Mathematical modeling of heat transfer in tissues with skin tumor during thermotherapy.

The study of thermal therapy to tumors and the response of living cells to this therapy used to treat tumor is very important due to the complexity of heat transfer in biological tissues. In the past few years, there has been a growing interest among clinicians, mathematicians, and engineers regarding the use of computational and mathematical methods to simulate biological systems. Numerous medical proceedings also employ mathematical modeling and engineering techniques as a means to guarantee their safety and evaluate the associated risks effectively. This manuscript provides an analytical solution used for the first time to study the mechanism of biological thermal response during heat therapy on spheroidal skin tumor. The proposed method used a generalized thermoelasticity model with one relaxation time. The influence of relaxation times on the responses of diseased and healthy tissues is studied and interpreted graphically. Also, the impact of different laser irradiance on the thermal profile of the malignant tumor cells over a period of 2 minutes is interpreted graphically. To investigate the transfer of heat within biological tissues during the thermal therapy, the Laplace transform and inverse Laplace transform methods were applied. A comparison of the present generalized thermoelasticity model and different models based on Pennes bioheat transfer PBT shows that our proposed model yields more realistic and accurate predictions. The current model can be used to explain various therapeutic methods.

Observation of lymphadenopathy, systemic symptoms, and treatment in suspected indolent cutaneous B-cell lymphomas.

BACKGROUND: Following the initial diagnosis of a marginal zone or follicle center lymphoma on skin biopsy, patients undergo staging to determine the extent of disease. OBJECTIVE: We sought to characterize the frequency that these patients were found to have a systemic nodal disease upon work-up as well as the impact of imaging on disease management. METHODS: We conducted a retrospective chart review of patients presenting with a working diagnosis of PCMZL or PCFCL treated at The Ohio State University from 1990 to 2022. Data collected included: patient history, progress notes, virtual encounters, laboratory results, presentation features, imaging, and pathology. Biomarkers included ANA, SSA/SSB, BCL6 and H. Pylori labs, bone marrow biopsies, positive imaging, and need of systemic medication and mortality. RESULTS: 71 patients with suspected PCMZL and PCFCL were identified. 66 of 71 patients underwent imaging. Of this group, 12 patients (9 with suspected PCFCL and 3 with suspected PCMZL) demonstrated lymphadenopathy on imaging. Of these 12 patients, 5 underwent biopsy of suspected lymph nodes, and 3 had biopsy-proven nodal involvement and received systemic therapy. Of the remaining 7 patients with evidence of lymphadenopathy on imaging, 4 were thought to have reactive lymph nodes, and 3 were treated empirically with systemic chemotherapy due to the extent or progression of their disease. Of patients with imaging negative for lymphadenopathy, 3 of 52 (5.8%) patients with received systemic treatment, while 49 of 52 patients (94.2%) received localized treatment. LIMITATIONS: Most of the relationships between this data were correlational and patients selected for this study were limited to a single institution. CONCLUSION: Prospective study of the role of imaging without subsequent lymph biopsy to direct treatment decisions is warranted.

Vaccimel immunization is associated with enhanced response to treatment with anti-PD-1 monoclonal antibodies in cutaneous melanoma patients - a case reports study.

Cancer vaccines are gaining ground as immunotherapy options. We have previously demonstrated in cutaneous melanoma (CM) patients that adjuvant treatment with VACCIMEL, a mixture of four irradiated CM cell lines co-adjuvanted with BCG and GM-CSF, increases the cellular immune response to melanocyte differentiation antigens, cancer-testis antigens and neoantigens, with respect to basal levels. On the other hand, it is also known that treatment with anti-PD-1 monoclonal antibodies (MAbs), acting on pre-existing tumor-reactive lymphocytes, induces clinical responses in CM patients, albeit in a fraction of treated patients. A combination of both treatments would appear therefore desirable. In this paper, we describe CM patients who, having progressed even years after vaccination, were treated with anti-PD-1 MAbs. In 5/5 of such progressor patients, complete responses were obtained which lasted between 3 and 65+ months. Three of the patients remain disease-free and two recurred. One of the patients passed away after a recurrence of brain metastases. We suggest that clonally expanded reactive lymphocytes induced by VACCIMEL partially remain as memory cells, which may be recalled after tumor recurrence and may foster ulterior activity of anti-PD-1 MAbs.

