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Journal For Immunotherapy of Cancer Dec 2023Systemic treatment options for patients with locally advanced or metastatic basal cell carcinoma (BCC) are limited, particularly when tumors are refractory to...
Systemic treatment options for patients with locally advanced or metastatic basal cell carcinoma (BCC) are limited, particularly when tumors are refractory to anti-programmed cell death protein-1 (PD-1). A better understanding of immune checkpoint expression within the BCC tumor microenvironment may inform combinatorial treatment strategies to optimize response rates. CD3, PD-1, programmed death ligand-1 (PD-L1), lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3)+ cell densities within the tumor microenvironment of 34 archival, histologically aggressive BCCs were assessed. Tumor infiltrating lymphocyte (TIL) expression of PD-1, PD-L1, and LAG-3, and to a lesser degree TIM-3, correlated with increasing CD3+ T-cell densities (Pearson's =0.89, 0.72, 0.87, and 0.63, respectively). 100% of BCCs (34/34) demonstrated LAG-3 and PD-1 expression in >1% TIL; and the correlation between PD-1 and LAG-3 densities was high (Pearson's r=0.89). LAG-3 was expressed at ~50% of the level of PD-1. Additionally, we present a patient with locally-advanced BCC who experienced stable disease during and after 45 weeks of first-line anti-PD-1 (nivolumab), followed by a partial response after the addition of anti-LAG-3 (relatlimab). Longitudinal biopsies throughout the treatment course showed a graduated increase in LAG-3 expression after anti-PD-1 therapy, lending support for coordinated immunosuppression and suggesting LAG-3 as a co-target for combination therapy to augment the clinical impact of anti-PD-(L)1.
Topics: Humans; B7-H1 Antigen; Hepatitis A Virus Cellular Receptor 2; Programmed Cell Death 1 Receptor; Carcinoma, Basal Cell; Skin Neoplasms; Tumor Microenvironment
PubMed: 38101862
DOI: 10.1136/jitc-2023-007463 -
Dermatology Practical & Conceptual Oct 2023For patients with advanced basal cell carcinoma (BCC), including locally advanced or metastatic BCC not amenable to curative surgery or radiotherapy, hedgehog pathway... (Review)
Review
For patients with advanced basal cell carcinoma (BCC), including locally advanced or metastatic BCC not amenable to curative surgery or radiotherapy, hedgehog pathway inhibitors (HHI) vismodegib and sonidegib are approved as first-line systemic treatment. Results from clinical trials highlight that the overall discontinuation rate of HHI treatment varies from 88% to 92% with vismodegib and is approximately 92% with sonidegib, and half of patients will discontinue HHI after approximately 8 to 12 months. The main factors weighing in on the decision to discontinue HHI include efficacy (tumor response), adverse events and patient decision. In clinical practice, some of the patients that stop HHI may be re-evaluated if the tumor becomes amenable to surgery, or restart HHI at a later time, while others will need to switch to immunotherapy, depending on the reasons for HHI discontinuation. In this review, we revisit the therapeutic decisions considering a switch from HHI to immunotherapy with anti-PD-1 agent cemiplimab and we highlight the place of cemiplimab in the therapeutic ladder for patients with advanced BCC. We discuss the evidence on the efficacy and safety of anti-PD-1 agents as second-line systemic monotherapy, or in combination with other treatments, and the emergence of checkpoint immunotherapy as a neoadjuvant treatment.
PubMed: 37992360
DOI: 10.5826/dpc.1304a252 -
Biomedicines Nov 2023This review summarizes the effectiveness of photodynamic therapy (PDT) in the treatment of the pigmented subtype of basal cell carcinoma (BCC) based on the current... (Review)
Review
This review summarizes the effectiveness of photodynamic therapy (PDT) in the treatment of the pigmented subtype of basal cell carcinoma (BCC) based on the current literature. PDT is a light-activated treatment, non-invasive, that selectively destroys tumor cells and tissues via the interaction of a photosensitizer, light, and molecular oxygen. It can induce cancer cell death through direct tumor vascular damage or via the induction of immune response. However, human skin is also an absorption and scattering medium since it contains hemoglobin and melanin that act as chromophores. Eumelanin can be considered a light-absorber and an intracellular antioxidant that can neutralize PDT-induced ROS and, therefore, decrease PDT success. Various factors, including tumor depth, the degree of pigmentation in malignant cells, and the individual's skin phototype, can impact the outcome of this intricate biochemical process. It has been widely recognized that PDT exhibits limited efficacy in the treatment of pigmented lesions. However, new combination techniques such as curettage or debulking before PDT show promising results in the treatment of pigmented BCC.
