Colorectal Cancer Liver Metastasis

7/22/2019 Colorectal Cancer Liver Metastasis

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The Tower of Babel of livermetastases from colorectal cancer:

Are we ready for one language?Critical Reviews in Oncology/Hematology


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Case

54 year old male with Stage IV (T2N1cM1b) rectal cancers/p chemoradiation followed by low anterior resection.Preoperatively he had an anal canal metastasis thatclinically completely resolved after his chemoradiation.

During LAR, liver and lung nodules were found. F/U CTshowed 6 mm RLL nodule. On MRI, 2 superficial livermasses (2 cm x 3 cm) are noted and c/w metastasis withpatent hepatic veins and right anterior and posteriorportal vein thrombosis. Lung nodule remained unchanged

but hepatic metasteses decreased in size and wereresected after completing 5 rounds of FOLFOX w/Bevacizumab.


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Primary CRC mass 2.5 x 1.5 cm CEA: 1.5 Metastasis : 1 regional LN, 2 liver metastases V and VII 2.0 x 3.0 cm, RLL nodule

6.0 mm KRAS mutation is negative


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Liver CancerMost common liver cancer is metastasis usually from the GI

tractColorectal

Cancer

Heraldsdottir et al. 2013


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Resectability Past: defined as how much liver lost Today: defined as how much liver left 5 factor scoring system (Fong et al. 1999)

1. node-positive primary2. disease free interval < 12 months3. more than one lesion4. size >5 cm5. carcinoembryonic antigen (CEA) >200 ng/ml

5-year survival rate >1 RF: 14% with a median of 22 months 1 RF: 44% and a median of 51 months 0 RF: 60%


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5ySR Stratified by Clinical Risk Score for CRCLMResections

Tomlinson et al. 2007

Low: 0-2High: 3-5


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CRCLM Patient Groups Readily resectable

low risk of relapse 10% of the patients few liver metastases (70% liver invasion or all three

hepatic veins involved) major liver insufficiency

extrahepatic unresectable disease unfit for surgery Ultimately resectable

tumor shrinkage with chemotherapy Unresectable

metastases are never likely to be resectable


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CRCLM Patient Groups Potentially resectable

heterogeneous class of patients high risk of relapse Technically difficult

metastases are close to all hepatic veins or to both portal branches Biologically challenging

Indicators of short progression-free survival (PFS) synchronous presentation multiple metastases large (>5 cm) single lesion high CEA

Other factors age comorbities performance status


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EORTC 40983 Phase 3 Trial Study European Organization for Research and

Treatment of Cancer 40983 trial Randomized 364 patients with resectable liver

metastases to two treatment arms Surgery alone 6 months of perioperative chemotherapy with 5-

fluorouracil and oxaliplatin

administered 3 months before and 3 months after surgery maximum of four liver metastases not previously treated with oxaliplatin

Primary aim of the study was 3-year PFS

Nordlinger et al. 2013


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Chemotherapy Regimens FOLFOX: Oxaliplatin plus FU and leucovorin

5-fluorouracil: pyrimidine analog antimetabolite thatinterferes with DNA and RNA synthesi

Leucovorin: supplies the necessary cofactor blocked bymethotrexate and restores folate for DNA/RNAsynthesis, stabilizes the binding of 5-dUMP and thymidylatesynthetase, enhancing the activity of fluorouracil

FOLFIRI: Irinotecan plus FU and leucovorin Irinotecan: bind reversibly to topoisomerase I-DNA complex

XELOX: Oxaliplatin plus capecitabine Oxaliplatin: platinum compound binds to DNA forming cross-

links which inhibit DNA replication and transcription Capecitabine: undergoes hydrolysis in the liver and tissues to

form fluorouracil


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80% completed the preoperative part of the treatment 52% completed the postoperative six cycles 43% completed full perioperative treatment

Toxicity observed during the preoperative chemotherapy wasconsistent with the previous experiences with FOLFOX Postoperative complications observed in the experimental arm (25%

versus 16%; P = 0.04) No impact on postoperative death rate (1% in both arms)

