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
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