Treatment of Colorectal Cancer Metastases to the Liver David U. Kim, MD University of Wisconsin School of Medicine and Public Health Department of Radiology

Case 61-year-old male with no significant PMH presented with 3 months of fatigue, dyspnea on exertion, and syncopal episodes. He was found to have severe iron deficiency anemia (Hgb/Hct = 4.5/19) and was referred to gastroenterology for endoscopy. Colonoscopy demonstrated a large, ulcerated cecal mass (arrows) with biopsy yielding well-to-moderately differentiated, invasive adenocarcinoma.

A contrast-enhanced staging CT demonstrates the cecal mass (arrow) as well as a single hypoenhancing hepatic lesion (arrow), suspicious for metastasis. Contrast-enhanced MRI re-demonstrates the hypoenhancing lesion in hepatic segment 8 (arrow) as well as numerous additional small lesions in the right hepatic lobe (arrows) and a single lesion in the left hepatic lobe (arrow), all of which are suspicious for metastases.

Case (cont.) The patient underwent laparoscopic assisted right hemicolectomy with plans for adjuvant chemotherapy and staged treatment of the hepatic metastases. Approximately 6 weeks following his surgery, the patient underwent percutaneous microwave ablation (MWA) of the solitary left hepatic lobe metastasis with plans for subsequent right hepatectomy to treat the multifocal right lobe metastases.

Sonographic images (A) demonstrate a small hypointense lesion in the left hepatic lobe (arrow). A microwave ablation probe is advanced into the lesion (B, arrow). Non-contrast CT confirms probe placement (C, arrow). The ablation is monitored with US; echogenic gas bubbles are produced (D, arrow). Post-ablation contrast-enhanced CT demonstrates the ablation zone with adequate margins (E, arrow). ABC DE

Question 1 If a hypothetical CRC liver metastasis is 1 cm in diameter, what is the desired diameter of the ablation zone (in one dimension)? A. 1.5 cm B. 2.0 cm C. 2.5 cm D. 3.0 cm

Answer If a hypothetical CRC liver metastasis is 1 cm in diameter, what is the target size of the ablation (in one dimension)? A. 1.5 cm B. 2.0 cm C. 2.5 cm D. 3.0 cm (1 cm lesion + 1 cm margin on either side) An ablative margin of at least 1 cm should be obtained to reduce the rate of local tumor progression in CRC metastasis. This is larger than the 5 mm ablative margin for hepatocellular carcinoma. 1

Case (cont.) Adjuvant chemotherapy was administered, and follow-up CT demonstrated no new sites of metastatic disease or evidence of local tumor progression at the site of MWA. Approximately 3 months following MWA, the patient underwent right portal vein embolization (RPVE) to promote hypertrophy of the left hepatic lobe in anticipation of right hepatectomy.

Question 2 Do the images demonstrate ipsilateral or contralateral approach to RPVE?

Answer Do the images demonstrate ipsilateral or contralateral approach to RPVE? –Ipsilateral approach The terms ipsilateral and contralateral refer to the site of portal venous access with respect to the targeted lobe. With RPVE, ipsilateral approach is through the right lobe and contralateral approach is through the left lobe, also called the future liver remnant (FLR). 2,3 Ipsilateral approach avoids the possibility of damaging the FLR; however, more acute angles may be more technically challenging to navigate, and there is a theoretic risk of tumor seeding. 2,3

AB DC Liver volumes calculated prior to (A, B) and following (C, D) RPVE demonstrate increase in left lobe volume following embolization (rectangle). Note n-BCA glue and Lipiodol in the right portal veins (C, arrow).

Question 3 What is the target standardized FLR (sFLR) in this patient who has received chemotherapy? A. 20% B. 25% C. 40% D. 50%

Answers What is the target standardized FLR (sFLR) in this patient who has received chemotherapy? A. 20% B. 25% C. 40% D. 50% sFLR = FLR / TELV (total estimated liver volume, which is derived from body surface area) 2,3 sFLR of >20-25% is considered adequate for patients with normal background liver. 2,3 A higher sFLR is required for patients with compensated cirrhosis (>40%) or those who have received chemotherapy (>30-40%). 2,3

Case (cont.) Hypertrophy of the left hepatic lobe resulted in an increase in the sFLR from 34.5% to 48.8%. Successful right hepatectomy was performed approximately 6 weeks following right portal vein embolization. Laparoscopic image demonstrates the MWA site (arrow) in the left hepatic lobe, segment 3.

Discussion Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related death in the US. 1,4 The liver is the most common site of CRC metastasis. Approximately 20-25% of CRC patients present with liver metastasis at time of diagnosis while an additional 30-50% develop liver metastases subsequently. About two-thirds of patients with CRC liver metastases will die of metastatic liver disease. The median survival for untreated CRC is 6-8 months. 1,4 Surgical resection offers the best survival benefit with 5-year overall survival rates near 50%. In contrast, the median survival with systemic chemotherapy alone is 22 months. Unfortunately, only 20-25% of patients with CRC liver metastases are candidates for surgery. 1,4

Discussion The role for interventional oncology in the treatment of CRC liver metastases is to convert unresectable disease to resectable, potentially cure disease for those who are poor surgical candidates, or provide palliation. 3 Patients may not be surgical candidates because of bilobar distribution of disease or inadequate hepatic reserve following hepatectomy. PVE is an established method of promoting hypertrophy of the FLR. 2,3 However, following PVE, some studies have shown growth of tumor in the non- embolized segments. Thermal ablation has been used to treat disease in the non-embolized segments. 3 Overall 5-year survival in patients with CRC liver metastases treated with RF ablation alone or PVE + hepatectomy is lower than surgery alone. However, patients requiring interventional oncology are typically those with greater disease burden or substantial co-morbidities precluding surgery. 3

References 1.Wells SA, Hinshaw JL, Lubner MG, et al. Liver ablation: best practice. Radiologic Clinic of North America 2015;53: Madoff DC, Gaba RC, Weber CN, et al. Portal venous interventions: state of the art. Radiology 2016;278: Mahnken AH, Pereira PL, de Baere T. Interventional oncologic approaches to liver metastases. Radiology 2013;266: Xing M, Kooby DA, El-Ray BF, et al. Locoregional therapies for metastatic colorectal carcinoma to the liver – an evidence-based review. Journal of Surgical Oncology 2014;110: