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Applying Fong's CRS Liver Score in Patients with Colorectal Liver Metastases Treated by Cryotherapy
Original Article
Applying Fong’s CRS Liver Score in Patients with Colorectal Liver Metastases Treated by Cryotherapy Yi Yi Chen, Dayashan S. Perera, Tristan D. Yan, Lu Ming Schmidt and David L. Morris, Department of Surgery, The University of New South Wales, St George Hospital, Sydney, Australia.
BACKGROUND: A significant proportion of patients with liver metastases from colorectal cancer have unresectable disease and we have used cytoablative treatment such as cryotherapy in some of these patients. We retrospectively reviewed patients who underwent hepatic cryotherapy for colorectal metastases and studied the effect of the clinical risk score (CRS) reported by Fong et al, which can predict survival following liver resection. METHODS: A retrospective study was performed on patients who underwent hepatic cryotherapy between 1990 and 2000 in St George Hospital. There were 61 patients in this study and they were stratified into prognostic groups based on five preoperative CRS parameters: primary node positive, diseasefree interval from primary to metastases < 12 months, number of hepatic tumours > 1, largest hepatic tumour > 5 cm and carcinoembryonic antigen level > 200 ng/mL. The median follow-up was 25 months. RESULTS: The median survival was 26 months and the 3-year survival rate was 37%. Median survivals for patients with CRS scores 1 (13%), 2 (25%), 3 (53%), 4 (6%) and 5 (4%) were 37, 25, 30, 21 and 15 months, respectively (R2 = 0.81). CONCLUSION: The CRS score can be used to predict outcome of hepatic cryotherapy, but the difference in survival between CRS 2, 3 and 4 is modest. [Asian J Surg 2006;29(4):238–41] Key Words: clinical risk score, colorectal cancer, liver metastasis
Introduction Colorectal cancer is the most common cause of cancer death in nonsmokers in most of the Western world, with an estimated 130,000 new cases diagnosed in the United States in 2000.1 Liver metastasis is present in 5–25% of patients at the time of primary diagnosis and another 20% will develop it following resection of their primary tumour.2 Liver resection is possible in only 15–25% of patients and has been the only potentially curative therapy until
recently.3 However, ablative therapies including cryotherapy and radiofrequency ablation may now offer long-term survival to some patients with unresectable disease. Optimal selection of patients for invasive therapy in this group is clearly very important. Fong et al proposed a clinical risk scoring (CRS) system for patients who had liver resection for colorectal metastases based on a cohort of 1,001 patients over a 13-year period.4 Cryotherapy, like liver resection, is an ablative tool with the prospect of long-term survival and many of the same principles apply. The aim of our study was to apply
Address correspondence and reprint requests to Dr David L. Morris, Department of Surgery, The University of New South Wales, St George Hospital, Sydney, NSW 2217, Australia. E-mail: [email protected] ● Date of acceptance: 11 April 2005 © 2006 Elsevier. All rights reserved.
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ASIAN JOURNAL OF SURGERY VOL 29 • NO 4 • OCTOBER 2006
■ COLORECTAL LIVER METASTASES TREATED BY CRYOTHERAPY ■
the CRS to patients who were treated by cryotherapy alone in our unit. This is the first such report.
Methods Our prospective liver unit database has data on 2,077 patients with liver tumours. Of these, 1,270 had colorectal metastases, 397 were treated by resection and 321 by cryotherapy (with synchronous liver resection in 119). All of the cryotherapy was done through laparotomy. In patients who received this as their principal treatment, almost all had unresectable liver tumours (i.e. bilobar metastases, metastatic deposits close to major vessels or large number of metastases) and a minority of the patients were considered to be medically unfit for liver resection. In this study, we only included those with complete cryoablation, i.e. all of the liver metastases seen on intraoperative ultrasound were cryoablated. These patients were then retrospectively scored by Fong et al’s CRS,4 which were positive nodal status of the primary tumour, disease-free interval from primary diagnosis to detection of liver metastases
Table 1. Patient characteristics n (%) Dukes stage at presentation A B C D
0 (0) 10 (17) 22 (37) 28 (47)
Additional procedures Hepatic artery catheter Portal catheter Hepatic infusion pump Alcohol injection
58 (95) 1 (2) 5 (8) 3 (5)
< 12 months, multiple liver metastases, preoperative carcinoembryonic antigen (CEA) > 200 ng/mL and lesion diameter > 5 cm. Each criterion scored one point and the relationship to survival was studied by linear regression.
