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

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Case 13:

Discussant: ALAN VENOOK, MD

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Case Description:

A 40-year-old man presented postoperatively with an elevated CEA level after resection of K-ras wild-type primary tumor by a local surgeon, ahead of imaging or CEA evaluation. A postoperative PET/CT scan revealed a central solitary metastasis in the right/caudate liver lobe. He completed four cycles of FOLFIRI and cetuximab on-study for required tumor shrinkage. Subsequently, the patient underwent portal vein embolization (PVE) for left lobe hypertrophy followed by surgery. After resection of the metastasis, FOLFIRI was resumed for eight cycles without cetuximab at the patient’s request, due to the severe acne response to preoperative cetuximab.

Case Discussion:

This was a 40-year-old man who initially presented with a transient bleed from K-ras wild-type primary tumor located in the cecum and was treated with resection, ahead of imaging or CEA evaluation, by a local surgeon. The patient now presented postoperatively with an elevated CEA level and a central solitary metastasis in right liver lobe. If this patient had presented to me initially, I would have initially staged the liver disease in the operating room to ensure the metastasis was truly isolated or I would not have performed the primary resection at all because he had one episode of bleeding.

He was enrolled into a clinical trial and treated with four cycles of FOLFIRI and cetuximab. His tumor shrank, and we resected the metastatic disease. Because he presented immediately after surgery and because we contemplated performing another surgery soon, we did not use bevacizumab.

The other complicating factor for this gentleman was that the tumor was in the right lobe of the liver — in the caudate lobe — and we were afraid we didn’t have enough left lobe of the liver. So we had to perform a PVE to get the left lobe to hypertrophy over three to four weeks after the procedure. The PVE was successful and the patient underwent hepatic resection.

After hepatic resection, he was treated with eight additional cycles of FOLFIRI — he did not like the cetuximab because he developed severe acne.
He also did not want to receive bevacizumab because he was concerned about the potential side effects.

It is now about a year and a half later, and he is free of disease. He never received FOLFOX.

Patients should be evaluated thoroughly up front before they are rushed to surgery. We frequently see patients who have been mismanaged. This patient initially underwent resection two days after he was evaluated — that’s a sense of urgency that I don’t think is appropriate. His CEA level was in the 30s, and that certainly should have raised a concern that more was going on than met the eye. The patient asked his first surgeon if he should have a CT scan and the surgeon said he didn’t need one. We’ll assume that this was a surgeon who maybe isn’t as familiar with the literature as he or she should be.

Because the patient had a largely asymptomatic primary tumor that had bled once and had a normal hemoglobin level, I would have argued that neoadjuvant therapy would have been a better idea than surgery. Considering the complexity of the lesion’s location in the liver, I’m not sure we could have performed the surgical procedures simultaneously anyway. The other problem was that the patient never saw a medical oncologist after resection of his primary tumor.

Oxaliplatin, irinotecan and, certainly, 5-FU are associated with hepatic toxicities. Irinotecan/FOLFIRI may cause a little more steatohepatitis. FOLFOX seems to cause a somewhat different, less common lesion in terms of hepatic toxicity. 5-FU certainly causes fatty liver by itself.

The general belief is that this is a cumulative toxicity. We definitely see the occasional patient who has severe idiosyncratic hepatic disease from the start. However, our rule of thumb is that if we believe the tumor is resectable — and we are using chemotherapy to verify favorable tumor biology — we’ll use chemotherapy to keep the tumor under control or to shrink the tumor a bit, but we only administer four cycles. By administering only four cycles, the risk of morbidity at the time of surgery is greatly diminished. The literature suggests that treating with a vast amount of chemotherapy exposes patients to substantial risk, and this risk may be lessened if you minimize the exposure.

In the colorectal cancer setting, FOLFOX is generally used over the near equivalent, FOLFIRI. There may be a little less hepatic toxicity with FOLFOX, but as we fully intend to use four cycles preoperatively, FOLFIRI is sometimes a better choice.

If the patient experiences hepatic toxicity ahead of resection, you’re stuck because you must wait. It’s difficult to detect such toxicity before the surgeon is in the operating room. The dilemma is that you may figure it out when the surgeon is the middle of surgery. So that’s why we minimize the chemotherapy. I would say that only once or twice has my surgeon ever commented that severe toxicity was encountered after four doses of chemotherapy.



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