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Nonseminomatous Germ Cell Tumors: Brain Metastasis at presentation

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42 yr old Hispanic male presents with: Dyspnea, chest pain, ... Abx for epididymitis or orchitis. U/S testis. Radical orchiectomy. Staging workup. CBC ... – PowerPoint PPT presentation

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Title: Nonseminomatous Germ Cell Tumors: Brain Metastasis at presentation


1
Nonseminomatous Germ Cell Tumors Brain
Metastasis at presentation
  • Grand Rounds
  • April 16, 2004

2
Case Presentation
  • 42 yr old Hispanic male presents with
  • Dyspnea, chest pain, diaphoresis, fatigue
  • 20 pound weight loss
  • Hemetemesis after 2-3 ASA/d for weeks

3
Case
  • On admit, Hb was 3.8
  • Colonoscopy, EGD, RBC scan negative
  • PE found 4cm testicular mass (per wife it had
    been there a year)
  • CXR

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Case
  • Had a R orchiectomy cont bleeds
  • Transferred to BJC
  • Mesenteric angio () for SMA bleed
  • Duodenal mass found
  • Path from testes
  • Teratoma with choriocarcinoma

7
Case
  • AFP lt5.0
  • b-hCG 277, 236
  • UA 3.7
  • LDH 611
  • CT head

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12
Germ Cell Tumors
  • Most common between 15-35 yrs
  • 8000 cases per year
  • Usually presents in testes
  • Less often mediastinum, RP, etc
  • 30-50x more common in whites
  • Amplification of short arm of chromo 12 is seen
    in almost all cases

13
Risk Factors
  • Cryptoorchidism
  • Atrophic testes
  • Contralateral cancer
  • Trauma NOT a risk factor

14
Classification
  • Seminoma
  • Negative for AFP and b-hCG
  • More common in older age group
  • Non-seminoma
  • Embryonal (hemor and necrosis)
  • Yolk sac (AFP)
  • Choriocarcinoma (cyto/synctio)
  • Teratomas (dont metastasize)

15
Presentation
  • Painless swollen testicle
  • Lump, heavy sensation
  • Pain in 10 pts
  • Metastasis in 10-15 pts
  • 2 develop brain mets after chemo
  • Only 2-3 of patients have brain mets at
    presentation

16
Workup of testicular mass
  • Abx for epididymitis or orchitis
  • U/S testis
  • Radical orchiectomy
  • Staging workup
  • CBC
  • AFP, bhCG, LDH
  • CXR
  • CT C/A/P
  • CT or MRI head if neuro deficits

17
Serum Markers in NSGCTs
18
TNM Staging
  • Stage I
  • Confined to the testes
  • Stage II
  • Confined to retroperitoneum
  • Stage III
  • supradiaphrgmatic

19
International Consensus Criteria for Risk - NSGCT
  • International collaboration (NA, Austrailia and
    Europe)
  • 5200 pts with met NSGCTs
  • Risk groups defined by
  • b-hCG half life 30 hrs
  • AFP 5-7 days
  • LDH

20
International Consensus Criteria for Risk - NSGCT
  • Good Risk
  • Gonadal or RP primary
  • S1 markers
  • No non-pulmonary mets
  • Intermediate Risk
  • Gonadal or RP primary
  • S2 markers
  • No non-pulmonary mets
  • Poor Risk
  • Mediastinal primary
  • Or S3 markers
  • Or liver, brain or bone mets

21
Serum Markers
22
PFS for NSGCTs
  • 3 yr PFS
  • Good 90
  • Intermed 78
  • Poor 45
  • JCO 1997

23
Chemotherapy Evolution
  • Pre cisplatin cure rates were 10-20 from
    disseminated disease
  • 40 of dead pts had brain mets
  • Since PVB chemo in 1974, cure rates are 70-80
    and brain mets developing is 2
  • BEP has less neurotoxicity and more effective and
    is now SOC

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25
Brain mets at Diagnosis
  • 2-3 of NSGCTs
  • Poor prognosis
  • Mean survival of 2-3 months
  • No randomized trials
  • Those who present with mets are more
    chemosensitive

26
Management of brain mets - Turkey
  • 1990-1996 in Turkey
  • 167 pts with met NSGCT
  • 11 had brain mets (18-41 yr old)
  • 8 solitary and 3 multiple
  • 6 chemo, 1 CRT, 4 S/CRT
  • 1011 had symptoms
  • BEP or cis/VCR/MTX/B/Actin-D.CTX,VP/(POMB-ACE) IT
    MTX protocols

Mahalati et al BJU 1999
27
Management of brain mets
  • All pts with brain mets had bulky thoracic
    disease
  • Incidence of brain mets in pts with lung disease
    was 32

