Efficiency of Presurgical Basal Cell Carcinoma Margin Mapping Using Optical Coherence Tomography
Phase: NA
Conditions: Carcinoma, Basal Cell
Sponsor: Michelson Diagnostics Ltd.

Efficiency of Presurgical Basal Cell Carcinoma margin mapping using Optical Coherence Tomography  
 
Study Protocol 
 
V04 
 
19 January 2018 
 
 
J Holmes, CEO, Michelson Diagnostics Ltd 
  
Rationale: 
Basal Cell Carcinoma (BCC) is the most common malignancy in humans. Its incidence is continuously 
increasing. The head and neck areas are most commonly affected due to their increased lifetime 
exposure to sun compared to other body parts. BCC is often treated by surgical excision which has 
high cure rate compared to other treatment modalities, but leaves a visible scar which can affect the 
quality of life of the patient, depending on the location and size of the excision. Mohs Micrographic 
Surgery (MMS) was developed to minimize the size of the surgical excision whilst maintaining very 
high cure rate. The main drawback of MMS is that repeated surgery procedures may be required to 
eliminate all of the tumour using specialist resources located at the clinic.  
 
Optical Coherence Tomography (OCT) allows non-invasive in-vivo imaging of superficial skin lesions. 
It is in routine clinical use for diagnosis of BCCs, and the diagnostic sensitivity and specificity is well 
established in published multi-centre trials. A further potential application of OCT is the pre-surgical 
mapping of the lateral margins of BCC. If the margins of a BCC were accurately known prior to 
commencing an MMS treatment, the treatment could be performed much more quickly, resulting in 
shorter patient stays and more efficient use of surgical and operating room resources. Previously 
published research has already shown that OCT mapping of BCC margins is more accurate than 
clinical assessment; the objective of the present study is to demonstrate that pre-surgical mapping 
of BCC margins with OCT is also more efficient. 
 
Hypothesis: 
That presurgical margin mapping of BCCs with OCT results in a reduction of the number of MMS 
surgery stages to < 1.4 without adversely impacting clinical outcome.  
 
Objectives: 
Primary Objective: 

• 
Show that the average number of MMS stages by using pre-surgical margin mapping with 
OCT is < 1.4  
 
Secondary Objectives: 
• 
Validate that the reduction in MMS stages by use of OCT mapping does not result in an 
increase in the size of the surgical defect  
 
• 
Show that the average time taken to perform OCT margin mapping is < 5 minutes for lesions 
of area < 2 cm2 
 
Tertiary Objectives: 
• 
For those lesions for which OCT margin mapping did not result in a single stage operation: 
o 
Determine the proportion of each BCC subtype (nodular, superficial, or infiltrative BCC) 
o 
Determine the proportion for which the first surgery stage had margins that were not clear 
(i) laterally (ii) in depth 
o 
Determine whether anatomical location is a factor 
 
Population: 
Inclusion criteria: 
• 
200 patients with biopsy-proven BCCs who have been referred for MMS 
• 
Adults > 18 years of age  
• 
Informed consent 
  
Exclusion criteria: 
• 
Patients with BCCs larger than 6 cm2  
 
Study Design: 
Interventional Randomised Controlled Trial (RCT) 
 
Previously published research [1-5] has shown that, under controlled conditions, OCT mapping of 
BCC margins is more accurate than clinical assessment and so is expected to produce a reduction in 
the number of MMS stages. However, the efficiency of the technique, in terms of the reduction in 
MMS stages versus the additional time required to OCT map the lesion, has not been quantified. 

 
This RCT is designed to quantify the improvement in efficiency, and validate that it is more efficient 
than standard MMS. The study comprises two Arms, one is the OCT arm and one is the Control Arm. 
In the OCT Arm, OCT is used to map the tumour margins and the resulting number of MMS stages is 
recorded. 
 
In the Control Arm, standard MMS is performed. 
 
In order to be completely sure that the reduction in MMS stages using OCT has not been obtained at 
the cost of increasing the amount of tissue excised, all tumours are also mapped at initial 
consultation, prior to randomization, by a second observer. See Figure 1 Outline Protocol below. 
 
