6 research outputs found
Recurrent somatic chromosomal abnormalities in relapsed extraocular retinoblastoma
Most reports about copy number alterations (CNA) in retinoblastoma relate to patients with intraocular disease and features of children with extraocular relapse remain unknown, so we aimed to describe the CNA in this population. We evaluated 23 patients and 27 specimens from 4 centers. Seventeen cases had extraocular relapse after initial enucleation and six cases after an initial preservation attempt. We performed an analysis of CNA and BCOR gene alteration by SNP array (Single Nucleotide Polymorfism array), whole-exome sequencing, IMPACT panel and CGH array (Array-based comparative genomic hybridization). All cases presented CNA at a higher prevalence than those reported in previously published studies for intraocular cases. CNA previously reported for intraocular retinoblastoma were found at a high frequency in our cohort: gains in 1q (69.5%), 2p (60.9%) and 6p (86.9%), and 16q loss (78.2%). Other, previously less-recognized, CNA were found including loss of 11q (34.8%), gain of 17q (56.5%), loss of 19q (30.4%) and BCOR alterations were present in 72.7% of our cases. A high number of CNA including 11q deletions, 17q gains, 19q loss, and BCOR alterations, are more common in extraocular retinoblastoma. Identification of these features may be correlated with a more aggressive tumor warranting consideration for patient management.Fil: Aschero, MarĂa del Rosario. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Francis, Jasmine H.. Memorial Sloan-Kettering Cancer Center; Estados UnidosFil: Ganiewich, Daiana. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BioquĂmicas de Buenos Aires. FundaciĂłn Instituto Leloir. Instituto de Investigaciones BioquĂmicas de Buenos Aires; ArgentinaFil: Gomez Gonzalez, Soledad. Hospital Sant Joan de Deu Barcelona; EspañaFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; ArgentinaFil: Zugbi, Santiago. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Ottaviani, Daniela. Universite de Paris; Francia. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Lemelle, Lauriane. Universite de Paris; Francia. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Mena, Marcela Daniela C. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; ArgentinaFil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Correa Llano, Genoveva. Hospital Sant Joan de Deu Barcelona; EspañaFil: Lamas, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; ArgentinaFil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; ArgentinaFil: Szijan, Irene. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de GenĂ©tica y BiologĂa Molecular; ArgentinaFil: Mora, Jaume. Hospital Sant Joan de Deu Barcelona; EspañaFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BioquĂmicas de Buenos Aires. FundaciĂłn Instituto Leloir. Instituto de Investigaciones BioquĂmicas de Buenos Aires; ArgentinaFil: Doz, François. Universite de Paris; Francia. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Radvanyi, François. Universite de Paris; Francia. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Abramson, David H.. Memorial Sloan-Kettering Cancer Center; Estados UnidosFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BioquĂmicas de Buenos Aires. FundaciĂłn Instituto Leloir. Instituto de Investigaciones BioquĂmicas de Buenos Aires; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Lavarino, Cinzia. Hospital Sant Joan de Deu Barcelona; EspañaFil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de PediatrĂa "Juan P. Garrahan"; Argentina. Hospital Sant Joan de Deu Barcelona; España. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentin
NUT CARCINOMA IN CHILDREN: THE EXPERT EUROPEAN EXPERIENCE
Background and Aims: NUT-carcinoma is a rare, probably underdiagnosed
and highly aggressive tumor defined by the presence of a somatic
NUTM1 rearrangement. The tumor occurs mainly in adolescents
and young adults. We analyzed the clinical, radiologic, and biological
features of pediatric patients (â€18 years) with NUT-carcinoma.
Methods: This retrospective multicenter international study was
based on review of medical records of 24 childrenwith NUT-carcinoma
from 5 countries with specific rearrangement or positive anti-NUT
nuclear staining.
Results: Twenty-four patients with a median age of 14.6 years (range:
3.9â18 years) were analyzed. Thoracic/mediastinal tumors were the
primary in 14 patients, and head and neck in 7 cases. One patient
had multifocal tumor with unknown primary, another a vocal cord
and the last one a pancreas primary. Sixteen patients (67%) presented
with regional lymph node involvement and 17 patients (71%) with distant
metastases, in most cases lung (38%), distant lymph nodes (38%)
and bone marrow (30%). Approximately half of patients were initially
misdiagnosed and diagnosis was corrected after NUT immunochemistry
or NUT fusion sequencing. Chemotherapy was administered in all
patients; nine patients underwent major surgery and 19 radiotherapy.
Median overall survival was 0.75 years (range 0.2-11 years) median
event free survival 0.4 years (range 0.1-11 years), one patient is currently
treated for a subsequent relapse (1.9 years after diagnosis).
Three long-term survivors (11, 9.1 and 6.6 years after diagnosis) were
identified, these cases were associated with non-metastatic cervical
disease and non-metastatic disease with BRD3-NUT-fusion.
Conclusions: As in adults, NUT-carcinoma in pediatric patients is
poorly sensitive to conventional therapy in most cases. In a minority
of patients long-term survival is possible with multimodal treatment.
