Nonseminomatous Germ Cell Tumors: Brain Metastasis at presentation

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Nonseminomatous Germ Cell Tumors Brain
Metastasis at presentation

• Grand Rounds
• April 16, 2004

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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

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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

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Case

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

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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

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Risk Factors

• Cryptoorchidism
• Atrophic testes
• Contralateral cancer
• Trauma NOT a risk factor

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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)

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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

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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

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Serum Markers in NSGCTs
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TNM Staging

• Stage I
• Confined to the testes
• Stage II
• Confined to retroperitoneum
• Stage III
• supradiaphrgmatic

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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

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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

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Serum Markers
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PFS for NSGCTs

• 3 yr PFS
• Good 90
• Intermed 78
• Poor 45
• JCO 1997

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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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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

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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
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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
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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

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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
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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
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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
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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
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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
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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
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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
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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
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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

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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
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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
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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
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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

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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