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

Andrea Ferrari, Salvatore Lo Vullo, Daniele Giardiello, Laura Veneroni, Chiara Magni, Carlo Alfredo Clerici, Stefano Chiaravalli, Michela Casanova, Roberto Luksch, Monica Terenziani, Filippo Spreafico, Cristina Meazza, Serena Catania, Elisabetta Schiavello, Veronica Biassoni, Marta Podda, Luca Bergamaschi, Nadia Puma, Maura Massimino, Luigi Mariani

Research output: Contribution to journalArticle

23 Citations (Scopus)

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, nonrhabdomyosarcoma 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.

Original languageEnglish
Pages (from-to)479-485
Number of pages7
JournalPediatric Blood and Cancer
Volume63
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

Fingerprint

Regression Analysis
Prospective Studies
Survival
Neoplasms
Sarcoma
Early Diagnosis
Pediatrics
Wilms Tumor
Rhabdomyosarcoma
Germ Cell and Embryonal Neoplasms
Masks
Neuroblastoma
Brain Neoplasms
Bone and Bones
Mortality

Keywords

  • Adolescents
  • Cancer
  • Children
  • Diagnostic delay
  • Outcome
  • Symptom interval

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

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. / Ferrari, Andrea; Lo Vullo, Salvatore; Giardiello, Daniele; Veneroni, Laura; Magni, Chiara; Clerici, Carlo Alfredo; Chiaravalli, Stefano; Casanova, Michela; Luksch, Roberto; Terenziani, Monica; Spreafico, Filippo; Meazza, Cristina; Catania, Serena; Schiavello, Elisabetta; Biassoni, Veronica; Podda, Marta; Bergamaschi, Luca; Puma, Nadia; Massimino, Maura; Mariani, Luigi.

In: Pediatric Blood and Cancer, Vol. 63, No. 3, 01.03.2016, p. 479-485.

Research output: Contribution to journalArticle

Ferrari, Andrea ; Lo Vullo, Salvatore ; Giardiello, Daniele ; Veneroni, Laura ; Magni, Chiara ; Clerici, Carlo Alfredo ; Chiaravalli, Stefano ; Casanova, Michela ; Luksch, Roberto ; Terenziani, Monica ; Spreafico, Filippo ; Meazza, Cristina ; Catania, Serena ; Schiavello, Elisabetta ; Biassoni, Veronica ; Podda, Marta ; Bergamaschi, Luca ; Puma, Nadia ; Massimino, Maura ; Mariani, Luigi. / 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. In: Pediatric Blood and Cancer. 2016 ; Vol. 63, No. 3. pp. 479-485.
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AU - Clerici, Carlo Alfredo

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AU - Biassoni, Veronica

AU - Podda, Marta

AU - Bergamaschi, Luca

AU - Puma, Nadia

AU - Massimino, Maura

AU - Mariani, Luigi

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N2 - 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, nonrhabdomyosarcoma 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.

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