Improving Function and Quality of Life for Older Cancer Patients Receiving Radiotherapy, a Randomized Controlled Pilot Study
Phase: NA
Conditions: Cancer, Radiotherapy, Older Patients
Sponsor: Sykehuset Innlandet HF

1 
 
 
 
 
 
Improving function and quality of life for older 
cancer patients receiving radiotherapy, a 
randomized controlled pilot study 
NCT03881137 
Protocol dated 09.12.2018 
Amendment dated 09.03.2020 
 
 

2 
 
Overarching protocol with amendments1 
Improving function and quality of life for older 
cancer patients receiving radiotherapy, a 
randomized controlled pilot study 
 
A study emerging from Innlandet Hospital Trust in co-operation with the Norwegian 
University of Science and Technology (NTNU), Trondheim University Hospital Olavs 
Hospital, Trondheim and the primary health services in 30 municipalities in Innlandet 
County, Norway 
 
Funding  
The study is made possible by Innlandet Hospital Trust (grant number 150406), the Dam 
Foundation, a Norwegian non-profit organisation (grants number ref 19-3656) and the 
Norwegian Cancer Society reference 247593001), the Liaison Committee for Education, 
Research and Innovation in Central Norway (grant number 19/4740-3), and The Joint 
Research Committee between St. Olav’s hospital and the Faculty of Medicine and Health 
Sciences, NTNU – The Norwegian University of Science and Technology (FFU) (grant 
number 2018/42795 ).  
 
 
 
                                                 
1 Further details, please see “references”, open access paper: Røyset I et al. Geriatric 
assessment with management for older patients with cancer receiving radiotherapy. Protocol 
of a Norwegian cluster-randomised controlled pilot study. J Geriatr Oncol. 2022 
Apr;13(3):363-373. doi: 10.1016/j.jgo.2021.11.001. Epub 2021 Nov 12 
 
 

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Introduction  
The current study addresses a major challenge to our health care systems, i.e. to provide good, 
effective and personalized health services to a large and rapidly increasing group of older 
cancer patient with complex needs (1). 
The study is a randomised controlled pilot study for older cancer patients receiving 
radiotherapy (RT). It is designed to test the feasibility, potential effect and cost-effectiveness 
of an intervention aiming to improve function and quality of life (QoL), and thereby reduce 
the burden for the patients, their families and the society. The intervention program will be 
based on geriatric assessment with management, and comprises a targeted and personalised, 
primary health care based multicomponent intervention. In line with a proposal from the 
Norwegian Health Minister related to the new Norwegian cancer strategy (2), assigned 
municipal cancer nurses will serve as service coordinators to ensure a seamless treatment 
trajectory and a smooth transition of patients across sectors. The study will be conducted as a 
joint effort between specialists in geriatric and oncologic medicine as well as hospital and 
primary health care services, and represents the basis for a subsequent multicentre randomised 
trial (RCT).  
The study is part of a larger project emerging from Innlandet Hospital Trust (SI) (Figure 1, 
page 2).  Through this project, active collaboration is established between SI, St Olavs 
Hospital, 41 out 48 municipalities in Hedmark and Oppland counties and Trondheim 
municipality. Finances for one full-time and one part time (50%) project nurse are granted 
from SI. Furthermore, a 50% position for a project nurse for two years will be financed by 
grants from the Joint Research Committee between St. Olavs Hospital and the Faculty of 
Medicine and Health Sciences, NTNU. Running expenses will be covered by grants from the 
same committee, the Liaison Committee for Education, Research and Innovation in Central 
Norway and SI, jointly, and means to finance a PhD student connected to the pilot study are 
covered by grants from Extrastiftelsen. 
Background and current knowledge 
Older cancer patients (> 65 years) represent the majority of the cancer population, and their 
absolute number grows due to an aging population. In comparison to their younger 
counterparts, older cancer patients often present with a multiplicity of problems. They 
frequently suffer from somatic or psychiatric comorbidities, and are often frail with 
impairment in mobility, daily life functioning and cognition. When diagnosed with cancer and 
needs of therapy, these patients are at substantial risk of complications and functional decline 
(3-5). Thus, following cancer treatment, older patients have higher mortality and morbidity(6-
8). Recovery also takes longer and may not always be achieved (5). 
To avoid adverse outcomes that come at high personal and societal costs, and to ensure that 
optimal cancer treatment can be administered, a systematic assessment of the older patient’s 
overall health status and potential vulnerability is necessary (9). This is particularly important 
considering the result of a recent study by our study group, demonstrating that oncologists are 
poorly trained to recognize frailty in their patients (10). Measures should thereafter be 
undertaken to improve existing deficits and prevent deterioration, and targeted rehabilitation 
procedures should be planned and implemented. Presently no such assessments or procedures 
are systematically applied in Norwegian cancer care. 
Geriatric assessment (GA) addresses problems that are frequent in older age (3, 4) and 
includes systematic assessment of somatic health (such as comorbidity, medications, 
nutrition); mental health (such as cognition, anxiety and depression); functional aspects (such 

