Frank Meiss

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Verified

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• MD
• Deputy Head of Department at University of Freiburg

The mechanisms underlying the efficacy of anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) therapy are incompletely understood. Here, by immune profiling responding PD-1⁺CD8⁺ T (TResp) cell populations from patients with advanced melanoma, we identified differential programming of TResp cells...

This study investigated whether adjuvant treatments in stage III cutaneous melanoma (CM) influenced patterns of recurrence. Patients with primary (n = 1033) or relapsed CM (n = 350) who received adjuvant therapies with Nivolumab (N), Pembrolizumab (P), or Dabrafenib and Trametinib (D + T) were extracted from the prospective multicenter real‐world s...

How lipidome changes support CD8⁺ effector T (Teff) cell differentiation is not well understood. Here we show that, although naive T cells are rich in polyunsaturated phosphoinositides (PIPn with 3–4 double bonds), Teff cells have unique PIPn marked by saturated fatty acyl chains (0–2 double bonds). PIPn are precursors for second messengers. Polyun...

Zusammenfassung Hintergrund Die psychosoziale Versorgung von Krebspatienten nimmt über den gesamten Verlauf der onkologischen Behandlung einen wichtigen Stellenwert ein. Seit 2015 ist das psychosoziale Screening in den Ambulanzen des Hauttumorzentrums in Freiburg implementiert. Wir präsentieren hier eine Post-hoc-Analyse im Rahmen der Qualitätssic...

Background PD‐1 or BRAF + MEK inhibition is considered the current gold standard in adjuvant melanoma therapy. Little is known if, after the recurrence of the disease and surgery, a second course of adjuvant therapy might be beneficial. Methods A multicenter, retrospective study investigating a second course of adjuvant therapy after recurrence an...

Background Adjuvant treatment with anti‐PD1 antibodies has been shown to effectively reduce the risk of recurrence in patients with resected metastatic melanoma. Whether a full 12‐month duration of treatment is needed to achieve full clinical benefit is not known. This study investigated the survival outcome depending on the duration of adjuvant an...

Zusammenfassung Hintergrund Bislang wurde die optimale Behandlungsdauer mit Immuncheckpoint‐Inhibitoren (ICI) noch nicht in prospektiven Studien untersucht. In der Routineversorgung muss jedoch immer wieder eine Entscheidung über die Behandlungsdauer bei Patienten mit Komplettremission unter ICI getroffen werden. Patienten und Methodik Zur Ermitt...

Background Although systemic therapies have improved considerably over the last decade, up to 50% of patients with metastatic melanoma still die due to disease progression. Oncological treatment at the end-of-life phase is challenging. The aim of this study was to investigate the frequency and type of systemic therapy received by melanoma patients...

Background Up to now, the optimal duration of immune checkpoint inhibitors (ICI) has not been evaluated in prospective studies. However, current clinical practice requires decisions to be made regarding the duration of ICI in complete responders. Material and Methods A survey was sent to 80 DeCOG skin cancer centers to assess how decisions are mad...

Zusammenfassung Hintergrund Die weltweite Inzidenz von Hautkrebs ist in den letzten Jahren kontinuierlich gestiegen. Patienten benötigen daher Informationen über die Diagnose und Behandlungsmöglichkeiten. Gleichzeitig müssen sie lernen, mit den wahrgenommenen Konsequenzen der Diagnose umzugehen. Im Jahr 2015 hat die Bundesregierung das Recht auf e...

Background The global incidence of skin cancer has steadily increased in recent years. Accordingly, patients require information on diagnosis and treatment options while dealing with the perceived impact of the diagnosis. In 2015, the German government enacted legislation under the Social Code (SGB V, § 27b), granting patients the right to obtain a...

Background Immune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%–46%. However, irMyocarditis can be asymptomatic. Thus, improved monitoring, detection and therapy are needed. This study aims to generate knowledge on pathogenesis and assess outcomes in cancer centers with inte...

Introduction Adjuvant treatment with immune checkpoint inhibitors, such as PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT), has shown a significant improvement in disease-free survival (DFS) for high-risk melanoma patients. However, due to specific side effects, the choice of treatment is often influ...

