The extraordinary challenge of treating patients with congenital rhabdoid tumors—a collaborative European effort

EU-RHAB consortium

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Congenital rhabdoid tumors are rare and highly aggressive malignancies. In general, patients are considered to be incurable and are often treated using an exclusive, primarily palliative approach. Methods: A prospective and retrospective collection of 42 patients from the European Rhabdoid Registry (EU-RHAB), France and Moscow (2006–2016) diagnosed within the first 28 days of life was evaluated. Genetic and clinical reference evaluation included SMARCB1 and/or SMARCA4 (fluorescence-in-situ-hybridization, multiplex ligation-dependent probe amplification, and sequencing) mutation analysis and immunohistochemistry. Forty-eight percent (20/42) of patients were treated according to the EU-RHAB therapy, 7% (3/42) according to the pilot approach Rhabdoid 2007, 33% (14/42) with individual schedules, and 12% (5/42) received no chemotherapy at all. Results: Forty point five percent (17/42) of patients presented with extracranial rhabdoid tumors, 33.5% (14/42) with rhabdoid tumors of the central nervous system (atypical teratoid/rhabdoid tumor), and the remainder 26% (11/42) demonstrated synchronous tumors. Metastases at diagnosis were present in 52% (22/42) of patients. A germline mutation was detected in 66% (25/38) and was associated with a poor prognosis (4.2 ± 4.1% vs. 48 ± 16.4%, P < 0.00005). A gross total resection (GTR) was realized in 17%. A GTR (42.9 ± 18.7% vs. 4.9 ± 4.3%, P = 0.04), therapy according to a standardized approach (20.9 ± 8.7% vs. 7.1 ± 6.9 %, P = 0.0018), and a complete remission (CR) (23.6 ± 9.8% vs. 1.3 ± 3.6%, P = 0.04) were significant prognostic factors. Conclusions: The management of patients with congenital rhabdoid tumors requires a major multidisciplinary effort. In many instances, cure is not possible and a palliative approach is warranted. Our data indicate a positive impact of standardized therapeutic approaches on survival, making a tailored approach toward affected patients and their families mandatory.
Original languageEnglish
Article numbere26999
JournalPediatric Blood and Cancer
Volume65
Issue number6
DOIs
Publication statusPublished - 2018

