Neuroblastoma

Diagnostic workup, risk grouping and management of Neuroblastoma.

11. WELL DIFFERENTIATED:
ABSENT

INTERMIXED)

PRESENT

NODULAR

STROMA RICH

UNFAVORABLE STROMA POOR POOR: PROGNOSIS. GROUP

OVER 5 UNDIFF] OVER 100 OVER 200

D
A 1 M
>POOR—> Gy 1h 5 —+E DFE —K UNDER 100

M
LL UNDER 1% =

UNDER 200

12. International Neuroblastoma Pathology classification

Neuroblastoma
Favorable
15 yrs

155 ys
Unfavorable
< 15 yrs

25 yrs
Ganglioneuroblastoma, intermixed

Ganglioneuroma
Maturing
Mature
Ganglioneuroblastoma, nodular

(Schwannian stroma-poor)*

Pootly differentiated or differentiating
& low or intermediate MK! tumor
Differentiating & low MKI tumor

a) undifferentiated tumor?

b) high MK] tumor

a) undifferentiated or poorty
dfferentiated tumor

b) intermediate or high MKI tumor

All tumors

(Schwannian stroma-rich)

(Schwannian stroma-dominant)
omposite Schwannian stroma-rich/

stroma-dominate and stroma-
poor)

Original Shimada classification

Stroma-poor
Favorable

Unfavorable

‘Stroma-tich Intermixed
(favorable)

Well differentiated (favorable)
Ganglioneuroma
Stroma-tich nodular (unfavorable)

Prognostic group

Favorable

Unfavorable

Favorable‘

Favorable‘

Unfavorable®

13. Favorable

Age Tumor subtype MKI

14. Age

Unfavorable

Tumor subtype MKI

20. Staging

21. International Neuroblastoma Stagi
System (INSS)

22. Localized; GTR (RO/R1)
Localized; < GTR; NO
Localized; ipsilateral Node +ve (C/L —ve)

Unresectable disease crossing midline or C/L nodes +ve

Distant spread: Nodes, bone marrow/bone, liver, skin or
others

Localized; dissemination limited to skin, liver or marrow
(age < ly)

23. INSS Stage Age

MYCN status

Shimada

DNA index

Risk group

1 0-21 y
2A/2B <365 days
-365 days-21 years
=365 days-21 years
>365 days-21 years
<365 days
<365 days
>365 days-21 years
65 days-21 years
65 days-21 years
<365 days
<365 days
=365 days-21 years
<365 days
<365 days
<365 days
<365 days

Any
Any
Normal
Amplified
Amplified
Normal
Amplified
Normal
Normal
Amplified
Normal
Amplified
Any
Normal
Normal
Normal
Amplified

Any
Any

Any
Favorable
Unfavorable
Any

Any
Favorable
Unfavorable
Any

Any

Any

Any
Favorable
Any
Unfavorable
Any

Any
Any

Low
Low
Low
Low
High
Intermediate
High
Intermediate
High
High
Intermediate
High
High
Low
Intermediate
Intermediate
High

INSS, International Neuroblastoma Staging System.

25. Localized tumor not involving vital structures as defined by
the list of IDRFs and confined to one body compartment

2 Locoregional tumor with presence of one or more IDRFs

mo Distant metastatic disease (except stage MS)

Metastatic disease in children < 18 months with metastases
confined to skin, liver, and/or bone marrow (< 10%)

28. INRG Age
Stage (months)

Histologic
Category

Grade of Tumor 114
Differentiation MYCN Aberration _Ploidy

Pretreatment
Risk Group

11/02

GN maturing;
GNB intermixed

Very low

Any, except
GN maturing or
GNB intermixed

Very low

High

Any, except
GN maturing or
GNB intermixed

Low

Intermediate

GNB nodular;
neuroblastoma

Low

Differentiating

Poorly differentiated
or undifferentiated

Intermediate

High

<18

Hyperdiploid

Low

<12

Diploid

Intermediate

12 to<18

Diploid

Intermediate

<18

High

218

High

Very low

High

High

30. » Age < 2 yrs
+ Stage 1,2 ,4s
* Pathology Favourable
(Shimada)
* Ferritin <143 ng/ml
+ NSE <100
+ Urine
VMA/HVA <1
» N-myc single copy
+ DNA index > Al
+ 1p deletion Absent

Je Matthay KK. CA Cancer J Clin 1995

> 2 yrs
3,4
Unfavorable

> 143 ng/ml
< 143 ng/ml

>1
Amplified
|

Present

Favorable

71%
90-100%
90%

83%
79%

84%
70%
100%
90%

Unfavorable

38%
30-50%
23%

19%
10%

44%
5%
10%
10%

35. Carboplatin — Etoposide

Etoposide

Etoposide

Carboplatin — Cyclophosphamide — Doxorubicin
Cyclophosphamide — Etoposide

Etoposide

Etoposide

Carboplatin — Etoposide — Doxorubicin

Etoposide

Etoposide

36. 5

84
85
86

Cyclophosphamide — Etoposide
Etoposide

Etoposide

Carboplatin — Cyclophosphamide — Doxorubicin

Carboplatin — Etoposide
Etoposide
Etoposide

Carboplatin — Etoposide — Doxorubicin

37. Drug dosages

Carboplatin
Etoposide
Cyclophosphamide

Doxorubicin

560 mg/m? or 18 mg/kg iv over 1 hour

120 mg/m? or 4 mg/kg iv over 2 hours

1000 mg/m? or 33 mg/kg iv over 1 hour

Doxorubicin 30 mg/m? or 1 mg/kg iv
over 15-60 minutes

43. Role of Radiotherapy

51. Orbital metastases

Liver mets

Entire orbit

Entire liver need not be included, but
adequate margins must be taken (incl.
those for organ motion).

55. Intermediate risk

56. No Role