To investigate the efficacy and adverse events of modern adjuvant melanoma PD-1 and BRAF+MEK inhibitors in areal-life setting.

Cutaneous squamous cell carcinomas (SCCs) are a major complication of some subtypes of epidermolysis bullosa (EB), with high morbidity and mortality rates and unmet therapeutic needs. The high rate of endogenous mutations and the fibrotic stroma are considered to contribute to the pathogenesis. Patients with dystrophic EB (DEB) and Kindler EB (KEB)...

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.1–6 However, 40% of these patients will develop distant metastasis (DM) within 5 years, which require systemic treatments.2 5 L...

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 dat...

Purpose Adjuvant treatment with immune checkpoint inhibitors like PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT) in high-risk melanoma patients demonstrate a significant improvement in disease-free survival (DFS). Due to specific side effects, the choice of treatment is very often driven by the risk...

Background: Merkel cell carcinoma (MCC) is an immunogenic but aggressive skin cancer. Even after complete resection and radiation, relapse rates are high. PD-1 and PD-L1 checkpoint inhibitors showed clinical benefit in advanced MCC. We aimed to assess efficacy and safety of adjuvant immune checkpoint inhibition in completely resected MCC (ie, a se...

Cutaneous squamous cell carcinoma (cSCC) is a major complication of recessive dystrophic epidermolysis bullosa (RDEB) that has high morbidity and mortality rates and unmet therapeutic needs. The aim of this study was to evaluate the molecular pattern of cSCC and the clinical course of immunotherapy in 2 RDEB patients with multiple advanced cSCC. Cl...

Background Despite the availability of effective systemic therapies, a significant number of advanced melanoma patients develops brain metastases. This study investigated differences in incidence and time to diagnosis of brain metastasis and survival outcomes dependent on the type of first-line therapy. Methods Patients with metastatic, non-resect...

Background: Melanomas frequently harbour somatic mutations in BRAF (40%) or NRAS (20%). Impact of NRAS mutations on the therapeutic outcome of immune checkpoint inhibitors (ICI) remains controversial. Potential correlation of the NRAS mutational status and programmed cell death ligand-1 (PD-L1) expression in melanoma is unknown. Patients and meth...

Background and Aims Dual immune checkpoint blockade (ICB) therapy can result in immune-related-adverse events (irAE) such as ICB-hepatitis. An expansion of effector-memory (TEM) CD4 T cells associated with antiviral immunity against herpesviridae was implicated in ICB-hepatitis. Notably, these memory subsets are frequently associated with age. Here...

Background: 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 Switz...

Background and Aims Dual immune checkpoint blockade (ICB) therapy can result in immune-related-adverse events (irAE) such as ICB-hepatitis. An expansion of effector-memory (TEM) CD4 T cells associated with antiviral immunity against herpesviridae was implicated in ICB-hepatitis. Notably, these memory subsets are frequently associated with age. Here...

We report a case of cutaneous small-vessel vasculitis in a patient treated with clopidogrel after an ST-segment elevation myocardial infarction and with amiodarone caused by persistent atrial fibrillation 6 weeks before. (Level of Difficulty: Intermediate.)

Immune checkpoint inhibitors (ICI) induce T-cell-mediated antitumour responses. While ICI were initially successfully applied in metastasized melanoma, they are now approved for several tumour entities. Numerous autoimmune disorders have been reported to occur as adverse events of the treatment, among them bullous pemphigoid (BP), with less than 1%...

The global incidence of skin cancer has steadily increased in recent years, and malignant melanoma still has one of the fastest-growing incidence rates among all malignant tumors in the western world. Thus, newly diagnosed patients have an increased need for health information concerning their disease. Using a standardized questionnaire, our study...

e21597 Background: Trials of adjuvant treatment with immune checkpoint inhibitors like PD1-antibodies (ICI) or targeted therapy with BRAF/MEK inhibitors (TT) in high-risk melanoma patients demonstrate a significant improvement in recurrence-free survival (RFS) with a very similar relative risk reduction. Both treatment modalities are characterized...

