Prognostic value of xenograft engraftment in patients with metastatic high-risk neuroblastoma


Por: Aschero MR, Castillo H, Baulenas-Farrés M, Resa-Parés C, Jiménez-Cabaco A, Rodriguez E, Monterrubio C, Pérez-Jaume S, Suñol M, Chantada G, Lavarino C, Mora J and Carcaboso AM

Publicada: 1 jun 2023 Ahead of Print: 1 mar 2023
Resumen:
BackgroundSuccessful engraftment of human cancer biopsies in immunodeficient mice correlates with the poor prognosis of patients. This was reported 30 years ago for children with neuroblastoma, but the standard of care treatment evolved significantly during the last 15 years, leading to improved survival of these patients. Here, we evaluated the association of patient-derived xenograft (PDX) engraftment and prognosis in patients receiving up-to-date treatments for cancers classified as metastatic (stage M) high-risk neuroblastoma (HR-NB) by the International Neuroblastoma Risk Group Staging System (INRGSS). MethodsWe obtained biopsies from patients with stage M HR-NB. We inoculated biopsy fragments subcutaneously in mice. We studied the association of PDX engraftment with event-free survival (EFS) and overall survival (OS) of patients. ResultsSince 2009, we established 17 PDX from 97 samples of 66 patients with stage M HR-NB, with a follow-up of at least two years. Factors associated with higher probability of engraftment were the death as outcome (p = .0006) and the amplification of the gene MYCN in tumors (p = .0271). Patients whose biopsies established a PDX had significantly shorter EFS and OS (p = .0039 and .0002, respectively) than patients whose samples did not engraft. The association of PDX engraftment and OS was significant in patients without MYCN amplification (p = .0041), but not in patients with MYCN amplification (p = .2707). ConclusionPositive PDX engraftment is a factor related to poor prognosis and fatal outcome in patients with stage M HR-NB treated with up-to-date therapies.

Filiaciones:
Aschero MR:
 SJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain

 Institut de Recerca Sant Joan de Déu, Barcelona, Spain

 Hosp St Joan Deu, SJD Pediat Canc Ctr Barcelona, Barcelona, Spain

 Inst Recerca St Joan Deu, Barcelona, Spain

Castillo H:
 SJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain

 Institut de Recerca Sant Joan de Déu, Barcelona, Spain

 Hosp St Joan Deu, SJD Pediat Canc Ctr Barcelona, Barcelona, Spain

 Inst Recerca St Joan Deu, Barcelona, Spain

Baulenas-Farrés M:
 SJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain

 Institut de Recerca Sant Joan de Déu, Barcelona, Spain

 Hosp St Joan Deu, SJD Pediat Canc Ctr Barcelona, Barcelona, Spain

 Inst Recerca St Joan Deu, Barcelona, Spain

Resa-Parés C:
 SJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain

 Institut de Recerca Sant Joan de Déu, Barcelona, Spain

 Hosp St Joan Deu, SJD Pediat Canc Ctr Barcelona, Barcelona, Spain

 Inst Recerca St Joan Deu, Barcelona, Spain

Jiménez-Cabaco A:
 SJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain

 Institut de Recerca Sant Joan de Déu, Barcelona, Spain

 Hosp St Joan Deu, SJD Pediat Canc Ctr Barcelona, Barcelona, Spain

 Inst Recerca St Joan Deu, Barcelona, Spain

Rodriguez E:
 Department of Pathology, Hospital Sant Joan de Déu, Barcelona, Spain

 Hosp St Joan Deu, Dept Pathol, Barcelona, Spain

Monterrubio C:
 SJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain

 Hosp St Joan Deu, SJD Pediat Canc Ctr Barcelona, Barcelona, Spain

Pérez-Jaume S:
 SJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain

 Institut de Recerca Sant Joan de Déu, Barcelona, Spain

 Hosp St Joan Deu, SJD Pediat Canc Ctr Barcelona, Barcelona, Spain

 Inst Recerca St Joan Deu, Barcelona, Spain

Suñol M:
 Department of Pathology, Hospital Sant Joan de Déu, Barcelona, Spain

Chantada G:
 SJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain

 Institut de Recerca Sant Joan de Déu, Barcelona, Spain

 CONICET, Buenos Aires, Argentina

 Hosp St Joan Deu, SJD Pediat Canc Ctr Barcelona, Barcelona, Spain

 Inst Recerca St Joan Deu, Barcelona, Spain

 Consejo Nacl Invest Cient & Tecn, Buenos Aires, Argentina

Lavarino C:
 SJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain

 Institut de Recerca Sant Joan de Déu, Barcelona, Spain

 Hosp St Joan Deu, SJD Pediat Canc Ctr Barcelona, Barcelona, Spain

 Inst Recerca St Joan Deu, Barcelona, Spain

Mora J:
 SJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain

 Institut de Recerca Sant Joan de Déu, Barcelona, Spain

 Hosp St Joan Deu, SJD Pediat Canc Ctr Barcelona, Barcelona, Spain

 Inst Recerca St Joan Deu, Barcelona, Spain

Carcaboso AM:
 SJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain

 Institut de Recerca Sant Joan de Déu, Barcelona, Spain

 Hosp St Joan Deu, SJD Pediat Canc Ctr Barcelona, Barcelona, Spain

 Inst Recerca St Joan Deu, Barcelona, Spain
ISSN: 15455009





PEDIATRIC BLOOD & CANCER
Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ, Estados Unidos America
Tipo de documento: Article
Volumen: 70 Número: 6
Páginas:
WOS Id: 000956696000001
ID de PubMed: 36973999
imagen Bronze

MÉTRICAS