PubMed: 38002098
DOI: 10.3390/biomedicines11113099 -
International Journal of Molecular... Jun 2023Skin cancers, including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), and melanoma, are the most common malignancies in the United States. Loss of... (Review)
Review
Skin cancers, including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), and melanoma, are the most common malignancies in the United States. Loss of DNA repair pathways in the skin plays a significant role in tumorigenesis. In recent years, targeting DNA repair pathways, particularly homologous recombination deficiency (HRD), has emerged as a potential therapeutic approach in cutaneous malignancies. This review provides an overview of DNA damage and repair pathways, with a focus on HRD, and discusses major advances in targeting these pathways in skin cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors have been developed to exploit HRD in cancer cells. PARP inhibitors disrupt DNA repair mechanisms by inhibiting PARP enzymatic activity, leading to the accumulation of DNA damage and cell death. The concept of synthetic lethality has been demonstrated in HR-deficient cells, such as those with BRCA1/2 mutations, which exhibit increased sensitivity to PARP inhibitors. HRD assessment methods, including genomic scars, RAD51 foci formation, functional assays, and BRCA1/2 mutation analysis, are discussed as tools for identifying patients who may benefit from PARP inhibitor therapy. Furthermore, HRD has been implicated in the response to immunotherapy, and the combination of PARP inhibitors with immunotherapy has shown promising results. The frequency of HRD in melanoma ranges from 18% to 57%, and studies investigating the use of PARP inhibitors as monotherapy in melanoma are limited. Further research is warranted to explore the potential of PARP inhibition in melanoma treatment.
Topics: Humans; Female; Poly(ADP-ribose) Polymerase Inhibitors; BRCA1 Protein; Homologous Recombination; Carcinoma, Squamous Cell; BRCA2 Protein; Skin Neoplasms; Poly(ADP-ribose) Polymerases; Melanoma; Ovarian Neoplasms
PubMed: 37445949
DOI: 10.3390/ijms241310771 -
Cells Nov 2023Basosquamous carcinoma (BSC), an uncommon and aggressive nonmelanoma skin cancer exhibiting characteristics ranging from basal cell carcinoma (BCC) to squamous cell... (Review)
Review
Basosquamous carcinoma (BSC), an uncommon and aggressive nonmelanoma skin cancer exhibiting characteristics ranging from basal cell carcinoma (BCC) to squamous cell carcinoma (SCC), is a subject of controversy in terms of its classification, pathogenesis, histologic morphology, biologic behavior, prognosis, and management. This narrative review is based on an electronic search of English-language articles in PubMed that included the terms "basosquamous carcinoma" and/or "metatypical carcinoma of the skin" in their titles. The review aims to succinctly present and assess current data on the epidemiology, clinical presentation, dermoscopic, LC-OCT, and histopathologic characteristics, as well as the genetics and management of BSC, providing insight into this intriguing entity. As a conclusion, dermoscopy, deep incisional biopsies, and immunohistologic techniques should be applied in clinically suspicious lesions to achieve an early diagnosis and better prognosis of this tumor. Surgical treatments, including wide excision and Mohs' micrographic surgery, remain the treatment of choice. Finally, Hedgehog pathway inhibitors and checkpoint inhibitors, must be thoroughly investigated with large controlled trials, since they may offer an alternative solution to irresectable or difficult-to-treat locally advanced cases of basosquamous carcinoma.
Topics: Humans; Carcinoma, Basosquamous; Hedgehog Proteins; Skin Neoplasms; Carcinoma, Basal Cell; Carcinoma, Squamous Cell
PubMed: 38067165
DOI: 10.3390/cells12232737 -
The Libyan Journal of Medicine Dec 2023We report our experience in surgical management of primary malignant tumors of the eyelids. We have specified the various surgical techniques used, as well as... (Review)
Review
We report our experience in surgical management of primary malignant tumors of the eyelids. We have specified the various surgical techniques used, as well as functional and anatomical results. A review of patients admitted for malignant tumor of the eyelids in the oculoplastic department of the Hedi Raies Institute of Ophthalmology from January 2012 to December 2021. One hundred and twenty-three patients with malignant eyelid tumors were hospitalized. Surgical treatment involved 114 tumor lesions, which represents 95% of the cases. One hundred and eleven lesions (97.4%) had been operated by simple tumor resection. Safety margins were, respectively, 4 mm in 63.2% and from 5 to 6 mm in 34.2%. Extemporaneous histological examination was performed in three cases (2.6%). Reconstruction involved the anterior lamella (AL) in 92 cases (80.7%), the posterior lamella (PL) in 66 cases (57.9%), the medial canthus in 18 cases (15, 8%), and lateral canthus in 4 cases (3.5%). The excision was oncological in 85 cases (74.6%) and incomplete in 19 cases (16.7%). Tumor recurrence occurred in seven cases (6.1%), after an average delay of 36 months. The anatomical and functional features of the eyelids require a good reconstruction of the transfixion eyelid defect. Many reconstruction methods are available, allowing extensive and complex palpebral repairs. Oncologic prognosis is conditioned by the surgical quality.