Background Despite of various therapeutic strategies, treatment of patients with melanoma brain metastasis (MBM) still is a major challenge. This study aimed at investigating the impact of type and sequence of immune checkpoint blockade (ICB) and targeted therapy (TT), radiotherapy, and surgery on the survival outcome of patients with MBM. Method...

Background: Variants in genes of the nucleotide excision repair (NER) pathway have been associated with heterogeneous clinical presentations ranging from xeroderma pigmentosum to Cockayne syndrome and trichothiodystrophy. NER deficiencies manifest with photosensitivity and skin cancer, but also developmental delay and early-onset neurological dege...

Background MEK inhibitors (MEKi) have shown clinical efficacy for NRAS-mutated, metastasized melanoma in randomised controlled trials, yet their clinical use is currently restricted to advanced, pre-treated patients, which is a different situation compared to previous trials. Data on their efficacy in the current real-world use are scarce. Methods...

Background Conjunctival melanoma is a rare type of ocular melanoma, which is prone to local recurrence and metastasis and can lead to patient death. Novel therapeutic strategies have revolutionized cutaneous melanoma management. The efficacy of these therapies in conjunctival melanoma, however, has not been evaluated in larger patient cohorts. Met...

Objectives Forty to sixty percent of patients with advanced melanoma show primary resistance to PD-1-based immunotherapy, 30–40% of initial responders also progress. Here, we evaluated the outcome of second-line targeted therapy (TT) after progression on PD-1-based immune checkpoint inhibition (ICI) in BRAFV600-mutated melanoma. In addition, we rep...

Simple Summary Despite the immense progress in systemic treatment of advanced unresectable melanoma with immunotherapies, there is still an unmet need for patients showing primary resistance. We show that addition of intratumoral injections of the immune modulator Interleukin-2 can overcome primary resistance in a distinct subset of patients and th...

Congenital melanocytic nevus (CMN) syndrome represents a mosaic RASopathy, typically caused by postzygotic NRAS codon 61 mutations, which originate in ectodermal precursor cells and result in melanocyte deposits in the skin and central nervous system (CNS). Affected patients are prone to develop uniformly fatal melanomas in the skin and CNS. Here,...

Patients with RDEB (RDEB) suffer from mucocutaneous fragility, high risk for cutaneous squamous cell carcinomas (SCC) on sites prone to trauma and different multiorgan complications, including esophageal strictures.¹⁻⁴ RDEB associated SCCs, though usually well differentiated, have an aggressive course and are the most common cause of death.2,3 Esop...

Zusammenfassung Hintergrund und Ziele Es fehlen Daten Daten über die Situation von Melanompatienten, die in ihren letzten Lebensmonaten systemische Therapien erhalten. Patienten und Methoden Alle Melanompatienten, die 2016 oder 2017 verstorben sind und die innerhalb der letzten drei Lebensmonate mit systemischen Therapien behandelt wurden, wurden...

Einleitung: Im Rahmen von Immuntherapien mit Checkpoint Inhibitoren (ICB) treten häufig immunvermittelte Nebenwirkungen (iNW) auf. Die Immun-Checkpoint-Blockade assoziierte Immunhepatitis (ICB-Hepatitis) stellt eine der häufigen und potentiell lebensbedrohlichen iNW dar. Die Mechanismen der ICB-Hepatitis in Abgrenzung zur klassischen Autoimmunhepat...

Background and objectives There is a lack of data regarding the situation of melanoma patients receiving systemic therapies in their last months of life. Patients and methods All melanoma patients who died in 2016 or 2017 and who had been treated by systemic therapies within the last three months of life were retrospectively analyzed. The study wa...

Introduction Cutaneous melanoma is notorious for the development of in-transit metastases (ITM). For unknown biological reasons, ITM remain the leading tumour manifestation without progression to distant sites in some patients. Methods In total, 191 patients with initially unresectable stage III ITM and satellite metastases from 16 skin cancer cen...

