Synopsis. The overall aim of the wider iToBoS projectis to build a new imaging and diagnostic tool for
the early detection of melanoma, incorporating all the available information of the
participant. This holistic assessment tool should incorporate the specific characteristics of
every participant in order to enable a personalised, early detection of melanoma.
The aim of this prospective clinical study is to collect imaging, phenotypic, clinical and
genetic data necessary to develop the iToBoS System as an integrative diagnostic platform for
melanoma detection. This will be completed by recruiting 600 participants across three study
sites (200 each at Barcelona Spain, Trieste Italy, and Brisbane Australia), to be imaged
using the iToBoS system and conventional dermoscopy. The data acquired in this study will be
used to achieve three key objectives;
- - To evaluate the resolution and usability (for diagnosis) of the iToBoS images compared
with traditional dermoscopic images.
(Primary Objective)
- - To collect an image database for training the AI component of the iToBos System.
- - To refine previous melanoma risk assessments to develop a holistic melanoma risk score.
A subsequent clinical study (separate protocol), will be conducted to validate the
developments from this study using a refined iToBoS System and AI Cognitive Assist Tool.
Study design. This is a prospective, multi-site, cohort study, recruiting participants with various medical
and melanoma history. All participants will be followed for a 12-month period, with study
visits scheduled every 6 months (Baseline, months 6 and 12). Participants will be imaged
using the iToBoS full body photography system, and individual lesion images will be taken
using a handheld dermatoscope. Relevant medical, phenotypic and sun behaviour data will be
collected at baseline, and saliva samples collected (optional) for genetic analysis.
Enrolment. People who expressed interest to participate, were referred to participate, or identified
through records (where consent to contact for future research has been granted) as
potentially eligible to participate, will be contacted via telephone. During this contact,
participants will be provided with study information verbally, and sent a copy of the
Participant Information and Consent Form (PICF) by email (or post), and given adequate time
to read, discuss with family members, and ask any questions about the PICF and study
participation. If the participant would like to proceed, the participant will be assessed for
eligibility and their risk for melanoma will be evaluated. Written informed consent will be
obtained at the baseline clinic visit. Both the participant and the investigator will sign
and date the PICF. All participants who have singed the PICF will be listed on the
Participant Screening and Enrolment Log and the Participant Identification Log (or similar).
Study Procedures. Baseline Clinic Visit (Visit 1, Day 0)
At the baseline clinic visit, participants will be provided with detailed information about
the study and what will be involved, including any foreseen risks or benefits (e.g., risk
relating to data privacy, and inconvenience of time and travel for appointments, and benefits
relating to the close monitoring of skin, and imaging). A clinic staff member will thoroughly
go through the Participant Information and Consent Form (PICF) and will give the participant
an opportunity to ask any questions. The participant will have received a copy of the PICF at
least one week prior to the appointment, giving them sufficient time to read in advance and
be prepared with any questions they have. A member of the trial staff will review the
inclusion and exclusion criteria with the participant and once consent is obtained, the
participants will complete a few questionnaires, undergo iToBoS Total Body Photography,
dermoscopy and provide a biological saliva sample.
Clinical History and Phenotypic Data Capture. At baseline a member of the research team will record information from the participant on
personal and family medical history (including number of melanomas and non-melanoma skin
cancers and ages at diagnoses, number of other skin excisions, solarium use, history of
severe sunburns, history of UV-exposure (e.g. chronic, intermittent, constant), medication
use, co-morbidities, family history of melanomas), demographic data (including age, date of
birth, gender and sex, place of birth, number of years living in current town, marital
status, educational level, ancestry) and phenotypic data such as skin and eye colour.
Clinical information on any suspicious lesions will be recorded including recent changes,
previous biopsy, or previous ablative treatments. This may include requesting previous or
future pathology reports. Consent for the collection of pathology reports and relevant
medical history will be included in the PICF. All data will be entered directly into an
Electronic Data Capture (EDC) system to ensure consistency and confidentiality of
participant's information.
iToBoS Total Body Photography. Participants will undergo Total Body Photography using the iToBos whole-body scanner. The
iToBoS System consists of a framework of 15 high-resolution industrial cameras equipped with
liquid lenses that arch over a horizontal bed that the participant will lay on. Participants
will undress to their underwear with hair tied up if applicable. Participants will be offered
the option of wearing disposable underwear to increase the area of skin to be imaged, which
may otherwise be covered by their own underwear. Participants will be instructed to lay on a
bed, with shoulders and elbows in line, in an angle 90 degrees to the body, with hands placed
slightly over the head. The framework of cameras will systematically move along rails of the
framework capturing several images at different focus points to capture the whole skin
surface. Participants will then be asked to change position to laying on their stomach. The
imaging process for each position will take less than 5 minutes. Software is then used to
merge images into a single composite picture and generate a 3D body map of the participant's
skin. To protect participant privacy, the 3D reconstruction of the participant will be
semi-anonymised by creating a 3D avatar, which allows mapping of precise location of moles.
