Advanced Basal Cell Carcinoma Research Articles

Biochemistry laboratory shift based on common terminology criteria in patients with advanced basal cell carcinoma receiving sonidegib 200 mg daily: Results from the 42-month BOLT study

Biochemistry laboratory shift based on common terminology criteria in patients with advanced basal cell carcinoma receiving sonidegib 200 mg daily: Results from the 42-month BOLT study

Hematology laboratory shift based on common terminology criteria in patients with advanced basal cell carcinoma receiving sonidegib 200 mg daily: Results from the 42-month BOLT study

Hematology laboratory shift based on common terminology criteria in patients with advanced basal cell carcinoma receiving sonidegib 200 mg daily: Results from the 42-month BOLT study

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

Nevoid Basal Cell Carcinoma Syndrome: A Review

Introduction: Gorlin syndrome (GS) or nevoid basal cell carcinoma syndrome (NBCCS) is a rare genetic disorder characterised by development of multiple basal cell carcinomas (BCCs) at a young age. NBCCS occurs because of mutations in the PTCH1 gene, which functions as a tumour suppressor gene.
 Patients with GS can have varied manifestations, both cutaneous and extra-cutaneous. The most notable cutaneous manifestations are BCCs, which are also the most characteristic tumours in GS, and palmar/plantar pits. Besides the BCC, medulloblastomas are the second most characteristic malignant presentation.
 There are a set of criteria for the diagnosis of GS, which have a high predictability in making an accurate diagnosis of GS. Genetic testing for PTCH1 gene is one of the diagnostic criteria, which is positive in about 60% of patients.
 Patients with GS need a multidisciplinary approach. Mohs micrographic surgery is recommended for BCCs on high risk areas. SMO receptor inhibitors such as Vismodegib and Sonidegib have been approved by FDA for the treatment of advanced BCCs.

Vismodegib en el tratamiento del carcinoma basocelular localmente avanzado

Vismodegib en el tratamiento del carcinoma basocelular localmente avanzado

Comparison of the Basal Cell Carcinoma (BCC) Tumour Microenvironment to Other Solid Malignancies

Basal cell carcinoma (BCC) is the most common form of skin cancer, contributing to nearly a third of new cancer cases in Western countries. Most BCCs are considered low risk "routine" lesions that can either be excised through surgery or treated with chemotherapeutic agents. However, around 1-2% of BCC cases are locally aggressive, present a high risk of metastasis, and often develop chemoresistance, termed advanced BCC. There currently exists no animal model or cell line that can recapitulate advanced BCC, let alone intermediate-risk and high-risk early BCC. We previously found that aggressive BCC tumours presented a Th2 cytokine inflammation profile, mesenchymal stem cell properties, and macrophage-induced tumoral inflammation. In this study, we aimed to identify potential BCC "relatives" among solid-organ malignancies who present similar immune cell proportions in their microenvironment compositions. Using immune cell type deconvolution by CIBERSORTx, and cell type enrichment by xCell, we determined three cancers with the most similar tumour microenvironments as compared to BCC. Specifically, chromophobe renal cell carcinoma, sarcoma, and skin cutaneous melanoma presented significance in multiple cell types, namely in CD4+ T lymphocytes, gammadelta T lymphocytes, and NK cell populations. Consequently, further literature analysis was conducted to understand similarities between BCC and its "relatives", as well as investigating novel treatment targets. By identifying cancers most like BCC, we hope to propose prospective druggable pathways, as well as to gain insight on developing a reliable animal or cell line model to represent advanced BCC.

Use of intraoperative photodynamic therapy in the treatment of recurrent locally advanced scalp basal cell carcinoma

Use of intraoperative photodynamic therapy in the treatment of recurrent locally advanced scalp basal cell carcinoma

Types of surgical approaches in locally advanced forms of basal cell carcinoma of the scalp in elderly patients

