WILMS TUMOR GERM CELL TUMORs

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WILMS TUMORGERM CELL TUMORs

• Alan D. Friedman, M.D.

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Wilms Tumor

• Presentation
• mass/pain/hematuria/HTN
• Associations
• WAGR - WT1, 11p13
• Hemi/BW, IGF2, 11p15
• Inheritance
• 12 hereditary
• poor penetrance

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Wilms Tumor

• Pathology
• HE diagnostic
• FH vs. UH
• Nephrogenic rests - PLNR, ILNR
• Nephroblastomatosis - HPLN, DHPLN (rx)
• Hyperplastic are T2 bright vs sclerotic
• Staging
• I - renal/excised, 37, 90 RFS
• II - beyond capsule/excised- 20, 90 RFS
• III - resid. abd., 20, 85 RFS
• IV - Distant, 23, 66 RFS
• II -IV UH, 66 RFS

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Wilms Tumor

• Metastases
• nodes, liver, lung
• Work-up
• CT abd/chest, CXR, U/S with IVC Doppler,
• U/A, catechols
• Surgical approach
• Excisional Bx after examine other kidney
• Preserve parenchyma if bilat.
• if inoperable try again post 6 wks chemo

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Wilms Tumor

• NWTS I, II
• VCR/ActD better than VCR or ActD
• no XRT for St. I, II
• NWTS III
• St. I - VA, 10 wk 6m.
• St. II - VA VA, Adria for 15m, /- XRT
• St. III - Adria helps 1000 cGy 2000 cGy
• St. IV - trend towards CTX benefit
• UH - CTX helps

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Wilms Tumor

• NWTS IV
• St. I - VA VpiA, 6m.
• St. II - VA VpiA, 6m 15m.
• St. III - VA/Adr VpiA/Adr 6m 15m.
• St. IV, UH - CTX benefits UH.

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Wilms Tumor

• NWTS V (POG 9440)
• St. I - VpiA, 18 wks. Including 0-550 gm.
• St. II - VpiA, 18 wks
• St. III - VpiA/Adr, 1080 cGy, 6 mos
• St. IV, UH - VpiA/Adr, VP16, CTX/
  MESNA, 1080 cGy
• Pre-op - VpiA

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AREN0532 St I lt2 yr, lt550gm - Nephrectomy St I,
II no LOH - EE4A (VCR, ActD) St I, II, LOH 1p/16q
- DD4A (VCR, ActD, Adria) St III no LOH - DD4A,
abd XRT AREN0533 St IV (lung), no LOH, RER -
DD4A, abd XRT if local III St III/IV LOH or IV
not RER or non-lung - VAA, C/E, XRT AREN03B2 -
biology study
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• AREN0321
• FA St I-III, DA St I - DD4A (VCR/ActD/Adria)
• DA StII-III, DA/FA St IV, rhabdoid, CCSK IV - UH1
• (CTX/carbo/VP16, VCR/Adria/CTX)
• CCSK I-III - Reg I (CTX/VP16, VCR/Adria/CTX)
• DA St IV measurable disease or rhabdoid III-IV -
• (ironotecan/VCR window)
• Renal cell carcinoma - surgery only if complete
  resection

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Wilms Tumor

• Relapse (POG 9444)
• Low vs. High Risk
• Low - CTX/VP16/VpiA/Adr, surg., XRT
• High - CTX/VP16, CBCDA/VP16, surg., XRT,
  more chemo
• /- ABMT.

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Wilms Tumor
unilateral, resected 1o
Must enroll also on Biology Study, AREN03B2
St I, FH St II, FH St III, FH with no 1p16q LOH
St III, FH, LOH St IV, FH
UH rhabdoid CCSK
bilateral
inoperable 1o/IVC
AREN0532 no tx, EE4A,or DD4A
DD-4A or UH-1 per stage and grade consider early
RT resect week 5
St I/II FH EE-4A DD-4A if not respond St III/IV
FH DD-4A UH Reg. UH-1 operate week 5
AREN0533 DD4A or M
AREN0321 DD4A, I, UH-1
EE4A - Vcr, ActD (VA) DD4A - VA, Adria M -
VAAdria, CTX/Etop (CE) I - VadriaC, CE UH-1 -
adds Carbo to I
Renal Ca
AREN0321 surgery, indiv.
radiation therapy
relapse
(consider surgery of 1o)
St I/II FH - none St I/II UH, III - 1080 cGy
post-op St III diffuse anapl. 1980 cGy St IV -
add whole liver or lung lt18 mos try to avoid lung
RT
initial tx EE-4A
initial tx DD-4A, I, M, UH-1
NWTSG 4942 Stratum B (CyE, VAdrC)
Auto BMT
2nd relapse
2nd relapse
nephroblastomatosis

Cetuximab
DHPLN, consider EE-4A others follow MRI, bx if
grows
Relapse after no tx give DD4A perAREN0532)
Oxaloplatin/5FU
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Germ Cell Tumors

• 3 childhood cancer, peaks at 2 and 20 yrs
• Often midline only 5 Sertoli/granulosa/Leydig
  cell
• i(12p)/aneuploidy vs. del(6q or 1p) in infants

placenta
endodermal sinus tumor
yolk sac
sperm, ovum
chorion
choriocarcinoma
gastrula
embryo
seminoma, germinoma
embryonal carcinoma
teratoma
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Germ Cell Tumors

• Endodermal Sinus
• 44, High AFP, sacrum/testes of infants,
• ovary/testes in adolescents
• Choriocarcinoma
• 4, High ?HCG which can give signs/sympt.,
• is a gestational form
• Germinoma (Seminoma, Dysgerminoma)
• 15, ovary, undesc. testes, dysgenetic gonads,
• CNS, very XRT sensitive.

