A 48-year-old female with acute abdominal pain was found to have a pelvic abscess secondary to a perforated sigmoid cancer associated with extensive hepatic metastases. Bilobar liver lesions ranged in size from one to five centimeters and demonstrated involvement of almost every segment. Emergent abscess drainage and resection of the sigmoid tumor was performed. Postoperatively, she was enrolled on the UK neoadjuvant COIN trial and was randomly assigned to receive FOLFOX and cetuximab. After a dramatic response to treatment, she underwent partial left hepatectomy, extended right hepatectomy and wedge excisions in each remnant lobe, followed by three additional months of postoperative FOLFOX alone. Approximately one year after hepatic resection, she experienced a liver only recurrence, treated successfully with percutaneous radiofrequency ablation (RFA).
Case Discussion:
DR PRIMROSE: This was a 48-year-old woman who presented to the hospital with acute abdominal pain in June 2006. Immediate CT showed a pelvic abscess, a perforated sigmoid cancer and extremely extensive liver metastases in most segments of the liver.
To deal with her sigmoid cancer, a Hartman’s procedure was performed to remove the diseased bowel, drain the abscess, perform a colostomy and close over the rectum. She recovered well, and was entered into the UK neoadjuvant COIN trial, an open-label trial of oxaliplatin and a fluoropyrimidine with or without weekly cetuximab. The patient was randomly assigned to FOLFOX and cetuximab. In 2006, no data existed about the effects of K-ras mutation on cetuximab treatment outcomes. Although the patient’s K-ras status was unknown at the time, she had a dramatic response to chemotherapy. As a result, despite the extremely disseminated nature of her disease, the patient underwent a left hepatectomy with some wedge excisions, an extended right hepatectomy with some wedge excisions, and she made a completely unremarkable postoperative recovery.
Approximately one year later, she developed an additional metastasis in the liver remnant that was treated by percutaneous RFA. According to the patient’s most recent scan, she remains disease free. The use of RFA is controversial in colorectal liver metastasis — in hepatoma, the evidence base for its use is much clearer. For patients with colorectal liver metastasis, I do not feel RFA should be used if excisional surgery is feasible and safe. For instance, we use RFA in some elderly patients who are not eligible for open resection, and we sometimes use it in patients with recurrent disease after a resection, because we know that re-resections tend to be difficult to perform technically.
The lesion certainly was resectable by a further operation. It was peripherally situated and would have been no major technical problem to remove surgically, but resection would have been a pretty drastic intervention for a patient who may not have a good outlook in terms of her disease, and hence the decision for RFA. By contrast, if she developed a recurrence at the RFA site, we would certainly re-resect the disease. In this case, RFA seems to have been successful. No signs of recurrence were present at the ablation site, and the patient does not have any other disease at distal sites. So the decision was possibly justified.
Postoperatively, she was no longer eligible to receive cetuximab on the COIN trial. My personal argument with the COIN investigators is that it would have been appropriate to administer to the patient the same chemotherapy as she received preoperatively, but the trial protocol didn’t allow it, so she was just treated with FOLFOX for three months.
Neither cetuximab nor bevacizumab are reimbursed by the UK National Health Service, so the patient would have had to pay for the bevacizumab, if she had wanted it. I think it is expensive and unless a patient is privately insured, it’s difficult for them to afford it. For that reason, it would not have been offered. The alternative to being in the clinical trial would be FOLFOX alone, which is the current standard. Continued activity toward reimbursement of cetuximab costs for patients who have K-ras wild-type tumors and bevacizumab for all patients is still in progress. I’m fairly confident that bevacizumab will not become reimbursable here, because of the cost effectiveness ratios.