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as activities of daily living (ADL) and instrumental ADL (IADL) and physical function); and 
social network and living situation. GA is currently the best established method to identify 
older patients’ vulnerability (11). Performed by an interdisciplinary geriatric team and 
followed by adequate management of identified vulnerabilities (GA with management), the 
approach has documented success in improving outcomes in non-cancer populations (12, 13).  
During the last decades, GA has been adapted for cancer care, and mounting evidence shows 
that GA may identify remediable problems, affect oncological treatment decisions and predict 
survival or adverse effects from chemotherapy and cancer surgery (3, 14, 15). Despite this, 
and strong recommendations from current guidelines (3, 9, 16), GA has not been integrated 
into common oncology practice.(17) All GA domains cover problems that may negatively 
affect outcomes of cancer and cancer treatment (4). On the other side, these problems may 
also be prevented, alleviated or improved. For instance may treatment of comorbidities be 
optimised and inappropriately described medications withdrawn (4, 18).  Interdisciplinary 
rehabilitation addressing physical activity and nutritional counselling may improve physical 
and nutritional deficits (19, 20). Mobility, independency and QoL are highly prioritized by 
older patients (21, 22). These outcomes are interconnected and may all be promoted by 
tailored physical exercise (23). GA with management (GAM) interventions are therefore 
strongly recommended to optimise treatment and care for older cancer patients (17).  
Evidence for the potential benefits is lacking (17). 
Radiotherapy in cancer treatment: RT is a main treatment modality in cancer, and may be 
used with curative or palliative intent. Short- and long-term side effects occur in both settings, 
and may be local, i.e. related to the involved organs, or general, e.g. fatigue and physical 
deterioration. Curative RT is conventionally given in higher total doses over a longer period 
of time, and have more frequent side effects compared to palliative treatment. There is 
evidence to suggest that older patients benefit from RT equally to younger patients (24, 25). 
However, high incidence of co-existing problems, higher toxicity rates, impaired QoL and 
physical deterioration are serious concerns (24, 25). Thus, using GA for both predictive and 
interventional purposes in older patients receiving RT has been advocated (24). To our 
knowledge, no studies on GAM interventions in this context have previously been published.  
The overarching research project: The present pilot study is an essential part of a larger 
project designed to develop, test 
and evaluate a cost effective, 
multicomponent, 
interdisciplinary treatment 
model for older cancer patients 
(≥65 years) receiving RT. The 
project is designed in 
accordance with 
recommendations for 
development and evaluation of 
complex interventions (Fig 1) 
(26). To obtain sufficient 
knowledge to develop a feasible, 
targeted intervention, we have 
performed an observational 
study of older cancer patients (n 
= 301) receiving RT to identify 
needs and problems (REK SØ-A 2016/2031). The study was closed for inclusion July 2018, 
and results of preliminary analyses are pending. Focus group interviews with relevant hospital 
Focus group
interviews with
health
professionals
Collaboration:
expert group,
user
representatives,
community
health
professionals
Phase III
multicentre
cluster-RCT
Figure 1. Design of the overarching project
Randomised controlled
pilot study comparing
intervention and control
Increasing levels of evidence, adapted from Campbell et al, BMJ 2000
Matched retrospective
controls for comparion to 
intervention
Observational
study
Patient
interviews
Aquiering 
essential 
knowledge 
Modelling the 
intervention 
Evaluating feasibility, testing 
potential effect and economic 
impact of the intervention 
Definitive 
evaluation 
2016- 2018 
2018 
2019 - 2021 
2022 - 2025 
 