Development of Personalized Strategies for Precisely Battling Malignant Melanoma.

Melanoma is the most severe and fatal form of skin cancer, resulting from multiple gene mutations with high intra-tumor and inter-tumor molecular heterogeneity. Treatment options for patients whose disease has progressed beyond the ability for surgical resection rely on currently accepted standard therapies, notably immune checkpoint inhibitors and targeted therapies. Acquired resistance to these therapies and treatment-associated toxicity necessitate exploring novel strategies, especially those that can be personalized for specific patients and/or populations. Here, we review the current landscape and progress of standard therapies and explore what personalized oncology techniques may entail in the scope of melanoma. Our purpose is to provide an up-to-date summary of the tools at our disposal that work to circumvent the common barriers faced when battling melanoma.

The Use of Natural Therapies in Patients With Skin Cancer: A Scoping Review.

Complementary and alternative medicine (CAM) use has become a field of growing interest in dermatology. However, the prevalence of CAM use is difficult to quantify as it varies based on many factors. Given the exploratory nature of the topic, a scoping review was conducted to identify studies that quantify biologically based CAM use in skin cancer patients. A comprehensive search of Embase, PubMed, and Web of Science databases from inception to August 28th, 2023, was performed. A total of 3,150 articles were identified through the database search. After article screening, 6 studies were suitable for inclusion in this review. Articles included were all questionnaire, survey, or interview style. Biologically based CAM use is prevalent in skin cancer patients. It can be associated with many factors such as location, stage of cancer, and age. CAM use can interact with conventional therapy; therefore, physicians should employ a culturally competent approach to inquiring about CAM use in order to improve patient outcomes and identify patterns and predictors of use.J Drugs Dermatol. 2024;23(5):322-326. doi:10.36849/JDD.8077.

Understanding the Association Between Social Determinants of Health and Receipt of Immunotherapy for Melanoma.

PURPOSE: In this review article, we sought to elucidate how the social determinants of health, including socioeconomic status, education, neighborhood or physical environment, access to healthcare, and race/ethnicity, affect the likelihood of receiving immunotherapy, a novel and expensive treatment for melanoma.  Methods: The PubMed database was queried up to May 2023, for studies pertaining to health disparities in melanoma, including studies examining the utilization of immunotherapy agents for the treatment of melanoma across various social determinants of health. RESULTS: Disparities in the utilization of immunotherapy exist across various social determinants. A total of 10 studies were found to report on disparities in receipt of immunotherapy. These studies reported an association between insurance status, education level, socioeconomic status, as well as proximity to a cancer research center, and a lower likelihood of receiving immunotherapy. CONCLUSION: As the number of novel immunotherapy drugs grows, it is important to understand the various disparities affecting the delivery of immunotherapy across social determinants. The findings from this study can help to drive public health policy aimed at addressing inequities in the treatment of melanoma as well as other cancers.    J Drugs Dermatol. 2024;23(5):311-315. doi:10.36849/JDD.7803.

Interdisciplinary management of skin cancer. / Die interdisziplinäre Behandlung von Hautkrebs.