Results From 1990 to 2000, 61 patients received complete cryotherapy in our unit. Among them, 50 had bilobar diseases, 10 had distant metastases, seven had great vessel involvement and two were not fit for liver resection. There were 47 (77%) men and the mean age was 60 years (range, 31–74 years). The majority of these patients (95%) had simultaneous hepatic artery catheter insertion (Table 1) and 92% subsequently received regional chemotherapy (5-FU). The mean (median) diameter of liver metastases treated was 4 cm (3 cm) (range, 1–13 cm), and 19.6% of patients had tumours > 5 cm. The mean (median) number of liver metastases was 3.38 (3) (range, 1–9), and 19.6% of patients had one tumour. The mean (median) preoperative CEA level was 142 ng/mL (16.3 ng/mL) (range, 0.6–1,400 ng/mL). Fifty patients had lymph node involvement of the primary tumour, and the mean (median) interval between the primary diagnosis and liver cryotherapy was 11.3 months (5 months) (range, 0–108 months) (Table 2). Operative mortality rate was 1.6% (n = 1, myocardial infarction). The median survival was 26 months. The actual 1-, 2- and 3-year survival rates were 87% (53/61), 54% (33/61) and 36% (22/61), respectively. In the final calculation, only eight (13%) patients could not be classified according to the CRS. Among them, seven were due to unknown CEA level and one was due to unknown lymph node status. The median survivals in the five CRS groups are shown in Table 3 and varied from 37 months (CRS 1) to 15 months (CRS 5), with a R2 value of 0.81 (Figure).
Table 2. Fong et al’s4 prognostic factors in 61 patients who underwent hepatic cryotherapy for colorectal liver metastases
Nodal status of primary tumor — positive Disease-free interval from primary to detection of liver metastases < 12 mo Number of lesions > 1 Preoperative carcinoembryonic antigen > 200 ng/mL Size of largest tumour > 5 cm
ASIAN JOURNAL OF SURGERY VOL 29 • NO 4 • OCTOBER 2006
n (%)
3-yr survival, n (%)
50/60 (83) 39/61 (64) 49/61 (80.3) 10/54 (18.5) 12/61 (19.6)
19/50 (38) 13/39 (33) 17/49 (35) 2/10 (20) 2/12 (17)
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■ CHEN et al ■
Table 3. Clinical risk scores and survival Clinical risk score 0 1 2 3 4 5
Patients, n (%)
Median survival (mo)
Range (mo)
1-yr survival (%)
2-yr survival (%)
3-yr survival (%)
0 (0) 7/53 (13) 13/53 (25) 28/53 (53) 3/53 (6) 2/53 (4)
– 37 25 30 21 15
– 20–122 9–86 8–76 15–29 12–18
– 100 92 89 100 50
– 86 54 61 33 0
– 57 38 39 0 0
Series 1 Linear (series 1) y = –4.8x + 40 R2 = 0.8136
Median survival (mo)
40 35 30 25 20 15 10 5 0 0
2
4
6
CRS group Figure. Median survival versus clinical risk score (CRS).
