title: Tumor histology during induction therapy in patients with high-risk neuroblastoma.
abstract: BACKGROUND
  In high-risk neuroblastoma patients, response to induction chemotherapy is emerging as an important determinant of overall survival. We sought to determine whether histological changes in the primary tumor following induction therapy could be used as a marker of response.
  
  
  METHODS
  Second-look primary tumor specimens from 43 patients were reviewed according to specific morphological features.
  
  
  RESULTS
  In the majority, induction therapy resulted in a shift from an intermediate/high to low mitosis-karyorrhexis index (MKI) (P = 0.0009) and from undifferentiated/poorly differentiated to differentiating tumors (P < 0.0001). Following induction therapy, persistence of intermediate/high tumor MKI and ≥90% persistent neuroblastic cells were predictive of a poor outcome (P = 0.001 and 0.03, respectively). Less than 10% tumor necrosis was associated with a trend towards lower survival.
  
  
  CONCLUSIONS
  High proliferative activity in the primary tumor following induction therapy portends a poor outcome in patients with high-risk neuroblastoma. If confirmed in a larger cohort, tumor histology at second-look surgery could be used to define a subset of very high risk patients who would benefit from alternative therapies prior to myeloablative dose-intensive transplant.
authors.affiliation: Department of Pediatric Hematology and Oncology, Dana-Farber Cancer Institute and Children's Hospital, Boston, MA 02115, USA. rani_george@dfci.harvard.edu
authors.forename: Rani E
authors.initials: RE
authors.lastname: George
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Perez-Atayde
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Yao
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: Robert C
authors.initials: RC
authors.lastname: Shamberger
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Lisa
authors.initials: L
authors.lastname: Diller
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D006801:Humans; D060828:Induction Chemotherapy; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008940:Mitotic Index; D020360:Neoadjuvant Therapy; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D012306:Risk; D024162:Second-Look Surgery; D016896:Treatment Outcome