Ricarda Rauschenberg

Systemic therapy of metastatic melanoma

For patients with metastatic melanoma, there are currently several effective therapeutic options. The BRAF inhibitors vemurafenib and dabrafenib are characterized by rapid tumor control and high response rates. In combination with one of the two MEK inhibitors trametinib and cobimetinib, they achieve response rates (CR + PR, complete plus partial remissions) of 70 %, while delaying the development of treatment resistance, as well as a median overall survival of > 2 years with tolerable side effects.

Hirnmetastasen des malignen Melanoms

The majority of patients with metastatic melanoma will develop brain metastases, which are the most common cause of death. Until recently, local therapies (e. g., neurosurgery, radiotherapy) were the only options for brain metastases; however, effective systemic treatment options are now available. Upon suspicion of brain metastases, diagnostic staging with brain MRI and a neurological investigation are indicated. Prognostic factors such as number of cerebral metastases and symptoms, serum lactate dehydrogenase and S‑100 levels, extracerebral metastases, and ECOG status are considered during therapeutic planning. Treatment planning and therapeutic interventions should be based on an interdisciplinary and multimodal approach. Established treatments for singular brain metastases are neurosurgical resection and stereotactic radiotherapy, which can prolong survival. In patients with asymptomatic BRAF V600E-mutant brain metastases, the BRAF inhibitors dabrafenib, vemurafenib, and immunotherapy with ipilimumab are used. In the case of multiple symptomatic brain metastases, palliative whole-brain radiotherapy is used for treatment, although it has failed to show an overall survival benefit. Increased intracranial pressure and epileptic seizures are addressed with corticosteroids and anticonvulsants. Current clinical studies for melanoma patients with brain metastases are investigating new treatment options such as PD-1 antibodies, combined ipilimumab and nivolumab, combined BRAF inhibitors and MEK inhibitors, and stereotactic radiation in combination with immunotherapy or targeted therapy.ZusammenfassungHirnmetastasen treten bei der Mehrheit der Patienten mit metastasiertem Melanom auf und sind die häufigste Todesursache. Bis vor Kurzem war die Lokaltherapie die einzige Option für die Kontrolle von Hirnmetastasen. Inzwischen stehen wirksame systemische Therapieoptionen zur Verfügung. Bei Verdacht auf Hirnmetastasen sind eine Staging-Diagnostik mit Craniale Magnetresonanztomographie (cMRT) sowie eine neurologische Untersuchung indiziert. Für die Therapieplanung sollten prognostische Faktoren wie Anzahl und Symptomatik der zerebralen Metastasen, der LDH- und S100-Wert im Serum, die extrazerebrale Metastasierung sowie der ECOG (Eastern Cooperative Oncology Group)-Status einbezogen werden. Die Therapieentscheidung bzw. -durchführung sollte interdisziplinär bzw. multimodal erfolgen. Bei singulären Hirnmetastasen sind die neurochirurgische Resektion und die stereotaktische Radiatio etabliert. Das Behandlungsspektrum hat sich durch die Neuzulassung von wirksamen Immuntherapien (CTLA-4- und PD-1-Antikörper) sowie zielgerichteten Therapien (BRAF-und MEK-Inhibitoren) erheblich erweitert. Die palliative Ganzhirnradiatio wird bei multiplen symptomatischen Hirnmetastasen eingesetzt, wobei bisher kein signifikanter Vorteil für das Gesamtüberleben gezeigt werden konnte. Bei erhöhtem intrakraniellem Druck und epileptischen Anfällen sind Kortikosteroide und Antikonvulsiva indiziert. In aktuellen klinischen Studien werden für Melanompatienten mit Hirnmetastasen neue Therapieoptionen wie PD-1-Antikörper, Ipilimumab plus Nivolumab, BRAF-Inhibitoren plus MEK-Inhibitoren sowie stereotaktische Radiatio in Kombination mit Immuntherapie bzw. zielgerichteter Therapie untersucht.AbstractThe majority of patients with metastatic melanoma will develop brain metastases, which are the most common cause of death. Until recently, local therapies (e. g., neurosurgery, radiotherapy) were the only options for brain metastases; however, effective systemic treatment options are now available. Upon suspicion of brain metastases, diagnostic staging with brain MRI and a neurological investigation are indicated. Prognostic factors such as number of cerebral metastases and symptoms, serum lactate dehydrogenase and S‑100 levels, extracerebral metastases, and ECOG status are considered during therapeutic planning. Treatment planning and therapeutic interventions should be based on an interdisciplinary and multimodal approach. Established treatments for singular brain metastases are neurosurgical resection and stereotactic radiotherapy, which can prolong survival. In patients with asymptomatic BRAF V600E-mutant brain metastases, the BRAF inhibitors dabrafenib, vemurafenib, and immunotherapy with ipilimumab are used. In the case of multiple symptomatic brain metastases, palliative whole-brain radiotherapy is used for treatment, although it has failed to show an overall survival benefit. Increased intracranial pressure and epileptic seizures are addressed with corticosteroids and anticonvulsants. Current clinical studies for melanoma patients with brain metastases are investigating new treatment options such as PD-1 antibodies, combined ipilimumab and nivolumab, combined BRAF inhibitors and MEK inhibitors, and stereotactic radiation in combination with immunotherapy or targeted therapy.

