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Article ; Online: Anti-PD-1 shows promise against advanced paediatric Hodgkin lymphoma - Author's reply.

Geoerger, Birgit

2020 Volume 21, Issue 3, Page(s) e127

MeSH term(s)	Antibodies, Monoclonal, Humanized ; B7-H1 Antigen ; Child ; Hodgkin Disease ; Humans ; Lymphoma ; Melanoma
Chemical Substances	Antibodies, Monoclonal, Humanized ; B7-H1 Antigen ; pembrolizumab (DPT0O3T46P)
Language	English
Publishing date	2020-07-01
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	2049730-1
ISSN	1474-5488 ; 1470-2045
ISSN (online)	1474-5488
ISSN	1470-2045
DOI	10.1016/S1470-2045(20)30105-4
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Zs.A 5696: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 460: Show issues

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Book ; Thesis: Erzeugung muriner monoklonaler Antikörper gegen definierte Zielantigene antimitochondrialer Autoantikörper mit Hilfe der In-vitro-Immunisierung

Geörger, Birgit

1989

Author's details	vorgelegt von Birgit Geörger
Language	German
Size	2 Mikrofiches : 24x
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Mainz, Univ., Diss., 1989
Note	Manuskript: 103 Bl. : Ill.
HBZ-ID	HT003730017
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Article ; Online: Precision Cancer Medicine: Large Studies Indicate Steady Progress.

Eggermont, Alexander / Geoerger, Birgit / Curigliano, Giuseppe

Cancer discovery

2021 Volume 11, Issue 11, Page(s) 2677–2678

Abstract: Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions provide the basis of precision cancer medicine. In this issue ... ...

Abstract	Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions provide the basis of precision cancer medicine. In this issue of
MeSH term(s)	Child ; Genomics ; Humans ; Neoplasms/genetics ; Precision Medicine
Language	English
Publishing date	2021-11-02
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2625242-9
ISSN	2159-8290 ; 2159-8274
ISSN (online)	2159-8290
ISSN	2159-8274
DOI	10.1158/2159-8290.CD-21-1069
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Zs.A 6916: Show issues

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Article ; Online: A new generation of comprehensive precision oncology trials.

Geoerger, Birgit / Bautista, Francisco / Gatz, Susanne A / Marshall, Lynley V / André, Nicolas

The Lancet. Oncology

2023 Volume 24, Issue 12, Page(s) e452

MeSH term(s)	Humans ; Neoplasms/drug therapy ; Precision Medicine ; Medical Oncology ; Molecular Targeted Therapy
Language	English
Publishing date	2023-11-30
Publishing country	England
Document type	Letter
ZDB-ID	2049730-1
ISSN	1474-5488 ; 1470-2045
ISSN (online)	1474-5488
ISSN	1470-2045
DOI	10.1016/S1470-2045(23)00476-X
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Zs.A 5696: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Insight into the interplay between mitochondria-regulated cell death and energetic metabolism in osteosarcoma.

Lai, Hong Toan / Naumova, Nataliia / Marchais, Antonin / Gaspar, Nathalie / Geoerger, Birgit / Brenner, Catherine

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 948097

Abstract: Osteosarcoma (OS) is a pediatric malignant bone tumor that predominantly affects adolescent and young adults. It has high risk for relapse and over the last four decades no improvement of prognosis was achieved. It is therefore crucial to identify new ... ...

Abstract	Osteosarcoma (OS) is a pediatric malignant bone tumor that predominantly affects adolescent and young adults. It has high risk for relapse and over the last four decades no improvement of prognosis was achieved. It is therefore crucial to identify new drug candidates for OS treatment to combat drug resistance, limit relapse, and stop metastatic spread. Two acquired hallmarks of cancer cells, mitochondria-related regulated cell death (RCD) and metabolism are intimately connected. Both have been shown to be dysregulated in OS, making them attractive targets for novel treatment. Promising OS treatment strategies focus on promoting RCD by targeting key molecular actors in metabolic reprogramming. The exact interplay in OS, however, has not been systematically analyzed. We therefore review these aspects by synthesizing current knowledge in apoptosis, ferroptosis, necroptosis, pyroptosis, and autophagy in OS. Additionally, we outline an overview of mitochondrial function and metabolic profiles in different preclinical OS models. Finally, we discuss the mechanism of action of two novel molecule combinations currently investigated in active clinical trials: metformin and the combination of ADI-PEG20, Docetaxel and Gemcitabine.
Language	English
Publishing date	2022-08-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.948097
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Article ; Online: Dabrafenib, alone or in combination with trametinib, in BRAF V600-mutated pediatric Langerhans cell histiocytosis.

