Influence of Frailty and Life Expectancy on Guideline Adherence and Outcomes in Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Prospective Pilot Study.

BACKGROUND: Cutaneous squamous cell carcinoma is the second most common malignancy of the skin, often occurring in older patients and in the head and neck area (cSCCHN). Age, life expectancy, and frailty are not taken into consideration by current guidelines. OBJECTIVES: The objective of this study was to evaluate the influence of frailty and life expectancy on guideline deviation, treatment outcomes, and quality of life (QoL) after treatment in patients with cSCCHN. METHODS: Patients with cSCCHN were prospectively included. A geriatric assessment was performed, including the Geriatric 8 (G8), Groningen Frailty Indicator, and Timed Up and Go test (TUG). The Lee index was used to predict a limited life expectancy, and the Adult Comorbidity Evaluation-27 was used as a comorbidity index. QoL was assessed by the Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire at three time points. RESULTS: Seventy-seven patients with cSCCHN were included. Frail patients had significantly more high-risk tumours. Guideline deviation occurred in 7.8% and was more common in patients who were frail (G8), with high-risk tumours (≥T2), with a limited life expectancy or an increased TUG. Guideline deviation did not lead more often to progression of disease in our study. No predictors for post-operative complications were found. BaSQoL subscores were very low at each time point and did not change significantly with time in the total group. Frail patients reported more fear of recurrence or new tumours 3 months after treatment, and less concern about other people's skin 6 months after treatment, compared to non-frail patients. Complication rate, gender, or guideline deviation did not affect any subscale scores. CONCLUSIONS: Assessment of frailty and life expectancy can guide physicians and patients in treatment decisions. Deviation from guidelines towards less aggressive treatment schedules can be considered in frail patients with a limited life expectancy, since it did not negatively affect short-term outcomes or QoL in patients with cSCCHN in our study. However, these results should be confirmed by other, larger prospective studies with a longer follow-up period.

Age-related Differences in Tumour Characteristics and Prognostic Factors for Disease Progression in Cutaneous Squamous Cell Carcinoma of the Head and Neck.

Guidelines for cutaneous squamous cell carcinoma of the head and neck do not take the age of the patient into account, but instead assume equal tumour characteristics and prognostic factors for poor outcome in younger and elderly patients. The aim of this study was to compare tumour characteristics of younger (< 75 years) and elderly (≥ 75 years) patients and identify age-specific risk factors for progression of disease, comprising local recurrence, nodal metastasis and distant metastasis. Patient and tumour characteristics were compared using χ2 or Fisher's exact tests. Multivariable competing risk analyses were performed to compare risk factors for progression of disease, incorporating the risk of dying before developing progression of disease. A total of 672 patients with primary cutaneous squamous cell carcinoma of the head and neck were retrospectively included. Larger tumour diameter, worse differentiation grade and deeper invasion were observed in older patients. In elderly patients, but not in younger patients, tumour diameter ≥ 40 mm, moderate differentiation grade and an invasion depth ≥ 2 mm were independent risk factors for progression of disease.

Eight years of experience with vismodegib for advanced and multiple basal cell carcinoma patients in the Netherlands: a retrospective cohort study.

BACKGROUND: Vismodegib has been used for the treatment of locally advanced basal cell carcinoma (laBCC) and metastatic BCC (mBCC) since 2011. Most efficacy and safety data are provided by clinical trials. This study evaluates the effectiveness of vismodegib for the treatment of laBCC, mBCC and basal cell nevus syndrome (BCNS) patients, and the tumour characteristics associated with a higher probability of achieving a complete response in the Netherlands. METHODS: A retrospective cohort study that included all patients ≥18 years with histologically proven basal cell carcinoma that received ≥1 dose of vismodegib between July 2011 and September 2019 in the Netherlands. RESULTS: In total, 48 laBCC, 11 mBCC and 19 BCNS patients were included. Median progression-free survival was 10.3 months (95% confidence interval (CI), 7.5-22.6) for laBCC, 11.7 (95% CI, 5.2-17.5) for mBCC and 19.1 (95% CI, 7.4-20.2) for BCNS. Larger laBCCs were associated with a lower probability of complete response (hazard ratio (HR) 0.77 per increase in cm, p = 0.02). Of all BCNS patients, 63% received ≥2 treatment sequences with vismodegib; all achieved partial responses. CONCLUSIONS: Half of the aBCC patients progress within 1 year after the start of vismodegib treatment. More research is needed to investigate other treatment strategies after vismodegib progression and to evaluate long-term effects of repetitive vismodegib treatment.

