TY  - JOUR
A1  - Livingstone, E.
A1  - Zaremba, A.
A1  - Horn, S.
A1  - Ugurel, S.
A1  - Casalini, B.
A1  - Schlaak, M.
A1  - Hassel, J.C.
A1  - Herbst, R.
A1  - Utikal, J.S.
A1  - Weide, B.
A1  - Gutzmer, R.
A1  - Meier, F.
A1  - Koelsche, C.
A1  - Hadaschik, E.
A1  - Sucker, A.
A1  - Reis, H.
A1  - Merkelbach‐Bruse, S.
A1  - Siewert, M.
A1  - Sahm, F.
A1  - von Deimling, A.
A1  - Cosgarea, I.
A1  - Zimmer, L.
A1  - Schadendorf, D.
A1  - Schilling, B.
A1  - Griewank, K.G.
T1  - GNAQ and GNA11 mutant nonuveal melanoma: a subtype distinct from both cutaneous and uveal melanoma
JF  - British Journal of Dermatology
N2  - Background
GNAQ and GNA11 mutant nonuveal melanoma represent a poorly characterized rare subgroup of melanoma with a gene mutation profile similar to uveal melanoma.

Objectives
To characterize these tumours in terms of clinical behaviour and genetic characteristics.

Methods
Patients with nonuveal GNAQ/11 mutated melanoma were identified from the prospective multicentre tumour tissue registry ADOREG, Tissue Registry in Melanoma (TRIM) and additional cooperating skin cancer centres. Extensive data on patient, tumour and treatment characteristics were collected retrospectively. Targeted sequencing was used to determine tumour mutational burden. Immunohistochemistry staining was performed for programmed death‐ligand 1 and BRCA1‐associated protein (BAP)1. Existing whole‐exome cutaneous and uveal melanoma data were analysed for mutation type and burden.

Results
We identified 18 patients with metastatic GNAQ/11 mutant nonuveal melanoma. Tumours had a lower tumour mutational burden and fewer ultraviolet signature mutations than cutaneous melanomas. In addition to GNAQ and GNA11 mutations (nine each), six splicing factor 3b subunit 1 (SF3B1), three eukaryotic translation initiation factor 1A X‐linked (EIF1AX) and four BAP1 mutations were detected. In contrast to uveal melanoma, GNAQ/11 mutant nonuveal melanomas frequently metastasized lymphatically and concurrent EIF1AX, SF3B1 and BAP1 mutations showed no apparent association with patient prognosis. Objective response to immunotherapy was poor with only one partial response observed in 10 treated patients (10%).

Conclusions
Our findings suggest that GNAQ/11 mutant nonuveal melanomas are a subtype of melanoma that is both clinically and genetically distinct from cutaneous and uveal melanoma. As they respond poorly to available treatment regimens, novel effective therapeutic approaches for affected patients are urgently needed.

What is already known about this topic?
The rare occurrence of GNAQ/11 mutations in nonuveal melanoma has been documented.
GNAQ/11 mutant nonuveal melanomas also harbour genetic alterations in EIF1AX, SF3B1 and BAP1 that are of prognostic relevance in uveal melanoma.

What does this study add?
GNAQ/11 mutant nonuveal melanomas show metastatic spread reminiscent of cutaneous melanoma, but not uveal melanoma.
GNAQ/11 mutant nonuveal melanomas have a low tumour mutational burden that is higher than uveal melanoma, but lower than cutaneous melanoma.

What is the translational message?
Primary GNAQ/11 mutant nonuveal melanomas are a subtype of melanoma that is clinically and genetically distinct from both cutaneous and uveal melanoma.
As metastatic GNAQ/11 mutant nonuveal melanomas respond poorly to available systemic therapies, including immune checkpoint inhibition, novel therapeutic approaches for these tumours are urgently needed.
KW  - melanoma
KW  - GNAQ
KW  - GNA11
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215434
VL  - 183
IS  - 5
SP  - 928
EP  - 939
ER  - 
TY  - JOUR
A1  - Barlinn, J.
A1  - Winzer, S.
A1  - Worthmann, H.
A1  - Urbanek, C.
A1  - Häusler, K. G.
A1  - Günther, A.
A1  - Erdur, H.
A1  - Görtler, M.
A1  - Busetto, L.
A1  - Wojciechowski, C.
A1  - Schmitt, J.
A1  - Shah, Y.
A1  - Büchele, B.
A1  - Sokolowski, P.
A1  - Kraya, T.
A1  - Merkelbach, S.
A1  - Rosengarten, B.
A1  - Stangenberg-Gliss, K.
A1  - Weber, J.
A1  - Schlachetzki, F.
A1  - Abu-Mugheisib, M.
A1  - Petersen, M.
A1  - Schwartz, A.
A1  - Palm, F.
A1  - Jowaed, A.
A1  - Volbers, B.
A1  - Zickler, P.
A1  - Remi, J.
A1  - Bardutzky, J.
A1  - Bösel, J.
A1  - Audebert, H. J.
A1  - Hubert, G. J.
A1  - Gumbinger, C.
T1  - Telemedizin in der Schlaganfallversorgung – versorgungsrelevant für Deutschland
T1  - Telemedicine in stroke—pertinent to stroke care in Germany
JF  - Der Nervenarzt
N2  - Hintergrund und Ziel
Telemedizinische Schlaganfall-Netzwerke tragen dazu bei, die Schlaganfallversorgung und insbesondere den Zugang zu zeitkritischen Schlaganfalltherapien in vorrangig strukturschwachen, ländlichen Regionen zu gewährleisten. Ziel ist eine Darstellung der Nutzungsfrequenz und regionalen Verteilung dieser Versorgungsstruktur.