  
 Figure 1. Outline Protocol 
 
 
Initial Steps 
1. 
Informed consent is obtained from eligible patients 
2. 
Observer #1 (not the surgeon) maps the extent of the BCC tumour using OCT. The time 
taken, size and shape of the mapped border is recorded. 
3. 
The OCT marks are removed and the patient is asked to return at a later date for the surgical 
procedure 
4. 
Patients are randomized into two groups, A. OCT Arm and B. Control Arm 
 
A. 
OCT Arm 
5. 
Observer #2 (the Mohs surgeon) maps the extent of the BCC tumour using OCT. The time 
taken, size and shape of the mapped border is recorded. 
6. 
The Mohs surgeon performs Mohs surgery using the marked OCT mapped borders as the 
first stage estimate. The number of MMS stages is recorded.  
 
B. 
Control Arm 
7. 
Standard Mohs surgery is performed, using clinical assessment for the first MMS stages 
 
Final Observations 

8. 
Finally, prior to closure of the wound, the size of the surgical defect of all lesions is measured 
by tracing the extent on squared transparent paper and also photographed with a scale. The subtype 
of the BCC from the Mohs histology is recorded (nodular / superficial / infiltrative / other) 
 
Avoiding Bias: 
The initial OCT mapping, prior to randomization, by another Observer who is not the surgeon, is to 
detect any bias on behalf of the surgeon who might consciously or unconsciously increase the size of 
the excision in the OCT Arm (therefore unnecessarily increasing the amount of healthy tissue 
excised) in order to reduce the number of MMS stages. This first Observer does not know which Arm 
the patient will end up in and so will simply do their best to map the tumour as accurately as 
possible. It is then straightforward to compare their results (size of mapped margins) with the 
surgeon’s to confirm the absence of any bias. Their OCT mapping results will also be compared with 
the size of the final surgical defect (for all lesions) to confirm that (as in all previous studies) OCT 
mapped borders are no larger than the final surgical defect by conventional MMS. 
 
Case Number Estimation: 
N=200 patients will be included in the study (100 in each arm). 
 
According to published literature, the average number of MMS stages per lesion is in the range 1.5 
to 1.7 [6]. Previous studies with small numbers of patients in non-RCT conditions indicate that 
presurgical margin mapping with OCT reduces the average number of stages to approximately 1.2 
[1-5]. Analysis by a qualified statistician has shown that assuming the true value is 1.2, then 83 
patients in the OCT arm will be sufficient to show that the average number of MMS stages is < 1.4 
with a confidence level of 95% (P<0.025). This study will be performed with 100 patients in each arm 
in order to exceed this criterion and show that OCT mapping improves on standard MMS with 1.5 – 
1.7 stages. 
 
Termination Criteria: 
The patient will be excluded from the study on personal demand (see informed consent). 
 
Start and Duration 
The study is designed for 2 years starting immediately after approval by ethics committee. 
Recruitment will be 2 patients per week. 
 
Study-related interventions 
The OCT device is CE marked and has been on the market in first and second generations since 2011. 
A methodology for using OCT to map the lesion margins has been developed since 2011 and results 
published [refs] and then further optimized.  

 
The study involves manual measurement of the lesion at 3 stages (on clinical assessment, after OCT 
mapping, and after surgery. The measurement procedure is very simple and involves placing 
transparent squared paper over the lesion and tracing the extent. This procedure is a well-
established technique for measuring the extent of wounds  
 
In the OCT arm of the study, the Mohs surgeon will make a first incision using the marked OCT 
margins as the first estimation of the tumour border. 
 
Risks and adverse effects 
There are no risks or adverse effects from the OCT mapping procedure or lesion measurement 
procedure.  
 
The OCT scanner is a CE marked device using a low power, eye-safe, Class I laser for the scanning 
process. The scan does not exposure the patient to any unsafe optical radiation. 
 
For this study, the CE-marked OCT scanner has been modified by the addition of a non CE-marked 
prototype Marking Accessory (‘Marker’). This Marker produces a small dot of ink on the subject’s 
skin at the centre of the OCT scan when a trigger is depressed by the operator. The ink is approved 
for use in surgical markers. The Marker contacts the skin but is cleaned between each patient using 
disinfectant wipes. After mapping and before surgery the patient’s skin is prepared in the normal 
manner, so there is no risk of infection. As the Marker is not CE-marked, MHRA approval of its use is 
being obtained. 
 
