European Low and Intermediate Risk Neuroblastoma Protocol

• LOW RISK STUDY

The low risk group of patients includes NB patients without MYCN amplification with or without life threatening symptoms in the following clinical situations:

• Children aged ≤ 18 months with localised neuroblastoma associated with image defined risk factors precluding upfront surgery (stage INRG L2).
• Children aged ≤ 12 months with disseminated neuroblastoma without bone, pleura, lung or CNS (Central Nervous System) disease (stage INRG Ms)

• INTERMEDIATE RISK STUDY

The intermediate risk group of patients includes NB patients in the following clinical situations:

• Children aged >18 months with localised neuroblastoma without MYCN amplification, associated with image defined risk factors precluding upfront surgery (stage INRG L2).
• Children aged ≤12 months with disseminated neuroblastoma involving bone, pleura, lung and/or CNS (stage INRG M), without MYCN amplification.
• Children with localised resected NB (stage INSS I) with MYCN amplification. NEONATAL SUPRARENAL MASSES

The incidence of suprarenal tumours/masses has increased in the last decade due to the expanded use of prenatal ultrasonography in routine obstetric care and in the neonatal and early infancy care. The differential diagnosis of these masses ranges from benign (adrenal haemorrhage) to malignant processes (neuroblastoma, adrenal carcinoma). Knowledge on perinatal suprarenal masses, although based on a relatively large literature, is scattered amongst studies on very few cases with no methodical approach and often short follow up. Therefore, the optimal management of these masses has not been clearly defined. Neuroblastoma at this age is an intriguing entity with a very good prognosis in most cases. The SIOPEN Group, based on their results in the first multicenter European Trial for infants with neuroblastoma (INES) and the world-wide experience provided in the literature, is launching this European surveillance study (Multi-centre, non-blinded, one armed prospective trial) for these masses. Treatment: Observation

• 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
• 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
• 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.