Background. Basal cell cancer is the most common type of skin cancer in fair-skinned adults older than 50 years. The incidence rate of this disease is growing around the world. Basal cell carcinomas (BCC) are heterogeneous: from superficial or nodular lesions with benign prognosis to large lesions which are very difficult to cure. The prognosis of treatment is connected with the risk of recurrence of basal cell cancer or its local destructive ability. Hedgehog pathway activation is a distinctive molecular event in these tumors, which has allowed Hedgehog inhibitors for lesions that are difficult to cure to be developed, and which are also beyond the reach of surgical treatment or radiation therapy. Immunotherapy may be offered for the treatment of tumors with a high mutational load which leads to tumor resistance to Hedgehog inhibitors. Surgical intervention is a standard treatment method for most BCCs because it allows excision margins to be controlled and it shows a low risk of recurrence. The issue of removal of locally advanced forms with simultaneous reparative stage in elderly patients remains challenging.
 Purpose – to prove the high effectiveness of the surgical approach with simultaneous plastic surgery in locally advanced forms of BCC of the scalp in elderly patients.
 Materials and methods. Clinical observation of female patient A., 87 years old, who was receiving treatment in the Department of Surgical Oncology regarding multiple advanced BCC of facial skin, and patient V., 91 years old, who was undergoing treatment in the Department of Surgical Oncology regarding advanced basal cell skin carcinoma of the left pinna. Observation and treatment were performed in the State Organization «Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine».
 Results. Clinical cases of locally advanced basal cell skin cancer in 2 elderly patients (87 and 91 years old) are presented. The effectiveness of the surgical approach with broad excision of the tumor and simultaneous reparative stage has been proven: in one case – a free split-skin autoplastic graft, in the other one – a full-thickness musculo-subcutaneous flap with axial blood circulation. In both cases there was no rejection of transplants; the scalp defects were completely covered, and a good cosmetic appearance was successfully achieved. In both cases, there were no significant complications observed. These examples have proven that the patients’ age of more than 90 years is not a counterindication to broad resections with simultaneous reparative stage in locally advanced BCC of the scalp.
 Conclusions. Thus, modern methods of diagnostics and treatment of BCC allow the disease to be controlled in most cases. It is also possible to cure locally advanced BCCs in patients older than 85 years surgically with a simultaneous reconstructive stage, given the reasonable selection of the patients.

Three year results of Blessed: Expanded access for DeltaRex-G for an intermediate size population with advanced pancreatic cancer and sarcoma (NCT04091295) and individual patient use of DeltaRex-G for solid malignancies (IND# 19130).

Background: Innovative treatments are urgently needed for metastatic cancer. DeltaRex-G, a tumor-targeted retrovector encoding a dominant-negative/cytocidal cyclin G1 (CCNG1 gene) inhibitor construct-has been tested in over 280 cancer patients worldwide in phase 1, phase 2 studies and compassionate use studies, demonstrating long term (>10years) survivorship in patients with advanced cancers, including pancreatic cancer, osteosarcoma, malignant peripheral nerve sheath tumor, breast cancer, and B-cell lymphoma. Patient and Methods: Endpoints: Survival, response, treatment-related adverse events. Study one is entitled "Blessed: Expanded Access for DeltaRex-G for Advanced Pancreatic Cancer and Sarcoma (NCT04091295)". Study two is entitled "Individual Patient Use of DeltaRex-G for Solid Malignancies (Investigational New Drug#19130). In both studies, patients will receive DeltaRex-G at 1-3 x 10e11cfu i.v. over 30-45min, three x a week until significant disease progression or unacceptable toxicity or death occurs. Results: Seventeen patients were enrolled, nine sarcoma, two pancreatic adenocarcinoma, one non-small cell lung cancer, two breast carcinoma, one prostate cancer, one cholangiocarcinoma and one basal cell carcinoma and actinic keratosis. Three patients were enrolled in Study 1 and 14 patients were enrolled in Study 2. Twelve of 17 enrolled patients were treated with DeltaRex-G monotherapy or in combination with United States Food and Drug Administration-approved cancer therapies. Five patients died before receiving DeltaRex-G. Efficacy Analysis: Of the 12 treated patients, 5 (42%) are alive 15-36months from DeltaRex-G treatment initiation. Two patients with early-stage HR + HER2+ positive or triple receptor negative invasive breast cancer who received DeltaRex-G as adjuvant/first line therapy are alive in complete remission 23 and 16months after DeltaRex-G treatment initiation respectively; three patients with metastatic chordoma, chondrosarcoma and advanced basal cell carcinoma are alive 36, 31, and 15months after DeltaRex-G treatment initiation respectively. Safety Analysis: There were no treatment-related adverse events reported. Conclusion: Taken together, the data suggest that 1) DeltaRex-G may evoke tumor growth stabilization after failing standard chemotherapy, 2) DeltaRex-G may act synergistically with standard chemotherapy/targeted therapies, and 3) Adjuvant/first line therapy with DeltaRex-G for early-stage invasive carcinoma of breast may be authorized by the USFDA when patients refuse to receive toxic chemotherapy.

