Feasibility of Semi-Permanent Tattoo for Treatment Alignment in Radiation Therapy

• ClinicalTrials.gov Identifier: NCT05248009
• Recruitment Status: Active, not recruiting
• First Posted: February 21, 2022
• Last Update Posted: June 22, 2023
• Sponsor: Henry Ford Health System
• Collaborator: Ephemeral Solutions Inc.
• Information provided by (Responsible Party): Farzan Siddiqui, Henry Ford Health System

Tracking Information

• First Submitted Date: September 13, 2021
• First Posted Date: February 21, 2022
• Last Update Posted Date: June 22, 2023
• Actual Study Start Date: June 23, 2022
• Estimated Primary Completion Date: April 7, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 2, 2023)

Skin Adverse Events - During Treatment [ Time Frame: Subjects will be followed weekly during their treatment course ]

Adverse events related to the tattooing process including skin toxicity during the completion of radiation therapy will be assessed using Common Terminology Criteria for Adverse Events (CTCAE v5). The type, incidence, severity, timing, serious, and relatedness of AE and laboratory abnormalities will be reported and tabulated. The CTCAE is assessed according to grades 1-5, where grade 5 constitutes the highest severity and worse outcome.

Original Primary Outcome Measures (submitted: February 9, 2022)

Skin Adverse Events - During Treatment [ Time Frame: Subjects will be followed weekly during their 5-7 week treatment course ]

Adverse events related to the tattooing process including skin toxicity during the completion of radiation therapy will be assessed using Common Terminology Criteria for Adverse Events (CTCAE v5). The type, incidence, severity, timing, serious, and relatedness of AE and laboratory abnormalities will be reported and tabulated. The CTCAE is assessed according to grades 1-5, where grade 5 constitutes the highest severity and worse outcome.

Current Secondary Outcome Measures (submitted: February 9, 2022)

• Mean 3D Vector Shifts [ Time Frame: Subjects will be followed until completion of their 5-7 week treatment course ]
  The primary endpoint is the mean 3D vector shifts as determined by couch shifts from initial setup using tattoo to final treatment position which is verified and shifted based on further imaging including x-ray or cone-beam CT scan. Mean and standard deviation of 3D vector shifts will be summarized, and t-test or Mann-Whitney test will be used to compared with historical data.
• Skin Adverse Events - Post Treatment [ Time Frame: Subjects will be followed every 3 months for 15 months after completion of treatment ]
  Adverse events related to the tattooing process including skin toxicity during the completion of radiation therapy will be assessed using Common Terminology Criteria for Adverse Events (CTCAE v5). The type, incidence, severity, timing, serious, and relatedness of AE and laboratory abnormalities will be reported and tabulated. The CTCAE is assessed according to grades 1-5, where grade 5 constitutes the highest severity and worse outcome.
• Change from Baseline Tattoo Visibility at 15 Months [ Time Frame: Subjects will be followed weekly during their 5-7 week treatment course and every 3 months for 15 months after completion of treatment ]
  The second primary endpoint will be tattoo visibility which will be scored on a 4-point scale and assessed until end of follow up. The scoring ranges from 0-3, with 0 representing not visible and 3 representing easily visible. This will be assessed weekly during treatment by both the treating physician/research team as well as the patient. Tattoo fading will be compared to baseline which is measured during the first week of radiation therapy to give time to heal after tattoo placement at time of simulation. Tattoo visibility score from baseline for each patient will be summarized by spaghetti plot. Time to complete invisible will be summarized by Kaplan-Meier method.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Feasibility of Semi-Permanent Tattoo for Treatment Alignment in Radiation Therapy
• Official Title: Feasibility of Semi-Permanent Tattoo for Treatment Alignment in Radiation Therapy
• Brief Summary: Consenting subjects will receive a semi-permanent tattoo in place of the standard of care permanent tattoo for radiation marking at the time of the radiation planning scan. Subjects will be monitored to ensure alignment is the same with the semi-permanent tattoo as the current standard of care. Subjects will be monitored to ensure there are no skin reactions or other side effects. Subjects will be followed for 15 months and will send pictures to the treatment team to ensure that the tattoo fades away within 12 months as expected.

