Research Study: Tattooing of Skin Landmarks in Radiotherapy: Comparison Between the System Traditional and Comfort Marker 2.0® (COMFORTATTOO)
Phase: NA
Conditions: Radiotherapy, Tattooing
Sponsor: Instituto Portugues de Oncologia, Francisco Gentil, Porto

 
 
 
 
 
Study protocol 
 
 
 
 
Research study: Tattooing of skin set-up markings in 
Radiotherapy: comparison between the traditional system 
and the Comfort Marker 2.0® 
 
 
 
Abbreviated Study Title: COMFORTATTOO 
Version 3.0 of 10/4/2021 
 
 
The COMFORTATTOO trial has been approved by the IPO-Porto ethics committee. 
This protocol is a controlled document and should not be copied, distributed, or reproduced without 
the written permission of the ICR-CTSU. 
 
Primary Investigator: André Luis Miranda Pires, MD 
Portuguese Institute of Oncology of Porto FG, R. Dr. António Bernardino de Almeida 865, 4200-072 
Porto 
e-mail: i2489@ipoporto.min-saude.pt 
 
Co-Investigator: Ana Filipa Barros, RTT 
Portuguese Institute of Oncology of Porto FG, R. Dr. António Bernardino de Almeida 865, 4200-072 
Porto 
e-mail: i11271@ipoporto.min-saude.pt  
 
 
 

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Background 
 
Most radiotherapy (RT) treatments performed nowadays rely on conformational techniques that 
encompass the use of a computed tomography (CT) as part of the planning workflow. In this process, 
a three-dimensional image, generally known as CT simulation, is obtained in the planning position, 
using positioning supports and immobilization systems. In selected cases, one of the steps after 
acquiring the CT simulation is the realization of reference markings on the skin of the patient, that are 
tattooed at defined points, using a laser system. These markings must remain on the patient's skin in 
a visible, clear, and unambiguous way, to guarantee a reproducible positioning in the linear 
accelerator in all fractions of the treatment. The location of the set-up markings is variable, depending 
on the anatomical area to be treated, and is defined in service protocols. 
Currently, at the External Radiotherapy service of the IPO in Porto, set-up marking is performed 
using disposable lancets (produced primarily for capillary blood sample collection) and India ink. Since 
it is not possible to regulate the depth of pigment application according to the thickness of the skin of 
each patient, it is a process that is typically accompanied by discomfort or transient pain for the 
patient, in addition to which the markings remain visible on the skin for several years old. 
To circumvent these limitations, the Comfort Marker 2.0® emerged, developed by CIVCO® 
Medical Precision. The device was designed to tattoo set-up markings with controlled and adjustable 
depth applications. As potential benefits, this feature may translate into less pain for the patient 
compared to the traditional system, with the benefit of potentiating earlier fading of the ink, with 
cosmetic advantages. 
The present study aims to compare the two systems of cutaneous reference point tattooing: the 
lancet-based system (hereinafter referred to as the traditional system) and the Comfort Marker 2.0® 
system. 
 
 

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Identification of the research study 
 
Full title: Tattooing of skin set-up markings in Radiotherapy: comparison between the traditional 
system and the Comfort Marker 2.0® 
 
Short Title: comfoRTattoo 
 
 
Primary Investigator: André Luis Miranda Pires, MD 
Portuguese Institute of Oncology of Porto FG, R. Dr. António Bernardino de Almeida 865, 4200-072 
Porto 
e-mail: i2489@ipoporto.min-saude.pt 
 
Co-Investigator: Tech. Ana Filipa Barros 
Portuguese Institute of Oncology of Porto FG, R. Dr. António Bernardino de Almeida 865, 4200-072 
Porto 
e-mail: i11271@ipoporto.min-saude.pt  
 
 
 
Number of investigation sites: One 
 
 
Number of participants included planned: 100 
 
 
 

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General information of the research study 
 
Study design: single-center, experimental, prospective, longitudinal, parallel with 2 groups (1:1), 
randomized, double-blinded 
 
 
Statistical considerations: Eligible patients will be randomized via computer-generated random 
permuted blocks (block sizes of 10), stratified by the number of set-up markings (≤ 4 vs. >4), to one of 
two possible groups. To guarantee the concealment of the attribution, a computer-generated list will 
be prepared by a person external to the study, which will serve for the preparation of closed white 
envelopes, of the same size, sequentially numbered, opaque and sealed, which will be distributed by 
the principal investigator to the TC simulation technicians. 
 
 
Objectives: To compare two set-up tattooing systems: lancet-based vs. Comfort Marker 2.0® system. 
 
