Colorectal neuroendocrine tumors

The number of patients currently analyzed in our department only allows limited insight into the degree of vascularity that can be expected in different types of tumors. Based on our preliminary data, highest T/N ratios were observed in patients with neuroendocrine tumors, followed by HCC, breast cancer and pancreatic carcinoma (Fig. 8.7). Acceptably high T/N ratios were also observed in patients with colorectal cancer and choroid carcinoma. 

Jakobs et al. [35] reported results on 39 treated patients (17 women, 22 men) that included colorectal cancer, metastatic breast cancer, hepatocellular carcinoma, neuroendocrine tumors, and a mixed group composed of metastatic pancreatic cancer, carcinoma of unknown primary, cholangiocellular carcinoma, thymus carcinoma, malignant melanoma, and choroid melanoma. In this mixed tumor group, two patients were lost for follow-up immediately after treatment. Two patients died before first follow-up 3 months after SIRT (one patient with choroid melanoma and one with carcinoma of unknown primary). However, at the first followup 3-4 months after SIRT, five of six patients presented with stable disease or partial response. The same applied for two of three patients at the followup at 5-6 months. Stable disease was noted in two of three patients at 10-11 months after SIRT. The median time to progression was 8 months (range 3-11 months), although two patients were lost and two died before first follow-up and were therefore not included in this analysis. The median survival was 2.2 months. 

SST receptors have been identilied in vitro on the membrane of a variety of tumor cells, especially in neuroendocrine tumors, tumors of the nervous system, lymphomas, breast cancers, prostate cancers, gastric cancers, and so on (116,117). In addition, some human tumors (such as colorectal cancers) that exhibit no detectable SST receptor still have a high receptor density in vascular systems surrounding the tumor tissues (119). 

A response to chemoembolization can be expected in liver tumors, such as HCC, metastases from colorectal tumors, metastases from neuroendocrine tumors, metastases from ocular melanoma, and gastrointestinal sarcomas (Gates et al. 1999 VoGL et al. 2000, 2003 Zangos et al. 2001 Kress et al. 2003 Roche et al. 2003). Other tumor types showed only a little response after chemoembolization. In every patient the advantages of treatment should be balanced against possible risks. 

In the USA, SIRT was approved for the treatment of unresectable primary hepatic malignancies and metastases from colorectal cancer together with intrahepatic artery chemotherapy (IHAC) using floxuridine (FUDR). Nevertheless, worldwide SIRT may be used in patients with hepatic malignancies originating from various primaries, such as neuroendocrine tumors, breast, colorectal, and bronchial cancer, where the disease appears to be limited to the liver and other treatment options are no longer available. 

Treatment concepts for liver metastases are determined by the biology of tbe disease and, in the case of the disease being confined to the liver, by the number and topographic location of the metastases. Colorectal liver metastases are the most frequent indication for the use of regional treatment concepts for the liver. Liver metastases from other primary tumors, such as the breast, neuroendocrine tumors (carcinoids), ocular melanoma, renal cell cancer, and sarcoma, have also been removed by treatment approaches confined to the liver with curative intent. 

Weitman et al. showed by Northern blot analysis and immunoassays that the folate receptor (type-a) has a very restricted normal tissue distribution (4). Highly elevated receptor expression was only found in the choroid plexus and malignant tissues (4). Garin-Chesa et al. showed by immunohistochemi-cal staining that 52 of 56 ovarian tumor samples displayed highly elevated folate receptor (type-a) expression (5). Receptor overexpression was also found in 10 of 11 endometrial, 6 of 27 colorectal, 11 of 53 breast, 6 of 18 lung, 9 of 18 renal cell, 4 of 5 brain metastases, and 3 of 21 neuroendocrine carcinomas (5). 

These findings are in line with the literature, which reports high hepatic arterial perfusion in liver metastases of neuroendocrine and adrenal tumors [3]. Similarly, high vascularity has been described for HCC [48]. Metastases from colorectal cancer are known to initially show a moderate arterial blood supply. With growth of the metastases, the supply... 

Another area worthy of future investigation is the treatment of non-colorectal, non-neuroendocrine cancers metastatic to the liver. Often referred to as mixed neoplasia, these refer to patients with liver-dominant metastatic disease to the liver from various primaries (breast, melanoma, pancreas, and lung). Although several reports have been described, controlled phase II studies using time-to-progression, tumor response, or progression-free-survival would be clinically relevant given the dearth of options for some of these patients [51-54]. 

Haddad FF, Chapman WC, Wright JK, et al (1998) Clinical experience with cryosurgery for advanced hepatobiliary tumors. J Surg Res 75 104-108 Henn AR, Levine EA, McNulty W, et al (2003) Percutaneous radiofrequency ablation of hepatic metastases for symptomatic relief of neuroendocrine syndromes. AJR Am J Roentgenol 181 1005-1010 Hughes KS, Simon R, Songhorabodi S, et al (1986) Resection of the liver for colorectal carcinoma metastases a multi-institutional study of patterns of recurrence. Surgery 100 278-284... 

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