Treatment Of Superficial Skin Cancers Research Articles

Millimeter-Wave Pulsed Heating in Vitro: Effect of Pulse Duration

The aim of this work is to compare the response of A375 melanoma cells following 90 min of exposure to trains of 1.5 or 6 s millimeter-waves (MMW)-induced thermal pulses with the same temperature dynamics. Phosphorylation of heat shock protein 27 (HSP27) and activation of cleaved Caspase-3 were used as markers of cellular stress and apoptosis, respectively. Immunofluorescence was used to observe and precisely quantify the cellular response as a function of the spatial distribution within the exposed area. Results show that cellular response was stronger when cells were exposed to a train of 1.5 s compared to 6 s heat pulses despite the same average temperature dynamics. Cellular apoptosis induced by 1.5 s pulses was about 50% greater compared to the one induced by 6 s pulses in the area of maximal thermal stress. Similarly, HSP27 phosphorylation was approximately 20% stronger than the one induced by 6 s pulses, and mainly focused within a small area of a few mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . Cellular response to MMW induced by pulsed heating does not only depend on the peak, average, and minimum temperature. It is a function of combination of the pulse parameters, including duration, peak power, and period. MMW-induced heat pulses can be efficiently used to induce cellular stress and apoptosis in melanoma cells as a promising innovative tool for the treatment of superficial skin cancer. Adaptative therapies might be envisaged by tuning the pulse shape as a function of the desired effect.

Millimeter-Wave Heating In Vitro: Local Microscale Temperature Measurements Correlated to Heat Shock Cellular Response.

Cellular sensitivity to heat is highly variable depending on the cell line. The aim of this paper is to assess the cellular sensitivity of the A375 melanoma cell line to continuous (CW) millimeter-waves (MMW) induced heating at 58.4GHz, between 37 °C and 47 °C to get a deeper insight into optimization of thermal treatment of superficial skin cancer. Phosphorylation of heat shock protein 27 (HSP27) was mapped within an area of about 30mm 2 to visualize the variation of heat-induced cellular stress as a function of the distance from the waveguide aperture (MMW radiation source). A multiphysics computational approach was then adopted to yield both electromagnetic and thermal field distributions as well as corresponding specific absorption rate (SAR) and temperature elevation. Induced temperature rise was experimentally measured using a micro-thermocouple ( μTC). Coupling of the incident electromagnetic (EM) field with μTC leads was first characterized, and optimal μTC placing was identified. HSP27 phosphorylation was induced at temperatures ≥ 41 °C, and its level increases as a function of the thermal dose delivered, remaining mostly focused within 3mm 2. Phosphorylation of HSP27 represents a valuable marker of cellular stress of A375 melanoma cells under MMW exposure, providing both quantitative and spatial information about the distribution of the thermal stress. These results may contribute to the design of thermal treatments of superficial melanoma through MMW-induced heating in the hyperthermic temperature range.

Novel design and development of a 3D-printed conformal superficial brachytherapy device for the treatment of non-melanoma skin cancer and keloids

BackgroundSkin tumors are the most predominant form of cancer in the United States. Radiation therapy, particularly high dose-rate (HDR) brachytherapy, provides an effective form of cancer control when surgery is not possible or when surgical margins are incomplete. The treatment of superficial skin cancers on irregular surfaces, such as the nose, lips or ears, present challenges for treatment. To address this issue, we designed and constructed a novel conformal superficial brachytherapy (CSBT) device prototype to improve patient-specific treatment for complex sites. The device is mounted on an automated remote after-loader, providing limited radiation exposure to operating personnel, is inexpensive to construct, and offers a unique method of conformal surface radiation therapy.ResultsA prototype of the CSBT device was successfully manufactured. A computed tomography (CT) scan of a Rando phantom was used to plan the target treatment area. The CSBT device has a hexagonal lattice array of retractable rods with radioactive seeds placed at the tip of each rod. A 3D-printed conformal shape insert with a hexagonal array of cylindrical projections of varying length is driven into the rods by a single linear actuator. The rods are displaced to conform to the patient’s skin. This elegant device design permits the delivery of radiation to complex targets using readily available beta-emitting radionuclides, such as Yttrium-90 (Y-90) or Strontium-90 (Sr-90).ConclusionA working prototype of a novel CSBT device was built using 3D-printing technology that provides a safe and economically attractive means of improving radiation delivery to complex treatment sites.