Molecular testing in metastatic basal cell carcinoma.

BACKGROUND: Metastatic basal cell carcinoma (mBCC) is a very rare entity, and diagnosis can be challenging. Therapeutic options are limited, and response to targeted therapy is poor. OBJECTIVE: To demonstrate a clonal relationship between BCCs and their metastases and to explore which hedgehog pathway-related mutations are involved in mBCC. METHODS: Genetic analysis was conducted in 10 primary BCCs and their metastases. Genes relevant for BCC development were analyzed in tumor and metastasis material with small molecule molecular inversion probes (smMIPs) for PTCH1, PTCH2, SMO, SUFU, GLI2, and TP53 or with targeted next generation sequencing of the same genes and CDKN2A, CDKN2B, CIC, DAXX, DDX3X, FUBP1, NF1, NF2, PTEN, SETD2, TRAF7, and the TERT promoter. RESULTS: In 8 of 10 patients, identical gene mutations could be demonstrated in the primary tumors and their metastases. A broad spectrum of mutations was found. Four patients had SMO mutations in their tumor or metastasis, or both. All SMO mutations found were known to cause resistance to targeted therapy with vismodegib. LIMITATIONS: In 2 patients there was insufficient qualitative DNA available for genetic analysis. CONCLUSIONS: Molecular testing can help to identify the origin of a BCC metastasis and may be of prognostic and therapeutic value.

Effect of Patient Characteristics on Treatment Decisions Regarding Keratinocyte Carcinoma in Elderly Patients: A Review of the Current Literature.

There are straightforward guidelines for treatment of keratinocyte carcinoma (formerly known as non-melanoma skin cancer); however, there are no clear recommendations specifically for elderly patients. The aim of this review was to provide an overview of the current literature about the effect of patient characteristics, specifically life expectancy, frailty and comorbidity, on treatment decisions in elderly patients with keratinocyte carcinoma, by searching PubMed database. It was found that the literature is limited and based mostly on small retrospective studies. Therefore, it is difficult to give firm recommendations about how to treat elderly people who have keratinocyte carcinoma. A "one-size-fits-all" approach to this population is not sufficient: life expectancy and frailty need to be considered in the decision-making process regarding treatment for elderly people with keratinocyte carcinoma. Among the comorbidity scores, Adult-Comorbidity-Evaluation-27-index seems to have the best prognostic value. Prospective studies are needed to generate more individualized recommendations for this increasing and often vulnerable group.

Breast implant causes allergic contact dermatitis or foreign body reaction?

In this case report we describe a 55-year-old Caucasian female who had developed an itching, erythematous plaque on the right breast seven months after she received a permanent tissue expander. Topical corticosteroids had no effect upon which a capsulectomy was performed and the complaints disappeared.

[A woman with a growing mass close to the fingernail]. / Een drukpijnlijke tumor bij de vingernagel.

A 23-year-old woman had a painful, growing mass close to the nail of her left index finger. The differential diagnosis consisted of acquired digital fibrokeratoma, digital fibromyxoma, periungual fibroma or verruca vulgaris. Surgical excision of the mass was performed, and histopathological analysis revealed a subungual exostosis.

Low recurrence rate of head and neck basal cell carcinoma treated with Mohs micrographic surgery: A retrospective study of 1021 cases.

