Metastatic Basal Cell Carcinoma Research Articles

Hedgehog pathway inhibitors for locally advanced and metastatic basal cell carcinoma: A real-world single-center retrospective review.

Basal cell carcinoma (BCC) is highly curable by surgical excision or radiation. In rare cases, BCC can be locally destructive or difficult to surgically remove. Hedgehog inhibition (HHI) with vismodegib or sonidegib induces a 50-60% response rate. Long-term toxicity includes muscle spasms and weight loss leading to dose decreases. This retrospective chart review also investigates the impact of CoQ10 and calcium supplementation in patients treated with HHI drugs at a single academic medical center from 2012 to 2022. We reviewed the charts of adult patients diagnosed with locally advanced or metastatic BCC treated with vismodegib or sonidegib primarily for progression-free survival (PFS). Secondary objectives included overall survival, BCC-specific survival, time to and reasons for discontinuation, overall response rate, safety and tolerability, use of CoQ10 and calcium supplements, and insurance coverage. Of 55 patients assessable for outcome, 34 (61.8%) had an overall clinical benefit, with 25 (45.4%) having a complete response and 9 (16.3%) a partial response. Stable disease was seen in 14 (25.4%) and 7 (12.7%) progressed. Of the 34 patients who responded to treatment, 9 recurred. Patients who were rechallenged with HHI could respond again. The median overall BCC-specific survival rate at 5 years is 89%. Dose reductions or discontinuations for vismodegib and sonidegib occurred in 59% versus 24% of cases, or 30% versus 9% of cases, respectively. With CoQ10 and calcium supplementation, only 17% required a dose reduction versus 42% without. HHI is highly effective for treating advanced BCC but may require dosing decreases. Sonidegib was better tolerated than vismodegib. CoQ10 and calcium supplementation can effectively prevent muscle spasms.

Metastatic basal cell carcinoma with neuroendocrine differentiation. Complete response to cemiplimab.

We report a patient with a metastatic basal cell carcinoma with neuroendocrine differentiation who responded well to cemiplimab and not to previous therapies. The different histological variants could determine treatment response.

Metastatic basal cell carcinoma: a case report and review of current literature

Metastatic basal cell carcinoma: a case report and review of current literature

Patterns of metastasis from a multicenter cohort of metastatic basal cell carcinoma

Patterns of metastasis from a multicenter cohort of metastatic basal cell carcinoma

Japanese Dermatological Association guidelines: Outlines of Japanese clinical guidelines for basal cell carcinoma 2021.

To summarize the current therapies for skin cancers, the Japanese Skin Cancer Society issued the first guidelines for skin cancers, including melanoma, squamous cell carcinoma, basal cell carcinoma (BCC), and extramammary Paget's disease, in 2007. These guidelines were revised in 2015. Herein, we present the English version of the 2021 edition of the Japanese clinical guidelines for BCC. In the latest edition, all procedures were performed according to the Grading of Recommendations, Assessment, Development and Evaluation systems. The clinical questions that could not be answered were selected for further analysis. A comprehensive literature search, systematic review, and recommendations for each clinical question were determined by a multidisciplinary expert panel comprising dermatologists, a plastic and reconstructive surgeon, and a pathologist. Surgical resection is the gold-standard therapy of BCC. Radiotherapy or topical treatments, other than surgical resection, have been used in some cases. Patients with unresectable or metastatic BCC require systemic therapy. Novel agents, such as immune response modifiers or hedgehog pathway inhibitors, are emerging worldwide for the treatment of BCC. Based on these viewpoints, four relevant clinical questions regarding, surgical resection, radiotherapy, topical treatment, and systemic therapy, were raised in this report that aims to help clinicians select suitable therapies for their patients.