CSRT Initiative: Process of Introducing a New Technique to Treat Superficial Skin Cancers

Skin cancer incidence is predicted to double in the next 30 years. Surgery is considered the gold standard however with the potential for negative cosmetic outcomes. For superficial lesions a non- invasive approach is preferable. Photodynamic Therapy (PDT) is non- invasive treatment involving a photosensitizing drug activated by light, which in turn destroys targeted cells. The aim of this work is to describe a CSRT led PDT program from inception to clinical. A systematic approach to the implementation of the PDT program was undertaken by the CSRT beginning with building a business case which included a comprehensive literature review. The next step by the CSRT was the planning and execution of the program which included a site visit to an existing PDT program, purchasing of equipment, and grant application to develop patient education materials and creams. Patient education brochures were designed and reviewed by staff and patients. All departmental protocols and work sheets for the new treatment were developed by the CSRT and presented to the skin site group. Employing the CSRT skill set, all potential patients referrals are triaged by the CSRT and pre teaching completed. Clinical skills are used in skin preparation, cream application, teaching, treatment and follow up which are all completed by the CSRT. Staff training was conducted by the CSRT. To date, 76 patients have been treated constituting 158 treatment sites. Topical PDT represents an innovative therapeutic approach for non- surgical treatment of superficial skin cancer. Transplant and Gorlins Syndrome patients benefit greatly from having this treatment option. There is a critical need for localized cancer therapies that are effective, well tolerated and can be repeatedly used after other modalities have failed. Continued staff training and purchasing extra equipment will allow more superficial skin cancer patients to receive this noninvasive treatment.

SU‐E‐T‐421: Failure Mode and Effects Analysis (FMEA) of Xoft Electronic Brachytherapy for the Treatment of Superficial Skin Cancers

Purpose:To perform a failure mode and effects analysis (FMEA) of the process for treating superficial skin cancers with the Xoft Axxent electronic brachytherapy (eBx) system, given the recent introduction of expanded quality control (QC) initiatives at our institution.Methods:A process map was developed listing all steps in superficial treatments with Xoft eBx, from the initial patient consult to the completion of the treatment course. The process map guided the FMEA to identify the failure modes for each step in the treatment workflow and assign Risk Priority Numbers (RPN), calculated as the product of the failure mode's probability of occurrence (O), severity (S) and lack of detectability (D). FMEA was done with and without the inclusion of recent QC initiatives such as increased staffing, physics oversight, standardized source calibration, treatment planning and documentation. The failure modes with the highest RPNs were identified and contrasted before and after introduction of the QC initiatives.Results:Based on the FMEA, the failure modes with the highest RPN were related to source calibration, treatment planning, and patient setup/treatment delivery (Fig. 1). The introduction of additional physics oversight, standardized planning and safety initiatives such as checklists and time‐outs reduced the RPNs of these failure modes. High‐risk failure modes that could be mitigated with improved hardware and software interlocks were identified.Conclusion:The FMEA analysis identified the steps in the treatment process presenting the highest risk. The introduction of enhanced QC initiatives mitigated the risk of some of these failure modes by decreasing their probability of occurrence and increasing their detectability. This analysis demonstrates the importance of well‐designed QC policies, procedures and oversight in a Xoft eBx programme for treatment of superficial skin cancers. Unresolved high risk failure modes highlight the need for non‐procedural quality initiatives such as improved planning software and more robust hardware interlock systems.

The Process of Introducing a New Technique for Treatment of Superficial Skin Cancer into an Established Radiation Therapy Department

The Process of Introducing a New Technique for Treatment of Superficial Skin Cancer into an Established Radiation Therapy Department

Comparison of the uptake of 5-aminolevulinic acid and its methyl ester in keratinocytes and skin

Photodynamic therapy is widely used in the treatment of superficial skin cancers. 5-Aminolevulinic acid (ALA) and its methylated form, methyl-ALA (MAL), are frequently used as precursors to photosensitizing substances. Nevertheless, the mechanism of the uptake of ALA and MAL in keratinocytes and of their skin penetration is still controversial. Since both compounds are not sufficiently lipophilic to penetrate through lipid membranes, they must employ specific uptake systems which may vary between different cell types. Here, we studied ALA and MAL uptake in keratinocyte cell lines originating from healthy cells (CCD 1106 KERTr cells) or keratinocyte tumors (A431 cells). ALA uptake resulted in faster protoporphyrin IX (PpIX) production than MAL uptake. A pharmacological characterization of the uptake systems revealed that PpIX formation was most efficiently reduced with GABA transporter (GAT) substrates. GABA, β-alanine, and (S)-SNAP-5114 reduced ALA uptake and, to a lesser extent, MAL uptake in the cell lines. The pharmacology of these compounds indicates that ALA and MAL are taken up by normal and pathological keratinocytes via GAT-3. Furthermore, the amino acids arginine, cysteine, and histidine also inhibited the uptake of ALA, and even more so MAL, suggestive of an additional involvement of amino acid transporters. To show that PpIX formation in vivo is restricted to the application site, which has been questioned for ALA in one other report, we applied clinically used ALA and MAL formulations to the skin of nude mice. Contrary to the results of these previous authors, the resulting PpIX fluorescence increased over time and was restricted to the application site for both preparations.

Photodynamic Therapy for Basal Cell Carcinoma in Recessive Dystrophic Epidermolysis Bullosa

A 22-year-old male with recessive dystrophic epidermolysis bullosa with a large superficial and nodular basal cell carcinoma on his right forehead was treated with photodynamic therapy. The treatment was well tolerated, and the site healed well. Patients with epidermolysis bullosa are at increased risk of developing skin cancers, particularly squamous cell carcinomas. However, basal cell carcinomas are rare in recessive dystrophic epidermolysis bullosa. As patients with epidermolysis bullosa have recurrent blistering and poor wound healing, surgery may not be the optimal choice in treating skin cancers. We present this case to highlight that photodynamic therapy may be a helpful and safe technique in the treatment of superficial skin cancers in patients with epidermolysis bullosa, as an alternative to more radical methods.

