Treatment of Liveronly Metastatic Colorectal Cancer

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Treatment of Liver-only Metastatic Colorectal
Cancer

• Benjamin Tan, MD
• Washington University
• School of Medicine

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Case

• 34 year old man with BRBPR 11/2006
• 3 cm mass 11 cm from the anal verge
• Bx moderately differentiated AdenoCa
• PET rectal and liver
• ? What to do next?

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Liver-Only Metastatic CRC

• Curable or potentially curable?
• The Role of PET
• Neoadjuvant Rx vs adjuvant Rx?
• Pros and Cons
• What is the best regimen?
• Duration of therapy?
• What to do when CR occurs?
• Toxicities
• What to do with the primary cancer?

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Curable?
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(No Transcript)
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PET-Staged CRC
100 patients
5-yr OS 58.6 5-yr DFS 34.8
Fernandez, Strasberg, Ann Surg 2004, 240 438.
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PET-Staged CRC
Fernandez, Strasberg, Ann Surg 2004, 240 438.
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PET

• Approximately 20 extrahepatic disease detected
  by PET not detected by CT
• Clinical Risk Score for recurrence
• Node positive primary
• Disease-free interval lt 12 months
• Tumor size gt 5 cm
• Tumor Number gt 1
• CEA gt 200 ng/ml

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PET-Staged
Taylor, astract 240, ASCO GI 2007
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Therapy Beyond Surgery?

• 60-70 recurrence after surgery
• 1/3 with liver only recurrence
• 2/3 with distant recurrence /- liver recurrence
• No published Phase III studies on systemic
  therapy vs surgery alone except for HAI /- 5FU
• In Stage III and high risk patients, adjuvant
  chemotherapy standard

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HAI CI 5FU
Kemeny, J Clin Oncol 20 1499, 2002
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Pros and Cons

• Neoadjuvant Rx
• No delay in chemotherapy
• In vivo response assessment to Rx
• Possible downsizing of mets to improve
  resectablility
• Possible progression excluding chance for surgery
  
• What if CR occurs?

• Adjuvant Rx
• No delay in potentially curative surgery
• Treat microscopic residual disease
• No chemotherapy induced liver changes
• Delay in using very effective chemotherapy
  (including bevacizumab)
• No prognostication based on response

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Neoadjuvant Chemotherapy
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EORTC 40983

• Surgery

364 patients Potentially resectable Liver-only
met CRC
FOLFOX 4 x 6 Surgery FOLFOX 4 x 6
Gruenberger, ASCO 2006, a3500
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Regimens
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Targeted agents
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Duration of Tx

• Neoadjuvant therapy until resectable
• Adjuvant therapy
• How long to give?
• Same chemotherapy?
• With Biologic Agents?

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CR, What to do?

• Frequency 3-4 with chemoRx, 7-10 with chemo
  bevacizumab or cetuximab
• Does it mean cure?

Nordlinger, ASCO 2006, a 3501
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CR, is it Cure?

• 66 liver lesions disappeared on imaging in 38
  patients
• Mean initial diameter 2 cm, all less than 4.5 cm
• 20/66 (24) lesions in 9 pts with macroscopic dz
  on exploration
• 15/66 with no macroscopic dz
• 12/15 with viable tumor
• 3/15 with necrosis
• 31/66 with no visible tumor- no resection
• 23/31 with in-situ recurrence after 1 year

55 out of 66 (83)lesions Which disappeared Not
cured
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Rene Adam, ASCO 2006
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Hepatic Toxicities
peliosis
Sinusoidal vasodilatation
Hemorrhagic centrolobular necrosis
Nodular regenerative hyperplasia
Aloia, T. et al. J Clin Oncol 244983-4990 2006
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Hepatic Toxicities

• 51 sinusoidal dilatation/peliosis in 87 pts
  (Rubbia-Brandt, 2004)
• More severe changes assd with intra-op rbc
  transfusion needs
• Apparent higher post-op complication rates
• Higher with gt 6 cycles of chemo (24.5 vs 13.3)
• No difference in length of stay
• VOD, steatohepatitis also seen

Aloia, T. et al. J Clin Oncol 244983-4990 2006
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What to do with the Primary?

• To resect first or not to resect?
• Bleeding?
• Obstruction/perforation?
• Symptomatic?
• Rectal primary---adding Rad Onc to the discussion
  table
• Shift in willingness of surgeons to wait?

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Hepatic CRC Metastases

• Ongoing debates at multiple levels of care
• Timing of surgery
• Adjuvant and neoadjuvant therapy
• Best regimen to use
• How to incorporate biologics
• What to do with the primary tumor
• What to do with toxicities
• EORTC will answer if perioperative chemo vs
  surgery superior
• FOLFOX-cetuximab in peotentially resectable
  liver-only metastatic CRC at Washington
  University

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Thank You!