. 
 
6.6 Follow-up of subjects withdrawn from treatment 
When patients withdraw from the study after time point 3, these data may (if authorized by 
the patient) be used for analyses.  
 
6.7 Premature termination of the study 
Situations in which the study should be terminated prematurely are not expected. Moreover, 
the use of ‘usual care’ and the FoodforCare products bring no additional risk to the patients. 
Therefore, we do not expect a large number of adverse events in either group.  
 

Version 3.0, 09-10-17 
 
21 of 30 
7. SAFETY REPORTING 
7.1 Section 10 WMO event 
In accordance to section 10, subsection 1, of the WMO, the investigator will inform the 
subjects and the reviewing accredited METC if anything occurs, on the basis of which it 
appears that the disadvantages of participation may be significantly greater than was 
foreseen in the research proposal. The study will be suspended pending further review by 
the accredited METC, except insofar as suspension would jeopardise the subjects’ health. 
The investigator will take care that all subjects are kept informed.  
 
7.2 AEs, SAEs and SUSARs 
7.2.1 
 
Adverse events (AEs) 
Adverse events are defined as any undesirable experience occurring to a subject during 
the study, whether or not considered related to the Food for Care products. All adverse 
events reported spontaneously by the subject or observed by the investigator or his staff 
will be recorded. 
 
Possible adverse events include: nausea, vomiting, gastrointestinal complaints. These 
events will already be identified by the EORTC-QoL-C30 questionnaire and the ‘Utrecht 
Symptoom Dagboek’. Other side effects including severe (very rare) side effects are not  
expected to occur. However, it is important to monitor these side effects as well and 
therefore, the patient will be asked to contact a staff member and the researchers directly 
when side effects are present. Our proposition will be to only register adverse events that 
have a possible causal relationship with the given food products. Examples of these 
events include gastrointestinal complaints and allergic reactions.  
7.2.2 
 
Serious adverse events (SAEs) 
 
A serious adverse event is any untoward medical occurrence or effect that at any dose:  
- 
results in death; 
- 
is life threatening (at the time of the event); 
- 
requires hospitalisation or prolongation of existing inpatients’ hospitalisation; 
- 
results in persistent or significant disability or incapacity; 
- 
is a congenital anomaly or birth defect; 
- 
Any other important medical event that may not result in death, be life threatening, 
or require hospitalization, may be considered a serious adverse experience when, 
based upon appropriate medical judgement, the event may jeopardize the subject 
or may require an intervention to prevent one of the outcomes listed above. 
 
Our proposition will be to only register serious adverse events that have a possible causal 
relationship with the given food products. Examples of these events include 
gastrointestinal complaints and allergic reactions, which cause the above mentioned.  
7.2.3 
Suspected unexpected serious adverse reactions (SUSARs) 
 
Not applicable for this study. 

Version 3.0, 09-10-17 
 
22 of 30 
7.3 Follow-up of adverse events 
All AEs will be followed until they have abated, or until a stable situation has been reached. 
Depending on the event, follow-up may require additional tests or medical procedures as 
indicated, and/or referral to the general physician or a medical specialist. (S)AEs will be 
reported till the end of study. 

Version 3.0, 09-10-17 
 
23 of 30 
 
8. STASTICAL ANALYSIS 
8.1 Descriptive statistics 
Nominal and ordinal variables will be described using frequency tables, modus and medians. 
Continuous variables will be described in terms of means and confidence intervals or with 
medians and range, dependent on normality of the data.  
 
Data will be analyzed using IBM SPSS version 22 for descriptive and statistical analyses. All 
analyses will be performed according to the intention-to-treat principle.  
  
8.2 Primary study parameter 
Repeated measures analysis by using mixed models will be performed to evaluate the 
course over time in quality of life and to analyze the difference between the two groups. The 
full maximum likelihood estimation will be used to assess the best fit of the model. In these 
analysis we will adjust for confounders in case of baseline imbalance.  
 
