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Intervention Protocol

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Retinoic acid post consolidation therapy for high-risk neuroblastoma

  1. Frank Peinemann1,*,
  2. Carmen Bartel2,
  3. Ulrich Grouven3,
  4. Frank Berthold4

Editorial Group: Cochrane Childhood Cancer Group

Published Online: 31 JUL 2013

DOI: 10.1002/14651858.CD010685


How to Cite

Peinemann F, Bartel C, Grouven U, Berthold F. Retinoic acid post consolidation therapy for high-risk neuroblastoma (Protocol). Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD010685. DOI: 10.1002/14651858.CD010685.

Author Information

  1. 1

    Children's Hospital, University of Cologne, Cologne, NW, Germany

  2. 2

    Cologne, Germany

  3. 3

    Hannover Medical School, Hannover, Germany

  4. 4

    Children's Hospital, University of Cologne, Pediatric Oncology and Hematology, Cologne, Germany

*Frank Peinemann, Children's Hospital, University of Cologne, Kerpener Str. 62, Cologne, NW, 50937, Germany. pubmedprjournal@gmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 31 JUL 2013

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This is not the most recent version of the article. View current version (29 JAN 2015)

 
Table 1. The International Neuroblastoma Risk Group consensus pretreatment classification schema

INRG stageAge (months)Histologic categoryGrade of tumour differentiationMYCN11q aberrationPloidyPretreatment risk group

CodeInterpretation

L1/L2Ganglioneuroma maturing; ganglioneuroblastoma intermixedAVery low

L1Any, except ganglioneuroma or ganglioneuroblastomaNot amplifiedBVery low

AmplifiedKHigh

L2< 18Any, except ganglioneuroma or ganglioneuroblastomaNot amplifiedNoDLow

YesGIntermediate

≥ 18Ganglioneuroblastoma nodular; neuroblastomaDifferentiatingNot amplifiedNoELow

YesHIntermediate

Poorly differentiated or undifferentiatedNot amplifiedHIntermediate

AmplifiedNHigh

M< 18Not amplifiedHyperdiploidFLow

< 12Not amplifiedDiploidIIntermediate

12 to < 18Not amplifiedDiploidJIntermediate

< 18AmplifiedOHigh

≥ 18PHigh

MS< 18Not amplifiedNoCVery low

YesQHigh

AmplifiedRHigh

 Reference: Cohn 2009
The International Neuroblastoma Risk Group consensus classification schema includes the criteria INRG stage, age, histologic category, grade of tumour differentiation, MYCN status, presence/absence of 11q aberrations, and tumour cell ploidy. Sixteen statistically and/or clinically different pretreatment groups of patients (lettered A through R) were identified using these criteria. The categories were designated as very low (A, B, C), low (D, E, F), intermediate (G, H, I, J), or high (K, N, O, P, Q, R) pretreatment risk subsets.
 
Table 2. The International Neuroblastoma Staging System

StageDefinition

1Localised tumour with complete gross excision, with or without microscopic residual disease; representative ipsilateral lymph nodes negative for tumour microscopically (nodes attached to and removed with the primary tumour may be positive).

2ALocalised tumour with incomplete gross excision; representative ipsilateral nonadherent lymph nodes negative for tumour microscopically.

2BLocalised tumour with or without complete gross excision, with ipsilateral nonadherent lymph nodes positive for tumour. Enlarged contralateral lymph nodes must be negative microscopically.

3Unresectable unilateral tumour infiltrating across the midline,(1) with or without regional lymph node involvement; or localised unilateral tumour with contralateral regional lymph node involvement; or midline tumour with bilateral extension by infiltration (unresectable) or by lymph node involvement.

4Any primary tumour with dissemination to distant lymph nodes, bone, bone marrow, liver, skin and/or other organs (except as defined for stage 4S).

4SLocalised primary tumour (as defined for stage 1, 2A or 2B), with dissemination limited to skin, liver, and/or bone marrow(2) (limited to infants less than 1 year of age).

 Reference: Brodeur 1993
Note: Multifocal primary tumours leg, bilateral adrenal primary tumours) should be staged according to the greatest extent of disease, as defined above, and followed by a subscript letter M e.g. 3M).
(1) The midline is defined as the vertebral column. Tumors originating on one side and crossing the midline must infiltrate to or beyond the opposite side of the vertebral column.
(2) Marrow involvement in stage 4S should be minimal, i.e., less than 10% of total nucleated cells identified as malignant on bone marrow biopsy or on marrow aspirate. More extensive marrow involvement would be considered to be stage 4. The (Meta-iodobenzylguanidine) MIBG scan (if performed) should be negative in the marrow.
 
Table 3. Response to treatment

ResponsePrimary tumourMetastatic sites

Complete responseNo tumourNo tumour; catecholamines normal.

Very good partial responseDecreased by 90% to 99%No tumour; catecholamines normal; residual 99Tc bone changes allowed.

Partial responseDecreased by more than 50%All measurable sites decreased by greater than 50%. Bones and bone marrow: number of positive bone sites decreased by greater than 50%; no more than 1 positive bone marrow site allowed.

Minimal responseNo new lesions; more than 50% reduction of any measurable lesion (primary or metastases) with less than 50% reduction in any other; less than 25% increase in any existing lesion.


No responseNo new lesions; less than 50% reduction but less than 25% increase in any existing lesion.


Progressive diseaseAny new lesion; increase of any measurable lesion by greater than 25%; previous negative marrow positive for tumour.

 Reference: Brodeur 1993
 
Table 4. Children's Oncology Group assignment to low, intermediate, and high risk group

INSS stageAgeMYCNINPC classificationDNA indexRisk group

10 to 21 yAnyAnyAnyLow

2A/2B< 365 dAnyAnyAnyLow

≥ 365 d to 21 yNonamplifiedAny-Low

≥ 365 d to 21 yAmplifiedFavourable-Low

≥ 365 d to 21 yAmplifiedUnfavourable-High

3< 365 dNonamplifiedAnyAnyIntermediate

< 365 dAmplifiedAnyAnyHigh

≥ 365 d to 21 yNonamplifiedFavourable-Intermediate

≥ 365 d to 21 yNonamplifiedUnfavourable-High

≥ 365 d to 21 yAmplifiedAny-High

4< 548 dNonamplifiedAnyAnyIntermediate

< 365 dAmplifiedAnyAnyHigh

≥ 548 d to 21 yAnyAny-High

4S< 365 dNonamplifiedFavourable> 1Low

< 365 dNonamplifiedAny= 1Intermediate

< 365 dNonamplifiedUnfavourableAnyIntermediate

< 365 dAmplifiedAnyAnyHigh

 Reference: NCI PDQ 2012
DNA index: favourable >1 (hyperdiploid) or <1 (hypodiploid); unfavourable =1 (diploid)
Abbreviations: d: days of age; y: years of age