Clinical case of surgical treatment of advanced basal cell carcinoma of the skin on the face

Introduction. Basal cell carcinoma is the most common type of non-melanocytic malignant tumors of the skin. The main treatment methods for this pathology are local methods such as surgery and radiation. In rare cases, basal cell carcinoma can become locally advanced and / or metastatic.Aim. To demonstrate the possibility of reconstructive surgery for large defects after removal of locally advanced tumors of the face and describe a rare case of basal cell carcinoma metastasis into the regional lymph nodes.Clinical case. The article presents a clinical case of treatment of basal cell skin cancer with metastases into the regional lymph nodes. According to the patient, tumor on the skin of the left cheekbone area first appeared in 2007. The patient did not seek medical help. In 2017, the tumor was resected at the local medical facility. In 2018, the patient noted repeat tumor growth. In November of 2021, when the patient first consulted at the Republican Clinical Oncological Dispensary of the ministry of Health of the Bashkortostan Republic, the tumor was 7 × 5 cm. Invasion depth was up to 1.5 cm, infiltration into the temporal and mastication muscles and destruction of the zygomatic bone were observed. On 18.11.2021 at Republican Clinical Oncological Dispensary of the ministry of Health of the Bashkortostan Republic, wide resection of the skin tumor with resection of the zygomatic arch, parotidectomy on the left with defect removal using anterolateral thigh flap was performed. per histological examination, basal cell carcinoma with lymphovascular and perineural invasion and advancement into the masticator muscle and zygomatic bone was diagnosed, as well as carcinoma metastases in 2 lymph nodes with advancement beyond the capsule.Conclusion. Implementation of revascularization flaps significantly widens choices for surgical treatment of this patient group in a regional oncological dispensary and gives satisfactory esthetic results due to removal of large defects after surgical intervention.

CO175 Systematic Literature Review of Outcomes in Patients With Advanced Basal Cell Carcinoma (ABCC) Who Progressed on or Are Intolerant to Hedgehog Inhibitors (HHI)

Cemiplimab is the first treatment approved in patients with aBCC who have progressed on or are intolerant to an HHI based on Study 1620 (NCT03132636), an open-label, multicentre, single arm, non-randomised trial. Prior to cemiplimab availability, there was no standard of care after HHI for advanced BCC patients. The objectives of the current study were to identify and characterise clinical trials and observational studies evaluating the response rates, progression-free survival, or overall survival (OS) of patients with aBCC following HHI receiving systemic therapy or best supportive care (BSC).

EE537 Cost-Effectiveness of Cemiplimab in Patients With Advanced Basal Cell Carcinoma (aBCC) Who Progressed on or Are Intolerant to a Hedgehog Inhibitor (HHI) in Italy

EE537 Cost-Effectiveness of Cemiplimab in Patients With Advanced Basal Cell Carcinoma (aBCC) Who Progressed on or Are Intolerant to a Hedgehog Inhibitor (HHI) in Italy

Aktuelles Management des Basalzellkarzinoms

We present the current standard in diagnosis and treatment of basal cell carcinoma. Useful procedures for clinical management should be derived from this. A systematic literature search was carried out in the PubMed online database. The collected information was analyzed and evaluated. An overall concept was created from the gained knowledge. Basal cell carcinoma is the most common tumor in humans and its incidence is expected to increase in the future. When managing the disease, a one-dimensional orientation towards the clinical or histological subtype is not sufficient because of the heterogeneity of the tumor. The primary implementation of risk stratification, which is decisive for the further diagnostic and therapeutic steps, is becoming increasingly important. The gold standard in treatment continues to be the surgical procedure, which should be carried out using 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, application of 5-fluorouracil or imiquimod), which can be used in certain cases. Hedgehog inhibitors are also effective drugs for advanced or metastatic basal cell carcinoma. Practitioners have gained several years of experience with regard to effectiveness and handling of adverse events. With the PD-1 inhibitor cemiplimab, another therapeutic option for inoperable or metastatic tumors has been available since June 2021. Basal cell carcinoma will continue to gain in relevance in daily dermatological practice in the coming years. A structured approach to the assessment of the existing risk category of the tumor and the subsequent determination of the optimal therapy regimen are of central importance. Advanced or metastatic tumors no longer represent a hopeless situation for the patient. With long-termhedgehog therapy, an adapted dosage scheme can avoid discontinuation of therapy due to side effects. The therapeutic potential of the PD-1 inhibitor cemiplimab can also be used with the side effect profile known from other types of skin cancer.