8.3 Secondary study parameter(s)  
The courses over time and the difference between the groups will also be analyzed for the 
secondary outcomes. The continuous variables like quality of life of the caregiver, nutritional 
status (hand grip strength, PG-SGA), nutritional intake and performance scale will be 
analyzed the same way as the primary outcome. The course over time and the difference 
between the groups in medication use like anti-emetics e.g. will be treated as a dichotomous 
outcome (yes/no) and analyzed by using the Chi-square test. The difference in patient 
satisfaction and severity of symptoms between the two groups will be analyzed using the 
independent samples t-test.   
 
8.4 Interim analysis  
No interim analyses will be performed in this study. 

Version 3.0, 09-10-17 
 
24 of 30 
9. ETHICAL CONSIDERATIONS 
9.1 Regulation statement 
This study will be directed according to the principles of the World Medical Association 
Declaration of Helsinki (64th WMA General Assembly, October 2013). Additionally, is it in 
agreement with the Medical Research Involving Human Subjects Act (WMO) and other 
guidelines, regulations and Acts. 
 
9.2 Recruitment and consent 
Patients will be recruited through the department of Medical Oncology at the Radboud 
University Medical Centre in Nijmegen. All patients admitted to this department en those 
who meet the inclusion criteria are asked to participate in the study. This request will be 
discussed with the patient by the nurse or one of the researchers. Additionally, patients 
will receive a patient information letter with further information about the study. When 
everything is clear and the patient is willing to participate in the study, the informed 
consent will be signed. When a patient is enrolled in the study, a personal number is 
assigned by one of the researchers. The researcher documents the patients’ data and the 
personal number in a designated protected document.  
 
9.3 Objection by minors or incapacitated subjects 
 
Not applicable. 
 
9.4 Compensation for injury 
There is a standard liability insurance available at the Radboud University Medical Centre 
for the study subjects. This is also written in the patient information letter. For the 
investigators there is also a liability insurance arranged at the Radboud University 
Medical Centre. In the proposal letter accompanying this protocol, we asked for release of 
a liability insurance for study subjects because this study includes usual nutritional care 
and meal service from FoodforCare which is already implemented in the medical centre. 
The patients will not be exposed to medical treatments during this study. 
 
9.5 Incentives  
Patients will not receive financial compensation for participating in the study. They will not 
have to pay additional hospital visits for this study and thus, they will have no additional 
travel costs or other costs. However, the intervention group will receive the meals and 
food products from FoodforCare for free. Due to the measurements that will be performed 
3 months after the intervention period, it will not be possible to continue with the 
FoodforCare meals after this period. Once the effectiveness of FoodforCare at Home has 
been demonstrated, it is likely that the meals will become available for regular use.  
 

Version 3.0, 09-10-17 
 
25 of 30 
10. ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 
10.1 Handling and storage of data and documents 
All study documents will be stored in the investigator site file. The informed consent forms 
will also be stored in Epic. The researchers will enter all data into the database of Castor 
by means of the study number with their personal password. Only the researchers who 
are directly involved in the study have access to this program. The key to the codes will be 
stored in a secure digital environment, so the privacy and anonymity of the patients is 
ensured. Both the written data and the entered data in Castor will be stored for up to 15 
years after the study. 
 
10.2 Monitoring and Quality Assurance  
Looking at the directives of the NFU for on-site monitoring, the monitoring-class of the 
study is negligible. Minimum monitoring is indicated. The monitoring will be performed by 
an independent gastroenterologist according to the monitoring plan. 
 
Monitorplan 
Monitor Frequency 
Once halfway the inclusion 
Patient flow 
Inclusion rate and drop-out percentage 
Trial Master File/ 
Investigator File 
Presence and completeness of research file 
Informed Consent 
100% 
In-/exclusie Criteria 
First 3 subjects, thereafter 10% 
Source Data Verification 
10% 
 
10.3 Amendments  
 
Not applicable with first version of the research protocol. 
 
10.4 Annual progress report 
The investigator will submit a summary of the progress of the trial to the accredited METC 
in case the study takes longer than a year. In this report, information will be provided on 
the date of inclusion of the first subject, numbers of subjects included and numbers of 
subjects that have completed the trial, serious adverse events/ serious adverse reactions, 
other problems, and amendments. 
  
