2. NEUROBLASTOMA
Enigmatic malignant neoplasm.
Third most common malignancy in
children.
Most common cancer diagnosed in infants.
Median age of diagnosis is 2 years.
Has highest spontaneous remission rate.
Usually by progression to mature
ganglioneuroma.
3. TUMOURS ARISING FROM
SYMPATHETIC GANGLIA
GANGLIONEUROMA
GANGLIONEUROBLASTOMA
NEUROBLASTOMA
17. MIBG SCAN
Meta Iodo Benzyl Guanidine
Concentrated by neurosecretory granules.
Used to image primary and metastatic sites
of neuroblastoma.
MIBG is labelled with I 131 or I 123
Sensitivity 85 – 90 %
Specificity 90 %
18. OTHER INVESTIGATIONS
Urinary HVA / VMA
Complete Blood Count
Serum Ferritin
Lactate Dehydrogenase
Liver Function Tests
19. STAGING
Evans and D ‘ Angio
Peadiatric Oncology Group
International Staging System
20. ISS
STAGE – 1
Localized tumour with
complete gross excision with
out microscopic residual
disease, LN negative
21. STAGE 2A
Localized tumour with incomplete gross
excision. Representative ipsilateral non
adherent LN negative
STAGE 2B
Localized tumour with or with out
complete gross excision, ipsilateral non
adherent LN positive
22. STAGE 3
Unresectable unilateral tumour
crossing the midline , localiszd
unilateral tumour with contralateral
LN involvement or midline tumour
with bilateral extention by infiltration
(unresectable ) or by LN involvement.
23. STAGE 4
Any primary tumour with dissemination to
distant lymph nodes, bone ,bone
marrow, liver , skin or other organs.
STAGE 4S
Localized primary tumour as defined for stage
1, 2A, 2B with dissemination limited to
skin, liver and or bone marrow. ( limited to
infants < 1 year of age.
24. PROGNOSTIC VARIABLES
PROGNOSTIC FACTOR FAVORABLE UNFAVOURABLE
AGE < 2 YRS > 2 YRS
STAGE 1 , 11, 1V S 111, 1V
PATHOLOGY FAVOURABLE UNFAVOURABLE
FERITTIN <143 ng/mL >143 ng/mL
NEURON SPECEFIC ENOLASE < 100 100
URINE VMA/HVA <1 1
N – myc SINGLE COPY AMPLIFIED
DNA INDEX > 1.1 1
1P DELETION NIL 1 P DELETION
25. INSS STAGE AGE MYCN SHIMADA DNA RISK GROUP
STATUS HISTOLOGY PLOIDY
1 0 – 21 YRS ANY ANY ANY LOW
2A/2B < 365 D ANY ANY ANY LOW
>365 D – 21 Y AMP FAV _ LOW
>365 D – 21 Y AMP UNFAV _ HIGH
3 < 365 D NON AMP ANY ANY INTERMEDIATE
< 365 D AMP ANY ANY HIGH
>365 D – 21 Y NON AMP FAV - INTERMEDIATE
>365 D – 21 Y NON AMP UNFAV - HIGH
>365 D – 21 Y AMP FAV - HIGH
26. STAGE AGE MYCN SHIMADA DNA RISK GROUP
STATUS HISTOLOGY PLOIDY
4 <365 D NON AMP ANY ANY INTERMEDIATE
<365 D AMP ANY ANY HIGH
>365 D – 21 Y ANY ANY - HIGH
4S < 365 D NON AMP FAV >1 LOW
< 365 D NON AMP ANY =1 INTERMEDIATE
< 365 D NON AMP UN FAV ANY INTERMEDIATE
< 365 D AMP ANY ANY HIGH
27. LOW RISK GROUP
Complete gross surgical excision
Adjuvant chemo and RT has not improved
the out come.
