Basal cell carcinoma treated with combined ablative fractional laser and ingenol mebutate – an exploratory study monitored by optical coherence tomography and reflectance confocal microscopy

Abstract

Background Basal cell carcinomas (BCCs) have previously been treated off‐label with ingenol mebutate (IM). Ablative fractional laser (AFL) may improve efficacy of IM by increasing drug uptake in the tumour. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) detect BCC non‐invasively. Our aim was to investigate BCC response and tolerability after combined AFL and IM treatment of low‐risk BCCs. Methods Twenty patients with histologically verified superficial (n = 7) and nodular (n = 13) BCCs were treated with combined fractional CO2‐laser (10 600 nm) and IM 0.015% or 0.05%, the concentration depending on anatomical location. BCC response was evaluated clinically, by OCT and RCM at day 29 and 90 after first treatment, and histologically at day 90. Treatment was repeated at day 29 if BCC persisted. Local skin reactions (LSRs) were assessed using LSR scale at all visits. Results At day 29, 18/20 patients received a second treatment due to residual BCC detected clinically, by OCT or RCM. OCT and RCM presented subclinical BCCs in five of 20 cases (25%). At day 90, overall histological cure rate was 70%, corresponding to clinical (65%) and OCT/RCM (60%) cure rates, and agreement between evaluation methods was substantial (kappa ≥ 0.796, P < 0.0001). Clearance rates were similar for sBCCs and nBCCs (P = 0.354) and for lesions treated with IM 0.015% and 0.05% (P = 0.141). LSRs were tolerable, but scarring was observed in the majority of cleared patients. Conclusion Two treatments of combined AFL and IM show potential to treat low‐risk BCCs with acceptable tolerability. OCT and RCM show promise to detect subclinical BCCs at short‐term follow‐up.

Efficacy and Safety of Laser‐Assisted Combination Chemotherapy: An Explorative Imaging‐Guided Treatment With 5‐Fluorouracil and Cisplatin for Basal Cell Carcinoma

“…Persisting erythema, here observed in 83% of patients, also appears common after AFL-assisted topical BCC therapy, with reported rates of 74% (4-8 weeks) and 73% (3 months) using 5-FU and PDT, respectively [45,46]. In regard to hyperpigmentation (57%), our rates were similar to Choi et al [41] (67%; AFL + PDT) and Banzhaf et al [43] (64%) who assessed at similar follow-up times, but higher than reported by Nguyen et al [45] (30%; AFL + 5-FU) and Genouw et al [40] (20%; AFL + PDT). These differences may reflect variations in laser settings or tumor location.…”

“…The bulk of these reports assess AFL-photodynamic therapy, where clearance rates of 100% (sBCC), 79% (nBCC; <2 mm thick) and 63% (nBCC; high risk) are reported 12 months after 1-2 treatments [40][41][42]. Two studies also evaluate AFL-assisted imiquimod and ingenol mebutate, observing clearance in 78% (FU: 20 days) and 70% (FU: 90 days) of sBCC and mixed tumors, respectively [43,44]. Resembling our study, Hsu et al showed that a single session of AFL-assisted 5-FU cleared 71% of sBCCs at 4-8 weeks (10/14; <20 mm), dropping to 67% at >9 months follow-up [45,46].…”

“…The modalities are thus complementary, providing real-time three-dimensional sampling and assessment of tumor depth and margins [50]. As such, RCM and OCT may prove useful in monitoring topical therapies where the risk of tumor residual in underlying skin layers is well known [43,51,52]. In this study, we applied an imaging-guided approach to tumor demarcation, determi-nation of tumor response, and biopsy location.…”

Subclinical effects of adapalene‐benzoyl peroxide: a prospective in vivo imaging study on acne micromorphology and transfollicular delivery

“…24,25 Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) are non-invasive optical imaging technologies capable of visualizing the cutaneous micromorphological response to a range of treatments in vivo. [26][27][28] Evidence on the clinical utility of RCM and OCT for diagnosis of dermatological conditions and monitoring treatment responses is growing rapidly. 29 Recent reports on the high correlation between clinical acne severity and optical imaging features substantiated the utility of non-invasive imaging.…”

Skin tags imaged by reflectance confocal microscopy, optical coherence tomography and multispectral optoacoustic tomography at the bedside

“…The challenge of differentiating benign skin lesions from malignant ones has in the recent years been overcome by advances in several non‐invasive optical imaging techniques 8 . In this study, we applied the three clinically most promising and relevant technologies: reflectance confocal microscopy (RCM) that provides cellular resolution and micro‐morphological information of skin disease, useful for diagnosis of BCC subtypes, MM and lentigo maligna, 9,10 to determine pre‐surgical margins for melanocytic lesions and keratinocyte carcinomas, 10,11 to monitor therapeutic interventions of skin cancers and various inflammatory skin diseases 12‐15 . By illuminating the skin with near‐infrared lasers, RCM creates images by light energy being absorbed and reflected depending on the refractive index of the structure of interest 9 .…”