Health-Related Quality of Life in Patients with Metastatic Basal Cell Carcinoma Treated with Cemiplimab: Analysis of a Phase 2 Open-Label Clinical Trial

Health-Related Quality of Life in Patients with Metastatic Basal Cell Carcinoma Treated with Cemiplimab: Analysis of a Phase 2 Open-Label Clinical Trial

Metastatic basal cell carcinoma on the neck of an elderly man

Skin cancer will affect 1 in 5 Americans by age 70 and is most common in White patients. Basal cell carcinoma (BCC) is the most common type of skin cancer, constituting roughly 80% of nonmelanoma cutaneous skin cancers with ~3.5 million cases annually. BCC is routinely treated with cutaneous excision and/or topical medications, with high cure rates for both. Despite its prevalence, BCC rarely metastasizes. In this report, we describe a case of metastatic BCC on the right neck of an elderly man. This highlights the importance of routine skin exams and rapid assessment of palpable lymphadenopathy in patients with a history of nonmelanoma skin cancer.

Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors

Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636). In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints were ORR per investigator assessment, progression-free survival (PFS), overall survival (OS), complete response rate, safety, and tolerability. Fifty-four patients were enrolled: 70% were male and the median age of patients was 64 [interquartile range (IQR) 57.0-73.0] years. The median duration of follow-up was 8 months (IQR 4-21 months). The ORR per ICR was 22% [95% confidence interval (CI) 12% to 36%], with 2 complete responses and 10 partial responses. Among responders, the median time to response per ICR was 3 months (IQR 2-7 months). The estimated median DOR per ICR was not reached [95% CI 10 months-not evaluable (NE)]. The disease control rate was 63% (95% CI 49% to 76%) per ICR and 70% (95% CI 56% to 82%) per investigator assessment. The median PFS per ICR was 10 months (95% CI 4-16 months); the median OS was 50 months (95% CI 28 months-NE). The most common treatment-emergent adverse events were fatigue [23 (43%)] and diarrhoea [20 (37%)]. There were no treatment-related deaths. Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.

P030 A rare case of metastatic head and neck basal cell carcinoma

P030 A rare case of metastatic head and neck basal cell carcinoma

Non-Surgical Therapeutic Strategies for Non-Melanoma Skin Cancers.

Non-melanoma skin cancer (NMSC) is a globally prevalent skin disease, with basal cell carcinoma and squamous cell carcinoma accounting for 99% of NMSC cases. While surgical excision is the most common approach, numerous non-surgical therapies have rapidly advanced in recent years. In cases of low-risk NMSC, alongside surgical excision, priority should be given to physical therapy and photodynamic therapy. Physical therapy modalities, exemplified by electrodessication and curettage, emerge as safe and efficacious alternatives. In juxtaposition, photodynamic therapy, albeit relatively more costly, assumes preference for patients exhibiting heightened cosmetic concerns owing to the scarring risks inherent to physical therapy and surgical excision. Notably, the combination of curettage and photodynamic therapy has exhibited remarkable efficacy in the treatment of nodular basal cell carcinoma. Additionally, for elderly patients who may be intolerant to stimulation, modified photodynamic therapy offers an almost painless option. When surgery is unavoidable, photodynamic therapy can be a valuable adjunct, allowing for a more conservative surgical approach, either before or after the procedure. Radiotherapy holds a prominent role in comprehensive treatment strategies, especially for patients ineligible for surgical intervention or those with lesions precluding further surgical measures. In cases of NMSC exhibiting perineural invasion or lymphovascular involvement, adjunctive radiotherapy is advised; however, potential adverse effects necessitate careful consideration. For advanced NMSC cases where surgery and physical therapy fall short, immunotherapy provide viable solutions. Systemic therapy employing Hedgehog pathway inhibitors can be considered for patients with distant metastatic basal cell carcinoma, despite its low incidence, or individuals with locally advanced lesions who are not surgical candidates, or those encountering recurrences after resection and radiotherapy. However, close monitoring of disease progression and adverse reactions is crucial. In this evolving landscape of NMSC treatment, personalized and multidisciplinary approaches are key, ensuring optimal outcomes while prioritizing patient safety and satisfaction.

