[Sarcopenia and immune-related toxicity in patients with malignant melanoma undergoing immune checkpoint inhibition]. / Die Bedeutung von Sarkopenie für die immunvermittelte Toxizität bei Patienten mit malignem Melanom unter einer Immuncheckpoint-Inhibition.

BACKGROUND AND OBJECTIVES: Sarcopenia is the generalized loss of muscle strength, mass, and function. The aim was to investigate whether pretherapeutic sarcopenia, as determined by the psoas muscles, affects therapy-mediated toxicity in patients with malignant melanoma undergoing immunotherapy. PATIENTS AND METHODS: Measurement of psoas musculature was performed pretherapeutically using computed tomography at the level of the third lumbar vertebra in the axial plane in 75 patients between January 2011 and December 2020. Sarcopenia was defined using the psoas muscle index (PMI). Immune-related toxicity was retrospectively assessed. RESULTS: Treatment-related toxicity was recorded in 33 of the 75 patients (44%). Of these, 16 patients (36.2%) experienced dose-limiting severe events (DLT). Pretherapeutic sarcopenia was identified in 25 patients (33.3%). Comparative analysis showed that the patients with a DLT had lower PMI values compared with the patient group without a DLT (4.65 ± 1.33 vs. 5.79 ± 1.67 cm2m-2, p = 0.015) (odds ratio = 0.60, 95% confidence interval 0.40-0.92, p = 0.02). CONCLUSIONS: Pretherapeutic sarcopenia measured based on the psoas muscle is not a significant predictor of immune-mediated toxicity in patients with malignant melanoma treated with immune checkpoint inhibitors. Patients with DLT have lower values for the psoas muscle parameters PMI compared to the group of patients without DLT.

S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Long-Term Management of Advanced Basal Cell Carcinoma: Current Challenges and Future Perspectives.

The first-line therapy for locally advanced basal cell carcinoma (laBCC) is Hedgehog pathway inhibitors (HHIs), as they achieve good efficacy and duration of response. However, toxicity in the course of long-term treatment may lead to a decrease in the quality of life, and consequently to interruption or even discontinuation of therapy. As HHI therapy is a balancing act between effectiveness, adverse events, quality of life, and adherence, numerous successful treatment strategies have evolved, such as dose reduction and dose interruptions with on-off treatment schedules or interruptions with re-challenge after progression. As a small percentage of patients show primary or acquired resistance to HHIs, the inhibition of programmed cell death protein 1 (PD-1) has been approved as a second-line therapy, which may also be accompanied by immune-related toxicities and non-response. Thus, optimization of current treatment schedules, novel agents, and combination strategies are urgently needed for laBCC. Here, we narratively model the treatment sequence for patients with laBCC and summarize the current state of approved treatment regimens and therapeutic strategies to optimize the long-term management of laBCC.

Low skeletal muscle mass is a predictor of treatment related toxicity in oncologic patients. A meta-analysis.

BACKGROUND & AIMS: The purpose of this meta-analysis was to summarize the published data regarding associations between occurrence of severe treatment related toxicity and low skeletal muscle mass (LSMM) in oncologic patients and to perform a meta-analysis based on a large sample. METHODS: MEDLINE, Cochrane, and SCOPUS databases were screened for associations between LSMM and treatment related toxicity in oncologic patients up to June 2021. Overall, 48 studies met the inclusion criteria. The following data were extracted: authors, year of publication, study design, number of patients, influence of LSMM on treatment toxicity (odds ratios and confidence intervals). The methodological quality of the involved studies was checked according to the QUADAS instrument. The meta-analysis was undertaken by using RevMan 5.4 software. DerSimonian and Laird random-effects models with inverse-variance weights were used to account for the heterogeneity between the studies. RESULTS: The included 48 studies comprised 4803 patients with different malignant diseases. LSMM occurred in 1966 patients (40.9%). LSMM was associated with therapy toxicity (simple logistic regression) with an odds ratio OR = 2.19, CI95%= (1.78-2.68). LSMM was associated with DLT in patients underwent curative treatment (16 studies, 2381 patients) with OR = 2.48, CI95%= (1.77-3.48). LSMM predicted DLT in patients underwent palliative chemotherapy (30 studies, 2337 patients)with OR = 2.06, CI95%= (1.56-2.74). In the subgroups received different palliative therapies, relationships between LSMM and DLT were as follows: conventional chemotherapies (7 studies, 600 patients) OR = 2.14, CI95%= (1.38-3.31); different kinases inhibitors (13 studies, 906 patients) OR = 3.08, CI95%= (1.87-5.09); checkpoint inhibitors (7 studies, 557 patients) OR = 1.30, CI95%= (0.79-2.11). CONCLUSIONS: LSMM is an essential factor of treatment toxicity in oncologic patients. Association between LSMM and DLT is strongest in patients received therapy with kinases inhibitors. The influence of LSMM on DLT is lowest in patients underwent treatment with checkpoint inhibitors. The presence of LSMM should be included into radiological reports and provided to oncologists to optimize chemotherapy. LSMM should be included into dose calculation for chemotherapy.

Patterns of care and follow-up care of patients with uveal melanoma in German-speaking countries: a multinational survey of the German Dermatologic Cooperative Oncology Group (DeCOG).

PURPOSE: Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting. METHODS: A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated. RESULTS: 44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures. CONCLUSION: Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed.

Patients with BRAF-Mutant Advanced/Metastatic Melanoma: Original Research on the Treatment Reality in Germany and Austria in the Era of Choice.