Grenz Rays: An Alternative Treatment for Superficial Skin Cancers in Elderly Patients

Grenz rays are electromagnetic waves (i.e., x-rays of very low energy and situated in the electromagnetic spectrum between UV and x-rays). This kind of x-ray is suitable for very superficial processes in the skin. This means that lesions up to a thickness of 1 mm can be irradiated. For these reasons, chronic dermatoses, precancerous lesions or superficial skin cancers can be treated. Since the introduction of this very superficial and low-energy treatment modality, Grenz rays have shown no serious side effects. Good indications for a Grenz ray treatment are psoriasis of the scalp and of the nails, chronic eczemas, disseminated superficial actinic porokeratosis, Bowen’s disease, Paget’s disease, lentigo maligna, superficial basal cell carcinoma or squamous cell carcinoma. The only side effects are slight hypo-/hyper-pigmentation of the skin and it has to be noticed that there is no hair loss after Grenz ray treatment, and no side effects to deeper situated structures.

Etretinate enhances the susceptibility of human skin squamous cell carcinoma cells to 5-aminolaevulic acid-based photodynamic therapy

Photodynamic therapy (PDT) with 5-aminolaevulinic acid (5-ALA) is a noninvasive and effective treatment for superficial skin cancers. Etretinate, a derivate of vitamin A, with the chemical formula ethyl(2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nona-tetraenoate, has been reported to have antitumour effects and to regulate the proliferation and differentiation of skin cancers. In order to develop more efficient PDT, we investigated whether etretinate enhanced the cytotoxic action of ALA-based PDT against human squamous cell carcinoma cell line, HSC-5. The in vitro cytotoxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptotic cells were detected by double-staining with fluorescent annexin V and propidium iodide. Intracellular protoporphyrin IX (PpIX) converted from exogenous ALA was measured by a fluorescence meter. HSC-5 cells pretreated with a nontoxic concentration of etretinate became more susceptible to the cytotoxic action of ALA-based PDT. Etretinate-pretreated cells underwent apoptosis in response to ALA-based PDT. Etretinate pretreatment resulted in enhanced accumulation of ALA-dependent intracellular PpIX. The results suggest that etretinate enhances the susceptibility of HSC-5 cells to ALA-based PDT via the intracellular increase of ALA-dependent PpIX. Etretinate might be useful for improvement of ALA-based PDT.

Photodynamic therapy in dermatooncology

Non-melanoma skin cancers are the most common skin tumors. Because of their frequent localization on the face and hand, aesthetic aspects of the therapeutic procedures should also be considered. Surgical excision still remains the first choice, but recently several new alternative therapies have emerged, especially for the treatment of superficial skin cancer. Photodynamic therapy has become a widely accepted therapeutic method for certain non-melanoma skin tumors. Photodynamic therapy involves the use of light to activate a photosensitizer, localized in diseased tissues. Photosensitizers are tumor-selective: their accumulation in rapidly proliferating cells and newly formed blood vessels is significantly higher than in the surrounding healthy tissues. During photodynamic therapy, cytotoxic reactive oxygen species are formed from the photosensitizer, leading to changes in subcellular pathways or apoptosis of the cells. Efficacy of the photodynamic therapy has been proven in solar keratosis, superficial basal cell carcinoma and morbus Bowen, with significantly better cosmetic outcome than that of the conventional therapeutic methods. Side effects, like erythema, crusting, serous discharge, or oedema, are usually moderate, and dissolve rapidly. The present article summarizes the authors' experiences with photodynamic treatment (212 non-melanoma skin cancer patients were treated with PDT between December 2003 and January 2006), at the Department of Dermatology and Allergology, University of Szeged, Hungary, and reviews the literature of photodynamic therapy in dermatooncology.

Our PDT experience in the treatment of non‐melanoma skin cancer over the last 7 years

Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) was first described by Kennedy et al. in 1990; currently, accumulated evidence shows that topical PDT is effective in the treatment of actinic keratoses, Bowen's disease and superficial basal cell carcinoma, being potentially advantageous where size, anatomical location or number of lesions limit the efficacy and/or the acceptability of conventional therapies. It involves the use of photosensitizing drugs and the administration of an appropriate light source to activate the sensitizing agent, which leads to the production of activated oxygen species for tissue destruction. The topically administered prodrug 5-ALA is converted within cells into the active photosensitizer protoporphyrin IX, via haem cycle, with preferential accumulation in tumour cells. The authors describe their experience with topical PDT, using 20% 5-ALA and two different incoherent light sources, 'Waldman 1200 L' and 'VersaLight', in the treatment of non-melanoma skin cancer and precursor lesions. More than 100 patients were treated since 1997, with up to a 7-year follow-up period. Cases are illustrated and results are presented and discussed in the light of the relevant Literature. The study suggests that 5-ALA PDT is effective in the treatment of superficial skin cancer and premalignant lesions.