Cellular Deconvolution Reveals Unique Findings in Several Cell Type Fractions Within the Basal Cell Carcinoma Tumor Microenvironment

Introduction: Despite therapeutic advancements, locally advanced and metastatic basal cell carcinomas continue to carry poor prognoses and high recurrence rates. Current treatment options remain suboptimal due to limited efficacy and associated adverse events. The objectives of this study are to 1) characterize the basal cell carcinoma immune cell microenvironment and 2) identify novel therapeutic targets.
 Methods: Transcriptome data representing 25 basal cell carcinoma and 25 control tissue samples were obtained from the Gene Expression Omnibus. Cell type fraction estimates were derived by least-squares deconvolution. Population differences were determined by Mann-Whitney U test.
 Results: Most significantly, two deconvolution algorithms similarly observed greater B cell infiltration in tumor samples compared to normal tissue (P<0.0001).
 Conclusion: Importantly, the results of this study provide new insight into the basal cell carcinoma tumor microenvironment and nominate testable immune cell populations for future therapeutic discovery. Study limitations include sample size and applicable background prediction levels of bulk deconvolution tools.

A multicenter real-world analysis of risk factors, therapeutics, and outcomes of patients with metastatic basal cell carcinoma

BackgroundMetastatic BCC (mBCC) is rare and there are limited data regarding patient and tumor risk factors, optimal treatments, and disease prognosis. ObjectiveTo assess patient and tumor characteristics, therapeutics, and outcomes of mBCC stratified by location of metastasis. MethodsRetrospective cohort study of fifty-three patients with mBCC treated at four large academic centers in Boston, Massachusetts; Philadelphia, Pennsylvania; and Cleveland, Ohio between January 1, 2005 to December 31, 2021. ResultsA total of 53 patients with mBCC were identified across 4 centers, 22 (42%) of whom had mBCC with spread limited to lymph nodes and 31 (58%) patients with distant organ spread (with or without lymph node involvement). Overall, half (n=11) of patients with nodal metastasis achieved complete remission of disease, compared to just 1 (3%) patient with distant metastasis. The 5-year survival for nodal and distant metastatic patients was 89.3% and 61.0%, respectively. LimitationsSmall sample size due to disease rarity Conclusions and RelevancePatients with nodal disease are more likely to have disease remission whereas patients with distant metastasis are more likely to have persistent disease and die from their disease. However, 5-year survival rates exceed 50%, even for stage IV disease.

[Current Management of Basal Cell Carcinoma].

For the management of basal cell carcinoma, the primary performance of a risk stratification, which is decisive for the further diagnostic and therapeutic steps, is becoming increasingly important.Various non-invasive methods are available to confirm the clinical diagnosis. Histological confirmation of the diagnosis is recommended in unclear cases. In poorly displaced lesions, preoperative cross-sectional imaging of the tumor area should be performed to exclude osseous infiltration.The gold standard in treatment remains surgery, which should be performed by means of micrographically controlled surgery if possible. In addition, there are other therapeutic methods such as radiotherapy or a number of topical therapy options (photodynamic therapy, cryotherapy or application of 5-fluorouracil or imiquimod), which can be used in certain cases. Also for advanced or metastatic basal cell carcinoma, effective drugs are available in the form of the hedgehog inhibitors, for which there is now several years of application experience with regard to efficacy and handling of adverse events. With the PD-1 inhibitor cemiplimab, a further therapeutic option for non-operable or metastatic tumors has been available since June 2021.The most important preventive measure is consistent textile or chemical UV protection in already affected individuals. In addition, nicotinamide and celecoxib can be used orally for prevention. For follow-up, the current S2k guideline recommends regular self-monitoring and standardized medical check-ups.

Utility of GLI1 RNA Chromogenic in Situ Hybridization in Distinguishing Basal Cell Carcinoma From Histopathologic Mimics

