Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis

Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of <i<NRAS</i< (<i<n</i< = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Alicia Baumgartner [verfasserIn] Natalia Stepien [verfasserIn] Lisa Mayr [verfasserIn] Sibylle Madlener [verfasserIn] Christian Dorfer [verfasserIn] Maria T. Schmook [verfasserIn] Tatjana Traub-Weidinger [verfasserIn] Daniela Lötsch-Gojo [verfasserIn] Dominik Kirchhofer [verfasserIn] Dominik Reisinger [verfasserIn] Cora Hedrich [verfasserIn] Saleha Arshad [verfasserIn] Stefan Irschik [verfasserIn] Heidrun Boztug [verfasserIn] Gernot Engstler [verfasserIn] Marie Bernkopf [verfasserIn] Fikret Rifatbegovic [verfasserIn] Christoph Höller [verfasserIn] Irene Slavc [verfasserIn] Walter Berger [verfasserIn] Leonhard Müllauer [verfasserIn] Christine Haberler [verfasserIn] Amedeo A. Azizi [verfasserIn] Andreas Peyrl [verfasserIn] Johannes Gojo [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	leptomeningeal melanomatosis leptomeningeal melanocytosis primary diffuse leptomeningeal melanomatosis melanocytic tumors targeted therapy precision medicine

Übergeordnetes Werk:	In: Journal of Personalized Medicine - MDPI AG, 2012, 11(2021), 4, p 292
Übergeordnetes Werk:	volume:11 ; year:2021 ; number:4, p 292