Nasal reconstruction after skin cancer surgery; presentation of treatment modalities for medically compromised patients.

Nasal reconstruction after surgical excision of non-melanoma skin cancer defects can be a challeng- ing condition for every head and neck surgeon. There are certain technical difficulties that may arise from the tissue deficit and the area that a locoregional flap could cover. What is more, patients with a compromised medical history cannot always receive surgical manage- ment under general anaesthesia, limiting even more the defect reconstruction options. The aim of the present study is to present two patients that were treated under local anaesthesia for advanced basal cell carcinomas of the nose, with modifications of paramedian and hemi- nasal flaps that provided excellent surgical and aesthetic outcomes, despite the limits of the surgical modality.

A Review of the Risk of Cutaneous Squamous Cell Carcinoma after Vismodegib Therapy

Since vismodegib’s approval for advanced or metastatic basal cell carcinoma, there has been concern over vismodegib’s potential to induce secondary neoplasms of the skin, such as cutaneous squamous cell carcinoma (cSCC). In this article, we provide a comprehensive review of the literature on vismodegib’s relationship to cSCC. A systematic search of PubMed and Ovid MEDLINE was performed with terms “vismodegib” AND “squamous cell carcinoma.” Studies ranged from May 2013 to January 2022 and 25 articles were ultimately included. In total, of the 2576 patients included in the review, there were 197 cSCCs reported. Numerous reports have published conflicting findings. While one retrospective cohort study did find an increased risk, additional studies have found that the rates of cSCC are comparable between those exposed and those not exposed. Because a causal relationship between vismodegib and cSCC has not been proven, its use should not be avoided due to concerns of causing cSCC. However, patients treated with vismodegib should be closely monitored by dermatologists to evaluate for any suspicious changes. Large-scale, prospective, multi-center studies should be performed to definitively determine the risk of cSCC and vismodegib. It has been proposed that vismodegib may select for tumor cells utilizing the Ras/MAPK pathways.

Reinduction of Hedgehog Inhibitors after Checkpoint Inhibition in Advanced Basal Cell Carcinoma: A Series of 12 Patients.

For patients with advanced basal cell carcinoma (aBCC) first-line treatment with hedgehog inhibitors (HHIs) and second-line treatment with PD1 inhibitors (PD1i) is available, offering combination and sequencing options. Here, we focus on the efficacy and safety of HHI reinduction after PD1i failure. Retrospective data analysis was performed with 12 patients with aBCC (locally advanced (n = 8)/metastatic (n = 4)). These patients (male:female 6:6, median age 68 years) initially received HHIs, leading to complete/partial response (66%) or stable disease (33%). Median treatment duration was 20.8 (2-64.5) months until discontinuation due to progression (n = 8), adverse events (n = 3), or patient request (n = 1). Subsequent PD1 inhibition (pembrolizumab 42%, cemiplimab 58%) yielded a partial response (8%), stable disease (33%), or progression (59%). Median treatment duration was 4.1 (0.8-16.3) months until discontinuation due to progression (n = 9), adverse events (n = 1), patient request (n = 1), or missing drug approval (n = 1). HHI reinduction resulted in complete/partial response (33%), stable disease (50%), or progression (17%). Median treatment duration was 3.6 (1-29) months. Response duration in the four responding patients was 2-29+ months. Thus, a subgroup of patients with aBCC responded to reinduction of HHI following PD1i failure. Therefore, this sequential treatment represents a feasible treatment option.

Atezolizumab for the treatment of advanced recurrent basal cell carcinoma and urothelial carcinoma of bladder: a case report

