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  1. Article ; Online: Refractory Stage M Ganglioneuroblastoma With Bone Metastases and a Favorable, Chronic Course of Disease: Description of a Patient Cohort.

    Tas, Michelle L / Molenaar, Jan J / Peek, Annemarie M L / Lequin, Maarten H / Verdijk, Rob M / de Krijger, Ronald R / Tytgat, Godelieve A M / van Noesel, Max M

    Journal of pediatric hematology/oncology

    2021  Volume 44, Issue 1, Page(s) e5–e13

    Abstract: Refractory stage M neuroblastoma (NB) is associated with a poor prognosis and a progressive course of disease. Here, we describe a unique group of patients with a discrepant clinical course. Seven histologically confirmed ganglioneuroblastoma (GNB) (n=6) ...

    Abstract Refractory stage M neuroblastoma (NB) is associated with a poor prognosis and a progressive course of disease. Here, we describe a unique group of patients with a discrepant clinical course. Seven histologically confirmed ganglioneuroblastoma (GNB) (n=6) and differentiating NB (n=1) patients were identified who were diagnosed with stage M disease based on iodine-123-metaiodobenzylguanidine avid bone metastases. Six patients started on high-risk treatment, without tumor response (stable disease). Treatment was discontinued before the start of consolidation treatment because of refractory response in all patients. Unexpectedly, after cessation of treatment no progression of disease occurred. In 2 patients, the primary tumors expanded (>25%) very slowly during 1.5 and 3 years, and remained stable thereafter. Metabolically, a slow decrease of urinary homovanillic acid and vanillylmandelic acid levels and iodine-123-metaiodobenzylguanidine avidity was observed. All patients are alive with presence of metastatic disease after a median follow-up of 17 years (range: 6.7 to 27 y). Interestingly, at diagnosis, 6 patients were asymptomatic, 6 patients had GNB morphology, and 5 patients had meningeal metastases. These are all features seen in only a small minority of stage M patients. This GNB entity illustrates the clinical heterogeneity of neuroblastic tumors and can be used to further study the developmental origin of different NB subtypes.
    MeSH term(s) Bone Neoplasms/drug therapy ; Bone Neoplasms/secondary ; Bone Neoplasms/urine ; Child, Preschool ; Chronic Disease ; Consolidation Chemotherapy ; Female ; Ganglioneuroblastoma/drug therapy ; Ganglioneuroblastoma/urine ; Humans ; Infant ; Male ; Neoplasm Metastasis ; Neoplasm Staging ; Retrospective Studies
    Language English
    Publishing date 2021-04-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1231152-2
    ISSN 1536-3678 ; 1077-4114 ; 0192-8562
    ISSN (online) 1536-3678
    ISSN 1077-4114 ; 0192-8562
    DOI 10.1097/MPH.0000000000002067
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1537: 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)

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  2. Article: Anti-GD2 Based Immunotherapy Prevents Late Events in High-Risk Neuroblastoma Patients over 18 Months at Diagnosis.

    Tas, Michelle L / Dootjes, Lisa W / Fiocco, Marta / de Krijger, Ronald R / Dierselhuis, Miranda P / van Eijkelenburg, Natasha K A / van Grotel, Martine / Kraal, Kathelijne C J M / Peek, Annemarie M L / Tytgat, Godelieve A M / van Noesel, Max M

    Cancers

    2021  Volume 13, Issue 19

    Abstract: Background: Anti-GD2 based immunotherapy has improved overall (OS) and event free survival (EFS) for high-risk neuroblastoma (HR-NBL) patients. Here, we evaluate the long-term efficacy of anti-GD2 immunotherapy in combination with isotretinoin, GM-CSF, ... ...

    Abstract Background: Anti-GD2 based immunotherapy has improved overall (OS) and event free survival (EFS) for high-risk neuroblastoma (HR-NBL) patients. Here, we evaluate the long-term efficacy of anti-GD2 immunotherapy in combination with isotretinoin, GM-CSF, and IL-2.
    Methods: Dutch HR-NBL patients treated with immunotherapy according to the COG-ANBL0032 protocol (
    Results: The study and control group were similar concerning baseline characteristics. In the complete cohort, 5 year OS was 64 ± 7% and 49 ± 8% for the immunotherapy group and the control group, respectively (
    Conclusions: This study is the first to confirm the results of the COG-ANBL0032 study in a cohort treated with a different induction regimen. Anti-GD2 immunotherapy prevents late events, most significantly in patients older than 18 months of age at diagnosis.
    Language English
    Publishing date 2021-09-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13194941
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Case series on clinical applications of liquid biopsy in pediatric solid tumors: towards improved diagnostics and disease monitoring.