Detailed Description

Over 3 million patients are treated each year with radiation therapy, with most of these patients receiving permanent tattoos for treatment alignment. The purpose of these tattoos is to ensure accurate initial patient position prior to treatment. In the case where further on-board imaging such as x-ray or cone-beam CT is used, the radiation tattoos help minimize large shifts which increase treatment time and radiation exposure as further imaging may be required. The tattoos are simple and effective, but also permanent. These permanent tattoos serve as a daily reminder of prior radiation therapy in cancer survivors which may have a negative psychological impact on the patients quality of life. Due to this, many patients will seek laser tattoo removal after completing radiation therapy. There have been attempts at non-permanent tattoo options such as henna as well as omitting tattoos altogether using surface imaging. Unfortunately, henna and other temporary tattoos start to fade quickly and do not last the 6-8 weeks required for longer radiation courses. This means that the tattoos must be reapplied over the course of treatment which can introduce inaccuracies as well as prolongs the treatment time.

A novel semi-permanent ink has been developed and recently released which begins to fade after 6 months and disappears after about 1 year. This is the first ink of its kind and is delivered using a needle into the dermis just like a permanent tattoo, however it is able to be resorbed by the body after approximately 1 year. While the original purpose is for cosmetic tattoos it has a possible application in medical tattoos for radiation therapy.

It is the goal of this study to show that the semi-permanent ink is safe, allows for accurate alignment of the patient prior to treatment, lasts long enough for a full treatment course, and fades over time. The goal in subsequent studies is to improve patient quality of life by decreasing the negative psychological impact of having permanent tattoos following radiation therapy.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Single Arm Pilot Trial

Masking: None (Open Label)
Primary Purpose: Supportive Care

Condition

• Tattoo; Pigmentation
• Cancer, Treatment-Related

Intervention

Device: Semi-Permanent Tattoo Ink

Subjects will receive semi-permanent tattoo ink in place of the permanent ink utilized in the standard of care. Subjects will be monitored during their treatment course and for 15 months following treatment completion.

Study Arms

Experimental: Semi-Permanent Tattoo Ink

Semi-Permanent Tattoo Ink

Intervention: Device: Semi-Permanent Tattoo Ink

Publications *

• Bryant AK, Banegas MP, Martinez ME, Mell LK, Murphy JD. Trends in Radiation Therapy among Cancer Survivors in the United States, 2000-2030. Cancer Epidemiol Biomarkers Prev. 2017 Jun;26(6):963-970. doi: 10.1158/1055-9965.EPI-16-1023. Epub 2017 Jan 17.
• Bregnhoj A, Haedersdal M. Q-switched YAG laser vs. punch biopsy excision for iatrogenic radiation tattoo markers--a randomized controlled trial. J Eur Acad Dermatol Venereol. 2010 Oct;24(10):1183-6. doi: 10.1111/j.1468-3083.2010.03617.x.
• Wurstbauer K, Sedlmayer F, Kogelnik HD. Skin markings in external radiotherapy by temporary tattooing with henna: improvement of accuracy and increased patient comfort. Int J Radiat Oncol Biol Phys. 2001 May 1;50(1):179-81. doi: 10.1016/s0360-3016(01)01439-0.
• Jimenez RB, Batin E, Giantsoudi D, Hazeltine W, Bertolino K, Ho AY, MacDonald SM, Taghian AG, Gierga DP. Tattoo free setup for partial breast irradiation: A feasibility study. J Appl Clin Med Phys. 2019 Apr;20(4):45-50. doi: 10.1002/acm2.12557.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 2, 2023): 15
• Original Estimated Enrollment (submitted: February 9, 2022): 20
• Estimated Study Completion Date: July 2024
• Estimated Primary Completion Date: April 7, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients requiring medical tattoo for treatment alignment.
• Patient being treated with some form of image guidance including kV, MV, or cone-beam CT.
• Age ≥ 18.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Patients will engage in the informed consent process and provide study-specific informed consent prior to study entry and must be willing to have photos taken of their tattoos through the treatment and follow-up process and may be required to take pictures of their own tattoo to submit to the research team.
• Patient able to send picture of tattoo via secure messaging.

Exclusion Criteria:

• Known allergies or hypersensitivity to tattoo ink.
• Personal or religious objection to medical tattooing.
• Autoimmune or skin disorders which may be worsened by medical tattooing.
• Inability to complete the required forms; however, verbal completion is adequate if recorded on the consent documents.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05248009
• Other Study ID Numbers: tattoo_schaff2021
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Farzan Siddiqui, Henry Ford Health System
• Original Responsible Party: Same as current
• Current Study Sponsor: Henry Ford Health System
• Original Study Sponsor: Same as current
• Collaborators: Ephemeral Solutions Inc.

Investigators

• Principal Investigator: Farzan Siddiqui, MD PhD; Henry Ford Health System

• PRS Account: Henry Ford Health System
• Verification Date: June 2023