The interdisciplinary treatment of skin cancer in the head and neck area requires close collaboration between different specialist disciplines. The most common non-melanoma skin cancer tumor entities are cutaneous squamous cell carcinoma and basal cell carcinoma as well as their precursor lesions. One of the less common tumors is Merkel cell carcinoma, which also occurs primarily in light-exposed areas and, in contrast to squamous and basal cell carcinoma, is more likely to metastasize. Due to the low tendency of basal cell carcinoma as well as cutaneous squamous cell carcinoma to metastasize, a cure can often be achieved by surgery. If the tumor growth exceeds certain levels it may require collaboration between dermatology and otorhinolaryngology. The primary goal of this interdisciplinary collaboration is to achieve a functional, cosmetically and aesthetically acceptable result in addition to adequate tumor treatment. Depending on the stage of the tumor and the clinical course, a case may be discussed in an interdisciplinary tumor board in order to determine a personalised, appropriate and adequate treatment concept for each patient, including prevention, therapy and follow-up.

Incidence Rates and Outcomes of Nodular and Superficial Spreading Melanoma along the Rural-Urban Continuum in Kentucky and Their Relationship to Provider Care Access.

OBJECTIVES: This study compared incidence rates, stage at presentation, and cause-specific mortality of nodular and superficial spreading melanoma along the rural-urban continuum in Kentucky. We compared resulting patterns in our data with sample demographic and other potential factors, including population by county and primary care provider rate. METHODS: Retrospective patient data were extracted from the Surveillance, Epidemiology, and End Results database from 2010 through 2017. These data were supplemented by environmental, demographic, and socioeconomic data derived from publicly accessible databases. Correlation and χ2 analyses were used to test for significant differences in outcome variables by US Department of Agriculture Rural-Urban Continuum Code (RUCC) categories and other potential predictor variables. RESULTS: Incidence rates by Kentucky county were not associated with RUCC or population; likewise, there was no relationship between stage at presentation and RUCC category. There was, however, a highly significant association between cause-specific mortality and RUCC; patients from rural areas were significantly more likely to die from melanoma than those in urban areas. This overall difference was due to differences in mortality for superficial spreading melanoma. CONCLUSIONS: Our results suggest that a disparity in patients' ability or tendency to access primary care and/or specialist providers postdiagnosis may be critical factors in determining the ultimate outcome of a melanoma diagnosis. Further studies should explore the availability of dermatologists and/or treatment options for melanoma in rural areas. Our data also provide additional support for inclusion of melanoma subtype in the American Joint Committee on Cancer guidelines.

[Clinical characteristics and research progress of ocular Merkel cell carcinoma].

Merkel cell carcinoma (MCC) is a rare, aggressive epithelial and neuroendocrine tumor. MCC typically presents as painless nodules or patches rapidly growing in sun-exposed skin areas. Ocular MCC accounts for approximately 2.5% of all cases and may be misdiagnosed as granuloma or basal cell carcinoma. Risk factors for development include advanced age, ultraviolet exposure, male gender, immunosuppression, and Merkel cell polyomavirus infection. Treatment involves wide local excision with adjuvant radiotherapy, chemotherapy is typically reserved for metastatic disease, and immunotherapy and targeted therapy are currently under investigation showing promising early outcomes. This article summarizes the clinical characteristics and research progress of ocular MCC.

Primary prophylaxis with mTOR inhibitor enhances T cell effector function and prevents heart transplant rejection during talimogene laherparepvec therapy of squamous cell carcinoma.

The application of mammalian target of rapamycin inhibition (mTORi) as primary prophylactic therapy to optimize T cell effector function while preserving allograft tolerance remains challenging. Here, we present a comprehensive two-step therapeutic approach in a male patient with metastatic cutaneous squamous cell carcinoma and heart transplantation followed with concomitant longitudinal analysis of systemic immunologic changes. In the first step, calcineurin inhibitor/ mycophenolic acid is replaced by the mTORi everolimus to achieve an improved effector T cell status with increased cytotoxic activity (perforin, granzyme), enhanced proliferation (Ki67) and upregulated activation markers (CD38, CD69). In the second step, talimogene laherparepvec (T-VEC) injection further enhances effector function by switching CD4 and CD8 cells from central memory to effector memory profiles, enhancing Th1 responses, and boosting cytotoxic and proliferative activities. In addition, cytokine release (IL-6, IL-18, sCD25, CCL-2, CCL-4) is enhanced and the frequency of circulating regulatory T cells is increased. Notably, no histologic signs of allograft rejection are observed in consecutive end-myocardial biopsies. These findings provide valuable insights into the dynamics of T cell activation and differentiation and suggest that timely initiation of mTORi-based primary prophylaxis may provide a dual benefit of revitalizing T cell function while maintaining allograft tolerance.