    Gelineau, Nina U / van Barneveld, Astrid / Samim, Atia / Van Zogchel, Lieke / Lak, Nathalie / Tas, Michelle L / Matser, Yvette / Mavinkurve-Groothuis, Annelies M C / van Grotel, Martine / Zsiros, Jószef / van Eijkelenburg, Natasha K A / Knops, Rutger R G / van Ewijk, Roelof / Langenberg, Karin P S / Krijger, Ronald De / Hiemcke-Jiwa, Laura S / Van Paemel, Ruben / Cornelli, Lotte / De Preter, Katleen /
    De Wilde, Bram / Van Der Schoot, Ellen / Tytgat, Godelieve

    Frontiers in oncology

    2023  Volume 13, Page(s) 1209150

    Abstract: Background and aims: Solid tumors account for about 30% of all pediatric cancers. The diagnosis is typically based on histological and molecular analysis of a primary tumor biopsy. Liquid biopsies carry several advantages over conventional tissue biopsy. ...

    Abstract Background and aims: Solid tumors account for about 30% of all pediatric cancers. The diagnosis is typically based on histological and molecular analysis of a primary tumor biopsy. Liquid biopsies carry several advantages over conventional tissue biopsy. However, their use for genomic analysis and response monitoring of pediatric solid tumors is still in experimental stages and mostly performed retrospectively without direct impact on patient management. In this case series we discuss six clinical cases of children with a solid tumor for whom a liquid biopsy assay was performed and demonstrate the potential of liquid biopsy for future clinical decision making.
    Methods: We performed quantitative real-time PCR (RT-qPCR), droplet digital PCR (ddPCR) or reduced representation bisulphite sequencing of cell-free DNA (cfRRBS) on liquid biopsies collected from six pediatric patients with a solid tumor treated between 2017 and 2023 at the Princess Máxima Center for Pediatric Oncology in the Netherlands. Results were used to aid in clinical decision making by contribution to establish a diagnosis, by prognostication and response to therapy monitoring.
    Results: In three patients cfRRBS helped to establish the diagnosis of a rhabdomyosarcoma, an Ewing sarcoma and a neuroblastoma (case 1-3). In two patients, liquid biopsies were used for prognostication, by MYCN ddPCR in a patient with neuroblastoma and by RT-qPCR testing rhabdomyosarcoma-specific mRNA in bone marrow of a patient with a rhabdomyosarcoma (case 4 and 5). In case 6, mRNA testing demonstrated disease progression and assisted clinical decision making.
    Conclusion: This case series illustrates the value of liquid biopsy. We further demonstrate and recommend the use of liquid biopsies to be used in conjunction with conventional methods for the determination of metastatic status, prognostication and monitoring of treatment response in patients with pediatric solid tumors.
    Language English
    Publishing date 2023-08-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1209150
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy.

    Wienke, Judith / Visser, Lindy L / Kholosy, Waleed M / Keller, Kaylee M / Barisa, Marta / Poon, Evon / Munnings-Tomes, Sophie / Himsworth, Courtney / Calton, Elizabeth / Rodriguez, Ana / Bernardi, Ronald / van den Ham, Femke / van Hooff, Sander R / Matser, Yvette A H / Tas, Michelle L / Langenberg, Karin P S / Lijnzaad, Philip / Borst, Anne L / Zappa, Elisa /
    Bergsma, Francisca J / Strijker, Josephine G M / Verhoeven, Bronte M / Mei, Shenglin / Kramdi, Amira / Restuadi, Restuadi / Sanchez-Bernabeu, Alvaro / Cornel, Annelisa M / Holstege, Frank C P / Gray, Juliet C / Tytgat, Godelieve A M / Scheijde-Vermeulen, Marijn A / Wijnen, Marc H W A / Dierselhuis, Miranda P / Straathof, Karin / Behjati, Sam / Wu, Wei / Heck, Albert J R / Koster, Jan / Nierkens, Stefan / Janoueix-Lerosey, Isabelle / de Krijger, Ronald R / Baryawno, Ninib / Chesler, Louis / Anderson, John / Caron, Hubert N / Margaritis, Thanasis / van Noesel, Max M / Molenaar, Jan J