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Germ Cell Tumors

• Embryonal Carcinoma
• 10, testes, /- mild AFP
• Teratoma
• 24, 3 germ layers, malignant part often neural.
  65benign, 5 immature, 30 malignant.
  neonates-sacral
• serosal implants often mature/neural

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Germ Cell Tumors

• STAGING
• St I - Completely resected
• St II - Microscopic Residual
• St III- Lymph nodes or gross residual
• St IV - Distant mets (lung, liver, bone, brain)
• POOR PROGNOSTIC FACTORS
• Mediastinal primary, AFPgt10,000 - peds
• liver/bone/brain mets/high bHCG or LDH
• Slowly falling markers or rapid relapse

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Germ Cell Tumors

• Surgery
• gross resection if feasible
• ideal to remove all residual masses gt 1 cm, and
  be aware of growing teratoma syndrome
• testes - inguinal incision with high ligation of
  spermatic cord - remove even if burned out
  Retroperitoneal node biopsy if 2-4 cm on CT (to
  confirm St III) - debated, can follow
• sacral - include coccyx in resection
• ovary - surgery depends on exent/frozen remove
  omentum if nodules present

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Germ Cell Tumors

• Radiotherapy
• Seminoma very sensitive, 1st line in adults and
• CNS lesions, otherwise consider at relapse
• Chemotherapy
• VAC 30-50 RFS
• PEB
• Cisplatin 20 mg/M2/day x 5
• Etoposide 100 mg/M2/day x 5
• Bleomycin 15 Units/M2/day x 1 (qwk vs q3wk)

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Germ Cell Tumors

• POG 9048/49
• St. I/II test. lt 10 yr imm. teratoma had surgery
  alone 82 avoided chemo, 11/11 salvaged
• I/II ovarian I/II test gt 10 yr intermediate risk
• EFS 94
• St. III/IV gonadal I-IV other are high risk,
• EFS 85
• for high-risk, did 200 vs. 100 mg/M2 cisplatin,
• III/IV extragonadal 84vs 72, otorenal toxic

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Germ Cell Tumors

• CCG AGCT0132-LOW/INT RISK
• Stage I (testes or ovary), no therapy
• vascular invasion 48 recur, vs 22 if none
• II-IV gonadal, II extragonadal PEB x 3, second
• look, repeat PEB x 3 if positive.
• PEB over 3 days, bleo q3 weeks
• CCG AGCT01P1-HIGH RISK (closed)
• III/IV extragonadal
• PEB with increasing cytoxan
• 4 cycles, 2nd look, 2 more cycles if positive

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Germ Cell Tumors

• SALVAGE THERAPY
• VeIP (velban, ifosfamide, cisplatin)
• VIP (VP16, ifosfamide, cisplatin)
• salvage 25-30 of patients, but high risk
  patients (mediastinal, platinum refractory,
  progressive disease on VeIP, HCGgt1,000) do worse
• High dose chemotherapy with stem cell rescue
• Einhorn - carboplatin/etoposide x 2
• 63 DFS (116/184)
• Good risk 70, Inter. 48, Poor - 32
• carboplatin/etoposide/cytoxan 6/33 poor risk.
• CCG AGCT0521 paclitaxel, ifosfamide, carboplatin
• prior to HSC

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Germ Cell Tumors (non-CNS)
yolk sac tumor, choriocarcinoma, embryonal,
malignant teratoma
germinoma
testes 15
Stage I-IV testes lt15 yr Stage I-III ovarian
21 Stage I-II extragonadal 21
Stage III-IV extragonadal 21
St I - no tx II-IV PEB with weekly bleo
PEB x 3-4 or XRT if older
AGCT0132 St I gonad - no initial tx others - PEB
x 3 3 cycles if path. PR
PEB x 4 2 cycles if path. PR (high-risk study
closed)
Stage IV ovarian 21
St I-III lt1 - consider follow post-surgery, chemo
if progress
PEB x 4 2 cycles if path. PR
relapse post-chemotherapy
VeIP reinduction x1-2 (Velban, ifosfamide,
cisplatin) then tandem auto-BMT (etoposide,
carboplatin)
surgery remove 1o initially or at 2nd look remove
residual mets post.-chemo
(or AGCT0521- paclitaxel/ifosfamide/carbo x
2, then tandem auto-BMT)