A 32-year-old man with HNPCC-positive disease underwent an extended right hemicolectomy for Stage III disease (12 nodes involved). He received three months of adjuvant 5-FU/leucovorin, but shortly thereafter experienced a CEA rise and PET/CT revealed three liver metastases involving segments III, IV and VI in addition to enlarged and FDG-avid porta hepatis lymph nodes. No additional sites of disease were identified. He was treated with six cycles of FOLFOX/bevacizumab. Considering the good response to systemic therapy, it was recommended he proceed to resection. He underwent left hepatectomy with wedge resection of the solitary lesion in segment VI and a complete porta hepatis lymphadenectomy. Final pathology showed four of eight resected lymph nodes positive and more than 80 percent of the liver lesions appearing necrotic and/or fibrosed. He reinitiated another six cycles of postoperative FOLFOX/bevacizumab.
Case Discussion:
DR CURLEY: A 32-year-old male underwent an extended right hemicolectomy for a transverse colon tumor. He was found to have more than 12 metastatic nodes and was treated with 5-FU/leucovorin for three months. FOLFOX was recommended, but he refused to receive oxaliplatin because the patient was a concert violinist, and he felt that any change in sensation would be problematic for him from a professional point of view.
We counsel patients about all of the things that, at least putatively, seem to reduce oxaliplatin-associated neurotoxicity. These things may include calcium/magnesium, and possibility vitamin supplements, although I haven’t been totally convinced. Once a patient reaches the ninth or tenth cycle of FOLFOX, most of them begin to experience some troublesome neuropathies, if they receive full-dose oxaliplatin. The degree of inconvenience depends on the individual. Some patients are still able to work full time and have no real issues. Others, such as a secretary or someone who works on a computer or types, will find it difficult to work. Patients who require fine manual dexterity at the workplace tell me that it really affects them adversely — they have a real problem with it. We ask people what kind of work they do, how much walking they do and if it is difficult to walk because of the neuropathy. We also ask them if it is difficult to use their fingers for fine dexterity. If we feel they may be strongly affected, we will watch them closely and will dose-reduce when they start developing any neuropathy.
Because of his young age,we recommended genetic testing, which revealed that he was the proband of a family with hereditary nonpolyposis colorectal cancer (HNPCC). We subsequently counseled multiple family members and found that one of his siblings had the same genetic profile. In fact, his sibling had several adenomatous polyps, some flap polyps in the right colon, and he subsequently decided to undergo a subtotal colectomy. So, if the patient is young when diagnosed or if a strong family history of colon cancer exists among first- or second-order family members, we look for genetic details and recommend genetic screening in those patients.
After three months of chemotherapy, his serum CEA was elevated despite normalization following his colon resection. Follow-up CT revealed three liver metastases involving segments III, IV and VI in addition to possible activity in the porta hepatis lymph nodes. The patient was counseled once again that despite his concerns with potential neurotoxicities, FOLFOX would be an appropriate regimen. Consequently, he was treated with six cycles of FOLFOX with bevacizumab, and the volume of his metastatic disease was reduced.
If patients are in good health, we treat them aggressively despite their age, by combining multimodality therapy, which includes major liver resections for metastatic disease. Because this patient had metastatic nodes in the porta hepatis, many would not have considered her a candidate for a resection 10 to 15 years ago and would have used palliative chemotherapy only.
Based on his good response, he underwent a left hepatectomy wedge resection of the solitary tumor in segment VI and a complete porta hepatis lymphadenectomy. Intraoperative ultrasound performed during the operation showed no additional hepatic lesions and exploration of the rest of the peritoneal cavity was unremarkable. His final pathology confirmed that he had metastatic disease in four of eight resected lymph nodes, with significant response both in the liver metastases and the lymph node metastases, and 80 percent of the lesion was necrotic or fibrotic.
He went on to receive an additional six cycles, or three months of FOLFOX and bevacizumab, and the dose of oxaliplatin was reduced after the tenth dose because he was starting to develop some neurotoxicity. He has been able to maintain his career as a professional violinist.
