Treatment management for BRAF-mutant melanoma patients with tumor recurrence on adjuvant therapy: a multicenter study from the prospective skin cancer registry ADOREG.

BACKGROUND: Adjuvant therapy with immune-checkpoint inhibitors (CPI) or BRAF/MEK-directed targeted therapy (TT) improves recurrence-free survival (RFS) for patients with advanced, BRAFV600-mutant (BRAFmut) resected melanoma. However, 40% of these patients will develop distant metastases (DM) within 5 years, which require systemic therapy. Little data exist to guide the choice of upfront adjuvant therapy or treatment management upon DM. This study evaluated the efficacy of subsequent treatments following tumor recurrence upon upfront adjuvant therapy. METHODS: For this multicenter cohort study, we identified 515 BRAFmut patients with resected stage III melanoma who were treated with PD-1 inhibitors (anti-PD1) or TT in the adjuvant setting. Disease characteristics, treatment regimens, details on tumor recurrence, subsequent treatment management, and survival outcomes were collected within the prospective, real-world skin cancer registry ADOReg. Primary endpoints included progression-free survival (PFS) following DM and best tumor response to first-line (1L) treatments. RESULTS: Among 515 eligible patients, 273 patients received adjuvant anti-PD1 and 242 adjuvant TT. At a median follow-up of 21 months, 54.6% of anti-PD1 patients and 36.4% of TT patients recurred, while 39.6% (anti-PD1) and 29.3% (TT) developed DM. Risk of recurrence was significantly reduced in patients treated with TT compared with anti-PD1 (adjusted HR 0.52; 95% CI 0.40 to 0.68, p<0.001). Likewise, median RFS was significantly longer in TT-treated patients (31 vs 17 months, p<0.001). Patients who received TT as second adjuvant treatment upon locoregional recurrence had a longer RFS2 as compared with adjuvant CPI (41 vs 6 months, p=0.009). Patients who recurred at distant sites following adjuvant TT showed favorable response rates (42.9%) after switching to 1L ipilimumab+nivolumab (ipi+nivo). Patients with DM during adjuvant anti-PD1 achieved response rates of 58.7% after switching to 1L TT and 35.3% for 1L ipi+nivo. Overall, median PFS was significantly longer in patients who switched treatments for stage IV disease (median PFS 9 vs 5 months, p=0.004). CONCLUSIONS: BRAFmut melanoma patients who developed DM upon upfront adjuvant therapy achieve favorable tumor control and prolonged PFS after switching treatment modalities in the first-line setting of stage IV disease. Patients with locoregional recurrence benefit from complete resection of recurrence followed by a second adjuvant treatment with TT.

Dermatopathology - Current status and development in German-speaking dermatology.

Dermatopathology has been an integral part of dermatology for more than 100 years and is essential for high quality patient care. In German-speaking countries, dermatologists can acquire an additional qualification in dermatopathology after appropriate further training. For many years, dermatopathological diagnostics has advanced far beyond morphology. Immunohistochemistry and molecular pathology are nowadays an essential part and a prerequisite for the preservation of our discipline. Due to the increasing implementation of digitalization and artificial intelligence, dermatopathology is forward-looking and offers an attractive working environment for young colleagues. Dermatopathology is also indispensable for research, and this fact should also be taken into account by creating academic positions and professorships in the future.

[Acquired progressive lymphangioma in a 13-year-old boy]. / Erworbenes progressives Lymphangiom bei einem 13­jährigen Jungen.

Acquired tumors of lymphatic vessels are rare. Clinically, progressive lymphangioma usually appears as circumscribed plaques of small to medium size. In contrast, our case of a 13-year-old boy demonstrates a case of progressive lymphangioma with a solitary large indurated plaque. No extracutaneous manifestation was found. Systemic therapy with corticosteroids and methotrexate resulted in an improvement of the patient's condition. Dependent on clinical course and appearance of the disease, therapy with mTOR inhibitors may be considered as a therapeutic option.

Stage-related PD-L1 expression in Kaposi sarcoma tumor microenvironment.

BACKGROUND: The immune checkpoint molecule PD-L1 represents an important target in oncological immune therapy. The aim of our study was to evaluate PD-L1 expression and the composition of the tumor microenvironment (TME) in Kaposi sarcoma. METHODS: Immunohistochemical stains were performed for PD-L1, CD3, CD33, CD68, and CD168 in 24 Kaposi sarcoma samples. In PD-L1-positive cases, the double stains for PD-L1, CD31, podoplanin, and HHV8 were added. RESULTS: PD-L1 was observed in 71% of the samples and was predominantly located in the TME. PD-L1 expression was significantly higher in nodular stage than in patch/plaque stage. The TME consisted of CD68+/CD163+ macrophages, CD33+ myloid-derived suppressor cells and monocytes and CD3+ T-cells. The TME showed a peritumoral distribution in nodular stage, in contrast to a diffuse distribution in patch/plaque stage. In 12 samples (50%), no plasma cells were found. CONCLUSION: In nodular stage of KS, the TME is pushed back in the periphery of the tumor nodules. The PD-L1-positive TME between the tumor cells might protect them from the immune attack. An anti-PD-L1 treatment might be promising in KS patients.

S2k Guidelines for Cutaneous Basal Cell Carcinoma - Part 2: Treatment, Prevention and Follow-up.

Basal cell carcinoma (BCC) is the most common malignant tumor among fair-skinned individuals, and its incidence had been steadily rising in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 2 addresses issues such as proper risk stratification, the various therapeutic approaches, and prevention as well as follow-up of patients with basal cell carcinoma.