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/jpm11040292

Katalog-ID:	DOAJ029944538

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allfields	10.3390/jpm11040292 doi (DE-627)DOAJ029944538 (DE-599)DOAJd111f27131d4419fac0b080812c40b56 DE-627 ger DE-627 rakwb eng Alicia Baumgartner verfasserin aut Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of <i<NRAS</i< (<i<n</i< = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type. leptomeningeal melanomatosis leptomeningeal melanocytosis primary diffuse leptomeningeal melanomatosis melanocytic tumors targeted therapy precision medicine Medicine R Natalia Stepien verfasserin aut Lisa Mayr verfasserin aut Sibylle Madlener verfasserin aut Christian Dorfer verfasserin aut Maria T. Schmook verfasserin aut Tatjana Traub-Weidinger verfasserin aut Daniela Lötsch-Gojo verfasserin aut Dominik Kirchhofer verfasserin aut Dominik Reisinger verfasserin aut Cora Hedrich verfasserin aut Saleha Arshad verfasserin aut Stefan Irschik verfasserin aut Heidrun Boztug verfasserin aut Gernot Engstler verfasserin aut Marie Bernkopf verfasserin aut Fikret Rifatbegovic verfasserin aut Christoph Höller verfasserin aut Irene Slavc verfasserin aut Walter Berger verfasserin aut Leonhard Müllauer verfasserin aut Christine Haberler verfasserin aut Amedeo A. Azizi verfasserin aut Andreas Peyrl verfasserin aut Johannes Gojo verfasserin aut In Journal of Personalized Medicine MDPI AG, 2012 11(2021), 4, p 292 (DE-627)71862713X (DE-600)2662248-8 20754426 nnns volume:11 year:2021 number:4, p 292 https://doi.org/10.3390/jpm11040292 kostenfrei https://doaj.org/article/d111f27131d4419fac0b080812c40b56 kostenfrei https://www.mdpi.com/2075-4426/11/4/292 kostenfrei https://doaj.org/toc/2075-4426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 4, p 292
spelling	10.3390/jpm11040292 doi (DE-627)DOAJ029944538 (DE-599)DOAJd111f27131d4419fac0b080812c40b56 DE-627 ger DE-627 rakwb eng Alicia Baumgartner verfasserin aut Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of <i<NRAS</i< (<i<n</i< = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type. leptomeningeal melanomatosis leptomeningeal melanocytosis primary diffuse leptomeningeal melanomatosis melanocytic tumors targeted therapy precision medicine Medicine R Natalia Stepien verfasserin aut Lisa Mayr verfasserin aut Sibylle Madlener verfasserin aut Christian Dorfer verfasserin aut Maria T. Schmook verfasserin aut Tatjana Traub-Weidinger verfasserin aut Daniela Lötsch-Gojo verfasserin aut Dominik Kirchhofer verfasserin aut Dominik Reisinger verfasserin aut Cora Hedrich verfasserin aut Saleha Arshad verfasserin aut Stefan Irschik verfasserin aut Heidrun Boztug verfasserin aut Gernot Engstler verfasserin aut Marie Bernkopf verfasserin aut Fikret Rifatbegovic verfasserin aut Christoph Höller verfasserin aut Irene Slavc verfasserin aut Walter Berger verfasserin aut Leonhard Müllauer verfasserin aut Christine Haberler verfasserin aut Amedeo A. Azizi verfasserin aut Andreas Peyrl verfasserin aut Johannes Gojo verfasserin aut In Journal of Personalized Medicine MDPI AG, 2012 11(2021), 4, p 292 (DE-627)71862713X (DE-600)2662248-8 20754426 nnns volume:11 year:2021 number:4, p 292 https://doi.org/10.3390/jpm11040292 kostenfrei https://doaj.org/article/d111f27131d4419fac0b080812c40b56 kostenfrei https://www.mdpi.com/2075-4426/11/4/292 kostenfrei https://doaj.org/toc/2075-4426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 4, p 292
allfields_unstemmed	10.3390/jpm11040292 doi (DE-627)DOAJ029944538 (DE-599)DOAJd111f27131d4419fac0b080812c40b56 DE-627 ger DE-627 rakwb eng Alicia Baumgartner verfasserin aut Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of <i<NRAS</i< (<i<n</i< = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type. leptomeningeal melanomatosis leptomeningeal melanocytosis primary diffuse leptomeningeal melanomatosis melanocytic tumors targeted therapy precision medicine Medicine R Natalia Stepien verfasserin aut Lisa Mayr verfasserin aut Sibylle Madlener verfasserin aut Christian Dorfer verfasserin aut Maria T. Schmook verfasserin aut Tatjana Traub-Weidinger verfasserin aut Daniela Lötsch-Gojo verfasserin aut Dominik Kirchhofer verfasserin aut Dominik Reisinger verfasserin aut Cora Hedrich verfasserin aut Saleha Arshad verfasserin aut Stefan Irschik verfasserin aut Heidrun Boztug verfasserin aut Gernot Engstler verfasserin aut Marie Bernkopf verfasserin aut Fikret Rifatbegovic verfasserin aut Christoph Höller verfasserin aut Irene Slavc verfasserin aut Walter Berger verfasserin aut Leonhard Müllauer verfasserin aut Christine Haberler verfasserin aut Amedeo A. Azizi verfasserin aut Andreas Peyrl verfasserin aut Johannes Gojo verfasserin aut In Journal of Personalized Medicine MDPI AG, 2012 11(2021), 4, p 292 (DE-627)71862713X (DE-600)2662248-8 20754426 nnns volume:11 year:2021 number:4, p 292 https://doi.org/10.3390/jpm11040292 kostenfrei https://doaj.org/article/d111f27131d4419fac0b080812c40b56 kostenfrei https://www.mdpi.com/2075-4426/11/4/292 kostenfrei https://doaj.org/toc/2075-4426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 4, p 292
allfieldsGer	10.3390/jpm11040292 doi (DE-627)DOAJ029944538 (DE-599)DOAJd111f27131d4419fac0b080812c40b56 DE-627 ger DE-627 rakwb eng Alicia Baumgartner verfasserin aut Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of <i<NRAS</i< (<i<n</i< = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type. leptomeningeal melanomatosis leptomeningeal melanocytosis primary diffuse leptomeningeal melanomatosis melanocytic tumors targeted therapy precision medicine Medicine R Natalia Stepien verfasserin aut Lisa Mayr verfasserin aut Sibylle Madlener verfasserin aut Christian Dorfer verfasserin aut Maria T. Schmook verfasserin aut Tatjana Traub-Weidinger verfasserin aut Daniela Lötsch-Gojo verfasserin aut Dominik Kirchhofer verfasserin aut Dominik Reisinger verfasserin aut Cora Hedrich verfasserin aut Saleha Arshad verfasserin aut Stefan Irschik verfasserin aut Heidrun Boztug verfasserin aut Gernot Engstler verfasserin aut Marie Bernkopf verfasserin aut Fikret Rifatbegovic verfasserin aut Christoph Höller verfasserin aut Irene Slavc verfasserin aut Walter Berger verfasserin aut Leonhard Müllauer verfasserin aut Christine Haberler verfasserin aut Amedeo A. Azizi verfasserin aut Andreas Peyrl verfasserin aut Johannes Gojo verfasserin aut In Journal of Personalized Medicine MDPI AG, 2012 11(2021), 4, p 292 (DE-627)71862713X (DE-600)2662248-8 20754426 nnns volume:11 year:2021 number:4, p 292 https://doi.org/10.3390/jpm11040292 kostenfrei https://doaj.org/article/d111f27131d4419fac0b080812c40b56 kostenfrei https://www.mdpi.com/2075-4426/11/4/292 kostenfrei https://doaj.org/toc/2075-4426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 4, p 292