Whitlock, James A / Geoerger, Birgit / Dunkel, Ira J / Roughton, Michael / Choi, Jeea / Osterloh, Lisa / Russo, Mark / Hargrave, Darren

Blood advances

2023 Volume 7, Issue 15, Page(s) 3806–3815

Abstract: Langerhans cell histiocytosis (LCH) is a rare, heterogenous, neoplastic disorder primarily affecting children. BRAF mutations have been reported in >50% of patients with LCH. The selective BRAF inhibitor, dabrafenib, in combination with the MEK1/2 ... ...

Abstract	Langerhans cell histiocytosis (LCH) is a rare, heterogenous, neoplastic disorder primarily affecting children. BRAF mutations have been reported in >50% of patients with LCH. The selective BRAF inhibitor, dabrafenib, in combination with the MEK1/2 inhibitor, trametinib, has been approved in select BRAF V600-mutant solid tumors. Two open-label phase 1/2 studies were conducted in pediatric patients with BRAF V600-mutant, recurrent/refractory malignancies treated with dabrafenib monotherapy (CDRB436A2102; NCT01677741) or dabrafenib plus trametinib (CTMT212X2101; NCT02124772). The primary objectives of both studies were to determine safe and tolerable doses that achieve similar exposure to the approved doses for adults. Secondary objectives included safety, tolerability, and preliminary antitumor activity. Thirteen and 12 patients with BRAF V600-mutant LCH received dabrafenib monotherapy and in combination with trametinib, respectively. Investigator-assessed objective response rates per Histiocyte Society criteria were 76.9% (95% confidence interval [CI], 46.2-95.0) and 58.3% (95% CI, 27.7-84.8) in the monotherapy and combination studies, respectively. More than 90% of responses were ongoing at study completion. The most common treatment-related adverse events (AEs) were vomiting and increased blood creatinine with monotherapy and pyrexia, diarrhea, dry skin, decreased neutrophil count, and vomiting with combination therapy. Two patients each discontinued treatment with monotherapy and combination therapy because of AEs. Overall, dabrafenib monotherapy or in combination with trametinib demonstrated clinical efficacy and manageable toxicity in relapsed/refractory BRAF V600-mutant pediatric LCH, with most responses ongoing. Safety was consistent with that reported in other pediatric and adult conditions treated with dabrafenib plus trametinib.
MeSH term(s)	Adult ; Child ; Humans ; Proto-Oncogene Proteins B-raf/genetics ; Histiocytosis, Langerhans-Cell
Chemical Substances	BRAF protein, human (EC 2.7.11.1) ; dabrafenib (QGP4HA4G1B) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; trametinib (33E86K87QN)
Language	English
Publishing date	2023-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022008414
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Zs.A 7153: Show issues

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Article ; Online: Precision Medicine for Childhood Cancer: Current Limitations and Future Perspectives.

McCabe, Martin G / Geoerger, Birgit / Chesler, Louis / Hargrave, Darren / Parsons, D Williams / van Tilburg, Cornelis M / Schleiermacher, Gudrun / Hickman, John A / George, Sally L

JCO precision oncology

2024 Volume 8, Page(s) e2300117

Abstract: Greater collaboration needed to realize potential of molecular profiling initiatives for pediatric cancers. ...

Abstract	Greater collaboration needed to realize potential of molecular profiling initiatives for pediatric cancers.
MeSH term(s)	Humans ; Child ; Neoplasms/diagnosis ; Neoplasms/genetics ; Neoplasms/therapy ; Precision Medicine
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Journal Article
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.23.00117
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Article ; Online: Sequential or combined designs for Phase I/II clinical trials? A simulation study.

Rossoni, Caroline / Bardet, Aurélie / Geoerger, Birgit / Paoletti, Xavier

Clinical trials (London, England)

2019 Volume 16, Issue 6, Page(s) 635–644

Abstract: Background: Phase I and Phase II clinical trials aim at identifying a dose that is safe and active. Both phases are increasingly combined. For Phase I/II trials, two main types of designs are debated: a dose-escalation stage to select the maximum ... ...