Dermoscopy. Dermoscopic images will be taken, using a handheld device (standardised between the sites),
of any skin lesions that are of concern to the study participant or the medical practitioner
conducting the imaging and skin examination. In addition, any naevus 5mm or greater in
diameter will also be dermoscopically imaged up to a total of 30 lesions. If the participant
has more than 30 lesions, that the clinician believes should be imaged for monitoring, then
more than 30 lesions will be imaged for dermoscopy. If participants have less than 30 lesions
with a ≥ 5mm diameter, then images of smaller naevi will be taken to make up the total. The
clinician will attempt to take dermoscopy images from a range of body sites. These lesion
images will be mapped to the total body images taken with the iToBoS System.
Additionally, up to 10 dermoscopy images per participant will be taken of benign lesions
(e.g. seborrhoeic keratosis, dermatofibroma, angioma) from various body sites, for the
purpose of assessing image capabilities at different body locations and for training the AI
component of the iToBoS System.
Clinical Examination. Dermatologically-trained clinicians will conduct a clinical skin examination and record
phenotype details on a standard questionnaire. Eye colour and freckling density on the face,
dorsum of right hand and shoulders will be recorded (none = 1, mild = 2, moderate = 3, severe
= 4). Skin colour will be clinically assessed by Individual Topology Angle (measured using a
spectrophotometer) on the ventral upper arm (unexposed) and dorsal forearm (exposed). Height
and weight of participants will be measured. Clinical information on any suspicious lesions
will be recorded including recent change in size, shape, elevation, bleeding, itch, previous
biopsy, previous cryotherapy or other ablative treatments.
Management of skin lesions of concern. During the study period, the investigators may identify skin lesions that are suspicious for
malignancy that require further medical attention.
For sites where a dermatologist sees participants face-to-face, the dermatologist will manage
the treatment of any suspicious lesions as per standard care (i.e. monitoring, further
imaging with Reflectance Confocal Microscopy, biopsy, topical or cryotherapy as per standard
care).
For the other sites, imaged lesions will be reviewed within a fortnight by the consultant
dermatologist together with dermatologically-trained clinicians using the available clinical
information, 3D avatar and dermoscopic images to identify any skin lesions suspicious for
malignancy that require referral to the participant's regular medical practitioner for
management. A study report will be generated including images of any lesions requiring
action. This will be sent to the participant's nominated treating practitioner. Any referrals
will be followed-up and reports and pathologies will be requested.
Collection of Biospecimens. Participants will be asked to give a saliva sample using an Oragene DNA self-collection kit
(or similar). Samples will be sent to an accredited facility for processing and will be
genotyped using an array which will detect common variants in known low to moderate risk
susceptibility genes. This genetic information will be combined with clinical risk factors to
create a holistic risk score. This method builds on previously validated risk scoring
methods, and this study will be valuable in validating this modified algorithm. Due to time
and financial constraints, individual holistic risk scores will not be returned to
participants in this study. It is the investigators intention to return the results in a
separately funded study, under a separate protocol, where usefulness and psychosocial impact
of returning risk assessment results can be evaluated.
A subset of participants with family or medical history suggestive of an inherited mutation
will be offered additional panel testing of familial melanoma genes. It is predicted that
approximately 10% of participants may meet criteria for familial melanoma. In this instance,
participants will receive appropriate pre-test genetic counselling to inform them of the
benefits and limitations of genetic testing, and the likely outcomes of testing. This is to
allow participants to provide informed consent for additional genetic testing. The results of
genetic testing for high penetrance familial melanoma genes will be returned to the
participant by a genetic counsellor, or a clinician trained by a genetic counsellor.
Providing a saliva sample for genetic analysis in this study is optional. Participants may
still take part in the study if they do not wish to provide a genetic sample. A separate
consent page will be used for participants to provide consent for genetic analysis of saliva
sample.
Follow-up Clinic Visits. Participants will be asked to attend a follow-up clinic visit every 6 months, for a 12-month
period (baseline, 6, and 12 months). Follow-up visits will include iToBoS Total Body
Photography, and Dermoscopy. Any lesion that was photographed using dermoscopy at baseline,
will be repeated at the 12 month follow up visit. At the 6 month follow up visit only
suspicious lesions will be photographed using dermoscopy. Furthermore, any new lesions that
are concerning will additionally be imaged using dermoscopy. Any suspicious lesions
identified will be either followed-up by an onsite dermatologist, or referred to the
participant's nominated treating.
There will be a ± 8-week window for participants to complete visits 2 and 3.
