epidemiology and treatment of childhood adrenocortical tumors
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Epidemiology and Treatment of Childhood Adrenocortical Tumors. Bhaskar N. Rao, MD Carlos Rodriguez-Galindo, MD St Jude Children’s Research Hospital. St Jude Children’s Research Hospital Memphis, TN. Hospital de Clinicas Curitiba, Parana. Dr Raul C. Ribeiro Dr Bonald Figueiredo

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epidemiology and treatment of childhood adrenocortical tumors

Epidemiology and Treatment of Childhood Adrenocortical Tumors

Bhaskar N. Rao, MD

Carlos Rodriguez-Galindo, MD

St Jude Children’s Research Hospital

slide2

St Jude Children’s Research Hospital

Memphis, TN

Hospital de Clinicas

Curitiba, Parana

Dr Raul C. Ribeiro

Dr Bonald Figueiredo

Dr Gerry Zambetti

Dr Richard Kriwacki

incidence of childhood adrenocortical carcinoma in southern brazil
Incidence of childhood adrenocortical carcinoma in Southern Brazil

The incidence of childhood ACT is at least 10 times greater in southern Brazil than in other geographic regions of the world

  • Worldwide: 0.30.4 per million
  • Southern Brazil: 3.4 per million
constitutional abnormalities
Constitutional Abnormalities
  • Beckwith-Wiedemann syndrome
  • Hemihypertrophy
  • Genitourinary malformations
  • Multiple endocrine neoplasia I
  • Neurofibromatosis
  • Germline P53 Mutations (Li-Fraumeni, Li-Fraumeni-Like Syndrome)
li fraumeni syndrome
Li-Fraumeni Syndrome

Criteria (Li-Fraumeni, 1988)

  • A proband < 45 years of age with sarcoma
    • First-degree relative age < 45 years with any cancer
    • First- or second-degree relative in the same lineage with any cancer at age < 45 years or with sarcoma at any age
  • Multiple primary cancers
li fraumeni syndrome6
Li-Fraumeni Syndrome
  • Increased familial predisposition to diverse types of cancer
  • Associated with P53 mutations

In Li-Fraumeni families, childhood ACT accounts for 10% of all malignancies in children < 14 years of age

adrenocortical carcinoma biology
Adrenocortical CarcinomaBiology
  • Germline p53 mutations
    • U.S.50% of cases Exons 2-8 Li-Fraumeni syndrome
    • Brazil95% of cases Exon 10 No familial cancer Multiple cases in 15% families
clinical features in children and adolescents n 462
Clinical Features in children and adolescents (n=462)
  • Median age; 3 years
  • Fewer than 10% >15 years
  • Female/male ratio: 2.3:1
    • 0-9 years: 15:1
    • >10 years: 1:1
  • Functional: 90%

Ribeiro RC in Textbook of Uncommon Cancer, 2sd Ed. 611, 1999

slide9

Clinical Features

  • Virilization 80%
  • Cushing 8%
  • Mixed 30-40%
  • Feminization 2.0%
  • Conn 1.6%
  • Non-Functional 2-3%
j w 22675

J.W. #22675

18 mo boy with virilization

Labs: Mixed syndrome (virilization + hypercortisolism)

slide12

June 2005

August 2005

signs and symptoms 58 patients
Signs and Symptoms: 58 patients

Sandrini et al. J Clin End Metab 1997

diagnosis
Diagnosis
  • Determination of Hormonal Levels
    • Androgens and Corticosteroids
  • Imaging
    • CT
    • MRI
    • Bone scan
  • Pathology
pathology
Pathology

Adenoma

Carcinoma

  • Mitotic Index
  • Necrosis
  • Atypical Mitoses
  • Nuclear Grade

Bugg MF. Am J Clin Pathol 101:625, 1994

international adrenocortical tumor registry ipactr
International Adrenocortical Tumor Registry (IPACTR)
  • Established in 1990 as part of St Jude IOP:
    • St Jude + Clinics Hospital of Curitiba
  • Information-exchange website:
    • Strategy to improve knowledge and treatment
  • 200+ patients registered to date
arar0332

Group

Definition

Treatment

Group I

  • Small tumor

< 200 cc or < 100 g

  • Completely resected

Surgery alone

Group II

  • Large tumor

> 200 cc or > 100 g

  • Completely resected

Surgery

RPLN dissection

Group III

  • Residual tumor
  • Unresectable
  • Regional spread (liver, kidneys, RPLN)

Surgery

MIT/CDDP/ETO/DOX x 8

Surgery with RPLND

Group IV

  • Metastatic disease

Surgery

MIT/CDDP/ETO/DOX x 8

Surgery with RPLND

ARAR0332
prognosis
Prognosis
  • Disease Stage
    • Limited Stage Disease
      • Completely resected
        • Small tumors
        • Large Tumors
    • Advanced Stage Disease
      • Gross residual tumors
      • Metastatic
  • Histology
    • Adenoma
slide26

From fp0804.11

International Pediatric Adrenocortical Tumor Registry

slide27

From fp0804.11

International Pediatric Adrenocortical Tumor Registry

slide28

From fp0804.11

International Pediatric Adrenocortical Tumor Registry

treatment mitotane
TreatmentMitotane
  • Insecticide derivative
  • Inhibits corticoid biosynthesis and destroys adrenocortical cells
  • Low doses (< 3 g/day):
    • Suppresses secretion of adrenal steroids
  • High doses (> 3 g/day):
    • Adrenolytic effect
treatment mitotane32
TreatmentMitotane
  • Response Rates: 20-30%
  • Serum levels correlate with response:
    • Plateau 8 weeks
    • Optimal tumor responses
      • Therapeutic levels for prolonged periods
      • Levels > 14 mcg/mL
arar0332 research questions
ARAR0332Research Questions
  • Pilot Study 1:
    • Benefit of RPLN dissection for large tumors
  • Pilot Study 2:
    • Response rate to MIT/CDDP/ETO in Group III
    • Response rate to + DOX in Group IV
  • Pilot Study 3:
    • PK of MIT
    • PK-guided administration of MIT
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