Real-world outcomes using PD-1 antibodies and BRAF + MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland.

BACKGROUND: Programmed death-1 (PD-1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland. METHODS: Multicenter, retrospective study investigating stage III-IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib + trametinib (D + T) between 1/2017 and 10/2021. The primary endpoint was 12-month recurrence-free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear-regression machine learning model to assess the risk of early melanoma recurrence. RESULTS: In total, 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analysed. The vast majority received anti PD-1 therapies (n = 1003). Twelve-month RFS for anti PD-1 and BRAF + MEK inhibitor-treated patients were 78.1% and 86.5%, respectively (hazard ratio [HR] 1.998 [95% CI 1.335-2.991]; p = 0.001). There was no statistically significant difference in overall survival (OS) in anti PD-1 (95.8%) and BRAF + MEK inhibitor (96.9%) treated patients (p > 0.05) during the median follow-up of 17 months. Data indicates that anti PD-1 treated patients who develop immune-related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95% CI 0.443-0.754], p = 0.001). BRAF mutation status did not affect overall efficacy of anti PD-1 treatment (p > 0.05). In both, anti PD-1 and BRAF + MEK inhibitor treated cohorts, data did not show any difference in 12-month RFS and 12-month OS comparing patients receiving total lymph node dissection (TLND) versus sentinel lymph node biopsy only (p > 0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC = 0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials. CONCLUSIONS: Despite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that TLND does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk.

Patient Preferences in Hidradenitis Suppurativa (APProach-HS): a discrete choice experiment.

BACKGROUND AND OBJECTIVES: Treatment options for moderate-to-severe hidradenitis suppurativa (HS) comprise antibiotics, biologics, and different surgical methods. These approaches differ substantially regarding the treatment process, success rates, and adverse events. However, information on patient preferences for HS therapies is hitherto scarce. Our aim was to assess patient preferences for medicamentous and surgical treatment of HS with conjoint analysis. PATIENTS AND METHODS: In this cross-section study, computerized discrete choice experiments were used to quantify patient preferences for HS therapies decomposed into treatment modality (tablets, subcutaneous injections, surgery with secondary-intention healing or primary closure), probability of sustained therapeutic success, probability of mild or severe adverse events, and duration of treatment or wound healing. RESULTS: Averaged over the cohort (n  =  216 patients with HS), sustained therapeutic success was considered as most important (Relative Importance Score [RIS]: 36.2), followed by the treatment modality (RIS: 24.0), and duration of treatment/wound healing (RIS: 19.9), whereas mild or severe adverse events (RIS: 10.7 or 9.3) were regarded as less relevant. Patients preferred tablets, followed by subcutaneous injections, and disliked surgery with primary closure. Preferences differed significantly dependent on age and affected body regions. CONCLUSIONS: Awareness of patient preferences is essential for patient-centered care in HS.

Melanoma care during one year pandemic in Berlin: decreasing appointment cancellations despite increasing COVID-19 concern.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic poses a great challenge for cancer patients. Our aim was to assess its influence on treatment and appointments of melanoma patients after one year of pandemic. METHODS: Melanoma patients treated in the Vivantes Skin Cancer Centre in Berlin, Germany completed a postal survey on pandemic-related alterations in melanoma care. Impact factors on changes of appointments were examined with descriptive analyses and multivariate logistic regression. Data after one year of pandemic were compared to those after its first wave. RESULTS: Among 366 participants (57.7 % males; mean age 69.2 years, response rate: 36.1 %), 38 (10.1 %) reported postponed or missed appointments, mostly on their own demand (71.1 %) due to fear of COVID-19 (52.6 %). Current treatment was associated with a lower risk of changing appointments (Odds Ratio [OR]: 0.194, p = 0.002), higher age (OR: 1.037, p = 0.039), longer disease duration (OR: 1.007, p = 0.028), and higher school degree (OR: 2.263, p = 0.043) with higher probability. Among 177 patients currently receiving therapy, only 1.7 % experienced pandemic-related treatment alterations. Concern about COVID-19 was significantly higher after one year of pandemic than after its first wave, but the number of missed appointments was lower. CONCLUSIONS: Pandemic-related changes were rare in our cohort and decreased over time despite increasing concern.

Melanomversorgung während eines Jahres Pandemie in Berlin: abnehmende Terminstornierungen trotz zunehmender Besorgnis über COVID-19.

HINTERGRUND UND ZIELE: Die COVID-19-Pandemie stellt für Krebspatienten eine große Herausforderung dar. Unser Ziel war es, ihren Einfluss auf die Behandlung und auf Arzttermine von Melanompatienten nach einem Jahr Pandemie zu untersuchen. PATIENTEN UND METHODIK: Melanompatienten, die im Vivantes Hauttumorzentrum in Berlin behandelt wurden, beantworteten eine postalische Umfrage zu Pandemie-bedingten Änderungen ihrer Melanomversorgung. Einflussfaktoren auf Terminänderungen wurden mit deskriptiven Analysen und multivariater logistischer Regression untersucht. Daten nach einem Jahr Pandemie wurden mit Daten nach der ersten Welle verglichen. ERGEBNISSE: Von den 366 Teilnehmern (57,7 % Männer; Durchschnittsalter 69,2 Jahre, Rücklaufquote: 36,1 %) berichteten 38 (10,1 %) über verschobene oder verpasste Arzttermine, meist auf eigenen Wunsch (71,1 %) aus Angst vor COVID-19 (52,6 %). Eine aktuelle Therapie war mit einem geringeren Risiko, Termine zu verpassen, assoziiert (Odds Ratio [OR]: 0,194, p = 0,002), höheres Alter (OR: 1,037, p = 0,039), längere Krankheitsdauer (OR: 1,007, p = 0,028) und ein höherer Schulabschluss (OR: 2,263, p = 0,043) mit höherer Wahrscheinlichkeit. Von den 177 Patienten, die aktuell eine Therapie erhielten, erfuhren nur 1,7 % Pandemie-bedingte Behandlungsänderungen. Die Besorgnis über COVID-19 war nach einem Jahr Pandemie signifikant größer als nach der ersten Welle, die Zahl der verpassten Arzttermine jedoch niedriger. SCHLUSSFOLGERUNGEN: Pandemie-bedingte Änderungen waren in unserer Kohorte selten und nahmen trotz zunehmender Besorgnis mit der Zeit ab.

Patient preferences for treatment of advanced melanoma: impact of comorbidities.

BACKGROUND AND OBJECTIVES: Choice of treatment for advanced melanoma is crucially influenced by comorbidities and patient preferences. Our study aimed to investigate the impact of comorbidities on preferences. PATIENTS AND METHODS: 150 patients with melanoma stage IIC-IV completed a discrete choice experiment to determine preferences for outcome (overall response rate [ORR], 2-year survival, progression-free survival [PFS], time to response [TTR], kind of adverse events [AE], AE-related treatment discontinuation) and process attributes (frequency and route of administration [RoA], frequency of consultations) of systemic melanoma treatments. The impact of comorbidities was assessed by analysis of variance and multivariate regression. RESULTS: Participants with hypertension and other cardiovascular diseases attached significantly greater importance to TTR and RoA than others. Respondents with arthropathy cared more about TTR (ß = 0.179, P = 0.047) and RoA, but less about ORR (ß = -0.209, P =  0.021). Individuals with diabetes considered AE (ß = 0.185, P = 0.039) and frequency of consultations more essential, but ORR less relevant. Those with other malignancies were particularly worried about treatment discontinuation (ß = 0.219, P =  0.008), but less about ORR (ß = -0.202, P =  0.015). Participants with depression focused more on PFS (ß = 0.201, P =  0.025) and less on TTR (ß = -0.201, P =  0.023) and RoA (ß = -0.167, P =  0.050). CONCLUSIONS: Treatment preferences of melanoma patients vary significantly dependent on comorbidities.

Patient Preferences in Adjuvant and Palliative Treatment of Advanced Melanoma: A Discrete Choice Experiment.