Data and Analysis 
The following data and analysis will be performed: 
 
1. Primary Objective 
• 
The average number of MMS stages will be calculated for each arm by dividing the total 
number of MMS stages for all the patients in the arm, by the number of patients in the arm. The 
95% confidence levels for each arm will be calculated. 
 
2. Secondary Objectives 
• 
The area of lesions will be obtained from the tracings of the mark obtained by placing a 
transparent TegaDerm™ adhesive dressing over the mark, removing it (with ink transferred) and 
pasting on to squared graph paper and then counting the number of squares inside the traced 
borders. 

 
• 
The area of the surgical defect will be obtained by placing OpSite™ squared adhesive 
dressing over the defect prior to commencement of repair, using an ink marker to trace the defect 
on the dressing, and then counting the number of squares inside the traced borders. 
 
• 
The following will be calculated 
i. 
The mean, r.m.s. and maximum difference between the area of the OCT map made by Mohs 
surgeon and the area of the OCT map made by Observer #1, for lesions in the OCT Arm 
ii. 
The mean, r.m.s. and maximum difference of the area of the OCT map made by Observer #1 
and the area of final surgical lesion in the Control Arm. 
 
From (i) we will quantify the difference between the Mohs surgeon and Observer’s OCT mapping, 
and whether the Mohs surgeon’s margins are consistently smaller or larger. 
 
From (ii) we will determine whether the Observer’s margins are smaller or larger than the final 
surgical lesion, and from (i) then show whether the surgeon’s margin are expected to be smaller 
than the final surgical lesion, and by how much. 
 
 Figure 2. Schematic of process showing the areas. 
 
 
Finally, the average time taken to OCT map lesions will be calculated: 
• 
For all lesions 
• 
For lesions, divided into the following subcategories by clinically visible lesion size: 
o 
< 2.0 cm2 
o 
2.0 – 4.0 cm2 
o 
> 4.0 cm2 
 
3. Tertiary Objectives 
The results for all lesions in the OCT arm which took more than 1 MMS stage will be analysed as 
follows: 
 
Calculate the proportions of each BCC subtype (nodular, superficial, or infiltrative BCC, or other) as a 
% of the total  

 
Calculate the proportion for which the first surgery stage had margins that were not clear (i) laterally 
(ii) in depth (iii) both 
 
Calculate the proportions of lesions in each of the following anatomical locations: nose, periocular, 
perioral, ear, other facial location, neck, trunk, limbs. 
 
 
Privacy Statement 
Anonymization of patient data is compulsory (see privacy policy statement) 
  
References 
1.Rashed, D., Shah, D., Freeman, A., Cook, R.J., Hopper, C. and Perrett, C.M., 2017. Rapid ex vivo 
examination of Mohs specimens using optical coherence tomography. Photodiagnosis and 
Photodynamic Therapy. 
 
2. Alawi, S.A., Kuck, M., Wahrlich, C., Batz, S., McKenzie, G., Fluhr, J.W., Lademann, J. and Ulrich, M., 
2013. Optical coherence tomography for presurgical margin assessment of non‐melanoma skin 
cancer–a practical approach. Experimental dermatology, 22(8), pp.547-551. 
 
3. Wang, K.X., Meekings, A., Fluhr, J.W., McKenzie, G., Lee, D.A., Fisher, J., Markowitz, O. and Siegel, 
D.M., 2013. Optical Coherence Tomography–Based Optimization of Mohs Micrographic Surgery of 
Basal Cell Carcinoma: A Pilot Study. Dermatologic Surgery, 39(4), pp.627-633. 
 
4. Chan, C.S. and Rohrer, T.E., 2012. Optical coherence tomography and its role in Mohs 
micrographic surgery: a case report. Case reports in dermatology, 4(3), pp.269-274. 
 
5. Pomerantz, R., Zell, D., McKenzie, G. and Siegel, D.M., 2011. Optical coherence tomography used 
as a modality to delineate basal cell carcinoma prior to Mohs micrographic surgery. Case reports in 
dermatology, 3(3), pp.212-218. 
 
6. Macfarlane L, Waters A, Evans A, Affleck A, Fleming C. Seven years' experience of Mohs 
micrographic surgery in a UK centre, and development of a UK minimum dataset and audit 
standards. Clinical and experimental dermatology. 2013 Apr 1;38(3):262-9.