Systemtherapie des metastasierten malignen Melanoms

Für Patienten mit metastasiertem Melanom stehen aktuell mehrere wirksame Therapieoptionen zur Verfügung. Die BRAF‐Inhibitoren Vemurafenib und Dabrafenib zeichnen sich durch eine rasche Tumorkontrolle und hohe Ansprechraten aus. In Kombination mit den MEK‐Inhibitoren Trametinib bzw. Cobimetinib erreichen sie Ansprechraten (CR + PR, komplette plus partielle Remissionen) von 70 %, wobei die Entwicklung einer Therapieresistenz verzögert wird, sowie ein medianes Gesamtüberleben von > 2 Jahren bei tolerablen Nebenwirkungen.

Clinical outcome of concomitant vs interrupted BRAF inhibitor therapy during radiotherapy in melanoma patients

This corrects the article DOI: 10.1038/bjc.2017.85

[Melanoma brain metastases : Treatment options].

The majority of patients with metastatic melanoma will develop brain metastases, which are the most common cause of death. Until recently, local therapies (e. g., neurosurgery, radiotherapy) were the only options for brain metastases; however, effective systemic treatment options are now available. Upon suspicion of brain metastases, diagnostic staging with brain MRI and a neurological investigation are indicated. Prognostic factors such as number of cerebral metastases and symptoms, serum lactate dehydrogenase and S‑100 levels, extracerebral metastases, and ECOG status are considered during therapeutic planning. Treatment planning and therapeutic interventions should be based on an interdisciplinary and multimodal approach. Established treatments for singular brain metastases are neurosurgical resection and stereotactic radiotherapy, which can prolong survival. In patients with asymptomatic BRAF V600E-mutant brain metastases, the BRAF inhibitors dabrafenib, vemurafenib, and immunotherapy with ipilimumab are used. In the case of multiple symptomatic brain metastases, palliative whole-brain radiotherapy is used for treatment, although it has failed to show an overall survival benefit. Increased intracranial pressure and epileptic seizures are addressed with corticosteroids and anticonvulsants. Current clinical studies for melanoma patients with brain metastases are investigating new treatment options such as PD-1 antibodies, combined ipilimumab and nivolumab, combined BRAF inhibitors and MEK inhibitors, and stereotactic radiation in combination with immunotherapy or targeted therapy.ZusammenfassungHirnmetastasen treten bei der Mehrheit der Patienten mit metastasiertem Melanom auf und sind die häufigste Todesursache. Bis vor Kurzem war die Lokaltherapie die einzige Option für die Kontrolle von Hirnmetastasen. Inzwischen stehen wirksame systemische Therapieoptionen zur Verfügung. Bei Verdacht auf Hirnmetastasen sind eine Staging-Diagnostik mit Craniale Magnetresonanztomographie (cMRT) sowie eine neurologische Untersuchung indiziert. Für