From diagnosis to intervention: a review of telemedicine's role in skin cancer care.

Skin cancer treatment is a core aspect of dermatology that relies on accurate diagnosis and timely interventions. Teledermatology has emerged as a valuable asset across various stages of skin cancer care including triage, diagnosis, management, and surgical consultation. With the integration of traditional dermoscopy and store-and-forward technology, teledermatology facilitates the swift sharing of high-resolution images of suspicious skin lesions with consulting dermatologists all-over. Both live video conference and store-and-forward formats have played a pivotal role in bridging the care access gap between geographically isolated patients and dermatology providers. Notably, teledermatology demonstrates diagnostic accuracy rates that are often comparable to those achieved through traditional face-to-face consultations, underscoring its robust clinical utility. Technological advancements like artificial intelligence and reflectance confocal microscopy continue to enhance image quality and hold potential for increasing the diagnostic accuracy of virtual dermatologic care. While teledermatology serves as a valuable clinical tool for all patient populations including pediatric patients, it is not intended to fully replace in-person procedures like Mohs surgery and other necessary interventions. Nevertheless, its role in facilitating the evaluation of skin malignancies is gaining recognition within the dermatologic community and fostering high approval rates from patients due to its practicality and ability to provide timely access to specialized care.

An Explorative Study on Calcium Electroporation for Low-risk Basal Cell Carcinoma.

In electrochemotherapy, permeabilization of the cell membrane by electric pulses increases the anti-tumour effect of chemotherapeutics. In calcium electroporation, chemotherapy is replaced by calcium chloride with obvious benefits. This study explores the effect and underlying mechanisms of calcium electroporation on basal cell carcinomas using either high- or low-frequency electroporation. Low-risk primary basal cell carcinomas were treated in local anaesthesia with intratumoral calcium chloride followed by electroporation with high (167 kHz) or low (5 kHz) frequencies. Non-complete responders were retreated after 3 months. The primary endpoint was tumour response 3 months after last calcium electroporation. Plasma membrane calcium ATPase was examined in various cell lines as plasma membrane calcium ATPase levels have been associated with calcium electroporation efficacy. Twenty-two out of 25 included patients complete the study and 7 of these (32%) achieved complete response at 3 months with no difference in efficacy between high- and low-frequency pulses. High-frequency calcium electroporation was significantly less painful (p=0.03). Plasma membrane calcium ATPase was increased 16-32-fold in basal cell carcinoma cell lines compared with 4 other cancer cell lines. Calcium electroporation for low-risk basal cell carcinomas does not fulfil the requirements of a new dermatological basal cell carcinoma treatment but may be useful as adjuvant treatment to surgery in more advanced basal cell carcinomas. The elevated PMCA levels in basal cell carcinomas may contribute to low efficacy.

Therapies for cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: a systematic review of 157 cases.

