Neuroblastoma Flashcards

1
Q

Name genes associated with familial neuroblastoma and germline mutations associated with NBL

A

Familial:

  • ALK
  • PHOX2B

Germline mutations associated with NBL:

  • NF-1
  • BWS/WT2
  • p53
  • Noonan
  • deletion 1p36 or 1q14
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2
Q

Somatic changes with NBL

A
  • whole chromosome gains vs segmental aberrations (whole better)
  • MYCN (> 10 copies)
  • ALK
  • 17q (60%)
  • 1p36 - associated with Myc-N
  • 11q23
  • 14q
  • Telomerase mutations (ATRX only in adolescents and TERT)
  • ARID1a/1b
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3
Q

Classic pathology finding in BM in NBL

A

Homer-Wright rosette

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4
Q

Myoclonic jerking and random eye movements with cerebellar ataxia
- name, treatment, and outcomes

A

OMA syndrome

  • treat with IVIG/steroids or plasmapharesis/ritux
  • good tumor outcomes but poor long-term neurodevelopmental outcomes.
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5
Q

What % of tumors are MIBG avid and what is another option?

A

90%
FDG-PET scan recommended
–> PET scan
-> Technicium-99 bone scan can be used at diagnosis but not response as it remains positive for healing bone

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6
Q

NBL vs other SRBCT

A
  • Homer-rosette
  • cohesive clumps of cells
  • S100, CD56 and PGP9.5 on immunostaining
  • CD99 negative - ewing’s is positive
  • CD45 neg - positive in lymphoma
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7
Q

Principles of Low risk NBL therapy

A

EFS/OS > 90%

  • surgery is mainstay and complete resection not mandatory
  • observation alone - COG study of < 6m old with localized adrenal tumors <3cm
  • chemo/rads for life-threatening symp or relapse
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8
Q

Principles of Int risk NBL therapy

A

EFS>85% oS>90%
Surgery - for biopsy
- delayed debulking but complete resection not needed

Chemo:

  • 2-8 cycles with duration based on getting >50% reduction
  • longer if unfav histology

rads only if emergent- ex. spinal cord compression

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9
Q

Principles of HR NBL therapy

A

Induction:

  • chemo 6 cycles
  • harvest PBSC after 2 cycles
  • surgery after 5 cycles

Consolidation
SCT: tandem
Ext. beam rads regardless of extent of resection (2160Gy)

Maintenance:
- Ch14.18 and isotretinoin

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10
Q

INRG definition of MS

A

Metastatic disease in children younger than 18 months with metastases confined to skin, liver, and/or bone marrow. The primary tumor can be INSS stage 1, 2, or 3

MYC-N non-amplified
11q negative

*if last 2 are positive then high-risk disease

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11
Q

What is the Curie score?

A

Score for assessing extent of MIBG avid disease.

Score > 2 is a negative prognostic factor for HR NBL (both upfront and in response to induction)

  • EFS of HR-NBL is 15% with Curie >2 vs 45% < 2. (COG A3973)
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12
Q

INSS vs INRG

A

INSS

  • is based on surgical staging,
  • 4S up to 12 m and primary tumor must be stage 1/2

INRGSS

  • uses image-defined risk factors
  • 4S up to 18m and primary can be stage 1/2/3
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13
Q

Factors involved in INRG risk group assignment

A
INRG stage
Age
Histology
Grade of differentiation
Myc-N status
11q
ploidy

divided into very low, low, intermediate and high risk groups

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14
Q

INRC response criteria

A

CR - MIBG negative, < 10mm of primary or LN

PR ->30% decrease in primary tumor, no new lesions, MIBG stable/improve, and 50% reduction in MIBG bone score
* note ANBL 0531 used 50-90% reduction in tumor volume as PR

Progressive disease: new lesion, growth of known lesion > 20%, increase in MIBG score by 1.25% or greater

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15
Q

Minimum diagnostic criteria for NBL

A

Unequivocal pathologic diagnosis

Combination of bone marrow aspirate/trephine biopsy containing unequivocal tumor cells AND elevated HVA/VMA

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16
Q

What is the EFS and OS of LR, IR or HR?

A

Low: EFS > 90% (> 95%), OS 97%

Intermediate: EFS > 85% (80-95%), OS 96%

High: EFS 40-50%, OS 40-50%

17
Q

what are adverse risk factors associated with NBL?

A
  • low VMA to HVA ratio
  • Myc-N amplification
  • unfavourable INPC
  • tumour segmental chromosome aberrations
  • infants with tumour diploid DNA content