die Therapieplanung sollten prognostische Faktoren wie Anzahl und Symptomatik der zerebralen Metastasen, der LDH- und S100-Wert im Serum, die extrazerebrale Metastasierung sowie der ECOG (Eastern Cooperative Oncology Group)-Status einbezogen werden. Die Therapieentscheidung bzw. -durchführung sollte interdisziplinär bzw. multimodal erfolgen. Bei singulären Hirnmetastasen sind die neurochirurgische Resektion und die stereotaktische Radiatio etabliert. Das Behandlungsspektrum hat sich durch die Neuzulassung von wirksamen Immuntherapien (CTLA-4- und PD-1-Antikörper) sowie zielgerichteten Therapien (BRAF-und MEK-Inhibitoren) erheblich erweitert. Die palliative Ganzhirnradiatio wird bei multiplen symptomatischen Hirnmetastasen eingesetzt, wobei bisher kein signifikanter Vorteil für das Gesamtüberleben gezeigt werden konnte. Bei erhöhtem intrakraniellem Druck und epileptischen Anfällen sind Kortikosteroide und Antikonvulsiva indiziert. In aktuellen klinischen Studien werden für Melanompatienten mit Hirnmetastasen neue Therapieoptionen wie PD-1-Antikörper, Ipilimumab plus Nivolumab, BRAF-Inhibitoren plus MEK-Inhibitoren sowie stereotaktische Radiatio in Kombination mit Immuntherapie bzw. zielgerichteter Therapie untersucht.AbstractThe majority of patients with metastatic melanoma will develop brain metastases, which are the most common cause of death. Until recently, local therapies (e. g., neurosurgery, radiotherapy) were the only options for brain metastases; however, effective systemic treatment options are now available. Upon suspicion of brain metastases, diagnostic staging with brain MRI and a neurological investigation are indicated. Prognostic factors such as number of cerebral metastases and symptoms, serum lactate dehydrogenase and S‑100 levels, extracerebral metastases, and ECOG status are considered during therapeutic planning. Treatment planning and therapeutic interventions should be based on an interdisciplinary and multimodal approach. Established treatments for singular brain metastases are neurosurgical resection and stereotactic radiotherapy, which can prolong survival. In patients with asymptomatic BRAF V600E-mutant brain metastases, the BRAF inhibitors dabrafenib, vemurafenib, and immunotherapy with ipilimumab are used. In the case of multiple symptomatic brain metastases, palliative whole-brain radiotherapy is used for treatment, although it has failed to show an overall survival benefit. Increased intracranial pressure and epileptic seizures are addressed with corticosteroids and anticonvulsants. Current clinical studies for melanoma patients with brain metastases are investigating new treatment options such as PD-1 antibodies, combined ipilimumab and nivolumab, combined BRAF inhibitors and MEK inhibitors, and stereotactic radiation in combination with immunotherapy or targeted therapy.