Cite this

@article{53e0742183394d179f7dbdf1734a531f,
title = "The extraordinary challenge of treating patients with congenital rhabdoid tumors—a collaborative European effort",
abstract = "Background: Congenital rhabdoid tumors are rare and highly aggressive malignancies. In general, patients are considered to be incurable and are often treated using an exclusive, primarily palliative approach. Methods: A prospective and retrospective collection of 42 patients from the European Rhabdoid Registry (EU-RHAB), France and Moscow (2006–2016) diagnosed within the first 28 days of life was evaluated. Genetic and clinical reference evaluation included SMARCB1 and/or SMARCA4 (fluorescence-in-situ-hybridization, multiplex ligation-dependent probe amplification, and sequencing) mutation analysis and immunohistochemistry. Forty-eight percent (20/42) of patients were treated according to the EU-RHAB therapy, 7{\%} (3/42) according to the pilot approach Rhabdoid 2007, 33{\%} (14/42) with individual schedules, and 12{\%} (5/42) received no chemotherapy at all. Results: Forty point five percent (17/42) of patients presented with extracranial rhabdoid tumors, 33.5{\%} (14/42) with rhabdoid tumors of the central nervous system (atypical teratoid/rhabdoid tumor), and the remainder 26{\%} (11/42) demonstrated synchronous tumors. Metastases at diagnosis were present in 52{\%} (22/42) of patients. A germline mutation was detected in 66{\%} (25/38) and was associated with a poor prognosis (4.2 ± 4.1{\%} vs. 48 ± 16.4{\%}, P < 0.00005). A gross total resection (GTR) was realized in 17{\%}. A GTR (42.9 ± 18.7{\%} vs. 4.9 ± 4.3{\%}, P = 0.04), therapy according to a standardized approach (20.9 ± 8.7{\%} vs. 7.1 ± 6.9 {\%}, P = 0.0018), and a complete remission (CR) (23.6 ± 9.8{\%} vs. 1.3 ± 3.6{\%}, P = 0.04) were significant prognostic factors. Conclusions: The management of patients with congenital rhabdoid tumors requires a major multidisciplinary effort. In many instances, cure is not possible and a palliative approach is warranted. Our data indicate a positive impact of standardized therapeutic approaches on survival, making a tailored approach toward affected patients and their families mandatory.",
author = "{EU-RHAB consortium} and Karolina Nemes and Nathalie Cl{\'e}ment and Denis Kachanov and Susanne Bens and Martin Hasselblatt and Beate Timmermann and Reinhard Schneppenheim and Joachim Gerss and Reiner Siebert and Rhoikos Furtw{\"a}ngler and Franck Bourdeaut and Fr{\"u}hwald, {Michael Christoph} and Monica Zlatic and Tatyana Shamanskaya and Svetlana Varfolomeeva and Kornelius Kerl and Floor Abbink and Martin Ebinger and Stephan Tippelt and Norbert Graf and Pablo Hern{\'a}iz-Driever and Gil-da-Costa, {Maria Jo{\~a}o} and Thomas Klingebiel and Rolf-Dieter Kortmann and Jane Pears and Paul-Gerhardt Schlegel and Nicolas Andre and Anne-Isabelle Bertozzi and Nad{\`e}ge Corradini and Christelle Dufour and Fanny Fouyssac and Pierre Leblond and Olivier Delattre and Julien Masliah-Planchon and Thorsten Simon and Olaf Witt and Monica Zlatic and Tatyana Shamanskaya and Svetlana Varfolomeeva and Kornelius Kerl and Floor Abbink and Martin Ebinger and Stephan Tippelt and Norbert Graf and Pablo Hern{\'a}iz-Driever and Gil-da-Costa, {Maria Jo{\~a}o} and Thomas Klingebiel and Rolf-Dieter Kortmann and Jane Pears and Paul-Gerhardt Schlegel",
year = "2018",
doi = "10.1002/pbc.26999",
language = "English",
volume = "65",
journal = "Pediatric Blood and Cancer",
issn = "1545-5009",
publisher = "Wiley-Liss Inc.",
number = "6",

}

The extraordinary challenge of treating patients with congenital rhabdoid tumors—a collaborative European effort. / EU-RHAB consortium.

In: Pediatric Blood and Cancer, Vol. 65, No. 6, e26999, 2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The extraordinary challenge of treating patients with congenital rhabdoid tumors—a collaborative European effort

