SIOPEN LINES: This Phase III trial is managing the treatment (which may involve chemotherapy, radiotherapy and/or surgery) of people with low and intermediate risk patients with neuroblastomaEuropean Low and Intermediate Risk Neuroblastoma Protocol

Inclusion

1. LOW RISK STUDY

   Inclusion criteria for the whole low risk group:

   • informed consent and follow-up warranted; group assignment completed within 6 weeks from diagnosis; no prior chemotherapy or radiotherapy
   • Biopsy proven neuroblastoma
   • Tumour genomic profile obtained in a NRL according to guidelines
   • MYCN non-amplified

   Exclusion criteria for the whole low risk group:

   * Diagnosis of ganglioneuroma or ganglioneuroblastoma intermixed INRG Stage L2

   Inclusion criteria:

   *age ≤ 18 months

   Exclusion criteria:

   • any metastatic site
   • MYCN amplification
   • age > 18 months INRG Stage Ms

   Inclusion criteria:

   * age ≤ 12 months

   Exclusion criteria:

   • bone, pleura/lung and/or CNS metastasis
   • MYCN amplification
   • age > 12 months

2. INTERMEDIATE RISK STUDY

   Inclusion criteria for the whole intermediate risk group:

   • informed consent and follow-up warranted; group assignment completed within 6 weeks from diagnosis; no prior chemotherapy or radiotherapy
   • Tumour material available for biological studies according to guidelines
   • Biopsy proven neuroblastoma confirmed in a National Reference Laboratory (NRL)

   Exclusion criteria for the whole intermediate risk group:

   * Diagnosis of ganglioneuroma or ganglioneuroblastoma intermixed

   INRG Stage L1 and INSS stage 1:

   Inclusion criteria:

   * MYCN amplified

   Exclusion criteria:

   • MYCN non-amplified
   • INSS stages 2, 3, 4, 4s

   INRG Stage L2:

   Inclusion criteria:

   • Histology: differentiating, poorly differentiated, undifferentiated neuroblastoma or ganglioneuroblastoma nodular
   • MYCN non-amplified
   • age >18 months

   Exclusion criteria:

   • neuroblastoma NOS
   • MYCN amplification.
   • age ≤ 18 months

   INRG Stage M:

   Inclusion criteria:

   • Any histology
   • MYCN non-amplified
   • age ≤ 12 months

   Exclusion criteria:

   • MYCN amplification
   • age > 12 months
3. NEONATAL SUPRARENAL MASSES

Inclusion criteria:

• Age less than or equal to 90 days when the suprarenal mass is discovered.
• Suprarenal mass detected by ultrasound and/or MRI. The suprarenal mass may be cystic and/or solid, but IT CANNOT REACH THE MIDLINE AND should MEASURE ≤ 5 CM AT THE LARGEST DIAMETER.
• No regional involvement: MRI scan does not show evidence of positive ipsi/contralateral lymph nodes or other spread outside the suprarenal gland.
• No metastatic involvement.
• Frozen plasma available.
• Informed consent.
• Availability to do the adequate follow-up

Exclusion criteria:

• Age older than 90 days.
• Suprarenal mass bigger than 5 cm.
• Regional involvement.
• Metastatic involvement.
• Inability to undertake mandatory diagnostic studies (biological markers, US, MRI, MIBG).
• Follow-up not guaranteed by parents/guardians.