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and primary health care professionals have been conducted (2017). Individual patient 
interviews to obtain detailed information about their perception of potential areas for 
improvement are running (REK SØ B 2018/1068). Experience, results and preliminary results 
from these studies represent the basis for the development of the intervention to be tested in 
the present pilot study. 
Rationale for a pilot study: Before embarking on a larger multicenter RCT, the conduct of a 
pilot study is paramount. Although GAM has proven successful in other contexts (12, 13), 
there is no universally accepted recipe for how such an intervention should be performed and 
implemented. To be feasible and efficient, adjustments according to patient population, health 
care organization and available resources are necessary. A pilot study is needed to provide 
evidence for the feasibility from a patient as well as an organizational perspective. It is crucial 
to know if the intervention may be more relevant for some subgroups than others, to ensure 
that patients are able to adhere to all aspects of the intervention or if adjustments are needed, 
and to ensure that the intervention may be implemented within existing services and 
resources. A pilot study is also needed to enable adjustment of methods for evaluation and 
outcome assessment, and to enable precise sample size estimations for a future multicenter 
RCT. 
Study aims and objectives 
The present PhD-project will be conducted to provide the evidence needed to implement a 
cost-effective GAM intervention for older cancer receiving RT on a larger scale, aiming at 
improving QoL and function and thereby reduce the burden for the patients, their families and 
the society. 
The detailed objectives are to: 
1. assess the potential short- and long term effect of the intervention on global QoL and 
physical functioning for older cancer patients receiving RT  
2. assess the feasibility of the intervention  
a. at the patients’ level (recruitment, compliance and adherence) 
b. at the organizational level (structures facilitating or impeding implementation and 
collaboration across sectors and between professionals)  
3. study the use of health care services and related costs in the intervention and control group  
Scientific significance and new knowledge that can be derived from 
the project 
The present study will provide new knowledge on the needs of elderly cancer patients 
receiving RT, the feasibility of performing a multicomponent intervention based on 
collaboration across sectors and between disciplines, and on the potential benefits of GAM 
interventions on outcomes of particular relevance to older patients. Thus, the study will 
contribute to fill several knowledge gaps. Studies evaluating GAM interventions for cancer 
care are missing, and there is an urgent need to implement GA into routine clinical practice, 
and to establish the feasibility. Moreover, studies on older patients addressing treatment 
outcomes such as functioning and QoL are scarce, but highly advocated. The knowledge 
generated from the study will therefore be of major international interest, and essential for 
future planning of health services for an increasing number of patients with complex needs.  
Furthermore, introducing GA to the hospital and primary health care services will increase 
awareness and knowledge on geriatric problems, and provide experience with assessments 
and interventions that are beneficial for older patients in general. Likewise, the study includes 

