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The extraordinary challenge of treating patients with congenital rhabdoid tumors—a collaborative European effort
Author(s) -
Nemes Karolina,
Clément Nathalie,
Kachanov Denis,
Bens Susanne,
Hasselblatt Martin,
Timmermann Beate,
Schneppenheim Reinhard,
Gerss Joachim,
Siebert Reiner,
Furtwängler Rhoikos,
Bourdeaut Franck,
Frühwald Michael Christoph
Publication year - 2018
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.26999
Subject(s) - medicine , atypical teratoid rhabdoid tumor , smarcb1 , fluorescence in situ hybridization , retrospective cohort study , germline mutation , immunohistochemistry , oncology , pediatrics , mutation , dna , biochemistry , chemistry , biology , gene , chromatin remodeling , chromatin , chromosome , genetics
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.