Bittoni et al. 2013

Perioperative chemotherapy for resectable colorectalcancer liver metastases results


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Overall Survival Follow-up of 8.5 years, and 221 reported deaths (61% of all

randomized patients) No statistically significant difference in OS between the

patients in the chemotherapy arm and the patients whounderwent only surgery

5-year OS rate 51.2% in the chemotherapy arm 47.8% in the surgery arm 52.4% versus 48.3% in all eligible patients

Lack of a benefit in OS for chemotherapy influence of subsequent treatment lines increase in death unrelated to cancer in the chemotherapy arm


14/18Ercolani et al. 2011

Survival curves of peri-operative and post-operativechemotherapy strategies since intention-to-treat

Average (mos) 1 yr 3 yr 5 yr

Peri-op 54.56 .91 .62 .38

Post-op 52.62 .88 .59 .36

*Based on model probability parameters from MEDLINE and EMBASE search and excludes bev and cet


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WT, KRAS wild-type

Bevacizumab: Anti-VEGFCetuximab: Anti-EGFR


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Portal vein embolization


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ReferencesBittoni, A., Scartozzi, M., Giampieri, R., Faloppi, L., Maccaroni, E., Del Prete, M., et al. (2013). The tower

of babel of liver metastases from colorectal cancer: Are we ready for one language? Critical Reviewsin oncology/hematology, 85 (3), 332-341. doi:10.1016/j.critrevonc.2012.08.005;10.1016/j.critrevonc.2012.08.005

Ercolani, G., Cucchetti, A., Cescon, M., Peri, E., Brandi, G., Del Gaudio, M., et al. (2011). Effectivenessand cost-effectiveness of peri-operative versus post-operative chemotherapy for resectablecolorectal liver metastases. European Journal of Cancer (Oxford, England : 1990), 47 (15), 2291-2298. doi:10.1016/j.ejca.2011.05.014; 10.1016/j.ejca.2011.05.014

Fong, Y., Fortner, J., Sun, R. L., Brennan, M. F., & Blumgart, L. H. (1999). Clinical score for predictingrecurrence after hepatic resection for metastatic colorectal cancer: Analysis of 1001 consecutivecases. Annals of Surgery, 230 (3), 309-18; discussion 318-21.

Haraldsdottir, S., Wu, C., Bloomston, M., & Goldberg, R. M. (2013). What is the optimal neo-adjuvanttreatment for liver metastasis? Therapeutic Advances in Medical Oncology, 5 (4), 221-234.doi:10.1177/1758834013485111; 10.1177/1758834013485111

Nordlinger, B., Sorbye, H., Glimelius, B., Poston, G. J., Schlag, P. M., Rougier, P., et al. (2008).Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable livermetastases from colorectal cancer (EORTC intergroup trial 40983): A randomised controlledtrial. Lancet, 371 (9617), 1007-1016. doi:10.1016/S0140-6736(08)60455-9; 10.1016/S0140-6736(08)60455-9

Nordlinger, B., Sorbye, H., Glimelius, B., Poston, G. J., Schlag, P. M., Rougier, P., et al. (2013).

Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable livermetastases from colorectal cancer (EORTC 40983): Long-term results of a randomised, controlled,phase 3 trial. The Lancet Oncology, 14 (12), 1208-1215. doi:10.1016/S1470-2045(13)70447-9;10.1016/S1470-2045(13)70447-9

Soreide, K., Berg, M., Skudal, B. S., & Nedreboe, B. S. (2011). Advances in the understanding andtreatment of colorectal cancer. Discovery Medicine, 12 (66), 393-404.

Tomlinson, J. S., Jarnagin, W. R., DeMatteo, R. P., Fong, Y., Kornprat, P., Gonen, M., et al. (2007). Actual10-year survival after resection of colorectal liver metastases defines cure. Journal of ClinicalOncology : Official Journal of the American Society of Clinical Oncology, 25 (29), 4575-4580.doi:10.1200/JCO.2007.11.0833

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Colorectal Cancer Liver Metastasis