    Cancer cell

    2024  Volume 42, Issue 2, Page(s) 283–300.e8

    Abstract: Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. Since novel and improved immunotherapies may fill this need, we dissect the immunoregulatory interactions ... ...

    Abstract Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. Since novel and improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 24 tumors (10 pre- and 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated by natural killer (NK), T and B cells, and immunosuppressive myeloid populations. NK cells show reduced cytotoxicity and T cells have a dysfunctional profile. Interaction analysis reveals a vast immunoregulatory network and identifies NECTIN2-TIGIT as a crucial immune checkpoint. Combined blockade of TIGIT and PD-L1 significantly reduces neuroblastoma growth, with complete responses (CR) in vivo. Moreover, addition of TIGIT+PD-L1 blockade to standard relapse treatment in a chemotherapy-resistant Th-ALK
    MeSH term(s) Humans ; Child ; B7-H1 Antigen ; Neoplasm Recurrence, Local ; Neuroblastoma/drug therapy ; Neuroblastoma/genetics ; Receptors, Immunologic/genetics ; Immunotherapy ; Sequence Analysis, RNA
    Chemical Substances B7-H1 Antigen ; Receptors, Immunologic ; TIGIT protein, human
    Language English
    Publishing date 2024-01-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2023.12.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5650: 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.MG 104: Show issues

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  5. Article ; Online: Neuroblastoma stage 4S: Tumor regression rate and risk factors of progressive disease.

    Tas, Michelle L / Nagtegaal, Michelle / Kraal, Kathelijne C J M / Tytgat, Godelieve A M / Abeling, Nico G G M / Koster, Jan / Pluijm, Saskia M F / Zwaan, C Michel / de Keizer, Bart / Molenaar, Jan J / van Noesel, Max M

    Pediatric blood & cancer

    2019  Volume 67, Issue 4, Page(s) e28061

    Abstract: Background: The clinical course of neuroblastoma stage 4S or MS is characterized by a high rate of spontaneous tumor regression and favorable outcome. However, the clinical course and rate of the regression are poorly understood.: Methods: A ... ...

    Abstract Background: The clinical course of neuroblastoma stage 4S or MS is characterized by a high rate of spontaneous tumor regression and favorable outcome. However, the clinical course and rate of the regression are poorly understood.
    Methods: A retrospective cohort study was performed, including all patients with stage 4S neuroblastoma without MYCN amplification, from two Dutch centers between 1972 and 2012. We investigated the clinical characteristics, the biochemical activity reflected in urinary catecholamine excretion, and radiological imaging to describe the kinetics of tumor regression, therapy response and outcome.
    Results: The cohort of 31 patients reached a 10-year overall survival of 84% ± 7% (median follow-up 16 years; range, 3.3-39). During the regressive phase, liver size normalized in 91% of the patients and catecholamine excretion in 83%, both after a median of two months (liver size: range, 0-131; catecholamines: range, 0-158). The primary tumors completely regressed in 69% after 13 months (range, 6-73), and the liver architecture normalized in 52% after 15 months (range, 5-131). Antitumor treatment was given in 52% of the patients. Interestingly, regression rates were similar for treated and untreated patients. Four of seven patients < 4 weeks old died of rapid liver expansion and organ compression. Three patients progressed to stage 4, 3 to 13 months after diagnosis; all had persistently elevated catecholamines.
    Conclusion: Patients < 4 weeks old with neuroblastoma stage 4S are at risk of fatal outcome caused by progression of liver metastases. In other patients, tumor regression is characterized by a rapid biochemical normalization that precedes radiological regression.
    MeSH term(s) Cohort Studies ; Disease Progression ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Neoplasm Regression, Spontaneous/pathology ; Neuroblastoma/pathology ; Retrospective Studies ; Risk Factors
    Language English
    Publishing date 2019-11-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2131448-2
    ISSN 1545-5017 ; 1545-5009
    ISSN (online) 1545-5017
    ISSN 1545-5009
    DOI 10.1002/pbc.28061
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1131: 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)

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  6. Article: Immune Monitoring during Therapy Reveals Activitory and Regulatory Immune Responses in High-Risk Neuroblastoma.