Abstract	Background: Phase I and Phase II clinical trials aim at identifying a dose that is safe and active. Both phases are increasingly combined. For Phase I/II trials, two main types of designs are debated: a dose-escalation stage to select the maximum tolerated dose, followed by an expansion cohort to investigate its activity (dose-escalation followed by an expansion cohort), or a joint modelling to identify the best trade-off between toxicity and activity (efficacy-toxicity). We explore this question in the context of a paediatric Phase I/II platform trial. Methods: In series of simulations, we assessed the operating characteristics of dose-escalation followed by an expansion cohort (DE-EC) designs without and with reassessment of the maximum tolerated dose during the expansion cohort (DE-ECext) and of the efficacy-toxicity (EffTox) design. We investigated the probability to identify an active and tolerable agent, that is, the percentage of correct decision, for various dose-toxicity activity scenarios. Results: For a large therapeutic index, the percentage of correct decision reached 96.0% for efficacy-toxicity versus 76.1% for dose-escalation followed by an expansion cohort versus 79.6% for DE-ECext. Conversely, when all doses were deemed not active, the percentage of correct decision was 47% versus 55.9% versus 69.2%, respectively, for efficacy-toxicity, dose-escalation followed by an expansion cohort and DE-ECext. Finally, in the case of a narrow therapeutic index, the percentage of correct decision was 48.0% versus 64.3% versus 67.2%, respectively, efficacy-toxicity, dose-escalation followed by an expansion cohort and DE-ECext. Conclusion: As narrow indexes are common in oncology, according to the present results, the sequential dose-escalation followed by an expansion cohort is recommended. The importance to re-estimate the maximum tolerated dose during the expansion cohort is confirmed. However, despite their theoretical advantages, Phase I/II designs are challenged by the variations in populations between the Phase I and the Phase II parts and by the lagtime in the evaluation of toxicity and activity.
MeSH term(s)	Clinical Trials, Phase I as Topic/methods ; Clinical Trials, Phase II as Topic/methods ; Cohort Studies ; Dose-Response Relationship, Drug ; Humans ; Maximum Tolerated Dose ; Medical Oncology ; Models, Statistical ; Pediatrics ; Research Design
Language	English
Publishing date	2019-09-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2138796-5
ISSN	1740-7753 ; 1740-7745
ISSN (online)	1740-7753
ISSN	1740-7745
DOI	10.1177/1740774519872702
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Zs.A 5831: Show issues

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Article ; Online: METRO-PD1: Phase 1 study of nivolumab in combination with metronomic chemotherapy in children and adolescents with relapsing/refractory solid tumors.

André, Nicolas / Deley, Marie Cécile Le / Léguillette, Clémence / Probst, Alicia / Willems, Leen / Travers, Romain / Aerts, Isabelle / Faure-Conter, Cécile / Revond-Riviere, Gabriel / Min, Victoria / Geoerger, Birgit / Chastagner, Pascal / Entz-Werlé, Natascha / Leblond, Pierre

European journal of cancer (Oxford, England : 1990)

2024 Volume 198, Page(s) 113525

Abstract: Background: This multicenter Phase I study (NCT03585465) evaluated nivolumab in combination with 3 metronomic chemotherapy (MC) regimens in children with refractory/relapsing solid tumors.: Objectives: To evaluate the feasibility and safety of the ... ...

