title: The Sooner the Better? How Symptom Interval Correlates With Outcome in Children and Adolescents With Solid Tumors: Regression Tree Analysis of the Findings of a Prospective Study.
abstract: BACKGROUND
  The potential impact of diagnostic delays on patients' outcomes is a debated issue in pediatric oncology and discordant results have been published so far. We attempted to tackle this issue by analyzing a prospective series of 351 consecutive children and adolescents with solid malignancies using innovative statistical tools.
  
  
  METHODS
  To address the nonlinear complexity of the association between symptom interval and overall survival (OS), a regression tree algorithm was constructed with sequential binary splitting rules and used to identify homogeneous patient groups vis-à-vis functional relationship between diagnostic delay and OS.
  
  
  RESULTS
  Three different groups were identified: group A, with localized disease and good prognosis (5-year OS 85.4%); group B, with locally or regionally advanced, or metastatic disease and intermediate prognosis (5-year OS 72.9%), including neuroblastoma, Wilms tumor, non-rhabdomyosarcoma soft tissue sarcoma, and germ cell tumor; and group C, with locally or regionally advanced, or metastatic disease and poor prognosis (5-year OS 45%), including brain tumors, rhabdomyosarcoma, and bone sarcoma. The functional relationship between symptom interval and mortality risk differed between the three subgroups, there being no association in group A (hazard ratio [HR]: 0.96), a positive linear association in group B (HR: 1.48), and a negative linear association in group C (HR: 0.61).
  
  
  CONCLUSIONS
  Our analysis suggests that at least a subset of patients can benefit from an earlier diagnosis in terms of survival. For others, intrinsic aggressiveness may mask the potential effect of diagnostic delays. Based on these findings, early diagnosis should remain a goal for pediatric cancer patients.
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
authors.affiliation: Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Lo Vullo
authors.affiliation: Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Giardiello
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Veneroni
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Magni
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.|Section of Psychology, Department of Biomolecular Sciences and Biotechnology, Faculty of School of Medicine, University of Milan, Italy.
authors.forename: Carlo Alfredo
authors.initials: CA
authors.lastname: Clerici
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Chiaravalli
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Casanova
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Luksch
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Terenziani
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Spreafico
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Meazza
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Catania
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Schiavello
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Biassoni
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Podda
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Bergamaschi
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Puma
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Massimino
authors.affiliation: Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009369:Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
keywords: adolescents; cancer; children; diagnostic delay; outcome; symptom interval