Treatment paradigms for advanced melanoma have changed fundamentally over recent years. A discrete choice experiment was performed to explore patient preferences regarding outcome (overall response rate, 2-year survival rate, progression-free survival, time to response, type of adverse events, probability of adverse event-related treatment discontinuation) and process attributes (frequency and route of administration, frequency of consultations) of modern treatments for melanoma. Mean preferences of 150 patients with melanoma stage IIC-IV were highest for overall response rate (relative importance score (RIS) 26.8) and 2-year survival (RIS 21.6), followed by type of adverse events (RIS 11.7) and probability of adverse event-related treatment discontinuation (RIS 9.2). Interest in overall response rate and 2-year survival declined with increasing age, whereas process attributes gained importance. Participants who had experienced treatment with immune checkpoint inhibitors valued overall response rate more highly and worried less about the type of adverse events. In conclusion, patients with advanced melanoma consider efficacy of treatment options most important, followed by safety, but preferences vary with individual and disease-related characteristics.

Psychotrichology: psychosomatic aspects of hair diseases.

Hair growth and hair disorders with changes in hair density or quality not only influence an individual's appearance but also often lead to an enormous emotional burden with low self-confidence, impaired quality of life, and even psychological disorders. Psychosomatic hair diseases cover a wide spectrum of specific psycho-dermatological disease patterns. This review provides an overview and classification of psychosomatic hair diseases based on primary and secondary disorders. Somatoform disorders are among the primary psychiatric diseases, especially body dysmorphic disorder in which patients have an exaggerated and excessive preoccupation of normal and physiological hair loss. Self-inflicted skin diseases as trichotillomania, often with an impairment of impulse control, also belong to this group. Secondary/reactive psychosocial disorders may occur in congenital and acquired hair disorders. These may be accompanied by feelings of disfigurement, depressive and anxiety disorders including social avoidance. Furthermore, psychosomatic comorbidity could complicate coping with hair loss. Psychosomatic therapy and coping are based on an early and accurate differential diagnostic approach to psychosomatic disorders. Psychotrichological disorders need to be treated promptly with psychosomatic basic care, improvement of coping strategies, behavior therapy, depth psychology, and/or appropriate psychopharmacotherapy with antidepressants or anxiolytics.

Effects of the COVID-19 pandemic on care of melanoma patients in Berlin, Germany: the Mela-COVID survey

Background: The COVID-19 pandemic imposes major challenges for care of cancer patients. Objectives: Our aim was to assess the effects of the pandemic on treatment and appointments of patients with malignant melanoma based on a large skin cancer centre in Berlin, Germany, and identify reasons for, and impact factors associated with these changes. Materials & Methods: Patients with melanoma treated from January 1st 2019 received a postal survey with questions on impairment due to the pandemic, fear of COVID-19, fear of melanoma, changes in therapy and/or appointments, including reasons for the changes. Impact factors on postponed/missed appointments were examined using descriptive analyses and multivariate logistic regression. Results: The response rate was 41.3% (n = 324; 57.4% males; mean age: 67.9 years). Among 104 participants currently receiving therapy, four (3.8%) reported treatment changes due to the pandemic. Postponements or cancellations of appointments occurred in 48 participants (14.8%), most frequently, at their own request (81.3%) due to fear of SARS-CoV-2 infection (68.8%). Current treatment was associated with a reduced chance of post-poning/missing appointments (OR = 0.208, p = 0.003), whereas a high or very high level of concern for COVID-19 (OR = 6.806, p = 0.034; OR= 10.097, p = 0.038), SARS-CoV-2 infection among close acquaintances (OR = 4.251, p = 0.026), anxiety disorder (OR = 5.465, p = 0.016) and AJCC stage IV (OR = 3.108, p = 0.048) were associated with a higher likelihood of postponing/missing appointments. Conclusion: Among our participants, treatment changes were rare and the proportion of missed/delayed appointments was rather small. The main reasons for delays/cancellations of appointments were anxiety and concern for COVID-19.

Morgellons in dermatology.

Delusional parasitosis (DP) is the most frequent delusional disorder in dermatology. In DP there is a fixed belief of a usually skin-related invasion or infestation by a number of alleged infectious species (usually parasites and bacteria), whose identity has varied over the decades. Since 2002 worldwide an increasing number of patients have complained of unverifiable fibers and filaments in or on the skin, associated with numerous nonspecific complaints (arthralgias, altered cognitive function and extreme fatigue). This entity has been named "Morgellons disease" by the patients themselves, although medical evidence for its existence is lacking. As an example, we discuss a 55-year-old woman who complained of Morgellons disease and was treated as if she had DP. Currently the delusional assumption of infestation with Morgellons should be considered as a new type of DP with some kind of inanimate material. We therefore recommend in case of DP including Morgellons the use of the broader term "delusional infestation".