Topics: Humans; Female; Eyelids; Breast Neoplasms; Hospitalization; Skin Neoplasms
PubMed: 37731362
DOI: 10.1080/19932820.2023.2258668 -
Journal of Clinical Medicine Dec 2023(1) Background: The aim of this study was to correlate the diagnostic criteria described in dermatoscopy, ultrasonography (US), ex vivo confocal microscopy, and...
(1) Background: The aim of this study was to correlate the diagnostic criteria described in dermatoscopy, ultrasonography (US), ex vivo confocal microscopy, and histology to the most common subtypes of basal cell carcinoma (BCC). (2) Methods: We conducted a prospective study including 46 BCC cases, which were analyzed with dermatoscopy using the Delta 30 dermatoscope and Vidix 4.0 videodermoscope, with US using a high-resolution 20 MHz linear probe, with confocal microscopy, along with histopathological analysis. (3) Results: This study categorized BCC by histological subtype, with nodular being the most common (84.8%) and various other subtypes represented. US measurements of tumor thickness correlated strongly with the histopathological depth of invasion index (DI). Dermatoscopy analysis revealed significant associations between specific features and BCC subtypes. The DI was directly related to arborized vessels but inversely related to short, fine telangiectasias, maple-leaf-like areas, and spoke-wheel areas. The presence of ulceration was directly related to the DI. Confocal microscopy images exhibited several characteristics, including fluorescence, nuclear crowding, peripheral palisading, clefting, increased nuclear-cytoplasmic (N/C) ratio, and a "cauliflower-like" appearance. (4) Conclusion: The advanced detection of BCC through imagistic techniques like dermatoscopy, confocal microscopy, and ultrasound improves the diagnosis and may offer valuable insights for treatment in the future by evaluating lesion characteristics.
PubMed: 38202046
DOI: 10.3390/jcm13010039 -
Dermatology and Therapy Sep 2023Basal cell carcinoma (BCC) affects 3.3 million Americans annually. Treatment modalities for BCC include many surgical and nonsurgical options. The cost of BCC treatment... (Review)
Review
BACKGROUND
Basal cell carcinoma (BCC) affects 3.3 million Americans annually. Treatment modalities for BCC include many surgical and nonsurgical options. The cost of BCC treatment can pose a substantial burden to patients and the healthcare system. Cost can be an important consideration in BCC treatment planning.
OBJECTIVE
We present an approach to the management of BCC when cost reduction is a priority.
METHODS
A PubMed literature search identified studies on effectiveness of current BCC therapies. Treatment prices were obtained from the Medicare National Fee Schedule, GoodRx, and pharmaceutical companies. The American Academy of Dermatology's (AAD) guidelines for treating BCC were used to develop recommendations for cost-reductive treatment.
RESULTS
The cost of treating a primary superficial BCC < 0.5 cm arising on Area M (cheeks, forehead, scalp, neck, jawline, pretibial surface) was $143 with curettage and electrodesiccation (C&E), $143 with cryosurgery, $210 with standard excision and simple reconstruction (SE), $1221 with Mohs Micrographic Surgery (MMS) and simple reconstruction, $472 with imiquimod, $186 with 5-fluorouracil (5-FU), and $354-$371 for photodynamic therapy (PDT). The cost of treating a primary nodular BCC 1.1-2 cm arising on Area L (trunk and extremities, excluding pretibial surface, hands, feet, nail units and ankles) was $183 with C&E, $183 with cryosurgery, $251 with SE and simple reconstruction, $1163-1351 with MMS and simple reconstruction, $472 with imiquimod, $186 with 5-FU, and $354-$371 for photodynamic therapy (PDT). The cost of treating a giant BCC (BCC > 10 cm with aggressive behavior) was $465-3311 with radiation, $139,560 with vismodegib, $144,452 with sonidegib, ~ $44.5 with cisplatin (medication cost only), and at least $184,836 with cemiplimab-rwlc.
CONCLUSIONS
For a primary superficial BCC < 0.5 cm arising on Area M, the cost-conscious algorithm prioritizes C&E or cryosurgery. For a primary nodular BCC 1.1-2 cm arising on Area L, the cost-conscious algorithm prioritizes C&E, cryosurgery, or 5-FU. For a giant BCC, the cost-conscious algorithm identifies superficial radiation therapy as first line.
PubMed: 37531073
DOI: 10.1007/s13555-023-00989-x