Abstract	Background: This multicenter Phase I study (NCT03585465) evaluated nivolumab in combination with 3 metronomic chemotherapy (MC) regimens in children with refractory/relapsing solid tumors. Objectives: To evaluate the feasibility and safety of the three regimens METHODS: Patients aged < 18 years were enrolled. Nivolumab was combined with cyclophosphamide and vinblastine (arm A), capecitabine (arm B), or cyclophosphamide, vinblastine and capecitabine (arm C). Arm A and B were allocated sequentially. Arm C opened only if A and B were deemed safe. Dose-limiting toxicities (DLTs) were evaluated over the first two cycles. Patients were evaluable if they received > 2 cycles and > 70% of the planned dose. Population: Sixteen patients were enrolled, 3 in arm A, 6 in arm B, and 7 in arm C. Median age was 11.5 years (range, 5-19). Patients previously received a median of 3.5 (range, 1-4) lines of systemic treatment, 14 patients had surgery and 11 had radiotherapy. Results: Median number of cycles was 2 (1-24), median treatment duration was 56 days (18-714). In arm C, median number of cycles was 4 with median treatment duration of 95 days. No DLT was observed. Grade 3 adverse events (AE) and serious AE were observed in 8 patients (50%) and 1 patient (6%), respectively, over the first 2 cycles. No grade 4 AE occurred. The 6-month PFS and OS were 12% and 44%, respectively, in the whole population. Prolonged stable disease was observed in a high-grade glioma and an atypical teratoid rhabdoid tumor. Conclusion: Arm C appears safe. A randomized phase II trial evaluating the addition of nivolumab to the triple MC is ongoing.
MeSH term(s)	Adolescent ; Child ; Humans ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Capecitabine/therapeutic use ; Cyclophosphamide ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/pathology ; Nivolumab/therapeutic use ; Vinblastine/therapeutic use ; Child, Preschool
Chemical Substances	Capecitabine (6804DJ8Z9U) ; Cyclophosphamide (8N3DW7272P) ; Nivolumab (31YO63LBSN) ; Vinblastine (5V9KLZ54CY)
Language	English
Publishing date	2024-01-06
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article ; Multicenter Study
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2024.113525
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Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 583: Show issues

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Article ; Online: Histone deacetylase inhibitor panobinostat induces antitumor activity in epithelioid sarcoma and rhabdoid tumor by growth factor receptor modulation.

Harttrampf, Anne Catherine / da Costa, Maria Eugenia Marques / Renoult, Aline / Daudigeos-Dubus, Estelle / Geoerger, Birgit

BMC cancer

2021 Volume 21, Issue 1, Page(s) 833

Abstract: Background: Epithelioid sarcomas and rhabdoid tumors are rare, aggressive malignancies with poor prognosis. Both are characterized by INI1 alterations and deregulation of growth factor receptors albeit their interaction has not been elucidated.: ... ...

Abstract	Background: Epithelioid sarcomas and rhabdoid tumors are rare, aggressive malignancies with poor prognosis. Both are characterized by INI1 alterations and deregulation of growth factor receptors albeit their interaction has not been elucidated. Methods: In this study, we investigated the activity of a panel of epigenetic modulators and receptor tyrosine kinase inhibitors in vitro on respective cell lines as well as on primary patient-derived epithelioid sarcoma cells, and in vivo on xenografted mice. Focusing on histone deacetylase (HDAC) inhibitors, we studied the mechanism of action of this class of agents, its effect on growth factor receptor regulation, and changes in epithelial-to-mesenchymal transition by using cell- and RT-qPCR-based assays. Results: Pan-HDAC inhibitor panobinostat exhibited potent anti-proliferative activity at low nanomolar concentrations in A204 rhabdoid tumor, and VAESBJ/GRU1 epithelioid sarcoma cell lines, strongly induced apoptosis, and resulted in significant tumor growth inhibition in VAESBJ xenografts. It differentially regulated EGFR, FGFR1 and FGFR2, leading to downregulation of EGFR in epithelioid sarcoma and to mesenchymal-to-epithelial transition whereas in rhabdoid tumor cells, EGFR was strongly upregulated and reinforced the mesenchymal phenotype. All three cell lines were rendered more susceptible towards combination with EGFF inhibitor erlotinib, further enhancing apoptosis. Conclusions: HDAC inhibitors exhibit significant anticancer activity due to their multifaceted actions on cytotoxicity, differentiation and drug sensitization. Our data suggest that the tailored, tissue-specific combination of HDAC inhibitors with therapeutics which target cellular salvage mechanisms might increase their therapeutic relevance.
MeSH term(s)	Animals ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Epithelial-Mesenchymal Transition/drug effects ; Female ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; Mice ; Mice, Nude ; Panobinostat/pharmacology ; Panobinostat/therapeutic use ; Receptors, Growth Factor/metabolism ; Rhabdoid Tumor/drug therapy ; Rhabdoid Tumor/pathology ; Sarcoma/drug therapy ; Sarcoma/pathology
Chemical Substances	Histone Deacetylase Inhibitors ; Receptors, Growth Factor ; Panobinostat (9647FM7Y3Z)
Language	English
Publishing date	2021-07-20
Publishing country	England
Document type	Journal Article
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/s12885-021-08579-w
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