Facticious disorders in dermatology.

Facticious Disorders are self inflicted skin lesions and includes the creation of physical or psychiatric symptoms in oneself or other reference persons. In dermatology frequently, there are mechanical injuries by pressures, friction, occlusion, biting, cutting, stabbing, thermal burns or self-inflicted infections with wound-healing impairment, abscesses, mutilations or damages by acids and other toxic to the skin. The current classification differentiates between four groups: 1. Dermatitis artefacta syndrome in the narrower sense as unconscious/dissociated self-injury, 2. Dermatitis paraartefacta syndrome: Disorders of impulse control, often as manipulation of an existing specific dermatosis (often semi-conscious, admitted - self-injury), 3. Malingering: consciously simulated injuries and diseases to obtain material gain, 4. special forms, such as the Gardner Diamond Syndrome, Münchhausen Syndrome and Münchhausen-by-Proxy Syndrome. This categorization is helpful in understanding the different pathogenic mechanisms and the psychodynamics involved, as well as in developing various therapeutic avenues and determining the prognosis.

Successful treatment of pityriasis rubra pilaris (type 1) under combination of infliximab and methotrexate.

Pityriasis rubra pilaris (PRP) is often difficult to treat. A 65-year-old women presented with a two week history of widespread erythroderma and scaling with areas of sparing (nappes claires). She also had follicular hyperkeratoses and palmar fissuring. The clinical picture and histology led to the diagnosis of PRP. She failed to respond to initial therapy which included topical and systemic corticosteroids. She was then treated with intravenous methotrexate (MTX) 15-30 mg weekly. Because of the poor response we intensified her regime with infliximab (5 mg/kg). Altogether our patient received infliximab three times together with MTX, which was later given orally. We report for the first time the successful combination of infliximab and MTX for the treatment of PRP.

Complete remission of cutaneous and subcutaneous melanoma metastases of the scalp with imiquimod therapy.

Multiple cutaneous and subcutaneous melanoma metastases represent a therapeutic challenge. A 63-year-old man presented with multiple cutaneous and subcutaneous melanoma metastases on his right parieto-occipital region that appeared ten weeks after surgical excision of the primary tumor. Staging showed no further metastases. Because of the large area of cutaneous metastatic spread, the location and the limited possibility of a complete excision, we decided to begin immunomodulatory therapy with imiquimod applied for eight hours daily five days a week. After six weeks of imiquimod monotherapy, a partial remission of the cutaneous metastases had occurred. After 17 months, the remission of these metastases was complete. Four months later the patient is still free of cutaneous, visceral, cerebral and lymph node metastases.

Transplantation of chronic wounds with epidermal sheets derived from autologous hair follicles--the Leipzig experience.

BACKGROUND: An increasing number of chronic wounds in our society require strategies to improve wound healing and wound closure. One of several options is skin transplantation. In this article, we focus on the transplantation of tissue engineered autologous epidermal sheets derived from outer root sheath (ORS) cells of the patients' hair. PATIENTS AND METHODS: Out of the stem cells of the ORS of anagen hair, autologous keratinocytes are cultured ex vivo in organotypic cultures to form a multilayered epidermal equivalent (EpiDex, EuroDerm Biotech & Aesthetics, Stuttgart, Germany). These sheets are placed on the wound bed. Patients were observed twice a week in the first 2 weeks, then once weekly for 4 weeks, then every 4 weeks for up to 12 weeks after transplantation. A total of 23 patients with (n = 18) and without (n = 5) therapeutic improvement were analyzed retrospectively. We evaluated only the effect of a single transplantation in a selected ulcer per patient. Furthermore, a subgroup-analysis for responder patients with an ulcer area < 25 cm2 (n = 12) was performed. RESULTS: In the responder patients (n = 18), a total wound reduction of 23% was observed. Patients (n = 12) with ulcer area < 25 cm2 had an improvement of 64%. Complete wound closure in this subgroup after a single transplantation was achieved in 33 % (n = 4) cases. CONCLUSIONS: Autologous keratinocyte transplantation with EpiDex can be performed easily and safely in patients with chronic wounds with satisfying results. Our data suggest that patients with small ulcer area < 25 cm2 might profit the most from this method.