OBJECTIVE: Mohs micrographic surgery (MMS) is the treatment of choice for high-risk primary basal cell carcinoma (BCC) and recurrent BCC of the head and neck, showing fewer recurrences compared with surgical excision (SE). The objectives of this study were to determine the recurrence rate of head and neck BCC after MMS and to develop a prediction model with significant risk factors for recurrence. DESIGN: A retrospective study of patient records. METHODS: All BCCs treated with MMS between 1 January 1995 and 1 July 2013 at the University Medical Center Groningen (UMCG) were selected retrospectively. Recorded parameters were patient characteristics, tumour size, tumour location, histopathological subtype, previous treatment, the number of stages until microscopic clearance, defect size, adverse events, follow-up time and recurrence after MMS. RESULTS: The study covered 1021 MMS operations conducted on primary BCCs (57.4%), residual BCCs (25.6%) and recurrent BCCs (17.0%). The median follow-up time was 54.0 months (ranging from 1 to 221 months). The 5-year cumulative probability of recurrence was 3.3%: 2.6% for primary BCCs, 5.4% for residual BCCs and 2.9% for recurrent BCCs. An aggressive histopathological subtype, residual BCCs and recurrent BCCs were significant risk factors for predicting a higher risk of recurrence after MMS. CONCLUSION: This large-scale retrospective study showed low recurrence rates after MMS for primary and recurrent BCCs. Residual BCCs treated with MMS had relatively higher recurrence rates. The risk of recurrence for MMS-treated residual aggressive BCCs was more than four times higher than that for primary non-aggressive BCCs.

Effectiveness and Safety of Rituximab in Recalcitrant Pemphigoid Diseases.

Introduction: Rituximab (RTX) is a monoclonal antibody targeting CD20, a transmembrane protein expressed on B cells, causing B cell depletion. RTX has shown great efficacy in studies of pemphigus vulgaris, but data of pemphigoid diseases are limited. Objective: To assess the effectiveness and safety of RTX in pemphigoid diseases. Methods: The medical records of 28 patients with pemphigoid diseases that were treated with RTX were reviewed retrospectively. Early and late endpoints, defined according to international consensus, were disease control (DC), partial remission (PR), complete remission (CR), and relapses. Safety was measured by reported adverse events. Results: Patients with bullous pemphigoid (n = 8), mucous membrane pemphigoid (n = 14), epidermolysis bullosa acquisita (n = 5), and linear IgA disease (n = 1) were included. Treatment with 500 mg RTX (n = 6) or 1,000 mg RTX (n = 22) was administered on days 1 and 15. Eight patients received additional 500 mg RTX at months 6 and 12. Overall, DC was achieved in 67.9%, PR in 57.1%, and CR in 21.4% of the cases. During follow-up, 66.7% patients relapsed. Repeated treatment with RTX led to remission (PR or CR) in 85.7% of the retreated cases. No significant difference in response between pemphigoid subtypes was found. IgA-dominant cases (n = 5) achieved less DC (20 vs. 81.3%; p = 0.007), less PR (20 vs. 62.5%; p = 0.149), and less CR (0 vs. 18.8%; p = 0.549) compared to IgG-dominant cases (n = 16). Five severe adverse events and three deaths were reported. One death was possibly related to RTX and one death was disease related. Conclusion: RTX can be effective in recalcitrant IgG-dominant pemphigoid diseases, however not in those where IgA is dominant.

Multivariate analysis of potential risk factors for lymph node metastasis in patients with cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: The current knowledge about potential risk factors for lymph node (LN) metastasis in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) is primarily based on studies that lack adjustment for confounding variables. OBJECTIVES: We sought to identify independent risk factors for LN metastasis in patients with HNcSCC and to evaluate the impact of LN metastasis on prognosis. METHODS: Patients with primary HNcSCC were retrospectively included. Potential risk factors were analyzed by univariate and multivariate Cox regression models. Survival was compared using the Kaplan-Meier method. RESULTS: Three hundred thirty-six patients with 545 primary HNcSCCs were included. The median follow-up period was 43 months (range, 1-176 months). LN metastasis occurred in 55 patients (16.4%). The following independent risk factors of HNcSCC for the development of LN metastasis were identified: location on the ear, tumor diameter >50 mm, moderate and poor differentiation, and tumor thickness >2 mm. There was a significant decline in disease-specific survival and overall survival in patients with LN metastasis compared to patients without LN metastasis. LIMITATIONS: The retrospective study design. CONCLUSION: LN metastases from HNcSCC are common with diminished survival rates. This study confirmed some well-known risk factors, but also found moderate differentiation as an independent risk factor for LN metastasis.

mTHPC mediated, systemic photodynamic therapy (PDT) for nonmelanoma skin cancers: Case and literature review.