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collaboration with a range of municipalities of varying size and health care organization, and 
involves hospital with different level of expertise. Overall, the results will be broadly 
applicable for the management of older patients.  
Design, methodology and analyses  
The intervention2  
The intervention is developed by the interdisciplinary, experienced research group of this 
study in close collaboration with user representatives and hospital and primary health care 
professionals (reference group, page 12), and based on experience, results and preliminary 
results from the foregoing studies of the overarching project (Fig 1). Additionally, we have 
taken advantage of experience and results from another observational study by our study 
group “ Cancer in the elderly; a prospective, observational study” (REK SØ C 2012/104) (10, 
27) as well as studies evaluating GAM interventions in older, non-cancer patient conducted 
by members of our study group (12, 28, 29). 
The intervention is a 
multicomponent GAM 
intervention (Fig 2) that will be 
adjusted to each patient’s needs 
and capacity to comply. It 
focuses on somatic and mental 
health, function and social 
situation including living 
condition. Measures adapted to 
each patient will target these 
areas according to needs and 
deficits identified by a 
systematically applied GA. 
According to results from a former 
study by our group(10), as well as 
preliminary data from the 
foregoing studies (Fig 1), 
evaluation of comorbidities and 
medications, appropriate treatment 
of depressive and somatic 
symptoms, nutritional counselling 
and physical rehabilitation will be 
important components of the 
intervention.  
                                                 
2 Details on the intervention and intervention procedure were written in Norwegian in a protocol attachment and 
are to be found in the protocol paper: Røyset et al. Geriatric assessment with management for older patients with 
cancer receiving radiotherapy. Protocol of a Norwegian cluster-randomised controlled pilot study. JGO 2022 
 
Geriatric 
assessment 
and 
management
Somatic health
• Cancer
• Comorbidities
• Polypharmacy
• Nutrition
• Somatic symptoms
Mental health
• Cognition
• Depression 
• Anxiety
Social situation 
and living 
condition
Function
• Daily life 
activities
• Mobility
Figure 2
GAM and 
included domains
• Systematic assessment (GA) to identify needs 
and deficits
• Individually adapted interventions to improve 
deficits, alleviate symptoms, prevent decline
• Physical exercise program, individually 
adjusted to maintain/improve function
• Repeated assessments to ensure immediate 
management of changing needs
• Patient’s interventions will be
• initiated in hospital (RTU unit) 
• carried out in the municipalities using 
existing health care services and offers
• collaboration with relevant hospital 
professionals
• Coordinating nurse, following patient with 
regular contact
+
Figure 3. Intervention
Geriatric
assessment and
management
Collaboration 
accross sectors
and
coordination of
services

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The initial GA and start of the intervention will be handled by the PhD student or project 
nurse before RT commences. Pre-planned guidelines will be followed, and contribution from 
relevant hospital professionals will be sought according to needs. Then the intervention will 
be offered in the primary health care taking advantage of existing services, e.g. home care, 
meal delivery, rehabilitation services, exercise groups etc.  
A coordinating nurse will follow the patients with regular contact throughout RT and to end 
of intervention and 8 weeks post-RT. In Hedmark and Oppland this task will be assigned to 
those who are “cancer co-ordinators” or have a dedicated role as a “contact nurse” for cancer 
patients in their municipality. Repeated assessments will be performed by the end of RT and 
after 4 weeks to ensure that the intervention is properly adjusted to changing need (see also 
Fig 4).  
Before recruitment of patients to this pilot study starts, seminars will be arranged for 
information and training of involved primary health care professionals. Through the foregoing 
observational study (Fig 1), the relevant nurses in the SI catchment area are all extensively 
familiar with GA. 
Setting  
The primary study center is the Radiotherapy Unit (RTU) at SI providing RT to the 
population in Oppland and Hedmark counties (380 000 inhabitants), and treating about 700 
patients per year, 2/3 are ≥65 years. Palliative RT represents about 60 % of the patients, and is 
administered independent of diagnosis. Curative treatment is given to breast, prostate, lung 
and skin cancers only. Hedmark and Oppland comprise 48 municipalities, and 30 of these 
have consented to participate in the present study. The RTU, St Olavs hospital, Trondheim 
will be the second study center. This RTU provides all RT services to the inhabitants in the 
catchment area including Trondheim municipality (180 000 inhabitants). RT is administered 
to about 250 patients >65 years from Trondheim per year. The municipality of Trondheim is 
organized into 4 health care districts.    
 