 
Inclusion criteria: 
1. Patients referred to the External Radiotherapy Service for external beam RT; 
2. Patients in need of set-up markings as an inherent part of the Radiotherapy process; 
3. Age ≥18 years at the date of the first radiation oncology consultation; 
4. Good performance status (ECOG PS 0-1) 
5. RT treatments with an estimated fractionating schedule of ≥13 once-daily fractions; 
6. The signing of informed consent. 
 
 
Exclusion criteria: 
1. Patients requiring either immobilization thermoplastic masks (for head or head and shoulders) 
or vacuum cushion 
2. Patients referred to the external radiotherapy service under an inter-hospital protocol. 
 
 
 
 

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Criteria to be evaluated : 
1. 
Patients’ comfort (Pain inherent to the tattoo procedure); 
2. 
Radiation therapists’ satisfaction (Evaluation of the ease of application of the markings); 
3. 
Effectiveness (set-up markings visibility across RT fractions); 
4. 
Fading across RT fractions; 
5. 
Fading at 6 months after tattoo application; 
6. 
inadvertent sharps injuries. 
 
 
Considerations for Comfort Marker 2.0 ® 
The Comfort Marker 2.0® device consists of a Control Unit and a Pen Module, the latter being 
responsible for activating the marking needle. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
For the present study, the Comfort Marker 2.0 ® system will be transferred to the Portuguese Institute 
of Oncology in Porto, free of charge, without any charges. This will consist of 1 Medical Precision 
Comfort Marker 2.0 (consisting of the control unit and its Pen) and 1 Medical Precision Patient Marking 
Set (which includes: 50 needles, 50 pigments, and 50 pigment containers). 
 
 

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Study planning: 
 
 
 
 
Recruitment 
Eligible population 
Recruitment appointment: 
- Informed consent (Annex 1) 
- Information to the participant 
Randomization 1:1 
Set-up marking with  
Lancets (n=50) 
Set-up marking with 
Comfort Marker 2.0® (n=50) 
Completion of Questionnaire 1 
1st Photography assessment 
Start of RT 
Weekly assessment 
Final assessment 
2nd Photography assessment * 
Preenchimento do 
questionário 2 
6 months fading evaluation 
3rd photography assessment 
* photography assessment is allowed up 
to 2 days before the last RT fraction 

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Attachments 
 
 
Annex 1: Informed Consent 
Informed consent for the investigation 
Considering the “Declaration of Helsinki” of the World Medical Association (Helsinki 1964; Tokyo 1975; Venice 1983; Hong Kong 1989; 
Somerset West 1996; Edinburgh 2000; Washington 2002, Tokyo 2004 and Seoul, 2008) 
 
 
Research study: Tattooing of skin set-up markings in Radiotherapy: comparison between 
the traditional system and the Comfort Marker 2.0® 
 
I, the undersigned (full name of adult person or volunteer) __________________________ 
___________________________________________________________________________ 
have received the Participant Information text regarding the procedure I agreed to perform. 
I understood the explanation given to me by the researcher signing this document. I was also 
given an opportunity to ask such questions as I thought necessary, and to all of them I received 
a satisfactory answer. 
I have learned that, per the recommendations of the Declaration of Helsinki, the information 
or explanation provided to me covered the objectives, methods, expected benefits, potential 
risks, and possible discomfort. Furthermore, I was told that I have the right to cancel my 
participation in the study at any time, without this having the effect of having any effect on 
the assistance provided to me. 
Therefore, I consent to the method, treatment, or survey proposed by the researcher being 
applied to me. 
 
Signature of the person or volunteer:____________________________Date:___/___/202_ 
 
 
I confirm that I have explained to the person indicated above, in an adequate and intelligible 
manner, the procedures necessary for the activities referred to in this document. I answered 
all the questions that were put to me and made sure that there was a sufficient period of 
reflection to make the decision. I also guaranteed that, in case of refusal, the best possible 
care will be ensured in that context, with respect for their rights. 
Legible name of the Investigator in charge: _______________________________________ 
Signature of the Investigator in charge:___________________________Date:___/___/202_ 
 
 
Annulment of Informed Consent 
I declare that I have received the Information to the Participant regarding the study/research 
project in question, which was proposed to me by the researcher who signs this document 
and I intend to withdraw the consent given on the date ____/____/202___. 
Signature of the person or volunteer are: ________________________ Date:___/___/202_ 
Signature of the Responsible Investigator: _______________________ Date:___/___/202_ 
 
 
Note: This document is made in two copies - mandatory supply of a copy to the participant 
 
Ethics Committee for Health of the Portuguese Institute of Oncology of Porto Francisco Gentil, E.P.E. (Doc. CES-IPOP 04)_2017 