INTRODUCTION: Cutaneous melanoma is one of the most aggressive forms of skin neoplasms and represents a major cause of neoplastic or cancer death in Europe. Without adequate therapy, the 5-year survival rate is 15% when the disease metastasizes to distant organs. The objective of our study was to evaluate the status quo of the current treatment standards in stage IV melanoma and rationale for therapy decisions in Germany and Austria between January 2016 and September 2018. METHODS: In this retrospective, anonymized registry, data of male and female patients with unresectable advanced/metastatic BRAF-positive cutaneous melanoma treated in the first, second, and third line with registered substances were analyzed using descriptive statistics. RESULTS: Ninety-nine patients (50.5% male) received a total of 172 treatment lines. The first (99 patients), second (56 patients), and third (17 patients) treatment lines were documented. Within the 80.8% of patients with stage IV melanoma, targeted therapy (TT) was more frequently administered as a first-line treatment than immunotherapy (IO) with checkpoint inhibitors (59.6% TT vs. 40.4% IO). Across all lines, patients received TT in 54.7% and IO in 43.0% of the cases. As targeted agents, dabrafenib plus trametinib was predominantly prescribed (72.3%), whereas the monotherapy with anti-programmed cell death protein 1 and anti-cytotoxic T lymphocyte-associated protein 4 antibodies or their combination was prescribed similarly often (50.0% vs. 47.3%). Most commonly, the treatment type was switched from TT to IO or vice versa upon disease progression. The most frequent rationales for prescribing either TT or IO were remission pressure (72.9%) or physician's preference (45.0%), respectively. Disease progression was a more frequent cause of treatment discontinuation than undesired events. CONCLUSION: Patients in Germany and Austria with unresectable advanced or metastatic BRAF-mutant melanoma predominantly receive guideline-recommended treatments. TT was more frequently administered than IO while the rationale for prescribing a specific treatment type differed between the two.

Cutaneous manifestations of internal malignancy.

Skin lesions associated with internal malignancy may present as cutaneous metastases or as typical lesions occurring in the context of certain cancer-associated genetic syndromes. Paraneoplastic syndromes, on the other hand, are only indirectly associated with an underlying malignancy and are not malignant per se. Historically, a distinction has been made between "obligate" and "facultative" paraneoplastic disorders, depending on the likelihood with which they are potentially associated with malignancy. In addition, there are nonspecific cutaneous manifestations that are only rarely associated with an underlying malignancy. Another possible classification is based on the pathophysiological mechanisms underlying the cutaneous lesions. In everyday practice, it is essential that dermatologists recognize potentially cancer-associated dermatoses, as this will frequently contribute to the initial diagnosis of an underlying neoplasm.

Current diagnosis and treatment of basal cell carcinoma.

Basal cell carcinoma represents is most common tumor in fair-skinned individuals. In Germany, age-standardized incidence rates are 63 (women) and 80 (men) per 100,000 population per year. Early lesions may be difficult to diagnose merely on clinical grounds. Here, noninvasive diagnostic tools such as optical coherence tomography and confocal laser scanning microscopy may be helpful. The clinical diagnosis is usually confirmed by histology. Standard therapy consists of complete excision with thorough histological examination, either by means of micrographic surgery or, depending on tumor size and location as well as infiltration, using surgical margins of 3-5 mm or more. In particular, multiple basal cell carcinomas (such as in Gorlin-Goltz syndrome) and locally advanced as well as rarely also metastatic basal cell carcinoma may pose a therapeutic challenge. In superficial basal cell carcinoma, nonsurgical therapies such as photodynamic therapy or topical agents may be considered. In case of locally advanced or metastatic basal cell carcinoma, an interdisciplinary tumor board should issue therapeutic recommendations. These include radiation therapy as well as systemic therapy with a hedgehog inhibitor.

Non-melanoma skin cancer is reduced after switch of immunosuppression to mTOR-inhibitors in organ transplant recipients.

BACKGROUND: Organ transplant recipients are prone to the development of non-melanoma skin cancer. Organ transplant recipients often develop multiple non-melanoma skin cancers and the tumors show an aggressive growth pattern, therefore surgical therapy can be difficult. Switch of the immunosuppressive regimen to mTOR-inhibitors such as everolimus or sirolimus can have an antitumor effect. PATIENTS AND METHODS: In a monocentric retrospective study we evaluated organ transplant recipients who presented with non-melanoma skin cancer in the years 2008-2010. Experience with patients who were switched to an mTOR-inhibitor due to non-melanoma skin cancer are reported in detail, and recent clinical studies are reviewed. RESULTS: 60 organ transplant recipients with non-melanoma skin cancer were evaluated. Due to the development of multiple non-melanoma skin cancer within a few years, the immunosuppressive regimen was switched to everolimus in 7 patients and to sirolimus in 5 patients. Eight patients were evaluable for the effect of mTOR-inhibitors on the development of non-melanoma skin cancer; 4 patients had to discontinue the medication with mTOR-inhibitors early due to various side effects. In the year before the switch to mTOR-inhibitors, 8 patients developed 16 squamous cell carcinomas, 3 Basal cell carcinomas and 22 cases of Bowen's disease. All tumors were histologically confirmed. In the year after switch of immunosuppression, the rate of squamous cell carcinomas (n = 2) and Bowen's disease (n = 3), but not of basal cell carcinomas (n = 2) was significantly reduced. Moreover, 5 prospective randomized trials recently have demonstrated a reduced number of non-melanoma skin cancers in organ transplant recipients after switch of the immunosuppressive regimen to mTOR-inhibitors. CONCLUSION: Switch of the immunosuppressive regimen to mTOR-inhibitors should be considered for organ transplant recipients suffering from multiple non-melanoma skin cancers.