BACKGROUND: Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis. Outcomes of RDEB-cSCC therapies have primarily been described in case reports. Systematic studies are scarce. This systematic review aims to assess the pathophysiology, clinical characteristics, and outcomes of RDEB-cSCCs, with a focus on results and mechanisms of recent immunotherapies and anti-EGFR treatments. RESULTS: A systematic literature search of epidermolysis bullosa and cSCC was performed in February 2024, using PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and EudraCT databases. Cases with administration of systematic therapies and unpublished outcomes regarding death were tracked with corresponding authors. Data extraction and risk of bias assessment was performed by two independent reviewers. Of 1132 references in the original search, 163 relevant articles were identified, representing 59 case reports, 7 cohort studies, 49 abstracts, 47 in-vitro/in-vivo experiments, and 1 bioinformatic study. From these, 157 cases of RDEB-cSCCs were included. The majority of RDEB-cSCCs were well-differentiated (64.1%), ulcerated (59.6%), and at least 2 cm in size (77.6%), with a median age at diagnosis of 30 years old (range 6-68.4). Surgery was the primary form of treatment (n = 128), followed by chemotherapy and radiotherapy. Anti-EGFR therapy and immunotherapy was also reported beginning in 2009 and 2019, respectively. Survival time from first cSCC diagnosis to death was available in 50 cases. When stratified by their treatment regimen, median survival time was 1.85 years (surgery + chemotherapy, n = 6), 2 years (surgery only, n = 19), 4.0 years (+ anti-EFGR therapy, n = 10), 4 years (surgery + radiotherapy, n = 9), 4.6 years (+ immunotherapy, n = 4), and 9.5 years (surgery + chemotherapy + radiotherapy; n = 2). Treatment-related adverse events were primarily limited to impaired wound healing for immunotherapies and nausea and fatigue for anti-EGFR therapies. CONCLUSIONS: Despite the challenges of a limited sample size in a rare disease, this systematic review provides an overview of treatment options for cSCCs in RDEB. When surgical treatment options have been exhausted, the addition of immunotherapy and/or anti-EGFR therapies may extend patient survival. However, it is difficult to attribute extended survival to any single treatment, as multiple therapeutic modalities are often used to treat RDEB-cSCCs.

Effectiveness and safety of interferon α-2a combined with phototherapy for patients with early-stage mycosis fungoides - a single-arm prospective study in 13 patients.

Background: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma.Objectives: This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a combined with phototherapy for early-stage MF.Methods: Thirteen patients with early-stage MF received subcutaneous injections of IFN α-2a at 3 million IU combined with phototherapy three times per week for 6 months. Treatment efficacy was measured by changes in body surface area (BSA) score and modified severity-weighted assessment tool (mSWAT) score at 1, 3, and 6 months after treatment. Histopathologic examinations of skin lesions were performed before and after treatment.Results: After 3 months of treatment, all 13 patients achieved a partial response, and BSA and mSWAT scores were significantly lower than those at baseline (p < 0.001). After 6 months, BSA and mSWAT scores were significantly lower than those at baseline (p < 0.001) and after 3 months (p < 0.05). Eleven patients achieved complete remission and two patients achieved a partial response (overall response rate, 100%). Histopathologic examination showed a significant decrease in the number of atypical lymphocytes in both epidermis and dermis. No severe adverse effects occurred.Conclusion: IFN α-2a in combination with phototherapy may be an effective and safe alternative modality for early-stage MF.

Leukemia Cutis in Relapsed Acute Myeloid Leukemia: A Call for Distinct Classification.

BACKGROUND Acute myeloid leukemia is characterized by dysregulated proliferation and maturation arrest of myeloid precursors, precipitating a spectrum of complications. Among these, leukemia cutis refers specifically to ectopic deposition and proliferation of malignant myeloid cells within the skin. This infiltration pathogenesis remains unclear. Although there are numerous reports of leukemia cutis in the setting of acute myeloid leukemia or primary acute myeloid leukemia, there are no specific reports of leukemia cutis in the setting of relapsed acute myeloid leukemia. CASE REPORT A 59-year-old woman, with a history of remission from poor-risk acute myeloid leukemia, previously treated with chemotherapy and allogenic bone marrow transplant, presented with shortness of breath, lethargy, anemia, thrombocytopenia, and subcutaneous nodules on lower extremities. Leukemia cutis was diagnosed, in the setting of relapsed acute myeloid leukemia. After unsuccessful salvage chemotherapy and being deemed unsuitable for further treatment, she pursued palliative care and died a month later. CONCLUSIONS Our case highlights a lack of reporting or making a distinction of those patients with relapsed acute myeloid leukemia and leukemia cutis. Consequently, it can be deduced that patients who simultaneously have relapsed acute myeloid leukemia and leukemia cutis are expected to fare worse in terms of clinical outcomes than those with primary acute myeloid leukemia and leukemia cutis. Relapsed acute myeloid leukemia patients with leukemia cutis should be classified as a distinct group, warranting further research into aggressive therapeutic targets and survival rates, while emphasizing the need for more vigilant follow-up and lower biopsy thresholds for cutaneous lesions in patients with treated hematologic malignancies.

