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An educational tool to assist in the management of hepatic metastases in patients with colorectal cancer

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Case 16:

Discussant: MICHAEL CHOTI, MD

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Case Description:

A 41-year-old man initially presented with Stage IV colon cancer and underwent a palliative right hemicolectomy. Metastatic disease was confined to the liver, but notably occupied most of the right lobe, abutting the inferior vena cava, accompanied by some smaller lesions of undetermined significance in the left hemiliver. Prior to surgical referral, the patient completed 10 cycles of FOLFOX and bevacizumab, with a CEA response but limited radiologic response. He then received transarterial chemoembolization for two cycles. He now presents one year post initial diagnosis with isolated hepatic metastases, somewhat unchanged from baseline, and proceeded to surgical exploration. Eight bilobar metastases were found, including a large, dominant lesion in right liver lobe. An extended right hepatectomy was performed in addition to wedge resections of three left sided lesion, and a fourth was treated with RFA. Final pathology showed a microscopically positive margin and the patient elected not to complete any postoperative chemotherapy. Pulmonary recurrence was identified eight months post liver resection.

Case Discussion:

DR CHOTI: This is a 41-year-old man, a high school teacher and coach, who presented with Stage IV colon cancer (ie, metastatic disease at the time of presentation). He underwent a palliative laparoscopic right hemicolectomy and then was treated with FOLFOX and bevacizumab, which was stopped after 10 cycles because of neurotoxicity. He experienced a minimal radiologic response, but the CEA dropped from 344 to 76. Subsequently, he underwent two cycles of interarterial chemoembolization. After chemoembolization — a year since the diagnosis — the patient was referred to our multidisciplinary center to discuss how we would manage it at this point. The patient was not managed optimally — either initially or certainly after the chemotherapy.

Few data are available that show that transarterial chemoembolization (TACE) or standard chemoembolization therapy have any benefit for patients with colorectal metastases, so I would not recommend this therapy. The use of TACE therapy could potentially stress the liver. Colorectal metastases are typically not hypervascular, so we use TACE therapy for other forms of liver cancer that are vascular. But in this disease, it probably doesn’t do much. Indeed, it’s possible that TACE could stress or damage the liver, burning a bridge to other potential options, including further surgical therapy. The other problem is that it could delay therapy.

Another interarterial approach used selectively for some patients with unresectable colorectal metastases is interarterial yttrium-90 radioembolization, instead of chemoembolization. That is approved for metastatic colorectal cancer, but it wasn’t offered to this patient.

The optimal strategy would have been to discuss his case in a multidisciplinary setting that included a colorectal surgeon, a hepatic surgeon and a medical oncologist to develop the best treatment plan. In a patient that presents with Stage IV disease, we administer chemotherapy before colon surgery unless the colon tumor is obstructing or the patient needs emergency surgery. The details about the timing of this patient’s surgery are not clear, nor is it clear that the medical oncologist consulted with a surgical oncologist or liver surgeon before initiating chemotherapy to determine if the disease was resectable, convertible or borderline.

Intraoperative ultrasound showed a large tumor and adjacent tumors in the right hemiliver that were abutting the vena cava and involved most of the entire right lobe of the liver, compressing the structures on the left lobe of the liver. Additionally, two to four lesions were present on the left liver, making is difficult to determine if the disease was resectable or not. Ultimately, it was deemed resectable because the patient was young with relatively favorable tumor biology. Although he presented with Stage IV disease, he had been undergoing treatment with chemotherapy and chemoembolization, experienced a drop in his CEA, and did not experience rapid progression elsewhere.

The patient underwent a radical resection, including an extended right hepatectomy and removal of four lesions in the left liver. Three lesions were removed with wedge resections of the left liver, and one underwent radiofrequency ablation (RFA). All gross disease was resected and ablated. The final pathology showed viable tumor with a microscopically positive margin on one of the tumors. This patient was a good candidate for RFA because he had eight bilateral metastases. Although seven of the eight were resected, one lesion was in the deeper location and not amenable to resection — it was small and in a location not near a major structure.

RFA refers to the interstitial or intertumoral ablation of tumor, commonly using an electrical current to create a thermal ablation zone. Other methods of ablation include cryoablation, microwave ablation and other approaches. The most common ablation approach at this time is RFA.

RFA does not remove the tumor. The probe is typically placed in the desired zone using ultrasound guidance, and then a volume or sphere of thermal ablation destroys the area, which hopefully completely incorporates the tumor. It does not work well for larger tumors, and it is associated with a high local recurrence rate. RFA does not work as well in tumors that are close to large vascular structures, as in those that are further away. Risks are associated with its use in tumors that are located near a main bile duct or other structure adjacent to the liver, because burning those areas can cause damage to the vital structures either within the liver or adjacent to the liver. So it has to be used carefully and selectively so as not to cause damage, and it is not always effective. The goal of RFA should be complete destruction of the tumor, not palliation. It is the same as the goal of resection: complete negative margins. Using current technology, RFA is probably not quite as effective as resection, though it still has a benefit. We reserve RFA for tumors that are unresectable but are in location and size that are candidates for ablation.

The patient did not receive any chemotherapy after surgery. Because the patient had some residual neurotoxicity from prior chemotherapy, he was not a candidate for oxaliplatin therapy, and the medical oncology team opted not to administer FOLFIRI with or without bevacizumab. The patient elected not to receive 5-FU/leucovorin or capecitabine with or without bevacizumab. This patient was treated before the effects of K-ras status were known on treatment with cetuximab. It is not known if he would have received treatment with cetuximab if his K-ras status was known. However, the patient did not receive cetuximab.

Approximately eight months after liver surgery, pulmonary metastases were found.

 

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