Occupational immediate‐type allergy to locusts in a zookeeper

Locusts belong to the arthropod phylum and the insect class [1]. The European migratory locust (Locusta migratoria; genus Locusta) is characterized by its ability to migrate – also in form of dreaded plagues – as well as its quick adaptability to various environmental conditions [2]. It has long been the subject of biogeographic and ethologic research due to its population-dependent phenotypic plasticity (known as phase polymorphism, marked by the development from an individual phase [solitary phase] into a swarm phase [gregarious phase]) [3]. Migratory locusts – along with cockroaches and mealworms – are also used as feed for carnivorous reptiles and are available at pet shops. There have been reports of immediate hypersensitivity reactions, primarily in laboratory employees, after exposure to Locusta migratoria and other insects [4, 5]. We report on a 41-year-old female zookeeper whose occupational duties included feeding reptiles. Upon contact with migratory locusts (used as feed) she experienced hoarseness, lip paresthesia as well as pruritus, erythema, and wheals on her hands. Moreover, rubbing her eyes led to conjunctival erythema. Over the course of one year, she developed a productive cough and respiratory problems, for which she was initially treated with antibiotics. The results of off-site pulmonary function tests – as well as an examination by an ENT specialist – were normal. The patient denied any symptoms on weekends and during vacations as well as when feeding crustaceans (for example, daphnia) and mosquito larvae to her own fish at home. Neither she nor her family had a history of atopic disease, nor was she taking any medication. A rub test with a dead migratory locust resulted in severe contact urticaria (40/80 mm) (Figure 1). A hospital employee acting as control did not show any positive reaction. Skin exposure to a live locust – without iatrogenic alteration of the epidermis – also led to contact urticaria in our patient. ELISA testing (ImmunoCAP® Phadia) showed specific IgE antibodies to migratory locusts (1.7 kU/l – CAP 2). Specific IgE antibodies to tropomyosin, cockroaches, moths, mosquitoes, red mosquito larvae, mealworms, daphnia, and TetraminTM (feed) were not detected. Total IgE was slightly elevated at 102 kU/l (normal range for adults: < 100 kU/l). Prick testing for aeroallergens (including house dust mites) was negative. Mast cell tryptase was within normal limits. Clinical Letter Based on her clinical symptoms along with the evidence of type 1 sensitization to migratory locusts (ELISA, rub test, skin exposure test), the patient was diagnosed with an allergy to migratory locusts. There was no evidence of any sensitization to or cross-reactivity with other arthropods. For symptom relief, she was advised to take cetirizine tablets. She was also given an emergency kit that included an antihistamine, a corticosteroid, and a beta-adrenergic agent. Based on a dermatologist’s report, an occupational disease assessment procedure was initiated. The patient was forced to quit her job, because she would not have been able to avoid allergen exposure at her workplace. In terms of occupational skin diseases, arthropods are relevant for both infectious (primarily as vectors or pathogen reservoirs) and allergic disorders. Among laboratory workers at a research center where locusts were bred, Burge and colleagues reported exposure-related cases of respiratory disorders (26 %), rhinitis (35 %), and urticaria (33 %) [6]. While the authors suggested a connection between atopy and the prevalence (or early onset) of occupational asthma, later studies have failed to confirm such an association [4, 7]. Apart from elevated total IgE, our patient did not show any signs of atopic diathesis. Nevertheless, it is safe to assume that continued exposure, especially to a large number of insect allergens, would have entailed an increased risk for additional sensitizations and respiratory problems in case of [8]. To our knowledge, this is the first reported case of locust allergy in a zookeeper. Occupational allergies to locusts have rarely been published and predominantly relate to research lab workers. In migratory locusts, the peritrophic membrane, an intestinal membrane excreted in feces, has been identified as the primary allergen source [7]. Other epitopes have been found in the wings [4]. Although cross-reactivity presumably exists between different insect allergens, there has been no clear

Information-seeking and use of information resources among melanoma patients of German skin cancer centers: Information-seeking among melanoma patients

This study aimed to explore the information‐seeking behavior (ISB) of melanoma patients (MPs) and MP subgroups, in order to provide data for needs‐based adaptation of information provision.

Informationssuche und Nutzung von Informationsquellen durch Melanompatienten deutscher Hautkrebszentren: Informationssuche durch Melanompatienten

Mit dieser Studie sollte das Informationsverhalten (IV) von Melanompatienten (MP) und deren Subgruppen untersucht werden, um Daten für eine bedarfsgerechte Anpassung der Informationsversorgung zu erhalten.

Melanoma Brain Metastases: Local Therapies, Targeted Therapies, Immune Checkpoint Inhibitors and Their Combinations—Chances and Challenges

Recent phase II trials have shown that BRAF/MEK inhibitors and immune checkpoint inhibitors are active in patients with melanoma brain metastases (MBM), reporting intracranial disease control rates of 50–75%. Furthermore, retrospective analyses suggest that combining stereotactic radiosurgery with immune checkpoint inhibitors or BRAF/MEK inhibitors prolongs overall survival. These data stress the need for inter- and multidisciplinary cooperation that takes into account the individual prognostic factors in order to establish the best treatment for each patient. Although the management of MBM has dramatically improved, a substantial number of patients still progress and die from brain metastases. Therefore, there is an urgent need for prospective studies in patients with MBM that focus on treatment combinations and sequences, new treatment strategies, and biomarkers of treatment response. Moreover, further research is needed to decipher brain-specific mechanisms of therapy resistance.