BACKGROUND AND OBJECTIVE: Patients with multiple nonmelanoma skin cancers (NMSCs), like immunosuppressed or nevoid basal cell carcinomas, offer a therapeutic challenge. Photodynamic therapy (PDT) using the systemic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) has the ability to treat multiple NMSCs up to a depth of 10 mm in a single session. These unique properties offer an attractive alternative to regular therapies (e.g., surgery or radiation) to these patients. STUDY DESIGN: A systemic search was carried out that focused on the main clinical studies using mTHPC-PDT on NMSCs in humans. This review describes some of the basic principles of the treatment, the most effective treatment parameters as well as its possible adverse outcomes, which is illustrated with a short description of our own experiences using this treatment modality on four patients with multiple NMSCs. RESULTS: To date, only four clinical studies have been published. It was demonstrated that mTHPC-PDT could be highly effective. On illuminating 1-2 days after drug administration, plasma drug levels were high and the tumor clearance rates were high (up to 100%), with relative few side effects and excellent cosmetic and functional outcomes. These results were obtained with a relatively low, patient friendly photosensitizer dose (0.04-0.05 mg/kg) as skin photosensitivity was shorter after the procedure. Although the patients personally experienced consistently good cure rates, the healing times varied greatly between anatomical areas. The head and neck areas heal well with good cosmesis, while the lower leg and foot areas show delayed, at times compromised, healing with scarring. CONCLUSIONS: Although mTHPC-PDT is described in the literature as an interesting and promising therapeutic option, especially for multiple NMSCs, a randomized clinical trial is lacking and personal experiences warrant too much skepticism. With the recent introduction of the hedgehog pathway inhibitor vismodegib, mTHPC-PDT seems to be less suitable as a first line of treatment; it should be considered as a last resort therapy.

[A child with a S-shaped skin condition on his abdomen]. / Een kind met een S-vormige huidafwijking op zijn romp.

A 14-year-old boy with a pruritic erythematous plaque on his abdomen along the lines of Blaschko, visited the dermatology outpatient clinic. Histopathology of a skin biopsy confirmed the clinical diagnosis linear cutaneous lupus erythematosus. We treated the patient with potent topical corticosteroids.

Bullous pemphigoid as pruritus in the elderly: a common presentation.

IMPORTANCE: In the literature, patients with bullous pemphigoid have been reported to have itch without blisters. Clinical observations in these patients have varied from eczematous or urticarial to papular or nodular skin lesions. Here we investigated the spectrum of clinical variants. OBSERVATIONS: Fifteen patients with itch without blisters had immunopathologic findings of bullous pemphigoid. Mean age at diagnosis was 81.7 years. No blistering occurred during the mean 2.2 years of follow-up. Mean delay of diagnosis was 2.8 years. Clinical symptoms were heterogeneous: pruritus sine materia (no primary skin lesions), eczematous, urticarial, papular, and/or nodular skin lesions were seen. Treatment with potent topical corticosteroids or methotrexate sodium led to remission in 11 patients. CONCLUSIONS AND RELEVANCE: Itch without skin lesions can be the only symptom of bullous pemphigoid. Therefore, it is important to include serologic and direct immunofluorescence in the diagnostic algorithm of itch. We propose the unifying term pruritic nonbullous pemphigoid for all patients with immunopathologic findings of bullous pemphigoid, itch, and no blisters.

[Vulvar basal cell carcinoma with destructive consequences]. / Vulvair basaalcelcarcinoom met destructieve gevolgen.

BACKGROUND: Basal cell carcinoma is the most common form of skin cancer. Generally, the prognosis is relatively good and curative surgical treatment is accomplished in the great majority of patients. CASE DESCRIPTION: Here we report a case that illustrates the natural course of a vulvar basal cell carcinoma. It concerns an 80-year-old woman who was diagnosed with a so-called 'giant' vulvar basal cell carcinoma causing severe destruction of the anogenital anatomy. At the time of diagnosis, haematogenous metastases were strongly suspected and curative therapy was not possible. CONCLUSION: This case description illustrates that a basal cell carcinoma can transform into a 'giant' basal cell carcinoma if it is left untreated for many years. 'Giant' basal cell carcinomas carry a significantly higher risk of metastases than basal cell tumours smaller than 5 cm. In addition, 'giant' basal cell carcinoma is associated with higher morbidity and mortality rates.