M.D. Mari Salmivuori studied in her doctoral dissertation new options for non-invasive imaging and non-invasive treatment of skin cancers.
Aggressive subtypes of basal cell carcinoma are often ill-defined, which poses a clinical problem in preoperative margin assessment. Another ill-defined skin cancer type is lentigo maligna. Lentigo maligna is an in situ melanoma, and a precursor of lentigo maligna melanoma. These two forms are clinically challenging to distinguish from each other, which is crucial as melanoma has the worst prognosis of all skin cancers. Non-invasive imaging is an option for increasing the accuracy of preoperative diagnosis and the assessment. Hyperspectral imaging is a novel, fast, and computer-aided imaging modality with a wide field of view. In non-invasive treatment of non-aggressive basal cell carcinomas, photodynamic therapy has many advantages: an excellent cosmetic outcome as well as a shorter application time and recovery period. Notwithstanding these advantages, the efficacy of photodynamic therapy is lower when compared to topical pharmacological options such as imiquimod and 5- fluorouracil.
The dissertation focuses on non-invasive imaging and non-invasive treatment. In non-invasive imaging, the aim is to study the performance of a hyperspectral imaging system in separating lentigo maligna melanoma from lentigo maligna and assessing the preoperative margins of ill-defined basal cell carcinomas compared to clinical delineation assessments performed with a dermoscope. In non-invasive treatment, the aim is to compare the efficacy of three different photosensitisers in photodynamic therapy of non-aggressive basal cell carcinomas.
There are two pilot studies with hyperspectral imaging: one on lentigo maligna and lentigo maligna melanoma, and another one on ill-defined basal cell carcinoma. Tumours were preoperatively visually inspected utilising a dermoscope, and thereafter imaged with the hyperspectral imaging system. Next, surgical excision was performed. Hyperspectral images were created with computer-aided mathematical models. Additional mathematical models were subsequently developed. In the results analysis, the findings of the hyperspectral imaging and clinically assessed margins were compared to the histopathology results, where assessment was performed blind to the hyperspectral imaging findings.
A non-sponsored, prospective, randomised, controlled and double-blinded trial focused on non-invasive treatment. In this trial, two novel photosensitisers, 5- aminolevulinic acid nanoemulsion and low-concentration hexylaminolevulinate, were compared to the commonly used methylaminolevulinate in photodynamic therapy of non-aggressive basal cell carcinomas, i.e. thin nodular or superficial subtypes. The primary outcome was histological clearance at three months. Secondary outcomes included adverse events such as pain associated with the treatment while using a long-lasting local anaesthetic as pain management, post- treatment reaction, as well as cosmetic outcome, and fluorescence and photobleaching during the illumination. We used an experimental fluorescence imaging system. Punch biopsies were performed prior to treatment and during follow-up. Both patient and observers of outcomes were blind to the photosensitiser that was used.
Hyperspectral imaging exhibited a unique hyperspectral graph for lentigo maligna melanoma, lentigo maligna, and healthy skin. Based on these results, hyperspectral images were created where hyperspectral data was represented in several abundance maps. The maps showed differing abundances for lentigo maligna melanoma and lentigo maligna, and it was possible to localise the invasion site inside the lesion. For ill-defined basal cell carcinoma, the margins of the tumour were delineated more accurately than by clinical assessment, and the results were confirmed with histopathology.
The results of the clinical trial in photodynamic therapy showed that the histological clearance of hexylaminolevulinate was similar compared to 5- aminolevulinic acid nanoemulsion and methylaminolevulinate, with no differences in cosmetic outcome, pain or post-treatment reaction between the arms. In our fluorescence and photobleaching analyses the results were widely spread.
In conclusion, hyperspectral imaging seems to be a promising and useful new imaging modality with a wide field of view: it is fast, easy to use and it seems to be capable of visualising subclinical findings. In non-invasive treatment, hexylaminolevulinate is an interesting option for photodynamic therapy of non- aggressive basal cell carcinomas. Hexylaminolevulinate at low concentrations achieves a comparable efficacy to 5-aminolevulinic acid nanoemulsion and methylaminolevulinate at higher concentrations. No differences were observed in adverse events or cosmetic outcome between the arms.
The doctoral dissertation of M.D. Mari Salmivuori in the field of dermatology titled New Options for Non-invasive Imaging and Non-invasive Treatment of Skin Cancers will be publicly examined at the Faculty of Medicine and Health Technology of Tampere University at 12 o'clock on Friday 20 November. The event can be followed via remote connection. Associate Professor John Paoli from University of Gothenburg, Sweden, will be the opponent while Professor Emerita Erna Snellman will act as the custos.
The dossertation is available online at
http://urn.fi/URN:ISBN:978-952-03-1541-2
The public defence can be participated remotely.