Design  
The present study is a controlled cluster-randomized pilot study. Cluster-randomization is 
chosen to avoid contamination of the control group. It is paramount that control and 
intervention patients are not handled by the same primary health care professionals, and this 
can only be achieved by randomizing municipalities (or health care districts).  
Before patient recruitment commences, a selection of 32 municipalities/city districts (= 
clusters) will be stratified into blocks in accordance with number of inhabitants. The selection 
will include city districts, large and smaller municipalities to ensure sample size and 
representativity. Clusters within each block will be randomly assigned to one of the groups by 
using a computer-generated code, 16 in each group.  
Eligible patients from clusters assigned to intervention will enter the intervention group and 
enter the intervention program. Patients from control clusters will enter the control group. 

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These patients will receive treatment and care in accordance with usual routines and standards 
 
Consenting, eligible patients will be included when admitted to planning of RT. Baseline 
assessments will be performed by a project nurse/the PhD student at start of RT. As we 
believe that the intervention may have both a short- and long term impact on patients’ QoL 
and functioning, the patients will be followed for 52 weeks with specific study assessments 
and for survival up to 5 years. The main outcomes assessments will take place at 8 and 16 
weeks after the end of RT.  A blinded assessor will be used to assess outcomes other than 
those that are patient reported (PROMs) at these time points.  
Patients 
Patients will be consecutively recruited at the RTU, Gjøvik and St. Olavs hospital.  
The inclusion criteria are:3  
 ≥65 years of age 
 confirmed cancer diagnosis (histology/cytology) 
 living in one of the participating municipalities in the catchment area of SI or in the 
municipality of Trondheim 
 referred for palliative or curative RT 
 fluency in Norwegian, orally and in writing 
 ability to fill in self-report questionnaires 
 provide written informed consent 
The exclusion criteria are 
 severely ill with a life expectancy < 3months 
 referred to receive one fraction of RT only (one day treatment)  
Outcomes and assessments 
The effectiveness of the intervention will be tested by the use of patient-reported measures and 
tests for physical performance/mobility. Additionally, the use of health care services will be 
                                                 
3 A minor change of the inclusion criteria were made by February 2020 to include patients with a cancer 
diagnosis without cytological/histological confirmation, i.e. in cases where the referring oncologist affirmed the 
malignant diagnosis based on medical history, imaging and blood analyses, see attached amendment.  

9 
 
registered and evaluated. The pre-defined primary time point for outcome assessment is 8 
weeks post-RT. 
Physical function (PF) measured by the European Organisation for Research and Treatment of 
Cancer (EORTC) Quality of life Questionnaire-C30 (QLQ-C30)(30) is the defined primary 
outcome.  
Secondary outcomes are: 
 QoL assessed by the EORTC QLQ-C30 global QoL scale and EQ-5D-5L(31) 
 Physical performance/mobility assessed by the following performance tests: Short 
Physical Performance Battery (SPPB)(32), Timed Up and Go test(33), Grip Strength 
(measured by a dynamometer)(34), and one legged balance test (35) 
 Use of health care services (hospital in- and outpatient services and municipality 
services in terms of home care, nursing home care and use of other services such as 
physiotherapist, occupational therapists, and rehabilitation programs) 
Other defined outcomes: 
 Symptom occurrence assessed by the EORTC QLQ-C30, specifically fatigue, pain, 
dyspnea, and sleeping disturbances 
 Emotional function assessed by the EORTC QLQ-C30 
 Nutritional abnormalities assessed by BMI, weight loss and loss of appetite (subscale 
of the EORTC QLQ-C30).  
 