Abstract Purpose To examine treatment patterns, oncological outcomes and toxicity rates in elderly patients receiving radiotherapy for cutaneous squamous cell carcinoma (cSCC) of the head-and-neck region. Material and methods In this retrospective single-center analysis, locoregional control (LRC), progression-free survival (PFS) and overall surviv...

Background Ipilimumab has shown long-term overall survival (OS) in patients with advanced melanoma in clinical trials, but robust real-world evidence is lacking. We present long-term outcomes from the IMAGE study (NCT01511913) in patients receiving ipilimumab and/or non-ipilimumab (any approved treatment other than ipilimumab) systemic therapies....

We describe a case of a 65-year old patient presenting with unusual mucocutaneous melanocytic proliferations of a Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) imitating a multifocal melanoma in situ, which improved dramatically after plasmapheresis. The patient first presented at the dermatology department due to rapidly evolving brown...

Background The European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 trial in patients with resected, high-risk stage III melanoma demonstrated improved recurrence-free survival with adjuvant pembrolizumab compared with placebo (hazard ratio 0·57 [98·4% CI 0·43–0·74]; p<0·0001). This study reports the results from t...

Background The European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial assessed pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. At 15-month median follow-up, pembrolizumab improved recurrence-free survival (hazard ratio [HR] 0·57 [98·4% CI 0·43–0·74], p<0·0001) compared with pla...

Molecular precision oncology faces two major challenges: first, to identify relevant and actionable molecular variants in a rapidly changing field and second, to provide access to a broad patient population. Here, we report a four-year experience of the Molecular Tumor Board (MTB) of the Comprehensive Cancer Center Freiburg (Germany) including work...

PURPOSE We evaluated circulating tumor DNA (ctDNA) for detecting tumor burden in melanoma and examined whether early changes in the number of ctDNA copies predict response to treatment. PATIENTS AND METHODS We included 12 patients with stage III and 50 patients with stage IV melanoma with BRAF exon 15 or NRAS exon 3 mutations in tumor tissue. We u...

Radiotherapy can elicit abscopal effects in non-irradiated metastases, particularly under immune checkpoint blockade (ICB). We report on two elderly patients with oligometastatic melanoma treated with anti-PD-1 and stereotactic body radiation therapy (SBRT). Before treatment, patient 1 showed strong tumor infiltration with exhausted CD8+ T cells an...

Background: Circulating tumor DNA (ctDNA) in the blood plasma of cancer patients is an emerging biomarker used across oncology, facilitating noninvasive disease monitoring and genetic profiling at various disease milestones. Digital droplet PCR (ddPCR) technologies have demonstrated high sensitivity and specificity for robust ctDNA detection at rel...

A patient with severe autoimmune pneumonitis from immune checkpoint inhibitor therapy for metastatic melanoma had improved clinical and radiographic clearance of the pneumonitis associated with treatment with inhaled vasoactive intestinal peptide.

10070 Background: In the context of multiple in-transit melanoma metastases without nodal involvement, a variety of treatment modalities have historically been employed including surgery, laser, isolated limb perfusion/infusion, intralesional interleukin-2, T-VEC and electrochemotherapy. Unfortunately, most patients treated with these modalities ex...

Immune checkpoint inhibitor (ICI) therapy has shown a significant benefit in the treatment of a variety of cancer entities. However, immune-related adverse events (irAEs) occur frequently and can lead to ICI treatment termination. MicroRNA-146a (miR-146a) has regulatory functions in immune cells. We observed that mice lacking miR-146a developed sig...

Background Nivolumab combined with ipilimumab have shown activity in melanoma brain metastasis (MBM). However, in most of the clinical trials investigating immunotherapy in this subgroup, patients with symptomatic MBM and/or prior local brain radiotherapy were excluded. We studied the efficacy of nivolumab plus ipilimumab alone or in combination wi...

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive type of hematologic precursor malignancy primarily often manifesting in the skin. We sought to provide a thorough clinical characterisation and report our experience on therapeutic approaches to BPDCN. Methods: In the present multicentric retrospective study,...