Hirnmetastasen des malignen Melanoms: Therapiebesonderheiten

The majority of patients with metastatic melanoma will develop brain metastases, which are the most common cause of death. Until recently, local therapies (e. g., neurosurgery, radiotherapy) were the only options for brain metastases; however, effective systemic treatment options are now available. Upon suspicion of brain metastases, diagnostic staging with brain MRI and a neurological investigation are indicated. Prognostic factors such as number of cerebral metastases and symptoms, serum lactate dehydrogenase and S‑100 levels, extracerebral metastases, and ECOG status are considered during therapeutic planning. Treatment planning and therapeutic interventions should be based on an interdisciplinary and multimodal approach. Established treatments for singular brain metastases are neurosurgical resection and stereotactic radiotherapy, which can prolong survival. In patients with asymptomatic BRAF V600E-mutant brain metastases, the BRAF inhibitors dabrafenib, vemurafenib, and immunotherapy with ipilimumab are used. In the case of multiple symptomatic brain metastases, palliative whole-brain radiotherapy is used for treatment, although it has failed to show an overall survival benefit. Increased intracranial pressure and epileptic seizures are addressed with corticosteroids and anticonvulsants. Current clinical studies for melanoma patients with brain metastases are investigating new treatment options such as PD-1 antibodies, combined ipilimumab and nivolumab, combined BRAF inhibitors and MEK inhibitors, and stereotactic radiation in combination with immunotherapy or targeted therapy.ZusammenfassungHirnmetastasen treten bei der Mehrheit der Patienten mit metastasiertem Melanom auf und sind die häufigste Todesursache. Bis vor Kurzem war die Lokaltherapie die einzige Option für die Kontrolle von Hirnmetastasen. Inzwischen stehen wirksame systemische Therapieoptionen zur Verfügung. Bei Verdacht auf Hirnmetastasen sind eine Staging-Diagnostik mit Craniale Magnetresonanztomographie (cMRT) sowie eine neurologische Untersuchung indiziert. Für die Therapieplanung sollten prognostische Faktoren wie Anzahl und Symptomatik der zerebralen Metastasen, der LDH- und S100-Wert im Serum, die extrazerebrale Metastasierung sowie der ECOG (Eastern Cooperative Oncology Group)-Status einbezogen werden. Die Therapieentscheidung bzw. -durchführung sollte interdisziplinär bzw. multimodal erfolgen. Bei singulären Hirnmetastasen sind die neurochirurgische Resektion und die stereotaktische Radiatio etabliert. Das Behandlungsspektrum hat sich durch die Neuzulassung von wirksamen Immuntherapien (CTLA-4- und PD-1-Antikörper) sowie zielgerichteten Therapien (BRAF-und MEK-Inhibitoren) erheblich erweitert. Die palliative Ganzhirnradiatio wird bei multiplen symptomatischen Hirnmetastasen eingesetzt, wobei bisher kein signifikanter Vorteil für das Gesamtüberleben gezeigt werden konnte. Bei erhöhtem intrakraniellem Druck und epileptischen Anfällen sind Kortikosteroide und Antikonvulsiva indiziert. In aktuellen klinischen Studien werden für Melanompatienten mit Hirnmetastasen neue Therapieoptionen wie PD-1-Antikörper, Ipilimumab plus Nivolumab, BRAF-Inhibitoren plus MEK-Inhibitoren sowie stereotaktische Radiatio in Kombination mit Immuntherapie bzw. zielgerichteter Therapie untersucht.AbstractThe majority of patients with metastatic melanoma will develop brain metastases, which are the most common cause of death. Until recently, local therapies (e. g., neurosurgery, radiotherapy) were the only options for brain metastases; however, effective systemic treatment options are now available. Upon suspicion of brain metastases, diagnostic staging with brain MRI and a neurological investigation are indicated. Prognostic factors such as number of cerebral metastases and symptoms, serum lactate dehydrogenase and S‑100 levels, extracerebral metastases, and ECOG status are considered during therapeutic planning. Treatment planning and therapeutic interventions should be based on an interdisciplinary and multimodal approach. Established treatments for singular brain metastases are neurosurgical resection and stereotactic radiotherapy, which can prolong survival. In patients with asymptomatic BRAF V600E-mutant brain metastases, the BRAF inhibitors dabrafenib, vemurafenib, and immunotherapy with ipilimumab are used. In the case of multiple symptomatic brain metastases, palliative whole-brain radiotherapy is used for treatment, although it has failed to show an overall survival benefit. Increased intracranial pressure and epileptic seizures are addressed with corticosteroids and anticonvulsants. Current clinical studies for melanoma patients with brain metastases are investigating new treatment options such as PD-1 antibodies, combined ipilimumab and nivolumab, combined BRAF inhibitors and MEK inhibitors, and stereotactic radiation in combination with immunotherapy or targeted therapy.