Patient reported outcomes (EORTC QLQ-C30 and EQ-5D-5L) will be assessed at baseline, 
by the end of RT, and thereafter 4, 8, 16, 32 and 52 weeks after RT. Performance tests will be 
applied at baseline and 8 and 16 weeks after the end of RT. Data on primary care service 
utilization (home based and institutional care) and hospital services will be registered 
throughout the intervention period and during follow-up (one year, week 52).  
Feasibility will be assessed by a process evaluation aiming to identify facilitators and barriers 
for a successful implementation, using mixed methodology. Measures recommended for each 
patient’s intervention plan will be consecutively registered, as will patients’ compliance and 
adherence through weekly contact with the coordinating nurse (log notes). Further data will 
include interviews with patients and provider. Questionnaires to involved primary health care 
nurses and other relevant professionals will also be applied.  
Economic evaluation will be based on a comparison of costs and effects as measured by the 
main outcome measures, EQ-5D-5L particular. Costs include direct costs associated with 
GAM (intervention costs), as well as costs related to hospital admissions, home care and 
nursing home care. Data on service utilization will be obtained from hospital and municipal 
registers, respectively. Both intervention costs (GAM) and conventional care will be 
calculated in detail.. 
Sample size4 
Sample size estimations are based on a block-randomised cluster RCT. A total of 57 patients 
distributed in 16 clusters (proportionally to cluster size) in each group will enable the 
detection of a clinically significant difference (12 points)(36) on the physical functioning 
QLQ-C30 scale with a standard deviation (SD) of 22 at the significance level of 5% and a 
power of 80%, given an intracluster correlation (ICC) of 5%.  The ICC is assumed to be small 
                                                 
4 For detail see statistical analyses plan dated 12-3-19 and protocol amendment dated 9-3-20.  
 

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as the intervention primarily will be applied by municipal cancer nurses with similar training 
in collaboration with hospital specialists, similar to all intervention patients. According to a 
former study on older cancer patients by this study group, we expect an attrition of about 15-
20% at 16 weeks of follow-up post-RT. Furthermore, it is paramount to ensure that all 
municipalities are represented by included patients. To take this and attrition into account, we 
aim at including 81 patients in each group, i.e. a total of 162 patients. See also statistical 
analyses plan dated 12-3-19 and attached protocol amendment dated 9-3-20.  
Statistics 
All analyses will be pre-planned in collaboration with the study statistician before start of the 
study, and will follow the intention-to-treat principle. Descriptive statistics will be used to 
investigate quantitative data related to feasibility, compliance and adherence. Associations 
will be assessed by using suitable regression models. Interviews will be analysed by an 
interpretative approach, aiming at capturing interviewees' experiences with the intervention. 
To investigate the intervention effect, the trend in pre-defined outcomes will be compared 
between intervention and control groups by estimating linear mixed models accounting for 
intra-patient (due to repeated measurements per patient) and intra-municipality variations. The 
results will further be adjusted for relevant covariates.  
Due to the potential heterogeneity of the study sample, the effect of the intervention will also 
be tested against a retrospectively matched control group, extracted from the observational 
study in the first part of the overarching project (see Fig 1). Patients in the foregoing 
observational study have given their consent to this comparison, and the observational study 
makes use of the same patient-related outcome measures, assessed on the same points of time 
as the current study.  
For the economic evaluation, we measure outcome in terms of Quality Adjusted Life Years 
(QALY) by combining the preference based Health Related Quality of Life index from EQ-
5D-5L and the corresponding time periods. We evaluate cost-effectiveness by estimating the 
incremental cost-per-QALY ratio defined as the mean cost per patient for the intervention 
group minus mean cost per patient for the control group, divided by mean QALY intervention 
group minus mean QALY control group. We apply non-parametric bootstrapping methods to 
assess uncertainty and use cost-effectiveness plane and cost-acceptability curves for 
presentation of results.  
See also detailed statistical analyses plan dated 12-3-19. 
User involvement 
User involvement is essential for this project. At SI, a group of four user representatives is 
established, and have participated in the planning and conduct of the observational study. For 
the conduct of the present study, an additional representative from Board of senior citizens in 
Trondheim is contracted. These user representatives will participate in the design of the 
intervention and implementation procedures. They will further contribute during the study 
conduct, to the interpretation of results by evaluating the relevance for the users, and participate 
in the dissemination of results to the public, patients and relatives. Regular meetings are 
implemented and will continue during the overall study conduct. 
Ethics  
The study was approved by The Regional Committee for Medical Research Ethics, Health 
Region South-East (2018/2515/REK sør-øst A) and the Data Protection Official for 

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Research,Innlandet Hospital Trust and Trondheim University Hospital. The pilot study will be 
performed according to the rules of the Helsinki-declaration. Participation will not inflict 
upon the patients’ cancer treatment and not imply any health risks or deviation from good 
clinical practice. Patients in the control group will receive care according to routine. However, 
a more thorough assessment followed by advice according to findings may, however, 
contribute to improved care. Written informed consent will be provided.  
 
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Protocol amendment – 29-02-20  
Adjustment of inclusion criteria 
We have realized that some patients are referred for radiotherapy for a cancer disease that has 
not been confirmed histologically or cytologically.  In these cases, the referring oncologist has 
affirmed the malignant diagnosis based on medical history, imaging and blood analyses.  
As participating in the study does not have any impact on the patients’ cancer treatment, and 
neither the intervention, its results, or the patients potential benefit of the intervention 
program are in any way dependent on how the cancer diagnosis has been confirmed, we have 
decided to make a minor change of the inclusion criteria.  
 
Formerly stated criteria for eligibility (according to original protocol) 
Patients 
Patients will be consecutively recruited at the RTU, Gjøvik and St. Olavs hospital.  
The inclusion criteria are:  
 ≥65 years of age 
 confirmed cancer diagnosis (histology/cytology) 
 living in one of the participating municipalities in the catchment area of SI or in the 
municipality of Trondheim 
 referred for palliative or curative RT 
 fluency in Norwegian, orally and in writing 
 ability to fill in self-report questionnaires 
 provide written informed consent 
The exclusion criteria are 
 severely ill with a life expectancy < 3months 
 referred to receive one fraction of RT only (one day treatment)  
 
 
Adjustment of inclusion criteria 
 
Bullet point two “confirmed cancer diagnosis (histology/cytology” is changed to: “Confirmed 
cancer diagnosis (preferrably histologically or cytologically, but patients referred for 
radiotherapy for cancer based on medical history, imaging and blood analyses are also 
eligible» 
 
Otherwise, there are no changes to the inclusion and exclusion criteria. 
 
Adjustment of timing for baseline registrations 
According to original protocol, amendment 1, page 16, baseline registrations should be 
completed within the second day of treatment. We have realized that this is not feasible for all 
patients due to practical constraints. The patients often have several appointments during the 
first period of treatment like seeing their oncologist and/or cancer nurses, and are also often in 
short of time  to be able to comply with scheduled transportation. As this study is not only a 
pilot study testing the potential effect of the intervention program, but also a feasibility study, 

14 
 
these circumstances have to be taken into account to enable inclusion of all patients who 
potentially may benefit from the intervention program. Thus, we have decided on the 
following: 
 Patients who receive a radiotherapy regimen with less than 15 fractions (short term 
treatment, usually 10 fractions or less) should have their baseline registrations 
completed by the third day of treatment 
 Patients who receive radiotherapy with 15 fractions or more (long term treatment) 
should have their baseline registrations completed within the sixth day of treatment  
As any negative impact of radiotherapy generally occur by the end of treatment, we believe 
that these changes would not have any effect on the registrations or our results.   
 
Amendment B5 
Revision of sample size estimate 09.03.20  
 
The original estimates as stated in Amendment 8 (12-03-19) were as 
follows: 
Sample size estimations are based on a block-randomized cluster RCT. A total of 53 patients 
distributed in 16 clusters (proportionally to cluster size) in each group will enable the 
detection of a clinically significant difference (12 points)8 in the physical functioning QLQ-
C30 scale at week 8 with a standard deviation (SD) of 24 in each group at the significance 
level of 5% and a power of 80%, given an intra-cluster correlation (ICC) of 10%. The ICC is 
assumed to be small as the intervention primarily will be applied by municipal cancer nurses 
with similar training in collaboration with hospital specialists, similar to all intervention 
patients. Power calculation was performed for analysis of covariance, adjusting difference 
between groups for baseline values, and assuming the correlation between baseline and 
follow-up measurements to be 0.5. According to a former study on older cancer patients by 
this study group, we expect an attrition of about 15-20% at 16 weeks of follow-up post-RT. 
Furthermore, it is paramount to ensure that all municipalities are represented by included 
patients. To take this and attrition into account, we aim at increasing sample size by about 
28% and including 81 patients in each group, i.e. a total of 162 patients.  
 
Revision of estimates 
Background: 
The present study is a block cluster-randomized study where 32 municipalities/city districts 
have been allocated to either control or intervention using a computer generated code. Due to 
large differences in number of inhabitants between municipalities/city districts, the 
                                                 
5 Amendment 09-03-20. Improving function and quality of life for older cancer patients receiving radiotherapy, 
a randomized controlled pilot study 
 

15 
 
randomization units were stratified according to number of inhabitants prior to randomization 
(5 strata). Based on strata sizes and the estimated sample size, the preplanned number of study 
participants varied from 2 to 16 in different strata (as explained in the original application to 
the Ethical Review Board, attachment 7).   
 
Before embarking on the study, the following considerations were made (Original protocol 
amendment 5, page 34 -35):  
 the enrolment was estimated to take one year  
 the number of eligible patients referred for radiotherapy from each randomized unit 
would depend on/vary according to chance 
 there was a risk that there would not be enough eligible patients from the small 
municipalities to enable inclusion of the pre-planned number 
 it was thus likely that it would be necessary to increase the number of patients from 
some municipalities (most likely the larger ones), and reduction in number of strata 
would also require a larger number of patients  
 
Current status of inclusion 
Based on these considerations, the inclusion rate, in particular the inclusion from each 
municipality, has been continuously monitored. 
 
By the 25th of February 2020, the status was:  
 a total of 111 patient were included 
 one of the municipalities has withdrawn before including any patient 
 another four municipalities with preplanned two patients had not included any of the 
patients so far  
 in five other randomized smaller municipalities with preplanned two patients for 
inclusion, only one patient had been included from each so far 
 
This implies that the number of strata will be seriously reduced. Hence, sample size has to be 
adjusted correspondingly. Furthermore, to be able to include a required number of patients 
according to the new estimates the period for recruitment has to be extended. 
 
New sample size estimate 
The revised sample size estimate is based on the same end-point, assumed difference and SD 
estimates as well as requirements for significance and power as the original. However, due to 
the reduction in number of strata and smaller number of patients than preplanned from some 
strata, the new estimate indicates that at least 69 patients must be included in each trial arm. 
Considering attrition, as described for the original sample size estimates, we now estimate that 
a total of 186 patients, i.e. 93 patients in each trial arm, will be required to show the 
statistically significant difference between groups given it exists.   
 

16 
 
Conclusion:  
We aim at including a total of 186 patients, i.e. 24 patients more than originally estimated. It 
also means that more patients than preplanned will have to be included from some of the 
participating municipalities, i.e. from those that during the inclusion period present with 
eligible patients. 
For the analysis of the primary outcome, however, we need at least 138 evaluable patients, i.e. 
patients where the primary outcome is registered. Thus, by closely monitoring the inclusion 
and response rate, it may be possible to stop the enrolment before the end of Sep 2020, and 
before we reach 186 patients. We may also need to enroll more than the estimated 186 
patients to reach the target number of evaluable patients, and in this case, a new application to 
the Ethical Review Board will be submitted. 
 
To be noted: Due to the increase in sample size, the inclusion period was extended 
primarily to Sep 2020. However, study recruitment had to be paused in March 2020 due to the 
covid pandemic, and was thereafter opened again in the autumn 2020, please see published 
protocol paper .