Methoden
Die Kommission „Telemedizinische Schlaganfallversorgung“ der Deutschen Schlaganfall-Gesellschaft führte eine Umfragestudie in allen Schlaganfall-Netzwerken durch.

Ergebnisse
In Deutschland sind 22 telemedizinische Schlaganfall-Netzwerke aktiv, welche insgesamt 43 Zentren (pro Netzwerk: Median 1,5, Interquartilsabstand [IQA] 1–3) sowie 225 Kooperationskliniken (pro Netzwerk: Median 9, IQA 4–17) umfassen und an einem unmittelbaren Zugang zur Schlaganfallversorgung für 48 Mio. Menschen teilhaben. Im Jahr 2018 wurden 38.211 Telekonsile (pro Netzwerk: Median 1340, IQA 319–2758) durchgeführt. Die Thrombolyserate betrug 14,1 % (95 %-Konfidenzintervall 13,6–14,7 %), eine Verlegung zur Thrombektomie wurde bei 7,9 % (95 %-Konfidenzintervall 7,5–8,4 %) der ischämischen Schlaganfallpatienten initiiert. Das Finanzierungssystem ist uneinheitlich mit einem Vergütungssystem für die Zentrumsleistungen in nur drei Bundesländern.

Diskussion
Etwa jeder 10. Schlaganfallpatient wird telemedizinisch behandelt. Die telemedizinischen Schlaganfall-Netzwerke erreichen vergleichbar hohe Lyseraten und Verlegungen zur Thrombektomie wie neurologische Stroke-Units und tragen zur Sicherstellung einer flächendeckenden Schlaganfallversorgung bei. Eine netzwerkübergreifende Sicherstellung der Finanzierung und einheitliche Erhebung von Qualitätssicherungsdaten haben das Potenzial diese Versorgungsstruktur zukünftig weiter zu stärken.
N2  - Background and objective
Telemedical stroke networks improve stroke care and provide access to time-dependent acute stroke treatment in predominantly rural regions. The aim is a presentation of data on its utility and regional distribution.

Methods
The working group on telemedical stroke care of the German Stroke Society performed a survey study among all telestroke networks.

Results
Currently, 22 telemedical stroke networks including 43 centers (per network: median 1.5, interquartile range, IQR, 1–3) as well as 225 cooperating hospitals (per network: median 9, IQR 4–17) operate in Germany and contribute to acute stroke care delivery to 48 million people. In 2018, 38,211 teleconsultations (per network: median 1340, IQR 319–2758) were performed. The thrombolysis rate was 14.1% (95% confidence interval 13.6–14.7%) and transfer for thrombectomy was initiated in 7.9% (95% confidence interval 7.5–8.4%) of ischemic stroke patients. Financial reimbursement differs regionally with compensation for telemedical stroke care in only three federal states.

Conclusion
Telemedical stroke care is utilized in about 1 out of 10 stroke patients in Germany. Telemedical stroke networks achieve similar rates of thrombolysis and transfer for thrombectomy compared with neurological stroke units and contribute to stroke care in rural regions. Standardization of network structures, financial assurance and uniform quality measurements may further strengthen the importance of telestroke networks in the future.
KW  - Schlaganfall
KW  - Stroke-Unit
KW  - Telemedizin
KW  - Schlaganfall-Netzwerk
KW  - Umfragestudie
KW  - stroke
KW  - stroke unit
KW  - telemedicine
KW  - stroke networks
KW  - survey
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307752
SN  - 0028-2804
SN  - 1433-0407
VL  - 92
IS  - 6
ER  -