10.5 End of study report 
The investigator will notify the accredited METC of the end of the study within a period of 
8 weeks. The end of the study is defined as the last patient’s last visit. For this study, this 
will be after the last measurement moment of the last patient. 
 
In case the study is ended prematurely, the investigator will notify the accredited METC 
within 
15 
days, 
including 
the 
reasons 
for 
the 
premature 
termination. 
 
Within one year after the end of the study, the investigator/sponsor will submit a final 

Version 3.0, 09-10-17 
 
26 of 30 
study report with the results of the study, including any publications/abstracts of the study, 
to the accredited METC.  
 
10.6 Public disclosure and publication policy 
After analyzing all data, the goal is to present the results on (inter)national conferences 
and to publish the results in an international journal, independently on positive or negative 
results of the study. This will be agreed with the sponsor in a contract.  
  

Version 3.0, 09-10-17 
 
27 of 30 
 
11. STRUCTURED RISK ANALYSIS 
 
11.1 Potential issues of concern 
A risk analysis, in respect to the cooperation contract between Maison van den Boer and 
the Radboud University Nijmegen Medical Centre, will be described in the 
Aanbiedingnotitie to the Board of Directors and will also be contracted. For example, the 
risk of financial loss will be clearly described in this contract. This letter will also disclose 
that FoodforCare has no influence on publishing (positive or negative) results. 
 
11.2 Synthesis 
As described previously, we expect that this meal concept will have no additional risk to 
the patients. In daily practice, the dishes of FoodforCare are widely offered to all patients 
in the hospital. Matters such as patient safety and hygiene will be respected. In light of 
these arguments, it does not seem necessary to us to give a structured risk analysis.