Mahalati et al BJU 1999
28
Management of brain mets
  • Of the 11, 5 pts had brain mets at presentation
  • All with solitary mets
  • OS 45 alive
  • Mean f/u 21 mo (3-47 mo)
  • 25 who relapsed in brain are NED 3,6mo after
    salvage chemo
  • Mahalati et al BJU 1999

29
Management of brain mets - IU
  • Retrospective analysis of 24 pts with brain mets
    from NSGCTs
  • 1975-1988
  • All pts received cis-based chemo
  • All pts had seizures or deficits prior to
    confirmation of mets

Spears et al Int J Rad Onc Biol Phys 1992
30
Management of brain mets - IU
  • Group 1 10pt who presented with brain mets
  • They got WBI and PVB/- Adria or BEP
  • 310 lived 5 years with NED
  • 210 lived 5 years then died of dz

Spears et al Int J Rad Onc Biol Phys 1992
31
Management of brain mets - IU
  • Group I
  • Average age 25
  • 9 pts were stage III
  • 1 pt had stage I, had sx then disseminated
    disease
  • 3pts had one lesion 7 had multiple
  • All had lung disease 910 had RP

Spears et al Int J Rad Onc Biol Phys 1992
32
Management of brain mets IU Results
  • Group I
  • WBI started ASAP, usually during first cycle
    chemo
  • 3 pts alive at 5 years
  • 2 of the 3 had multiple mets
  • 6 pts died with PD /- brain dz
  • 1 died right away
  • Median survival for group 56 mo

Spears et al Int J Rad Onc Biol Phys 1992
33
Management of brain mets - IU
  • Group II
  • 4 pts
  • Average age 28 yrs
  • 1 pt with Stage II, 3 with Stage III
  • All treated with PVB /- Adria
  • All 4 had initial CR then relapse in brain only

Spears et al Int J Rad Onc Biol Phys 1992
34
Management of brain mets IU Results
  • Group II
  • 34 alive NED at 81-174 months
  • 23 had solitary met (sx, XRT, chemo)
  • 13 had multiple and had no sx and survived 13
    years
  • 13 solitary met sx/XRT/chemo and died 4 months
    after treatment with carcinomatous meningitis

Spears et al Int J Rad Onc Biol Phys 1992
35
Management of brain mets - IU
  • Group III
  • 10 pts
  • Average age 27 years
  • 5 had extragonadal disease (4 RP)
  • 5 pts had stage III
  • Nine got PVB /- Adria
  • 1 got BEP
  • All had PD and brain mets

Spears et al Int J Rad Onc Biol Phys 1992
36
Management of brain mets IU Results
  • Group III
  • No pt was free of systemic disease at any time
  • Median time to brain mets was 6 months (2-27
    months)
  • 40 had good palliation
  • No pt in this group survived
  • Median survival 3 months after XRT

Spears et al Int J Rad Onc Biol Phys 1992
37
Conclusions of IU
  • Patients with brain mets at presentation or
    relapse in the brain only (grps I and II) should
    be treated with curative intent
  • Group I OS 50
  • If CR to chemo, 60 OS
  • All long term survivors were treated with 40-50Gy
  • Image brain only if symptoms

38
Rustin et al 1986
  • 9 pts 7 with brain mets at diagnosis
  • Median OS 32 months (3-51 mo)
  • Had non-standard 6 drug regimen and IT MTX
  • None got WBI or surgery

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Management of NSGCTs with high b-hCG
  • Retrospective look at 41 patients at Indiana
    University 1976-96
  • b-hCG gt 50,000
  • Purpose was to see how quickly b-hCG fell and
    determine outcomes
  • Median age 23 (15-63)
  • Median b-hCG 189,500 (59,600-1.6million)
  • 71 had values gt100,000
  • Median F/U was 54 months

Zon et al JCO 1998
41
Management of NSGCTs with high b-hCG - Results
  • 54 (2241) NED after chemo
  • 20 (8) NED after salvage
  • Only 2 of 41 pts had a normal hCG level at the
    start of the 4th cycle
  • 31 pts had an abn level 1 month later, but 48 of
    these are NED with no further treatment
  • Their median b-hCG at cycle 4 40 (15-517)
  • Their median b-hCG at 1 month 24 (2-78)

Zon et al JCO 1998
42
Outcomes for pts who normalized their marker
  • When No. NED NED
  • cont chemo sx
  • Before 4th cycle 2 2
  • Within 1 month 8 5 2 1
  • gt1 month chemo 16 15 0 1

Zon et al JCO 1998
43
Pts with high hCG
  • Of 15 pts who NEVER normalized their b-hCG .
  • 12 received salvage chemo
  • 4 (33) of them are currently NED
  • 1 of them is alive w/disease at 3yr
  • 7 are dead of disease

44
Our patient
  • Still on surgical floor with ileus/SBO
  • Plan for BEP x 4 with WBI
  • Serial b-hCG, AFP
  • Monthly CXR and q3m chest CT
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