[Lifestyle drugs in medicine]. / Lifestyle-Medikamente in der Medizin.

Lifestyle drugs have become an important new group of medications, which are taken by healthy people to increase the individual well-being and quality of life. Nootropics, psychopharmaceuticals, hormones and "ecodrugs" are today the main groups. The wish for eternal youth, beauty and potency is central, and lifestyle medications are also requested to influence cosmetic findings, which are usually simply a result of the natural aging process. Lifestyle drugs seem to be harmless, but the physician must pay attention to possible abuse, side effects, risks and complications. Additionally, however, lifestyle drugs are also frequently used by patients suffering from emotional disorders such as somatoform disorders. Medicalization of physiological life is then expected to solve psychosocial problems, but without success. The use of lifestyle medications in somatoform disorders is contraindicated and psychotherapy or psychopharmacological treatment come first. With this overview article, we would like to make an update of new lifestyle drugs.

Tacrolimus: a new option in therapy-resistant chronic external otitis.

OBJECTIVE: To evaluate the efficacy of the novel topical immune modulator tacrolimus in chronic uninfectious otherwise therapy-resistant external otitis (EO). STUDY DESIGN: Prospective clinical study. PATIENTS AND METHODS: There were 53 patients aged 5 to 83 years. An ear wick containing 0.1% tacrolimus ointment (Protopic) was inserted into the external auditory canal every 2nd to 3rd day. Altogether, the wick was changed three times. The pre-, intra- and posttherapeutic state of the clinical parameters otalgia, edema, otorrhea, erythema, pruritus, and desquamation was rated by means of a 6-point score system. Treatment efficiency was evaluated on the basis of follow-up investigations at 3-month intervals, a standardized findings sheet, and photograph documentation. RESULTS: The short-term results showed a clear improvement in 85% of the patients and significant reductions of the severity levels for all clinical parameters investigated (P < .001). Concerning the long-term results, a one-time treatment cycle led to complete healing in 46% of the patients throughout a follow-up of 10 to 22 months. Of the patients, 54% had recurrent EO events with significantly extended mean symptom-free intervals. Reapplied tacrolimus treatment patterns attenuated the relapsing course of disease and significantly reduced the number of EO episodes. Within the observation period, no relevant side effects were observed, except for a local feeling of heat, occasional skin burning, and itching. CONCLUSIONS: The topical application of 0.1% tacrolimus ointment in the outer ear canal appears to be an effective and well-tolerated new option in corticosteroid-free treatment of chronic therapy-resistant EO.

Topical tacrolimus treatment for chronic dermatitis of the ear.

Recurrent exacerbation in chronic recalcitrant external otitis (EO) often warrants multidisciplinary treatment and collaboration with a dermatologist. The aim of this pilot study was to ascertain the efficacy of topical tacrolimus ointment application in chronic, non-infectious and therapy-resistant EO. In a prospective clinical study, the efficacy of tacrolimus ointment 0.1% was examined in 53 patients with therapy-refractory chronic EO of confirmed non-infectious etiology. Clinical examination took place prior to treatment (V1), at the end (V2) and during follow-up investigations (V3) of 28 patients over 10-22 months. Patients were evaluated for the symptoms otalgia, edema, otorrhea, erythema, pruritus and desquamation on a 6-point scale. The short-term results after topical application of tacrolimus (V2) showed a clear improvement in 85% of the patients (N = 45) and significant drop in severity scores for all clinical parameters (p < 0.001). The long-term follow-up studies (V3) revealed that a one-time treatment cycle led to complete remission in 46% of patients (N = 28). The remaining 54% had recurrent EO events, however, with significantly longer symptom-free intervals. Within the observation period, no relevant local or systemic side effects were observed, except for occasional skin burning, stinging, or itching. This interdisciplinary study between dermatologists and ENT specialists clearly demonstrates that the topical application of 0.1% tacrolimus ointment is an effective and well-tolerated new option in the treatment of chronic recalcitrant EO. Furthermore, it shows that dermatologists, with their experience in topical immunomodulatory therapy, can make valuable contributions to the treatment of inflammatory disorders in other medical fields.