allfieldsSound	10.3390/jpm11040292 doi (DE-627)DOAJ029944538 (DE-599)DOAJd111f27131d4419fac0b080812c40b56 DE-627 ger DE-627 rakwb eng Alicia Baumgartner verfasserin aut Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of <i<NRAS</i< (<i<n</i< = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type. leptomeningeal melanomatosis leptomeningeal melanocytosis primary diffuse leptomeningeal melanomatosis melanocytic tumors targeted therapy precision medicine Medicine R Natalia Stepien verfasserin aut Lisa Mayr verfasserin aut Sibylle Madlener verfasserin aut Christian Dorfer verfasserin aut Maria T. Schmook verfasserin aut Tatjana Traub-Weidinger verfasserin aut Daniela Lötsch-Gojo verfasserin aut Dominik Kirchhofer verfasserin aut Dominik Reisinger verfasserin aut Cora Hedrich verfasserin aut Saleha Arshad verfasserin aut Stefan Irschik verfasserin aut Heidrun Boztug verfasserin aut Gernot Engstler verfasserin aut Marie Bernkopf verfasserin aut Fikret Rifatbegovic verfasserin aut Christoph Höller verfasserin aut Irene Slavc verfasserin aut Walter Berger verfasserin aut Leonhard Müllauer verfasserin aut Christine Haberler verfasserin aut Amedeo A. Azizi verfasserin aut Andreas Peyrl verfasserin aut Johannes Gojo verfasserin aut In Journal of Personalized Medicine MDPI AG, 2012 11(2021), 4, p 292 (DE-627)71862713X (DE-600)2662248-8 20754426 nnns volume:11 year:2021 number:4, p 292 https://doi.org/10.3390/jpm11040292 kostenfrei https://doaj.org/article/d111f27131d4419fac0b080812c40b56 kostenfrei https://www.mdpi.com/2075-4426/11/4/292 kostenfrei https://doaj.org/toc/2075-4426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 4, p 292
language	English
source	In Journal of Personalized Medicine 11(2021), 4, p 292 volume:11 year:2021 number:4, p 292
sourceStr	In Journal of Personalized Medicine 11(2021), 4, p 292 volume:11 year:2021 number:4, p 292
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	leptomeningeal melanomatosis leptomeningeal melanocytosis primary diffuse leptomeningeal melanomatosis melanocytic tumors targeted therapy precision medicine Medicine R
isfreeaccess_bool	true
container_title	Journal of Personalized Medicine
authorswithroles_txt_mv	Alicia Baumgartner @@aut@@ Natalia Stepien @@aut@@ Lisa Mayr @@aut@@ Sibylle Madlener @@aut@@ Christian Dorfer @@aut@@ Maria T. Schmook @@aut@@ Tatjana Traub-Weidinger @@aut@@ Daniela Lötsch-Gojo @@aut@@ Dominik Kirchhofer @@aut@@ Dominik Reisinger @@aut@@ Cora Hedrich @@aut@@ Saleha Arshad @@aut@@ Stefan Irschik @@aut@@ Heidrun Boztug @@aut@@ Gernot Engstler @@aut@@ Marie Bernkopf @@aut@@ Fikret Rifatbegovic @@aut@@ Christoph Höller @@aut@@ Irene Slavc @@aut@@ Walter Berger @@aut@@ Leonhard Müllauer @@aut@@ Christine Haberler @@aut@@ Amedeo A. Azizi @@aut@@ Andreas Peyrl @@aut@@ Johannes Gojo @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	71862713X
id	DOAJ029944538
language_de	englisch
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author	Alicia Baumgartner
spellingShingle	Alicia Baumgartner misc leptomeningeal melanomatosis misc leptomeningeal melanocytosis misc primary diffuse leptomeningeal melanomatosis misc melanocytic tumors misc targeted therapy misc precision medicine misc Medicine misc R Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis
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topic_title	Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis leptomeningeal melanomatosis leptomeningeal melanocytosis primary diffuse leptomeningeal melanomatosis melanocytic tumors targeted therapy precision medicine
topic	misc leptomeningeal melanomatosis misc leptomeningeal melanocytosis misc primary diffuse leptomeningeal melanomatosis misc melanocytic tumors misc targeted therapy misc precision medicine misc Medicine misc R
topic_unstemmed	misc leptomeningeal melanomatosis misc leptomeningeal melanocytosis misc primary diffuse leptomeningeal melanomatosis misc melanocytic tumors misc targeted therapy misc precision medicine misc Medicine misc R
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title	Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis
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title_full	Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis
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title_sort	novel insights into diagnosis, biology and treatment of primary diffuse leptomeningeal melanomatosis
title_auth	Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis
abstract	Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of <i<NRAS</i< (<i<n</i< = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type.
abstractGer	Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of <i<NRAS</i< (<i<n</i< = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type.
abstract_unstemmed	Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of <i<NRAS</i< (<i<n</i< = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type.
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title_short	Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis
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Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of <i<NRAS</i< (<i<n</i< = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. 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