AU - EU-RHAB consortium

AU - Nemes, Karolina

AU - Clément, Nathalie

AU - Kachanov, Denis

AU - Bens, Susanne

AU - Hasselblatt, Martin

AU - Timmermann, Beate

AU - Schneppenheim, Reinhard

AU - Gerss, Joachim

AU - Siebert, Reiner

AU - Furtwängler, Rhoikos

AU - Bourdeaut, Franck

AU - Frühwald, Michael Christoph

AU - Zlatic, Monica

AU - Shamanskaya, Tatyana

AU - Varfolomeeva, Svetlana

AU - Kerl, Kornelius

AU - Abbink, Floor

AU - Ebinger, Martin

AU - Tippelt, Stephan

AU - Graf, Norbert

AU - Hernáiz-Driever, Pablo

AU - Gil-da-Costa, Maria João

AU - Klingebiel, Thomas

AU - Kortmann, Rolf-Dieter

AU - Pears, Jane

AU - Schlegel, Paul-Gerhardt

AU - Andre, Nicolas

AU - Bertozzi, Anne-Isabelle

AU - Corradini, Nadège

AU - Dufour, Christelle

AU - Fouyssac, Fanny

AU - Leblond, Pierre

AU - Delattre, Olivier

AU - Masliah-Planchon, Julien

AU - Simon, Thorsten

AU - Witt, Olaf

AU - Zlatic, Monica

AU - Shamanskaya, Tatyana

AU - Varfolomeeva, Svetlana

AU - Kerl, Kornelius

AU - Abbink, Floor

AU - Ebinger, Martin

AU - Tippelt, Stephan

AU - Graf, Norbert

AU - Hernáiz-Driever, Pablo

AU - Gil-da-Costa, Maria João

AU - Klingebiel, Thomas

AU - Kortmann, Rolf-Dieter

AU - Pears, Jane

AU - Schlegel, Paul-Gerhardt

PY - 2018

Y1 - 2018

N2 - Background: Congenital rhabdoid tumors are rare and highly aggressive malignancies. In general, patients are considered to be incurable and are often treated using an exclusive, primarily palliative approach. Methods: A prospective and retrospective collection of 42 patients from the European Rhabdoid Registry (EU-RHAB), France and Moscow (2006–2016) diagnosed within the first 28 days of life was evaluated. Genetic and clinical reference evaluation included SMARCB1 and/or SMARCA4 (fluorescence-in-situ-hybridization, multiplex ligation-dependent probe amplification, and sequencing) mutation analysis and immunohistochemistry. Forty-eight percent (20/42) of patients were treated according to the EU-RHAB therapy, 7% (3/42) according to the pilot approach Rhabdoid 2007, 33% (14/42) with individual schedules, and 12% (5/42) received no chemotherapy at all. Results: Forty point five percent (17/42) of patients presented with extracranial rhabdoid tumors, 33.5% (14/42) with rhabdoid tumors of the central nervous system (atypical teratoid/rhabdoid tumor), and the remainder 26% (11/42) demonstrated synchronous tumors. Metastases at diagnosis were present in 52% (22/42) of patients. A germline mutation was detected in 66% (25/38) and was associated with a poor prognosis (4.2 ± 4.1% vs. 48 ± 16.4%, P < 0.00005). A gross total resection (GTR) was realized in 17%. A GTR (42.9 ± 18.7% vs. 4.9 ± 4.3%, P = 0.04), therapy according to a standardized approach (20.9 ± 8.7% vs. 7.1 ± 6.9 %, P = 0.0018), and a complete remission (CR) (23.6 ± 9.8% vs. 1.3 ± 3.6%, P = 0.04) were significant prognostic factors. Conclusions: The management of patients with congenital rhabdoid tumors requires a major multidisciplinary effort. In many instances, cure is not possible and a palliative approach is warranted. Our data indicate a positive impact of standardized therapeutic approaches on survival, making a tailored approach toward affected patients and their families mandatory.

AB - Background: Congenital rhabdoid tumors are rare and highly aggressive malignancies. In general, patients are considered to be incurable and are often treated using an exclusive, primarily palliative approach. Methods: A prospective and retrospective collection of 42 patients from the European Rhabdoid Registry (EU-RHAB), France and Moscow (2006–2016) diagnosed within the first 28 days of life was evaluated. Genetic and clinical reference evaluation included SMARCB1 and/or SMARCA4 (fluorescence-in-situ-hybridization, multiplex ligation-dependent probe amplification, and sequencing) mutation analysis and immunohistochemistry. Forty-eight percent (20/42) of patients were treated according to the EU-RHAB therapy, 7% (3/42) according to the pilot approach Rhabdoid 2007, 33% (14/42) with individual schedules, and 12% (5/42) received no chemotherapy at all. Results: Forty point five percent (17/42) of patients presented with extracranial rhabdoid tumors, 33.5% (14/42) with rhabdoid tumors of the central nervous system (atypical teratoid/rhabdoid tumor), and the remainder 26% (11/42) demonstrated synchronous tumors. Metastases at diagnosis were present in 52% (22/42) of patients. A germline mutation was detected in 66% (25/38) and was associated with a poor prognosis (4.2 ± 4.1% vs. 48 ± 16.4%, P < 0.00005). A gross total resection (GTR) was realized in 17%. A GTR (42.9 ± 18.7% vs. 4.9 ± 4.3%, P = 0.04), therapy according to a standardized approach (20.9 ± 8.7% vs. 7.1 ± 6.9 %, P = 0.0018), and a complete remission (CR) (23.6 ± 9.8% vs. 1.3 ± 3.6%, P = 0.04) were significant prognostic factors. Conclusions: The management of patients with congenital rhabdoid tumors requires a major multidisciplinary effort. In many instances, cure is not possible and a palliative approach is warranted. Our data indicate a positive impact of standardized therapeutic approaches on survival, making a tailored approach toward affected patients and their families mandatory.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85041710194&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/29418059

U2 - 10.1002/pbc.26999

DO - 10.1002/pbc.26999

M3 - Article

VL - 65

JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

SN - 1545-5009

IS - 6

M1 - e26999

ER -