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.