Extracorporeal photopheresis has been an effective treatment for graft-versus-host disease. In this case, it was used to treat a patient with severe autoimmune colitis induced by checkpoint-inhibitor therapy for melanoma. The extracorporeal photopheresis resulted in an increased number of immunoregulatory natural killer cells.

Abstract Dystrophic epidermolysis bullosa (DEB) is a hereditary skin fragility disorder, characterized by trauma-induced blistering followed by soft tissue fibrosis. One of the most feared complications is the early development of aggressive cutaneous squamous cell carcinomas (SCC). For patients with locally advanced or metastasized SCCs treatment...

Purpose: BRAF/MEK inhibition is a standard of care for patients with BRAF V600E/K-mutated metastatic melanoma. For patients with less frequent BRAF mutations, however, efficacy data are limited. Methods: In the current study, 103 patients with metastatic melanoma with rare, activating non-V600E/K BRAF mutations that were treated with either a BR...

Background IPI has shown durable overall survival (OS) in patients (pts) with MEL in clinical trials, but robust RW evidence is lacking. We present long-term RW outcomes from the IMAGE study (NCT01511913) in which pts received IPI and non-IPI therapies. Methods IMAGE was a large, multinational, prospective, observational study that enrolled adult...

Systemic immunotherapy with PD-1 inhibitors is established in the treatment of metastatic melanoma. However, up to 60% of patients do not show long-term benefit from a PD-1 inhibitor monotherapy. Intralesional treatments with immunomodulatory agents such as the oncolytic herpes virus Talimogene Laherparepvec and interleukin-2 (IL-2) have been succe...

Cutaneous squamous cell carcinoma (SCC) is the most severe, life‐limiting complication of recessive dystrophic epidermolysis bullosa (RDEB).1 In RDEB, collagen VII deficiency results in permanent cutaneous damage, favoring bacterial colonization, inflammation and scarring. Particularities of SCCs in RDEB are: early onset2, multiple SCCs3, frequent...

Background and objectives Primary cutaneous diffuse large B‐cell lymphoma, NOS (PCLBCL/NOS) is a rare PCLBCL. Only few data are available for this tumor. The aim of this study was to identify clinical and/or immunohistochemical markers (in addition to Bcl‐2) that characterize PCLBCL/NOS, assist in differentiating it from PCLBCL, leg type (PCLBCL/LT...

Zusammenfassung Hintergrund und Ziele Das primär kutane diffus‐großzellige B‐Zell‐Lymphom, NOS (PCLBCL/NOS) ist ein seltenes PCLBCL. Über diesen Tumor liegen nur wenige Daten vor. Ziel dieser Studie war es, klinische und/oder immunhistochemische Marker (neben Bcl‐2) zu identifizieren, die das PCLBCL/NOS charakterisieren und helfen es vom PCLBCL/le...

Background Combining stereotactic radiosurgery (SRS) and active systemic therapies (STs) achieved favourable survival outcomes in patients with melanoma brain metastases (MBMs) in retrospective analyses. However, several aspects of this treatment strategy remain poorly understood. We report on the overall survival (OS) of patients with MBM treated...

INTRODUCTION: Treatment of patients with metastatic melanoma is hampered by drug-resistance and often requires combination with radiotherapy as last-resort option. However, also after radiotherapy, clinical relapses are common. METHODS & RESULTS: Our preclinical models indicated a higher rate of tumour relapse when melanoma cells were first treate...

Background Psycho-oncological care is a main component of comprehensive oncological care as stated in the National Cancer Plan of the German Federal Government. Correspondingly this goal has been adopted in the strategy of the German Skin Cancer Council. In certified skin cancer centers structural requirements for psycho-oncological care are establ...

MicroRNAs (miR) are small noncoding RNAs that regulate gene expression, posttranscription, and manipulate immune responses in different types of cancers. In this study, we identify miR-146a as a negative regulator of immune activation, comparable to immune-checkpoint molecules. miR-146a levels were increased in melanoma microenvironmental tissue, a...