A 60-year-old woman previously underwent a low anterior resection for T3N0 rectosigmoid cancer with no adjunctive systemic therapy. Three years post resection, she complained of early satiety and was found to have CT evidence of a large liver metastasis involving segments II, III, IV and VIII, encasing the left and middle hepatic veins and abutting the right hepatic vein. No extrahepatic disease was identified. She was treated with six cycles of FOLFOX/bevacizumab. Repeat CT demonstrated a decrease in tumor volume, but it still involved all three hepatic veins and, therefore, an additional six cycles of FOLFOX/bevacizumab were reinitiated. This yielded a response but with persistent vessel involvement. An additional six cycles were administered and restaging CT revealed that the right hepatic vein was now free of tumor. At this time, she underwent an extended left hepatectomy, yielding 3-mm negative margins. No further systemic therapy was administered and she currently maintains no evidence of disease at nine months postsurgery.
Case Discussion:
DR CURLEY: This was a 60-year-old woman who was diagnosed three years prior with T3N0 rectosigmoid cancer and underwent a low anterior resection without neoadjuvant chemoradiation therapy since the tumor was well above the peritoneal reflection, approximately 22 to 23 centimeters above the anal verge. On follow-up, CT revealed a large liver metastasis involving segments, II, III, IV and VIII, which encased the left and middle hepatic veins and abutted the right hepatic vein anteriorly over an approximately 2.5-centimeter length. The lesion was also causing some compression on the stomach, explaining her concerns over early satiety. Subsequently, CT of the chest in addition to a PET scan revealed no additional metastatic disease.
Based on the involvement of all three hepatic veins, the lesion was deemed unresectable at the time of presentation, and the patient went on to receive six cycles of FOLFOX with bevacizumab. She had had no chemotherapy as adjuvant therapy after resection of her primary tumor. She then underwent a repeat CT scan of the chest, abdomen and pelvis that demonstrated the tumor had reduced in volume slightly, but still involved all three hepatic veins. Therefore, she underwent an additional six cycles of the same chemotherapy, followed by restaging CT scans.
After a total of six months of chemotherapy, the hepatic vein was now free of tumor, although the left and middle hepatic veins were still clearly encased by this lesion. The patient underwent an extended left hepatectomy including “skeletonizing” approximately three centimeters of the anterior aspect of the “main line” hepatic vein trunk, right down to its entrance into the vena cava. The final pathology on the resected specimen confirmed metastatic adenocarcinoma consistent with a primary colonic tumor. The resection margins were both negative by three millimeters, again with the margin being close to where it had been taken off of the right hepatic vein. But because no additional margin could be attained, that was deemed adequate at that time.
Based on published data — which our experience mirrors closely — there’s roughly a 20-percent probability that neoadjuvant chemotherapy will convert an unresectable situation to resectable — so a one-in-five chance. The number has increased slightly over time. Initially, in René Adam’s experience, the chance of conversion was about 13 percent, and then it increased to 16 percent. More recent experience, including ours at MD Anderson, has been at about 20 percent. I tell patients that neoadjuvant treatment does not guarantee that they will become resectable. They all understand that resection provides them with their best chance for long-term survival, but we let them know that we may need to use more than one type of chemotherapy. We may use other local-regional therapies. We have occasionally used even focal radiation therapy, either an intensity modulated radiation therapy or a proton beam approach — if we have a single lesion that is problematic — in order to provide an adequate margin between critical vascular or biliary tract structures.
The patient did not receive adjuvant therapy. Despite the use of neoadjuvant treatment for a full six months, her final pathology revealed that the tumor had decreased by more than 25 to 30 percent in size, and much of the reason appeared to be that the lesion was fibrotic. About 90 percent of the tumor was either necrotic or fibrotic so we decided to simply follow her closely afterwards. At this point, she is approximately nine months postsurgery and she has no evidence of recurrent disease.
We almost always use adjuvant therapy, because we don’t administer all of the chemotherapy up front. We don’t treat to maximum response because chemotherapy can cause a number of hepatic toxicities. We will usually administer two to three months (ie, four to six cycles) of chemotherapy as neoadjuvant therapy followed by the resection, and then finish the remaining cycles of chemotherapy after surgery. We found that that is well tolerated. Most patients are able to receive their adjuvant chemotherapy six to eight weeks after the liver resection, and then they are closely followed from there.