If surgical margins positive or microscopic
disease is left behind
Favourable biology - no adjuvant therapy
Unfavourable biology - 6- 12 weeks of
chemo
28. RATIONALE
POG TRIAL
8104 patients with stage 1
Treatment surgery only
Regardless of microscopic residual disease , 2
yr DFS is 84 %
29. RATIONALE
CCG TRIAL
3881 patients with stage 1 & 2
Stage 1
4 yr EFS 93 %
OS 99 %
Stage 2
4 yr EFS 81 %
OS 98 %
30. INDICATION OF CHEMO OR RT
RESPIRATORY DISTRESS
SPINAL CORD COMPRESSION
PROGRESSIVE DISEASE
RECURRENT DISEASE
31.
32.
33. INTERMEDIATE RISK
Followed by
Complete surgical adjuvant
resection chemotherapy
12 – 24 weeks
Unresectable
cases, 5 cycles of Second look surgery
chemo
34. Followed by second look surgery
Radiation therapy was given to gross viable
residual tumour on second look surgery.
Children age 12 – 24 months received 24 Gy in 1.5
Gy per fraction.
Older children received 30 Gy in 1.5 Gy per
fraction.
Target volume includes viable microscopic or
gross residual tumour determined by CT , MRI or
MIBG scan with 2 cm margins
35. POG TRIALS
EFS of completely resected tumours at
diagnosis - 85 %
EFS of incompletely resected tumours at
diagnosis - 70 %
Maximum safe surgical excision followed by
5 cycles of chemo
36. CHEMO SCHEDULE
POG 8742 they received cisplatin and
etoposide alternating with
cyclophosphamide and doxorubicin
POG 9244 received alternating cycles of
OPEC (vincristine , cisplatin, etoposide and
cyclophosphamide ) and OJEC (vincristine,
carboplatin , etoposide and
cyclophosphamide )
39. ROLE OF RADIATION THERAPY
CONTROVERSIAL
In older children with LN metastasis adjuvant
radiation to primary and regional LN has
improved DFS & OS.
RCT showed that DFS is 31 % in chemo arm
and 58 % in chemo RT arm.
De Bernadi et al trials failed to show benefit
from adjuvant RT.
40. DEFENITIVE INDICATIONS OF RT
Respiratory distress secondary to massive
hepatoslenomegaly.
4.5 Gy to liver in 3 daily fractions.
Spinal cord compression
< 3 yrs 9 Gy in 5 daily fractions.
Older children 21.6 Gy in 12 daily fractions.
41.
42.
43. HIGH RISK DISEASE
CURRENT TREATMENT APPROACHES
Intensive induction chemotherapy
Myelo ablative consolidation chemo with stem cell
rescue.
Targeted therapy for residual disease.
45. This was followed by second look surgery
Radiation therapy is given to patients with
persistent disease at primary or metastatic
sites.
21.6 Gy in 12 daily fractions to post induction
chemo, pre op tumour volume followed by
boost of 14.4 GY to gross residual volume to a
total dose of 36 Gy.
46. IORT
Single fraction 10 Gy to primary tumour bed
was associated with local control rate of 100
% where as IORT was unable to control any
patients with gross residual disease
47. MYELO ABLATIVE THERAPY
HIGH DOSE OF CARBOPLATIN , MELPHELAN AND ETOPOSIDE
TOTAL BODY IRRADIATION
3 DAILY FRACTIONS
3.33 GY PER FRACTION
PURGED AUTOLOGOUS MARROW IS INFUSED WITH GM - CSF
48. TARGETED THERAPY
INVESTIGATIONAL PHASE
I 131 – MIBG
REFRACTORY DISEASE
AS A PART OF MYELO ABLATIVE REGIMEN
MAX. MARROW NON ABLATIVE DOSE – 444 MBq Kg
MAX. PRACTICAL HIGH DOSE – 666 MBq/ Kg
US AND EUROPEAN STUDIES SHOWED 30-40 %
RESPONSE RATE
49. TARGETED IMMUNO THERAPY
HUMAN MOUSE CHIMERIC MONO CLONAL
ANTIBODY ch.14.8
TARGETS TUMOUR ASSOCIATED ANTIGEN.
ANTI GD 2 MURINE MONOCLONAL
ANTIBODY 3F8 AND GD 2a