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Annex 2: Information to the participant 
INFORMATION TO PARTICIPANT 
Dear Sir/Madam, 
I would like to invite you to participate in the study “Tattooing of skin set-up markings in 
Radiotherapy: comparison between the traditional system and the Comfort Marker 2.0®”, to be carried 
out at the External Radiotherapy Department of IPO-Porto by Dr. André Luís Miranda Pires, resident 
in Radiation Oncology. 
The aim of the study is to compare two set-up marking systems, namely the traditional system 
(which uses lancets and India-ink) and the Comfort Marker 2.0® system (which uses an electrical 
device with an adjustable tattoo pen), to assess differences in terms of effectiveness, pain, fading and 
safety for the technical team. Your participation is very important and consists of: 1) tattooing the 
reference points (necessary to carry out the radiotherapy treatments) when performing the simulation 
computed tomography by one of the two methods previously presented; 2) filling in a questionnaire to 
assess pain/discomfort; 3) assessing the fading of the benchmarks after 6 months; 4) and making a 
photograph registry of the tattoos. If you choose to participate, you will be randomly selected by a 
computer to receive one of the tattoo methods. We do not anticipate risks from your participation in 
this study, nor will it translate into an increase in terms of exams or visits to the institution where it 
takes place. 
We clarify that participation in the study is completely voluntary, and you can ponder on the 
decision to participate, including consulting family members if deemed necessary. At any time, you 
can withdraw, without having to justify and without prejudice to the relationship with the doctor and 
other health professionals. The information will only be used for the purposes of this research and for 
the publication of scientific articles, being treated with the utmost secrecy and confidentiality, to 
preserve personal data, in accordance with the legislation in force. The participants in the study declare 
that there are no conflicts of interest. We also clarify that there is no economic value to be received or 
paid for your participation. This study was approved by the Ethics Committee and the Data Protection 
Officer of the IPO-Porto. 
Any questions or if you need further clarification, you can contact the responsible researcher, Dr. 
André Miranda Pires (email: i2489@ipoporto.min-saude.pt) or the Data Protection Officer of the 
Portuguese Institute of Oncology of Porto Francisco Gentil, who was aware of the approval of the study 
(email: epd@ipoporto.min-saude .pt). For more information about your privacy rights, you can contact 
the National Data Protection Commission, via email geral@cnpd.pt, by phone +351 213928400 or by 
writing to the following address: Av. D. Carlos I, 134 - 1.º, 1200-651 Lisbon. 
Ethics Committee for Health of the Portuguese Institute of Oncology of Porto Francisco Gentil, E.P.E. (Doc. CES-
IPOP 02) 

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Annex 3: Questionnaire 1 
 
Questionnaire 1 
 
Research study: Tattooing of skin set-up markings in Radiotherapy: comparison between 
the traditional system and the Comfort Marker 2.0® 
 
 
 
 
 
 
 
 
 
 
1. Randomization Arm:       ⃞ Lancets   
    ⃞ Comfort Marker 2.0 
 
2. Set-up Markings: 
2.1. Number of markings tattooed:  
2.2. Localization (identify in the figure with sequential numbering): 
 
3. Inadvertent sharps injuries.:      ⃞ Yes  
 
    ⃞ No 
 
 
 
 
4. Assessment of the ease of tattooing:      ⃞ Easy         ⃞ Medium 
    ⃞ Hard 
 
 
5. Patient-reported pain assessment: 
0 – none   
10 - worst imaginable pain 
If more than one reference mark is made, assign an overall score. 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
Date: ___/____/________ 
 
Signature:_______________    Mec. number:________ 
Nr 
Depth (mm) 
Nr 
Depth (mm) 
1 
 
9 
 
2 
 
10 
 
3 
 
11 
 
4 
 
12 
 
5 
 
13 
 
6 
 
14 
 
7 
 
15 
 
8 
 
16 
 
 
 
Patient ID 
If yes, explain the event. 

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Annex 4: Questionnaire 2 (in Portuguese) 
Questionnaire 2 
 
Research study: Tattooing of skin set-up markings in Radiotherapy: comparison between 
the traditional system and the Comfort Marker 2.0® 
 
 
 
 
 
 
 
 
 
 
1. Quality assessment of the patient set-up markings: 
Note: Perform the assessment for EACH set-up marking.  
Nr of 
tattoo 
Data 
Quality 
Evaluator 
(Mec. nr) 
Bad 
Reasonable 
Good 
Very Good 
1 
 
 
 
 
 
 
2 
 
 
 
 
 
 
3 
 
 
 
 
 
 
4 
 
 
 
 
 
 
5 
 
 
 
 
 
 
6 
 
 
 
 
 
 
7 
 
 
 
 
 
 
8 
 
 
 
 
 
 
 
Patient ID