BackgroundThe use of checkpoint inhibitors has become increasingly important in the treatment of different cancers, including advanced muscle-invasive urothelial cancer and even in basal cell carcinoma. We present the case of a patient with advanced basal cell carcinoma and metastatic muscle-invasive urothelial cancer, who was treated with the programmed death-ligand 1 inhibitor, atezolizumab for both cancers.Case presentationA 72-year-old Caucasian female patient, with a history of smoking without any comorbidities developed periocular basal cell carcinoma, which was surgically removed but relapsed 4 years later. Surgical excision was carried out twice, but with positive margins, therefore definitive radiotherapy was given. Subsequently, the patient developed non-muscle-invasive papillary urothelial carcinoma, which was removed by transurethral resection. Follow-up was irregular owing to the patient’s inadequate compliance, and within 2 years, the patient’s cancer relapsed and histology confirmed muscle-invasive urothelial carcinoma. Definitive radiochemotherapy was not accepted by the patient. Meanwhile, the patient’s basal cell carcinoma had also progressed, despite receiving vismodegib therapy. Therefore, the patient was administered epirubicin-cisplatin. Having reached the maximum cumulative dose of epirubicin, treatment with this chemotherapeutic agent could not be continued. The patient developed bladder cancer metastasis in her left suprainguinal lymph nodes. Owing to the presence of both types of tumors, programmed death-ligand 1 inhibitor atezolizumab treatment was chosen. In just over 1 year, the patient received 17 cycles of atezolizumab altogether, which was tolerated well without any adverse or side effects. Follow-up imaging scans indicated complete remission of the metastatic bladder cancer and stable disease of the basal cell carcinoma. The patient subsequently passed away in hospital due to a complication of COVID-19 infection.ConclusionsOur patient attained stable disease in advanced basal cell carcinoma and complete remission in metastatic muscle-invasive urothelial cancer after receiving programmed death-ligand 1 inhibitor, atezolizumab, therapy. To our knowledge, this is the first paper to report the use of programmed death-ligand 1 inhibitor, atezolizumab, as treatment for advanced basal cell carcinoma. This case may also be of interest for clinicians when treating patients with two synchronous cancers.

A Multi-Institutional Study of Definitive Radiotherapy for Locally Advanced Basal Cell Carcinoma

<h3>Purpose/Objective(s)</h3> The gold standard for management of basal cell carcinoma (BCC) is surgical resection with negative margins, which is associated with excellent control rates. However, a subset of locally advanced BCCs may not be amenable to resection alone. This includes disease that is locally invasive or located in a cosmetically or functionally challenging anatomic location. Definitive radiotherapy can be used in these cases; however, outcomes data is sparse and typically limited to small single-institutional series or case reports. We conducted a modern multi-institutional cohort study of locally advanced BCC treated with definitive radiation to further evaluate treatment outcomes. <h3>Materials/Methods</h3> Patients with locally advanced BCC treated with upfront definitive radiation between 2006-2020 from 3 academic institutions were included. Locally advanced BCCs were defined as patients with unresectable disease, or locations where surgery to achieve negative margins would lead to unacceptable cosmetic or functional deficit. Patient and tumor clinical characteristics, radiation treatment details, and outcomes were collected from medical records. <h3>Results</h3> A total of 474 locally advanced BCC cases were identified, of which 76 were treated with upfront definitive radiotherapy with a median follow up of 2.44 years. Patient characteristics are shown in Table 1. Median radiation dose used was 5000 cGy (range 2800-7000 cGy), with median 250 cGy per fraction (range 200-1000 cGy). Most patients (73.7%) were treated with electrons. Disease free survival was 81.6% (62/76 patients). There were 9 (11.8%) local recurrences, 2 (2.6%) with nodal metastases and 3 (3.9%) with distant metastases. On linear regression analysis, tumor size was predictive of recurrence (p=0.00035). Overall survival at time of most recent follow up was 61.8% with 6 (7.9%) of the deaths attributed to BCC. <h3>Conclusion</h3> In this modern study, definitive radiotherapy for locally advanced unresectable BCC has excellent local control rates, with tumor size remaining a risk factor for recurrence. Nodal and distant metastases are rare despite locally advanced disease and most long-term mortality in this cohort tends to be from non-BCC related causes.

Sonidegib improved quality of life in patients with advanced basal cell carcinoma: Results from the phase 2 Basal cell carcinoma outcomes with LDE225 treatment trial through 73 weeks

Sonidegib improved quality of life in patients with advanced basal cell carcinoma: Results from the phase 2 Basal cell carcinoma outcomes with LDE225 treatment trial through 73 weeks

Advanced basal cell carcinoma: What dermatologists need to know about treatment

To the Editor: We appreciate the comments provided by Cohen and Kurzrock1 in their recent letter, “Crucial conceptual concepts in the evaluation and management of advanced basal cell carcinoma.” In short, we agree that genomic characterization of advanced (particularly metastatic) basal cell carcinoma will enable individualized, targeted therapy. However, such genomic tests (eg, next-generation sequencing) are currently not commercially available or reimbursable for advanced basal cell carcinoma.