A 63-year-old woman status post left hemicolectomy and adjuvant FOLFOX for Stage IIIB cancer of the left colon diagnosed 26 months previously. Routine surveillance reveals CEA elevation from a nadir of 1.4 to a current value of 12. A PET/CT scan reveals a solitary 7-cm lesion occupying the central liver (within segments IV, V and VIII). No extrahepatic disease is seen. She completed four cycles of preoperative FOLFIRI with bevacizumab — bevacizumab was withheld during the last cycle — and experienced a partial response. An R0 central hepatectomy was performed, followed by delivery of eight additional cycles of FOLFIRI and bevacizumab — bevacizumab was withheld during the first cycle. The patient had no evidence of disease at the last follow-up.
Case Discussion:
DR CHOTI: This was a 63-year-old woman, an attorney, who underwent hemicolectomy for T3/N0/M0 cancer of her left colon. Her disease was originally classified as T3/N0/M0 Stage IIIB colon cancer with two of 16 nodes involved. After surgery, she received postoperative FOLFOX for six months. Overall, treatment was well tolerated. Although she experienced some neurotoxicity during treatment, her neurotoxicity completely resolved, and now she is followed by routine surveillance. Postoperatively, her baseline CEA of 1.4 slowly began to rise to 12, prompting further analysis, including a CT scan that initially revealed a solitary metastasis in the liver 26 months after hemicolectomy. A PET/CT scan was performed to further stage the extent of recurrent disease, and confirmed a single site in the liver with no other metastatic sites on any other imaging studies. The contrast-enhanced CT scan revealed a single hypodense lesion in the central liver, primarily in the anterior sector of the right hemiliver, extending somewhat into the left hemiliver. The metastasis was potentially resectable based on the location of the disease. Although this patient had a slightly elevated BMI of 24 and was treated with chemotherapy more than two years prior, the liver looked healthy on the scan, and we felt she would have a sufficient remnant liver.
Resectable disease can be defined as a tumor that is located in a part of the liver that can be completed resected while leaving sufficient liver behind. The factors that contribute to resectability include the extent of disease, the extent of tumor involvement in the liver, the tumor locations relative to the main hepatic branches, the main portal pedicles and the hepatic venous drainage. We base the decision about whether a tumor is resectable by which branches need to be divided or taken out to remove the tumor. The other concern is whether sufficient residual liver will remain if a large part of the liver must be removed. Will there be adequate inflow to the remaining liver — adequate hepatic artery flow, portal vein flow and bile duct flow? Is there adequate venous drainage in the proposed remnant liver? Is there adequate volume in the remnant liver, and how healthy is the proposed remnant liver? Is it a healthy piece of liver or is it a damaged liver? For example, in a patient with cirrhosis or hepatitis, the liver is unhealthy, and we cannot remove much of the liver at all. In contrast, in someone with a healthy liver with good inflow and outflow, we can remove up to 80 percent of the liver volume. The remaining 20 percent will regenerate nicely. However, in a patient who is a bit obese, the patient may have obesity-related damage to the liver referred to as steatosis. In that situation, the liver is a little less healthy. Also, the liver can be stressed after treatment with a fair amount of chemotherapy.
There are four categories of resectability: straightforward resectable disease, resectable disease with some nuances, unresectable but potentially convertible with chemotherapy and unresectable and unlikely to convert. At times, the optimal approach is not obvious. We can conduct volumetrics to determine whether the remnant liver will be of sufficient volume by using a formula to calculate the residual liver volume on CT scan. Another option would be to perform a procedure called portal vein embolization (PVE), in which we embolize the vein to the right half of the liver causing the right half of the liver to shrink slightly and causing the left part — the part that will remain — to grow and regenerate in advance of the surgery. So PVE could be used in patients who don’t need chemotherapy to shrink their tumors but need the liver to be prepared for resection.
The question in this patient was whether or not this resection would be straightforward or require special preparation, based on the location of the tumor. Her tumor was resectable, but because of its location in the middle of the liver, it would be a little tricky, requiring the removal of the middle third of the liver only — saving the left lateral third and the right posterior third, or removing the right two-thirds of the liver, leaving only the left third behind. One could also remove the left two-thirds of the liver, leaving the right third behind. Because the center third of the liver must be sacrificed in this case, PVE was not required. In fact, because some of the right liver would remain, embolization of the right portal vein was not necessary. We planned to perform a central hepatectomy, taking the middle third of liver out.
The choice of administering chemotherapy to a patient with resectable disease before and/or after surgery is controversial. This is in contrast to a patient with a tumor that was initially unresectable but convertible, in which the choice is clearly to use chemotherapy to convert the disease. Is there any role for chemotherapy in a resectable case? The answer seems to be yes. The EORTC trial showed that patients who underwent liver resection and received chemotherapy before and after surgery did better than those who were naïve to chemotherapy. However, no data exist that describe the benefits of using chemotherapy for patients who have already been treated with FOLFOX chemotherapy. Do you treat with FOLFIRI or administer FOLFOX again a year and a half later? It is controversial. The other issue is whether the patient should receive chemotherapy prior to surgery or after resection.
Because this patient had already undergone treatment with FOLFOX, she was not chemotherapy-naïve. She was in good health otherwise, so our feeling was to treat with four cycles of chemotherapy prior to surgery with an alternate regimen of FOLFIRI along with bevacizumab, rather than FOLFOX. The tumor diminished in size about 50 percent.
The concern is that bevacizumab, a VEGF receptor inhibitor, may have some impact on surgical complications, specifically related to either bleeding or to wound healing problems. Indeed, some data on patients undergoing colon surgery show that it can cause wound complications. The other factor is that the half-life of bevacizumab is approximately 21 days. Liver surgery is often elective, so it you wait six to eight weeks after the last dose of bevacizumab, the complication risk is negligible. Theoretically, treatment with bevacizumab can be reinitiated six to eight weeks after surgery. We typically hold the last dose of bevacizumab on the last of the four cycles in this case, then operate four to six weeks after the last chemotherapy and six to eight weeks after the last dose of bevacizumab.
For this patient, the last dose of bevacizumab was held and she underwent a central hepatectomy approximately four to six weeks after the final dose of FOLFIRI. Segments V, VIII, and IV were resected, and the resection was margin-negative. Postoperatively, she received an additional eight cycles of FOLFIRI and bevacizumab, but the dose of bevacizumab was held for the first cycle until about six weeks after surgery. She is without disease at this time.