Discussion This study is the first to apply Fong et al’s CRS4 to patients who underwent hepatic cryotherapy for unresectable colorectal liver metastases. Despite the small sample size, it is still one of the biggest studies in this area to date. It is clear that Fong et al’s CRS4 can be applied to cryotherapy. The 3-year survival in patients with CRS 1 reached 57%, while no one with CRS 5 survived more than 2 years. However, the difference between CRS groups 2, 3 and 4 is modest. While we used cryotherapy, it is likely that similar outcomes for Fong et al’s criteria would be seen with other ablation techniques such as radiofrequency ablation. Perhaps the most important issue with the use of the CRS is whether patients with high scores should be denied surgical treatment and offered adjuvant or palliative treatments. Cryotherapy has a median survival of 26–32 months.5–7 In our study, the median survivals of CRS 3, 4 and 5 were 30, 21 and 15 months, respectively, and there were only three and two patients with scores of 4 and 5, respectively. These results are not too different and are better than with regional8–10 or systemic chemotherapy.10–12 Even in the CRS 5 group, a 15-month
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median survival is at least as good as, and more likely to be better than, that seen with systemic chemotherapy (median survival, 10–16 months)10–12 and definitely better than with palliative treatment only (median survival, 5–9 months).12–16 Therefore, we do not believe in denying all patients with high CRS cytoablative treatments. One of the major advantages of using CRS is that all of the parameters are easily assessable. Only eight (13%) patients from among the 61 could not be classified according to the CRS in our study, mostly due to lack of preoperative CEA. This is not an issue with increased recognition of CEA’s importance both as a prognostic tool and as one of the most important measures of treatment outcome.3,17–19 The differences between prognostic factors for liver resection and cryotherapy are probably not great. We would argue that the lesion diameter is even more important in cryotherapy, and that the number of lesions is not as important.5 In this paper, only 17% of the patients with tumour > 5 cm in diameter had 3-year survival compared to 35% of the patients with multiple metastases.
Conclusion This report confirms that CRS has clinical relevance in the preoperative evaluation of patients with colorectal liver metastases and that CRS is a useful prognostic tool. Significant survival difference exists between CRS 1 and 5 but the difference between CRS 2, 3 and 4 is modest.
References 1. Greenlee RT, Murray T, Bolden S, et al. Cancer statistics, 2000. Cancer J Clin 2000;50:7–33. 2. Ballantyne GH, Qin J. Surgical treatment of liver metastases in patients with colorectal cancer. Cancer 1993;71:4252–66. 3. Fusai G, Davidson BR. Management of colorectal liver metastases. Colorectal Dis 2003;5:2–23.
ASIAN JOURNAL OF SURGERY VOL 29 • NO 4 • OCTOBER 2006
■ COLORECTAL LIVER METASTASES TREATED BY CRYOTHERAPY ■
4. Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 1999;230:309–21. 5. Seifert KJ, Joachim K, Morris DL. Prognostic factors after cryotherapy for hepatic metastases from colorectal cancer. Ann Surg 1998;228:201–8. 6. Weaver ML, Ashton JG, Zemel R. Treatment of colorectal liver metastases by cryotherapy. Semin Surg Oncol 1998;14:163–70. 7. Ruers T, Joosten J, Jager GJ, et al. Long term results of treating hepatic colorectal metastases with cryosurgery. Br J Surg 2001; 88:855–9. 8. Lorenz M, Muller HN. Randomized, multicenter trial of fluorouracil plus leucovorin administered either via hepatic arterial or intravenous infusion versus fluorodeoxyuridine administered via hepatic arterial infusion in patients with nonresectable liver metastases from colorectal carcinoma. J Clin Oncol 2000;18:243–54. 9. Rougier P, Laplanche A, Huguier M, et al. Hepatic arterial infusion of fluoxuridine in patients with liver metastases from colorectal carcinoma: long term results of a prospective randomised trial. J Clin Oncol 1992;10:1112–8. 10. Kemeny N, Daly J, Reichman B, et al. Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal cancer. A randomised trial. Ann Intern Med 1987; 107:459–65. 11. Martin JK Jr, O’Connel MJ, Wieand HS, et al. Intra-arterial fluoxuridine vs systemic fluorouracil for hepatic metastases from colorectal cancer. A randomized trial. Arch Surg 1990;125:1022–7.