Version 3.0, 09-10-17 
 
28 of 30 
 
12. REFERENCES 
 
1. Kubrak, C., et al., Nutrition impact symptoms: key determinants of reduced dietary intake, 
weight loss, and reduced functional capacity of patients with head and neck cancer 
before treatment. Head Neck, 2010. 32(3): p. 290-300. 
2. Farhangfar, A., et al., Nutrition impact symptoms in a population cohort of head and neck 
cancer patients: multivariate regression analysis of symptoms on oral intake, weight 
loss and survival. Oral Oncol, 2014. 50(9): p. 877-83. 
3. Johns, N., H. Hartwell, and M. Morgan, Improving the provision of meals in hospital. The 
patients' viewpoint. Appetite, 2010. 54(1): p. 181-5. 
4. Nederlandse Kankerregistratie, b.d.I. Nederlandse Kankerregistratie. 2016; Available 
from: http://www.cijfersoverkanker.nl/. 
5. Nederlandse Kankerregistratie, b.d.I. Incidentie darm. 2016; Available from: 
http://www.cijfersoverkanker.nl/selecties/Incidentie_darm/img57fb4e44dae0e. 
6. Sanchez-Lara, K., et al., Gastrointestinal symptoms and weight loss in cancer patients 
receiving chemotherapy. Br J Nutr, 2013. 109(5): p. 894-7. 
7. Rodrigues, C.S., M.S. Lacerda, and G.V. Chaves, Patient Generated Subjective Global 
Assessment as a prognosis tool in women with gynecologic cancer. Nutrition, 2015. 
31(11-12): p. 1372-8. 
8. Grosvenor, M., L. Bulcavage, and R.T. Chlebowski, Symptoms potentially influencing 
weight loss in a cancer population. Correlations with primary site, nutritional status, 
and chemotherapy administration. Cancer, 1989. 63(2): p. 330-4. 
9. Gamper, E.M., et al., Coming to your senses: detecting taste and smell alterations in 
chemotherapy patients. A systematic review. J Pain Symptom Manage, 2012. 44(6): 
p. 880-95. 
10. 
Vogel J, B.S., Doornink N, Wipkink A., Handboek voeding bij kanker. 2012: Utrecht 
de Tijdstroom. 
11. 
Coa, K.I., et al., The impact of cancer treatment on the diets and food preferences of 
patients receiving outpatient treatment. Nutr Cancer, 2015. 67(2): p. 339-53. 
12. 
Lis, C.G., et al., Role of nutritional status in predicting quality of life outcomes in 
cancer--a systematic review of the epidemiological literature. Nutr J, 2012. 11: p. 27. 
13. 
Potter, J., et al., Symptoms in 400 patients referred to palliative care services: 
prevalence and patterns. Palliat Med, 2003. 17(4): p. 310-4. 
14. 
Teunissen, S.C., et al., Symptom prevalence in patients with incurable cancer: a 
systematic review. J Pain Symptom Manage, 2007. 34(1): p. 94-104. 
15. 
Grande, A.J., V. Silva, and M. Maddocks, Exercise for cancer cachexia in adults: 
Executive summary of a Cochrane Collaboration systematic review. J Cachexia 
Sarcopenia Muscle. 2015 Sep;6(3):208-11. Epub 2015 Jul 7 doi:10.1002/jcsm.12055. 
16. 
Vigano, A.L., et al., The Abridged Patient-Generated Subjective Global Assessment 
Is a Useful Tool for Early Detection and Characterization of Cancer Cachexia. Journal 
of the Academy of Nutrition and Dietetics, 2014. 114(7): p. 1088-1098. 
17. 
Norman, K., et al., Prognostic impact of disease-related malnutrition. Clin Nutr, 2008. 
27(1): p. 5-15. 
18. 
Kondrup, J., Proper hospital nutrition as a human right. Clin Nutr, 2004. 23(2): p. 135-
7. 
19. 
Hartwell, H.J., et al., What do patients value in the hospital meal experience? 
Appetite, 2016. 96: p. 293-8. 
20. 
Watters, C.A., et al., Exploring patient satisfaction with foodservice through focus 
groups and meal rounds. J Am Diet Assoc, 2003. 103(10): p. 1347-9. 
21. 
Doorduijn, A.S., et al., At Your Request((R)) room service dining improves patient 
satisfaction, maintains nutritional status, and offers opportunities to improve intake. 
Clin Nutr, 2016. 35(5): p. 1174-80. 
22. 
S Mahoney, A.Z., and K Walton, Patient satisfaction and energy intakes are 
enhanced by point of service meal provision. Nutrition and Dietetics, 2009. 66(4): p. 
212-220. 