BRAF-Mutated Melanoma Journey in Latin America: Expert Recommendations From Diagnosis to Treatment.

OBJECTIVES: • Gather a panel of Latin American experts in testing and treating BRAF-melanoma. • Describe the current landscape of BRAF-mutated melanoma in Latin America. • Outline the current gaps in testing and recommend improvements for testing and treating BRAF-mutated melanoma in the region. INTRODUCTION: Melanoma prevalence in Latin America is lower than in high- and middle-income countries. However, recent data indicate that the region's incidence and mortality are rising, with more stage IV patients being diagnosed. According to international clinical practice guidelines, conducting BRAF-mutation testing in patients with stage III or stage IV melanoma and high-risk resected disease is imperative. Still, BRAF-mutation testing and targeted therapies are inconsistently available in the region. METHODS: Americas Health Foundation convened a meeting of Latin American experts on BRAF-mutated melanoma to develop guidelines and recommendations for diagnosis through treatment. RESULTS AND CONCLUSIONS: Some recommendations for improving diagnostics through improving access and reducing the cost of BRAF-mutation testing, enhancing efficiency in pathology laboratories, and creating country-specific local guidelines. The panel also gave treatment recommendations for neo-adjuvant therapy, adjuvant therapy, and therapy for patients with metastatic disease in Latin America.

Trackable Liposomes for In Vivo Delivery Tracing toward Personalized Medicine Care under NIR Light on Skin Tumor.

We report an near-infrared (NIR)-trackable and therapeutic liposome with skin tumor specificity. Liposomes with a hydrodynamic diameter of ∼20 nm are tracked under the vein visualization imaging system in the presence of loaded paclitaxel and NIR-active agents. The ability to track liposome nanocarriers is recorded on the tissue-mimicking phantom model and in vivo mouse veins after intravenous administration. The trackable liposome delivery provides in vitro and in vivo photothermal heat (∼40 °C) for NIR-light-triggered area-specific chemotherapeutic release. This approach can be linked with a real-time vein-imaging system to track and apply area-specific local heat, which hitchhikes liposomes from the vein and finally releases them at the tumor site. We conducted studies on mice skin tumors that indicated the disappearance of tumors visibly and histologically (H&E stains). The ability of nanocarriers to monitor after administration is crucial for improving the effectiveness and specificity of cancer therapy, which could be achieved in the trackable delivery system.

Enhancing tumor's skin photothermal therapy using Gold nanoparticles : a Monte Carlo simulation.

The aim of this study is to investigate how the introduction of Gold nanoparticles GNPs into a skin tumor affects the ability to absorb laser light during multicolor laser exposure. The Monte Carlo Geant4 technique was used to construct a cubic geometry simulating human skin, and a 5 mm tumor spheroid was implanted at an adjustable depth x. Our findings show that injecting a very low concentration of 0.01% GNPs into a tumor located 1 cm below the skin's surface causes significant laser absorption of up to 25%, particularly in the 900 nm to 1200 nm range, resulting in a temperature increase of approximately 20%. It is an effective way to raise a tumor's temperature and cause cell death while preserving healthy cells. The addition of GNPs to a tumor during polychromatic laser exposure with a wavelength ranging from 900 nm to 1200 nm increases laser absorption and thus temperature while preserving areas without GNPs.