    Szanto, Celina L / Cornel, Annelisa M / Tamminga, Sara M / Delemarre, Eveline M / de Koning, Coco C H / van den Beemt, Denise A M H / Dunnebach, Ester / Tas, Michelle L / Dierselhuis, Miranda P / Tytgat, Lieve G A M / van Noesel, Max M / Kraal, Kathelijne C J M / Boelens, Jaap-Jan / Huitema, Alwin D R / Nierkens, Stefan

    Cancers

    2021  Volume 13, Issue 9

    Abstract: Despite intensive treatment, including consolidation immunotherapy (IT), prognosis of high-risk neuroblastoma (HR-NBL) is poor. Immune status of patients over the course of treatment, and thus immunological features potentially explaining therapy ... ...

    Abstract Despite intensive treatment, including consolidation immunotherapy (IT), prognosis of high-risk neuroblastoma (HR-NBL) is poor. Immune status of patients over the course of treatment, and thus immunological features potentially explaining therapy efficacy, are largely unknown. In this study, the dynamics of immune cell subsets and their function were explored in 25 HR-NBL patients at diagnosis, during induction chemotherapy, before high-dose chemotherapy, and during IT. The dynamics of immune cells varied largely between patients. IL-2- and GM-CSF-containing IT cycles resulted in significant expansion of effector cells (NK-cells in IL-2 cycles, neutrophils and monocytes in GM-CSF cycles). Nonetheless, the cytotoxic phenotype of NK-cells was majorly disturbed at the start of IT, and both IL-2 and GM-CSF IT cycles induced preferential expansion of suppressive regulatory T-cells. Interestingly, proliferative capacity of purified patient T-cells was impaired at diagnosis as well as during therapy. This study indicates the presence of both immune-enhancing as well as regulatory responses in HR-NBL patients during (immuno)therapy. Especially the double-edged effects observed in IL-2-containing IT cycles are interesting, as this potentially explains the absence of clinical benefit of IL-2 addition to IT cycles. This suggests that there is a need to combine anti-GD2 with more specific immune-enhancing strategies to improve IT outcome in HR-NBL.
    Language English
    Publishing date 2021-04-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13092096
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  7. Article ; Online: Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell.

    Kildisiute, Gerda / Kholosy, Waleed M / Young, Matthew D / Roberts, Kenny / Elmentaite, Rasa / van Hooff, Sander R / Pacyna, Clarissa N / Khabirova, Eleonora / Piapi, Alice / Thevanesan, Christine / Bugallo-Blanco, Eva / Burke, Christina / Mamanova, Lira / Keller, Kaylee M / Langenberg-Ververgaert, Karin P S / Lijnzaad, Philip / Margaritis, Thanasis / Holstege, Frank C P / Tas, Michelle L /
    Wijnen, Marc H W A / van Noesel, Max M / Del Valle, Ignacio / Barone, Giuseppe / van der Linden, Reinier / Duncan, Catriona / Anderson, John / Achermann, John C / Haniffa, Muzlifah / Teichmann, Sarah A / Rampling, Dyanne / Sebire, Neil J / He, Xiaoling / de Krijger, Ronald R / Barker, Roger A / Meyer, Kerstin B / Bayraktar, Omer / Straathof, Karin / Molenaar, Jan J / Behjati, Sam

    Science advances

    2021  Volume 7, Issue 6

    Abstract: Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by ...

    Abstract Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (
    MeSH term(s) Child ; Humans ; Neural Crest/metabolism ; Neural Stem Cells/metabolism ; Neuroblastoma/genetics ; Neuroblastoma/metabolism ; Neuroblastoma/pathology ; RNA, Messenger/genetics ; Transcriptome
    Chemical Substances RNA, Messenger
    Language English
    Publishing date 2021-02-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abd3311
    Database MEDical Literature Analysis and Retrieval System OnLINE

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