Version 3.0, 09-10-17 
 
29 of 30 
23. 
van der Zanden, L.D., et al., Using a verbal prompt to increase protein consumption 
in a hospital setting: a field study. Int J Behav Nutr Phys Act, 2015. 12: p. 110. 
24. 
Kruizenga, B.S.v.d.M.H.M., Voedingsconcepten in de Nederlandse Ziekenhuizen. 
2016, Stuurgroep Ondervoeding. 
25. 
Campbell, A.D., et al., Does Participation in Home-Delivered Meals Programs 
Improve Outcomes for Older Adults? Results of a Systematic Review. J Nutr Gerontol 
Geriatr, 2015. 34(2): p. 124-67. 
26. 
Frongillo, E.A., et al., Adequacy of and satisfaction with delivery and use of home-
delivered meals. J Nutr Elder, 2010. 29(2): p. 211-26. 
27. 
DiMaria-Ghalili, R.A., et al., Benchmarking a Home-Delivered Meal Program's Annual 
Satisfaction Survey: A Metropolitan Area Neighborhood Nutrition Alliance (MANNA) 
Initiative in Philadelphia. J Nutr Gerontol Geriatr, 2015. 34(2): p. 189-206. 
28. 
Barton, A.D., et al., High food wastage and low nutritional intakes in hospital patients. 
Clin Nutr, 2000. 19(6): p. 445-9. 
29. 
Dashti, H.S. and K.M. Mogensen, Recommending Small, Frequent Meals in the 
Clinical Care of Adults: A Review of the Evidence and Important Considerations. Nutr 
Clin Pract, 2016. 
30. 
Lorefalt, B., U. Wissing, and M. Unosson, Smaller but energy and protein-enriched 
meals improve energy and nutrient intakes in elderly patients. J Nutr Health Aging, 
2005. 9(4): p. 243-7. 
31. 
Borm, G.F., J. Fransen, and W.A. Lemmens, A simple sample size formula for 
analysis of covariance in randomized clinical trials. J Clin Epidemiol, 2007. 60(12): p. 
1234-8. 
32. 
Marin Caro, M.M., A. Laviano, and C. Pichard, Nutritional intervention and quality of 
life in adult oncology patients. Clin Nutr, 2007. 26(3): p. 289-301. 
33. 
Baldwin, C., et al., Simple nutritional intervention in patients with advanced cancers of 
the gastrointestinal tract, non-small cell lung cancers or mesothelioma and weight 
loss receiving chemotherapy: a randomised controlled trial. J Hum Nutr Diet, 2011. 
24(5): p. 431-40. 
34. 
Hasenberg, T., et al., Early supplementation of parenteral nutrition is capable of 
improving quality of life, chemotherapy-related toxicity and body composition in 
patients with advanced colorectal carcinoma undergoing palliative treatment: results 
from a prospective, randomized clinical trial. Colorectal Dis, 2010. 12(10 Online): p. 
e190-9. 
35. 
Beelen, J., N.M.d. Roos, and C.P.G.M.d. Groot. Effects of protein-enriched familiair 
foods and drinks on protein intake and physical recovery of older patients during 12 
weeks in transmural context: the randomized controlled cater with care trial. 2016. 
36. 
Arends, J., et al., ESPEN guidelines on nutrition in cancer patients. Clin Nutr, 2016. 
37. 
Paddon-Jones, D. and B.B. Rasmussen, Dietary protein recommendations and the 
prevention of sarcopenia. Curr Opin Clin Nutr Metab Care, 2009. 12(1): p. 86-90. 
38. 
Aaronson, N.K., et al., The European Organization for Research and Treatment of 
Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in 
oncology. J Natl Cancer Inst, 1993. 85(5): p. 365-76. 
39. 
Fayers PM, A.N., Bjordal K, Groenvold M, Curran D, Bottomley A,, The EORTC QLQ-
C30 Scoring Manual, 3rd edition. Brussels: EORTC, 2001, 2001. 
40. 
Nijboer, C., et al., Measuring both negative and positive reactions to giving care to 
cancer patients: psychometric qualities of the Caregiver Reaction Assessment (CRA). 
Soc Sci Med, 1999. 48(9): p. 1259-69. 
41. 
Flood, A., et al., The use of hand grip strength as a predictor of nutrition status in 
hospital patients. Clin Nutr, 2014. 33(1): p. 106-14. 
42. 
Dodds, R.M., et al., Grip strength across the life course: normative data from twelve 
British studies. PLoS One, 2014. 9(12): p. e113637. 
43. 
Mueller, C., C. Compher, and D.M. Ellen, A.S.P.E.N. clinical guidelines: Nutrition 
screening, assessment, and intervention in adults. JPEN J Parenter Enteral Nutr, 
2011. 35(1): p. 16-24. 
44. 
Karnofsky DA, A.W., Craver LF, Burchenal JH., The use of the nitrogen mustards in 
the palliative treatment of carcinoma. With particular reference to bronchogenic 
carcinoma. Cancer, 1948(1): p. 634-656. 

Version 3.0, 09-10-17 
 
30 of 30 
45. 
Mijnarends, D.M., et al., Validity and reliability of tools to measure muscle mass, 
strength, and physical performance in community-dwelling older people: a systematic 
review. J Am Med Dir Assoc, 2013. 14(3): p. 170-8. 
46. 
Chang, V.T., S.S. Hwang, and M. Feuerman, Validation of the Edmonton Symptom 
Assessment Scale. Cancer, 2000. 88(9): p. 2164-71. 
47. 
Reichheld, F.F., The one number you need to grow. Harvard business review, 
December 2003. 
48. 
EORTC. Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. 
2009; Available from: https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf.