Follow-up of Cancer Patients Receiving Chemotherapy or Targeted Therapy by Electronic Patient Reported Outcomes-tool
Phase: NA
Conditions: Cancer
Sponsor: Oulu University Hospital

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Clinical Trial Protocol 
 
Study  
 
Follow-up of Cancer Patients Receiving Chemotherapy or Targeted Therapy by Electronic 
Patient Reported Outcomes-tool (ECHO) 
 
 
 
Principal Investigator Jussi Koivunen 
 
 
Oulu University Hospital, Dept of Oncology and Radiotherapy 

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OUTLINE: 
Study: 
 Follow-up of Cancer Patients Receiving Chemotherapy or Targeted 
Therapy by Electronic Patient Reported Outcomes-tool (ECHO) 
Protocol version 
1.1 28.2.2019 
Sponsor 
Jussi Koivunen, Oulu University Hospital 
 Indication 
Cancer patients with breast, lung, colorectal or pancreatic cancer 
receiving chemotherapy or targeted therapy 
Outcomes 
 
Overall cohort: 
1. Number of triggered alerts by the Kaiku Cancer medical 
therapy side-effects questionnaire and their correlation to 
treatment side-effects, cancer progression, other relevant 
medical events or survival 
2. QoL of patients using Kaiku QLQ-C30 QoL questionnaire and 
its correlation to treatment side-effects, cancer progression, 
other relevant medical events or survival  
3. Patient compliance using Kaiku Patient experience survey and 
response rates to symptom and QLQ-C30 questionnaires  
 Additionally, in the CRC cohort: 
1. Integration of laboratory values to patient reported symptoms 
when prescribing a new chemotherapy cycle  
2. Phone calls related to chemotherapy prescribing 
3. Unscheduled visits in oncology unit 
4. Additional investigations in health care 
5. ER visits 
6. Additional days in hospitalization 
7. Development of peripheral neurotoxicity 
8. Amount of chemotherapy dose reductions 
9. Number of delayed chemotherapy cycles 
10. Usability experience of health care personnel 
 
Study design 
Prospective one arm study 
Sample size 
100 patients of which, 60 CRC patients which are expected to be 
recruited in 42 months 
Criteria 
Inclusion criteria:  
1. Signed informed consent  
2. Advanced breast, lung, colorectal or pancreatic cancer 
3. Chemotherapy or targeted therapy initiated within +/- 2wks 
from signed consent 
4. Age ≥18y 
5. ECOG 0-2 
6. CRC cohort: Adjuvant treatment, or first or second metastatic 
treatment line 
7. Patient compliant with the study procedures 
 
Exclusion criteria: 
8. Chemotherapy or targeted therapy iniated ˃2 wks prior to 

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signed consent 
9. General vulnerability affecting the participation in the trial 
10. No internet access/email 
 
Study procedures 
Patient: 
1. Fills 16 question Kaiku Cancer medical treatment side-
effects questionnaire before initiation of the treatment or 
within 2 weeks and thereafter weekly up to disease 
progression or 24 weeks 
2. Answers Kaiku QLQ-C30 QoL questionnaire before initiation 
of the treatment or within 2 weeks and thereafter every four 
weeks up to disease progression or 24 weeks 
3. Answers Patient Experience survey every four weeks up to 
disease progression or 24 weeks 
 
Doctor/Nurse: 
1. Fills Kaiku baseline patient information before the initiation 
of treatment or within 2 weeks 
2.  Fills Kaiku follow-up information 6-12 weeks frequency up 
to disease progression or 24 weeks 
3. Fills Survival follow-up information after study closure 
Additionally, in the CRC cohort: 
4. Evaluates patient reported symptoms and laboratory values 
before prescribing new chemotherapy cycle 
5. Fills Kaiku Chemotherapy follow-up information before 
new chemotherapy cycle  
Study end-points  
Overall population: 
1. Number of triggered alerts by Kaiku Cancer medical 
treatment side-effects questionnaire and their correlation 
to treatment side-effects, cancer progression, other medical 
events or survival 
2. QoL of patients using Kaiku QLQ-C30 questionnaire and its 
correlation to treatment side-effects, cancer progression, 
other medical events or survival  
3. Patient compliance using KaikuHealth e-questionnaire and 
response rates to symptom and QLQ-C30 questionnaires  
 
Additionally, in the CRC cohort: 
4. Number of phone calls related to prescribing a new 
chemotherapy cycle per patient or treatment cycle 
5. Unscheduled doctor appointments in oncology unit per 
patient or treatment cycle 
6. ER visits per patient or treatment cycle  
7. Days in hospitalization per patient or treatment cycle 
8. Unscheduled medical investigations per patient or treatment 
cycle 
9. Development of Grade 1 peripheral neurotoxicity per patients 

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or treatment cycle and date  
10. Development of peripheral neurotoxicity due to oxalplatin 
verus other chemotherapies  
11. The number of chemotherapy dose reductions per patient or 
treatment cycle and date 
12. The number of chemotherapy cycle delays per patient and 
date 
Study course 
After signing of the informed consent, patient is trained on use of 
Kaiku software. Patient answers questionnaires with 1-4 weeks 
frequency up to 24 weeks. Patients survival is followed after 24 
weeks period. 
 
Study doctor/Nurse fills baseline information and thereafter follow-
up information with 6-12 weeks frequency up to 24weeks, and 
Chemotherapy follow-up information at every new chemotherapy 
cycle up to 24 weeks and Survival follow-up information after 
study closure. 
Study duration 
1.12.2018 – 30.6.2021 
 
 
 

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AMENDMENTS 
 
 
Amendment 
number 
Amendment 
Date 
Protocol 
version 
number 
Amendment type 
Amendment nature/purpose 
1. 
28.2.2019 
1.1 
Protocol change 
 
Establishment of colorectal 
cancer cohort 
 
Adding new study end-points 
to CRC cohort 
 
Integration of laboratory 
values to patient reported 
symptoms in CRC cohort 
 
Update of statistical plan 
 
Update of study duration and 
follow-up time 
 
 
 
 
 

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Table 1.  Study procedures in overall population excluding CRC cohort 
  
 
Baseline 
Cancer medical treatment 
duration or up to 24 weeks 
Follow-up 
Procedure 
within -2vko - +2wks 
from cancer 
treatment initiation 
1wks  
4wks   
6-12wks  
 
 
Written informed 
consent 
X 
 
Kaiku Cancer 
medical treatment 
side-effects 
questionnaire1,3 
X 
X 
Kaiku QLQ-C30 QoL 
questionnaire1,3 
X  
 
X 
 
 
Kaiku Patient 
experience survey1,3 
 
 
X 
Kaiku Patient 
baseline information2 
X 
 
Kaiku follow-up 
information2,3 
 
 
 
X 
 
Kaiku survival 
follow-up 
information4 
 
 
 
 
X 
 
(1) Patients fills 
(2) Doctor/Nurse fills 
(3) up to 24 weeks 
(4) from electronic records at study closure 
 
 
 

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Table 2.  Study procedures in CRC cohort 
  
 
Baseline 
Chemotherapy duration or up to 24 wks 
Follow-
up 
Procedure 
within -2vko - 
+2wks from 
chemotherapy 
initiation 
1wks  
2-3wks 
4wks 
6-12wks  
 
 
Written informed 
consent 
X 
 
 
Kaiku Cancer 
medical treatment 
side-effect 
questionnaire1,3 
X 
X 
 
Kaiku QLQ-C30 QoL 
questionnaire1,3 
X  
 
 
X 
 
 
Kaiku Patient 
experience survey1,3 
 
 
X 
Kaiku Patient 
baseline information2 
X 
 
 
Kaiku 
Chemotherapy 
follow-up 
information2,3,4 
 
 
X 
 
 
 
Kaiku follow-up 
information2,3 
 
 
 
 
X 
 
Kaiku survival 
follow-up 
information5 
 
 
 
 
 
X 
Health care user 
experience survey2 
 
 
 
X 
 
 
 
(1) Patient fills 
(2) Doctor/Nurse fills 
(3) up to 24 weeks 
(4) at every new chemotherapy cycle 
(5) from electoronic records after study closure 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
PAGE 
1. 
BACKGROUND 
9 
1.1. 
CHEMOTHERAPY AND TARGETED THERAPIES IN CANCER TREATMENT 
9 
1.2. 
STUDY RATIONALE 
9 
2. 
STUDY OBJECTIVES 
10 
3. 
STUDY DURATION 
10 
4. 
PATIENT SELECTION 
11 
4.1. 
PATIENT POPULATION 
11 
4.2. 
INCLUSION CRITERIA 
11 
4.3. 
EXCLUSION CRITERIA 
11 
5. 
STUDY NATURE 
11 
5.1. 
STUDY DESIGN 
11 
5.2. 
STUDY PROCEDURES 
11 
5.2.1. 
Baseline 
11 
5.2.2. 
Treatment period 
12 
5.2.3. 
Follow-up period 
13 
6. 
STUDY INSTRUMENTS 
13 
6.1 KaikuHealth questionnaires 
13 
7. 
MONITORING 
14 
8. 
STATISTICAL PLAN 
14 
8.1. 
STUDY END-POINT ANALYSIS 
14 
8.2. 
MISSING DATA 
16 
9. 
SIGNATURE 
16 
10. 
REFERENCES 
17 

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1.BACKGROUND 
1.1. Chemotherapy and targeted therapies in cancer treatment 
Cancer medical treatments aim to destroy mutated, malignant cells of the body. Even 
targeted cancer therapies have harmful effects on normal cells of the body. Selectivity of 
a drug is of importance from the point of side-effects. Unselectivity and wide side-effect 
spectrum are typical to traditional chemotherapies. 
 
Traditional chemotherapy agents have narrow therapeutic levels. Therefore, grave side-
effects are present even at therapeutic levels, typically. Most chemotherapy agents 
target rapidly dividing cells, and normal tissues like bone marrow and mucosa, in which 
cells proliferation is fast, are affected causing treatment related adverse events. Many 
traditional chemotherapy agents have multiple targets that widens the spectrum of side-
effects.  Typical side-effects of chemotherapy include neutropenia, oral cavity mucosal 
lesions, diarrhea and hair loss. 
 
Targeted therapies are drugs designed to interfere with specific molecules necessary for 
tumor growth and progression, such as tyrosine-kinase inhibitors or monoclonal 
antibodies. Because of the more specific way of action, targeted therapies have less side-
effects compared to chemotherapies. The more cancer specific mutation drug targets, 
the less adverse events exist.  The selectivity of targeted therapies varies, and some of 
the adverse events are class specific. Typical side-effects include among others blood 
pressure rise and skin rash.  
 
 
1.2. Study rationale 
Patient reported outcomes (PROs) consist of health-related questionnaires filled by the 
patients themselves which can capture symptoms and signs and their severity. PROs can 
be captures by traditional paper questionnaires or by Web-based approaches. Web-
based reporting of PROs has many advantages compared to paper questionnaires such 
as reducing timely and locational limitations. These advantages make web-based PRO 
capturing more likely to allow changes in symptoms or quality of life (QoL). 
Furthermore, web-based PROs can be coupled to urgency algorithm which sends an 
alert to the care unit on severe or altering symptoms of a patient. This enables rapid 
reaction and treatment of important medical events.  
 
ePROs have been studied in oncological care. An American randomized study has 
investigated use of ePROs coupled with urgency algorithm in the follow-up of patients 
receiving chemotherapy as palliative treatment of multiple tumor types. Use of ePROs 
resulted in improvement of QoL, decreased ER visits, and improvement of overall 
survival. Another French study has investigated use of urgency algorithm coupled ePROs 
in follow-up of lung cancer patients compared to traditional follow-up with more 
frequent assessments using physician visits and scans. ePRO follow-up resulted in better 
QoL, improved ECOG status and more active cancer treatments at disease relapse, and 
improved survival 
 (1-7). 
  

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Before prescribing a new chemotherapy cycle peripheral blood samples are taken to 
evaluate e.g. total blood cell count which need to be in pre-defined limits. Furthermore, 
patient´s clinical status is evaluated by nurse based on phone calls. The manual 
evaluation of laboratory values is prone to human mistakes. In addition, symptom 
evaluation is seldom systematic and often timely limited to present situation. Computer 
assisted laboratory test evaluation, and structured and timely consistent symptom 
follow-up could improve safety of chemotherapy treatments, QoL of patients and health 
care resource allocation. 
 
2. STUDY OBJECTIVES 
Objectives: 
 
1. The number of alerts triggered by Kaiku Cancer medical treatment side-
effects questionnaire and their correlation to treatment side-effects, other 
relevant medical events, tumor progression, and survival.  
2. Changes in Kaiku QLQ-C30 QoL questionnaire and their correlation to cancer 
treatment response, side-effects, other relevant medical event or survival 
3. Patient compliance to Kaiku ePRO surveillance during treatment period 
according to response rates of Patient experience survey, Kaiku Cancer 
medical treatment side-effects questionnaire and Kaiku QLQ-C30 QoL 
questionnaire  
In addition, in CRC cohort: 
 
1. Integration of laboratory values to patient reported symptoms when 
prescribing a new chemotherapy cycle  
2. Number of phone calls related to prescribing a new chemotherapy cycle  
3. Unscheduled doctor appointments in oncology unit 
4. ER visits 
5. Days in hospitalization 
6. Unscheduled investigations in health care  
7. Development of peripheral neurotoxicity 
8. The number of chemotherapy dose reductions 
9. The number of chemotherapy delays 
10. Health care user experience survey  
 
 
 
3.STUDY DURATION 
Patient recruiting started 1.12.2018 and is estimated last up to 30 months. The last visit 
of the last patient is estimated to happen 30.6.2021. The enrolment period is estimated 
to be 24 months. Survival data will also be collected at the study closure, and the 
collection of the survival data of a patient is limited to 12 months from the study entry. 
  

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4.PATIENT SELECTION 
4.1. Patient population 
Sample size of the study is 100 of which 60 are CRC patients,  and study patients are 
expected to be recruited within 24 months. 
    
4.2. Inclusion criteria 
1. Written informed consent prior to any study procedure 
2. Advanced breast, lung, colorectal, or pancreatiac cancer 
3. New cancer medical treatment, chemotherapy or targeted therapy initiated 
within -/+ 2 weeks from signed consent 
4. Age ≥18y 
5. ECOG 0-2 
6. CRC cohort: Patients with adjuvant treatment, or first or second line of 
treatment for metastatic disease 
7. Patient compliant with study procedures 
4.3. Exclusion criteria 
1. Initiation of new cancer medical treatment > 2 wks from signed consent 
2. Any medical condition that the Investigator considers significant to 
compromise the safety of the patient or that impairs the interpretation of 
study assessments 
3.  No internet access/email 
 
5.STUDY NATURE 
5.1. Study design 
A prospective one arm multicenter observational trial. 
5.2. Study procedures 
See Tables 1 and 2 from pages six and seven. 
5.2.1. Baseline 
A signed informed consent from every patient must be present before any study 
procedures. 
The parameters listed below are collected at baseline: 
- 
Demographics (age, gender, weight, height) 
- 
ECOG performance status 
- 
Cancer medical treatment (drug, indication, day of the first infusion) 
- 
Blood sampling to measure the following (blood cell counts: leucocytes, 
neutrophils, lymphocytes, thrombocytes; B-haemoglobin, P-creatinine, ALT, 
ALP, AST, bilirubin) 
- 
Possible prior cancer medical treatment lines 

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- 
Kaiku Cancer medical treatment side-effects questionnaire and Kaiku QLQ-
C30 QoL questionnaire filled ≤ 2weeks from 1st infusion or peroral drug dose 
 
5.2.2. Treatment period 
Study treatment period lasts the treatment phase of cancer medical treatment or up to 
24 weeks.  
The parameters listed below are collected during the treatment phase: 
- 
16 question Kaiku Cancer medical treatment side-effects questionnaire ≤2 
weeks from the 1st infusion and weekly after that 
- 
Kaiku QLQ-C30 QoL questionnaire ≤ 2weeks from the 1st infusion/per oral 
drug dose and every four weeks after that 
- 
Kaiku Patient experience survey  
- 
Kaiku follow-up information in 6-12 weeks cycle 
o Urgency algorithm alerts (grade, date, cause of the alert) 
o AE (type, date, related urgency alert if present) 
o Treatment of AE (type, date, treatment discontinuation) 
o Unscheduled appointments (ER, onkology unit, phone calls, type, date) 
o Treatment response (CR, PR, SD, PD, NE, date) 
o Treatment discontinuation (date, next treatment line) 
o Date of death 
In addition, in CRC cohort: 
- 
Kaiku Chemotherapy follow-up information at every new chemotherapy cycle 
o Phone calls to patient before new chemotherapy cycle (no/yes) 
o Unscheduled doctors’ appointments in oncology unit (no/yes, amount) 
o Unscheduled health care investigations after during the last given 
chemotherapy cycle (no/yes, laboratory tests/radiological 
investigations/other) 
o Days in hospitalization during last given chemotherapy cycle (no/yes, 
in-ward treatment duration in days) 
o Has there been > 10% dose reduction in the next chemotherapy cycle 
compared to previous cycle, or has the treatment been de-intensified 
(no/yes)  
o Has the next chemotherapy cycle been delayed due to patients’ 
laboratory values or symptoms (no/yes, duration in days) 
o Kaiku Follow-up information in 6-12wks cycle 
o ECOG (0-4) 
o Treatment related adverse events (no/yes, type, grade, date) 
o Treatment response (CR/PR/SD/PD/NE, date) 
o Possible discontinuation of treatment (no, yes, date, reason (cancer 
progression, side-effect, planned treatment duration, other), next 
treatment (cancer medical treatment, radiotherapy, other, no 
treatment), ECOG at the beginning of next treatment) 
 
 

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5.2.3. Follow-up period 
Patient survival will be collected in the end of the follow-up period at study closure.  
 
6. STUDY INSTRUMENTS 
6.1 KaikuHealth questionnaires 
Study patients will receive a short (5-15min) training on how to use Kaiku software by 
study physician or nurse. The training will include how the sign in to the system, login, 
navigation in Kaiku software, filling of ePRO questionnaires, function of urgency 
algorithms, messaging, and access email-address for technical assistance. Care unit will 
do the initial registration of the patient. KaikuHealth-service will send email reminders 
to fill in KaikuHealth questionnaires in prescheduled time line. First notification will be 
sent immediately when patient is registered to the study and weekly thereafter. If a 
patient doesn’t fill an ePRO questionnaire promptly, an email remainder is sent three 
days later. If patient doesn’t fill PRO questionnaire within six days, weekly PRO 
assessment will be missed, and notification of new PRO assessment period will be 
initiated with a new email notification seven days after previous. Patient data will stored 
on a server located in Finland. Anonymization will take place when data is analyzed. 
 
KaikuHealth ePRO follow-up module consists of 16 symptom questionnaire which will 
assess both presence and severity of the symptom. The symptoms selected for the Kaiku 
Health symptom tracking tool for cancer medical treatment include typical side-effects 
of chemotherapy and targeted therapies. The questions for each symptom in the 
instrument were developed based on NCI-CTCAE v.4.03 register by converting the 
description of gradings into a patient-friendly language. 
 
If algorithm analysis suggests a presence of grade 3 or higher symptom, alert will be 
sent to the care unit after which care unit contacts the patients and if necessary, further 
investigation and/or assessments will be ordered. It is recommended that care unit 
reacts to alerts promptly but no later than three days after an alert. Contact to the 
patient can be made by messaging properties of Kaiku software or phone call.  
Furthermore, patients are informed that Kaiku ePRO follow-up is intended for non-
urgent manners.   
 
 
 

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7. MONITORING 
Written informed consents are monitored by an independent single monitor in 12 
months cycles. 
. 
 
8.STATISTICAL PLAN 
Due to the study nature (one-arm study) statistical plans are not calculated. Data 
analysis will be carried out when the length of follow-up time of the last recruited 
patient is at least six months. For the final analysis statistical methods will be redefined 
based on actual distributions. The data of CRC cohort will be analyzed separately from 
other cancer types of the overall population.  
 
8.1. Study end-point analysis    
The number of alerts generated by Kaiku Cancer medical treatment side-effect 
questionnaire will analyzed per patient or per treatment cycle in percentages in the 
overall population or based on stratification by indication (advanced disease or adjuvant 
treatment), cancer medical treatment (chemotherapy, other) or cancer type depending 
on final patient population.  
 
The correlation of alerts triggered by Cancer medical treatment side-effect 
questionnaire to treatment side-effect, cancer progression, cancer relapse, other medical 
condition or survival will be analyzed with heat-map analysis or other valid statistical 
method. 
 
The changes in QLQ-C30 QoL questionnaire will be analyzed at 3 and 6 months 
timepoints compared to baseline in the overall population or based on stratification by 
indication (advanced disease or adjuvant treatment), cancer medical treatment 
(chemotherapy, other) or cancer type depending on final patient population.  
 
Patient compliance will be analyzed based on percentages of answers to Patient 
compliance survey in the overall population and/or in different timepoints. In addition, 
patient compliance will be analyzed based on answering rates to symptom and QoL 
questionnaires within 3 days from email reminder in percentages in the overall 
population and/or in different timepoints. Analysis can be made in the overall 
population or based on stratification by indication (advanced disease or adjuvant 
treatment), cancer medical treatment (chemotherapy, other) or cancer type depending 
on final patient population.  
 
Health care personnel user experience will be analyzed based on answers to user 
experience survey in percentages in the overall population and/or in different 
timepoints. 
 
Integration of laboratory values and symptom questionnaires will be analyzed as 
percentages of treatment cycles in three class: new chemotherapy cycle can be 
prescribed directly (≤grade 1 symptom and laboratory values within in limits), cycle 
prescribed after assessment of symptoms by study personnel (≥grade 2 symptoms and 
laboratory values within limits) and cycle delayed due to laboratory values outside 

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limits. Analysis can be made in the overall population or based on stratification by 
indication (advanced disease or adjuvant treatment), cancer medical treatment 
(chemotherapy, other) or cancer type depending on final patient population.  
In addition, feasibility of integration of laboratory values and symptom questionnaires 
will be analyzed based on answering rates in percentages to health care personnel user 
experience survey.  
 
The number of phone calls to patients are analyzed in percentages per patient or 
treatment cycle. Also, time to the first phone call to patient can be analyzed by Kaplan-
Meier method. Analysis can be made in the overall population or based on stratification 
by indication (advanced disease or adjuvant treatment), cancer medical treatment 
(chemotherapy, other) or cancer type depending on final patient population.  
 
The amount of unscheduled doctors’ appointments in oncology unit will be analyzed in 
percentages per patient or treatment cycle. Also, time to the first unscheduled doctors’ 
appointment can be analyzed by Kaplan-Meier method. Analysis can be made in the 
overall population or based on stratification by indication (advanced disease or adjuvant 
treatment), cancer medical treatment (chemotherapy, other) or cancer type depending 
on final patient population.  
  
The amount of unscheduled ER visits will be analyzed in percentages per patient or 
treatment cycle. Also, time to the first unscheduled ER visit can be analyzed by Kaplan-
Meier method. Analysis can be made in the overall population or based on stratification 
by indication (advanced disease or adjuvant treatment), cancer medical treatment 
(chemotherapy, other) or cancer type depending on final patient population.  
  
Days in hospitalization will be analyzed in percentages per patient or treatment cycle. 
Also, time to the first in-ward phase can be analyzed by Kaplan-Meier method. Analysis 
can be made in the overall population or based on stratification by indication (advanced 
disease or adjuvant treatment), cancer medical treatment (chemotherapy, other) or 
cancer type depending on final patient population.  
 
The amount of unscheduled medical interventions and investigation types will be 
analyzed in percentages and/or by type per patient or treatment cycle. Also, time to the 
first unscheduled medical intervention can be analyzed by Kaplan-Meier method. 
Analysis can be made in the overall population or based on stratification by indication 
(advanced disease or adjuvant treatment), cancer medical treatment (chemotherapy, 
other) or cancer type depending on final patient population.  
 
Development of peripheral neurotoxicity is evaluated based on Kaiku Cancer medical 
treatment side-effect question of distinct symptom and its’ severity in the latest 
symptom questionnaire filled before new treatment cycle and during the treatment 
period. Also, time to the development of neurotoxicity based on symptom 
questionnaires before new treatment cycle and its severity can be analyzed by Kaplan-
Meier method. Analysis can be made in the overall population or based on stratification 
by indication (advanced disease or adjuvant treatment), cancer medical treatment 
(chemotherapy, other) or cancer type depending on final patient population.  
 

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The number of chemotherapy dose reductions (>10%) will be analyzed in percentages 
per patient of treatment cycle. Also, time to the first chemotherapy dose reduction 
(>10%) can be analyzed by Kaplan-Meier method. Analysis can be made in the overall 
population or based on stratification by indication (advanced disease or adjuvant 
treatment), cancer medical treatment (chemotherapy, other) or cancer type depending 
on final patient population.  
 
The amount of chemotherapy cycle delays (> 2days) will be analyzed per patient or 
treatment cycle. Also, time to the first chemotherapy cycle delay (>2days) can be 
analyzed by Kaplan-Meier method. Analysis can be made in the overall population or 
based on stratification by indication (advanced disease or adjuvant treatment), cancer 
medical treatment (chemotherapy, other) or cancer type depending on final patient 
population.  
 
8.2. Missing data 
Patients who have filled at least to Kaiku Cancer medical treatment side-effects 
questionnaire will be included in the final analysis. 
 
9.SIGNATURE 
I promise to carry out investigation according to study protocol, good clinical practice 
and appropriate legislation.  
 
 
Principal investigator and sponsor: 
 
Place, date 
SIGNATURE 
Oulu, 13.5.2019 
___________________ 
__________________________________ 
Jussi Koivunen, adjuvant professor, medical oncologist 
Dept of Oncology and Radiation therapy 
Oulu University Hospital 
 
 
 
 
 
 
 

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10.REFERENCES 
 
1. CM Reilly, DW Brunner, SA Mitchell et al: A literature synthesis of symptom 
prevalence and severity in persons receiving active cancer treatment, Support Care 
Cancer 21:1525-1550, 2013 
 
2. Basch E, Jia X, Heller G, Bartz A, Sit L, Fruscione M et al. Adverse symptom reporting by 
patients vs clinicians. Relationships with clinical outcomes. J Natl Cancer Inst. 
2009;101(23):1624-32 
 
3. Velikova G, Booth L, Smith AB et al. Measuring quality of life in routine oncology 
practice improves communication and patient well-being: A randomized controlled trial. 
J Clin Oncology 2004;22:714-724 
 
4. Basch E, Allison MD, Mark GK, Howard IS, Clifford AH, Paul S: Symptom Monitoring 
With Patient-Reported Outcomes During Routine Cancer Treatment: A randomized 
Controlled Trial, J Clin Oncol 2016;34(6):557-565 
 
5. Denis F, Lethrosne C, Pourel N, Molinier O, Pointreau Y, Domont J, et al. Randomized 
Trial Comparing a Web-Mediated Follow-up With Routine Surveillance in Lung Cancer 
Patients. J Natl Cancer Inst 2017 Sep 1;109(9):10.1093/jnci/djx029. 
6. Basch E, Deal AM, Dueck AC, Scher HI, Kris MG, Hudis C, et al. Overall Survival Results 
of a Trial Assessing Patient-Reported Outcomes for Symptom Monitoring During 
Routine Cancer Treatment. JAMA 2017 Jul 11;318(2):197-198. 
7. Denis F, Yossi S, Septans AL, Charron A, Voog E, Dupuis O, et al. Improving Survival in 
Patients Treated for a Lung Cancer Using Self-Evaluated Symptoms Reported Through a 
Web Application. Am J Clin Oncol 2017 Oct;40(5):464-469.