Early diagnosis of undifferentiated or poorly differentiated carcinomas
to identify the specific rearrangement of NUT-gene is necessary
to initiate the optimal diagnostic and therapeutic strategy
Esthesioneuroblastoma in children, adolescents and young adults
International audienc
NUT carcinoma in children and adults: A multicenter retrospective study
Background: Nuclear protein of the testis (NUT) carcinoma (formerly NUT midline carcinoma) is an aggressive tumor defined by the presence of NUT rearrangement with a poor prognosis. This rare cancer is underdiagnosed and poorly treated. Objective: The primary objective of this study was to describe the clinical, radiologic, and biological features of NUT carcinoma. The secondary objective was to describe the various treatments and assess their efficacy. Methods: This retrospective multicenter study was based on review of the medical records of children and adults with NUT carcinoma with specific rearrangement or positive anti-NUT nuclear staining (>50%). Results: This series of 12 patients had a median age of 18.1 years (ranges: 12.3â49.7 years). The primary tumor was located in the chest in eight patients, the head and neck in three patients, and one patient had a multifocal tumor. Nine patients presented regional lymph node involvement and eight distant metastases. One-half of patients were initially misdiagnosed. Specific NUT antibody was positive in all cases tested. A transient response to chemotherapy was observed in four of 11 patients. Only two patients were treated by surgery and five received radiotherapy with curative intent. At the end of follow-up, only one patient was still in remission more than 12 years after the diagnosis. Median overall survival was 4.7 months (95% confidence interval [CI]: 2.1â17.7). Conclusion: NUT carcinoma is an aggressive disease refractory to conventional therapy. Early diagnosis by NUT-specific antibody immunostaining in cases of undifferentiated or poorly differentiated carcinoma to identify the specific rearrangement of NUT gene is useful to propose the optimal therapeutic strategy.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
NUT Carcinoma in Children and Adolescents: The Expert European Standard Clinical Practice Harmonized Recommendations
Background and Aims:
Nuclear protein of the testis (NUT) carcinoma (NC) is a rare and highly aggressive tumor mainly occurring in adolescents and young adults, defined by the presence of a somatic NUTM1 rearrangement. The aim is to establish internationally harmonized consensus recommendations for the diagnosis and treatment of adolescents and young adults with NC in the framework of the European Reference Network for Paediatric Oncology.
Methods:
The European Cooperative Study Group for Pediatric Rare Tumors developed recommendations according to the Consensus Conference Standard Operating procedure methodology and reviewed by external âexperts.â No evidence of level I to II exists. Recommendations were developed based on published prospective (level III), but more frequently retrospective series (level IV), case reports (level V), and personal expertise (level V). In addition, âstrengthâ of recommendations were categorized by grading (grade A to E).
Results:
Histology is mandatory for the diagnosis of NC, including immunolabeling with anti-NUT antibodies and molecular biology (NUTM1 rearrangement) (level V; grade A). Treatment of NC usually combines aggressive approaches in multimodal regimens. Chemotherapy should be considered as first-line treatment (neoadjuvant vincristine-adriamycin-ifosfamide/cisplatin-adriamycin-ifsofamide or vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide) for unresectable or metastatic tumor (ie, 3 courses), rapidly followed by local treatment (level IV; grade B). Referral to a specialized surgical oncology center is highly recommended (level V; grade A). In localized NC, a complete microscopic surgical resection should be attempted whenever and as soon as possible, followed by primary irradiation (60 to 70 Gy) and involved lymph nodes area (level IV; grade B). For head and neck tumors, a systematic neck dissection might be considered, even if N0 (level V; grade C). Adjuvant postirradiation chemotherapy is recommended, for a total of 9 to 12 courses (level IV; grade B). For first-line resected tumors, concomitant adjuvant chemotherapy to radiotherapy may be discussed (level IV; grade B). Targeted therapies and immunotherapeutic regimens should be delivered in the setting of prospective trials (level V; grade B)
Targeted therapies in children with renal cell carcinoma (RCC): An International Society of Pediatric OncologyâRenal Tumor Study Group (SIOPâRTSG)ârelated retrospective descriptive study
Abstract Introduction Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric OncologyâRenal Tumor Study Group (SIOPâRTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC. Methods This retrospective study describes the effects of tyrosine kinase inhibitors (TKI), antiâprogrammed cell death 1 (PDâ(L)1) monoclonal antibodies, and immunotherapeutic regimens in advancedâstage and relapsed pediatric RCC. Results Of the 31 identified patients (0â18âyears) with histologically proven RCC, 3/31 presented with TNM stage I/II, 8/31 with TNM stage III, and 20/31 with TNM stage IV at diagnosis. The majority were diagnosed with translocation type RCC (MiTâRCC) (21/31) and the remaining patients mainly presented with papillary or clearâcell RCC. Treatment in a neoadjuvant or adjuvant setting, or upon relapse or progression, included monoâ or combination therapy with a large variety of drugs, illustrating center specific choices in most patients. Sunitinib was often administered as first choice and predominantly resulted in stable disease (53%). Other frequently used drugs included axitinib, cabozantinib, sorafenib, and nivolumab; however, no treatment seemed more promising than sunitinib. Overall, 15/31 patients died of disease, 12/31 are alive with active disease, and only four patients had a complete response. The sample size and heterogeneity of this cohort only allowed descriptive statistical analysis. Conclusion This study provides an overview of a unique series of clinical and treatment characteristics of pediatric patients with RCC treated with targeted therapies