Basal cell carcinoma (BCC) is the most common human malignancy and is a leading cause of nonmelanoma skin cancer-related morbidity. BCC has several histologic mimics which may have treatment and prognostic implications. Furthermore, BCC may show alternative differentiation toward a variety of cutaneous structures. The vast majority of BCCs harbor mutations in the hedgehog signaling pathway, resulting in increased expression of the GLI family of transcription factors. GLI1 immunohistochemistry has been shown to discriminate between several tumor types but demonstrates high background signal and lack of specificity. In this study, we evaluated the utility of GLI1 RNA chromogenic in situ hybridization (CISH) as a novel method of distinguishing between BCC and other epithelial neoplasms. Expression of GLI1 by RNA CISH was retrospectively evaluated in a total of 220 cases, including 60 BCCs, 37 squamous cell carcinomas (SCCs) including conventional, basaloid, and human papillomavirus infection (HPV)-associated tumors, 16 sebaceous neoplasms, 10 Merkel cell carcinomas, 58 benign follicular tumors, and 39 ductal tumors. The threshold for positivity was determined to be greater than or equal to 3 GLI1 signals in at least 50% of tumor cells. Positive GLI1 expression was identified in 57/60 BCCs, including metastatic BCC, collision lesions with SCC, and BCCs with squamous, ductal, or clear cell differentiation or with other unusual features compared to 1/37 SCCs, 0/11 sebaceous carcinomas, 0/5 sebaceomas, 1/10 Merkel cell carcinomas, 0/39 ductal tumors, and 28/58 follicular tumors. With careful evaluation, GLI1 RNA CISH is highly sensitive (95%) and specific (98%) in distinguishing between BCC and nonfollicular epithelial neoplasms. However, GLI1 CISH is not specific for distinguishing BCC from most benign follicular tumors. Overall, detection of GLI1 RNA by CISH may be a useful tool for precise classification of histologically challenging basaloid tumors, particularly in the setting of small biopsy specimens, metaplastic differentiation, or metastatic disease.

Primary multiple malignant skin tumors: melanoma and basal cell carcinoma

The incidence of skin melanoma in the world is growing every year. Despite advances in diagnostics, the identification of the primary focus of melanoma in some cases is still difficult. The natural course sometimes manifests only with the appearance of melanoma metastases, which can mimic other diseases. Patient S., 52 years old, was admitted to the FCBRN of FMBA of Russia with complaints on periodic systemic dizziness, headaches of a pressing nature, episodes of speech impairment over the past three months. According to the brain MRI-scan results, a volumetric formation of the left frontal lobe was revealed. Upon examination, two non-pigmented lesions were found on the skin of the scalp and forehead. Due to the presence of focal neurological symptoms, it was decided to remove the brain tumor using neurophysiological monitoring and the scalp skin lesion, with histological verification. Morphological diagnosis of the removed brain tumor was a metastasis of amelanotic epithelioid melanoma. The skin lesion was basal cell carcinoma. Thus, the patient had primarily multiple malignant tumors: metastatic melanoma and basal cell carcinoma. The primary focus of melanoma could not be identified by available noninvasive research methods. The patient was referred to an oncologist to decide on the tactics of further examination and treatment. To date, the patient has been treated according to the scheme sh0876 1 line 1 course of pembrolizumab 400 mg IV, cycle 42 days.

New therapeutic developments for basal cell carcinoma.

In 2013, systemic therapy was introduced into the treatment of locally advanced (laBCC) and metastatic basal cell carcinoma (mBCC). Meanwhile, immunotherapy has been approved in this indication as well. Additional immunotherapies and other classes of drugs including combination regimens are currently being investigated in clinical trials. These agents might considerably expand the therapeutic armamentarium for laBCC and mBCC in the future.

HSR23-097: Health-Related Quality of Life in Patients With Metastatic Basal Cell Carcinoma Treated With Cemiplimab: Analysis of a Phase 2 Open-Label Clinical Trial

"HSR23-097: Health-Related Quality of Life in Patients With Metastatic Basal Cell Carcinoma Treated With Cemiplimab: Analysis of a Phase 2 Open-Label Clinical Trial" published on 31 Mar 2023 by National Comprehensive Cancer Network.

C-FOS Expression in Metastatic Basal Cell Carcinoma with Spontaneous Basosquamous Transition

Abstract is missing (Short communication)

Primary analysis of Phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma who progressed on or were intolerant to hedgehog inhibitors

Primary analysis of Phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma who progressed on or were intolerant to hedgehog inhibitors

Evaluating the medical management of locally advanced and metastatic basal cell carcinoma: A single institutional retrospective analysis investigating efficacy, safety, and tolerability

Evaluating the medical management of locally advanced and metastatic basal cell carcinoma: A single institutional retrospective analysis investigating efficacy, safety, and tolerability