ASIAN JOURNAL OF SURGERY VOL 29 • NO 4 • OCTOBER 2006
12. Scheithaucer W, Rosen H, Kornek GV, Sebesta C, et al. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ 1993;306:752–5. 13. Gorog D, Toth A, Weltner J. Prognosis of untreated liver metastasis from rectal cancer. Acta Chir Hung 1997;36:106–7. 14. Goslin R, Steele G Jr, Zamcheck N, et al. Factors influencing survival in patients with hepatic metastases from adenocarcinoma of the colon or rectum. Dis Colon Rectum 1982;25: 749–54. 15. Colorectal cancer collaborative group. Palliative chemotherapy for advanced colorectal cancer: systematic review and metaanalysis. BMJ 2000;321:531–5. 16. Blanke CD, Shultz J, Cox J, et al. A double blind placebocontrolled randomized phase III trial of 5-FU and leucovorin plus or minus trimetrexate, in previously untreated patient with advanced colorectal cancer. Ann Oncol 2002;13:87–91. 17. Grem JL, Steinberg SM, Chen AP, et al. The utility of monitoring CEA during systemic therapy for advanced colorectal cancer. Oncol Rep 1998;5:559–67. 18. Quentmeier A, Schlog P, Hobenbergerr P, et al. Assessment of serial CEA: determinations to monitor the prognosis and prognosis of metastatic liver disease treatment by regional chemotherapy. J Surg Oncol 1989;40:112–8. 19. Preketes AP, King J, Caplehorn JRM, et al. CEA reduction after cryotherapy for liver metastases from colon cancer predict survival. Aust N Z J Surg 1994;64:612–4.
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Applying Fong’s CRS Liver Score in Patients with Colorectal Liver Metastases Treated by Cryotherapy Yi Yi Chen, Dayashan S. Perera, Tristan D. Yan, Lu Ming Schmidt and David L. Morris, Department of Surgery, The University of New South Wales, St George Hospital, Sydney, Australia.
BACKGROUND: A significant proportion of patients with liver metastases from colorectal cancer have unresectable disease and we have used cytoablative treatment such as cryotherapy in some of these patients. We retrospectively reviewed patients who underwent hepatic cryotherapy for colorectal metastases and studied the effect of the clinical risk score (CRS) reported by Fong et al, which can predict survival following liver resection. METHODS: A retrospective study was performed on patients who underwent hepatic cryotherapy between 1990 and 2000 in St George Hospital. There were 61 patients in this study and they were stratified into prognostic groups based on five preoperative CRS parameters: primary node positive, diseasefree interval from primary to metastases < 12 months, number of hepatic tumours > 1, largest hepatic tumour > 5 cm and carcinoembryonic antigen level > 200 ng/mL. The median follow-up was 25 months. RESULTS: The median survival was 26 months and the 3-year survival rate was 37%. Median survivals for patients with CRS scores 1 (13%), 2 (25%), 3 (53%), 4 (6%) and 5 (4%) were 37, 25, 30, 21 and 15 months, respectively (R2 = 0.81). CONCLUSION: The CRS score can be used to predict outcome of hepatic cryotherapy, but the difference in survival between CRS 2, 3 and 4 is modest. [Asian J Surg 2006;29(4):238–41] Key Words: clinical risk score, colorectal cancer, liver metastasis
Introduction Colorectal cancer is the most common cause of cancer death in nonsmokers in most of the Western world, with an estimated 130,000 new cases diagnosed in the United States in 2000.1 Liver metastasis is present in 5–25% of patients at the time of primary diagnosis and another 20% will develop it following resection of their primary tumour.2 Liver resection is possible in only 15–25% of patients and has been the only potentially curative therapy until
recently.3 However, ablative therapies including cryotherapy and radiofrequency ablation may now offer long-term survival to some patients with unresectable disease. Optimal selection of patients for invasive therapy in this group is clearly very important. Fong et al proposed a clinical risk scoring (CRS) system for patients who had liver resection for colorectal metastases based on a cohort of 1,001 patients over a 13-year period.4 Cryotherapy, like liver resection, is an ablative tool with the prospect of long-term survival and many of the same principles apply. The aim of our study was to apply
Address correspondence and reprint requests to Dr David L. Morris, Department of Surgery, The University of New South Wales, St George Hospital, Sydney, NSW 2217, Australia. E-mail: [email protected] ● Date of acceptance: 11 April 2005 © 2006 Elsevier. All rights reserved.
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ASIAN JOURNAL OF SURGERY VOL 29 • NO 4 • OCTOBER 2006
■ COLORECTAL LIVER METASTASES TREATED BY CRYOTHERAPY ■
the CRS to patients who were treated by cryotherapy alone in our unit. This is the first such report.
Methods Our prospective liver unit database has data on 2,077 patients with liver tumours. Of these, 1,270 had colorectal metastases, 397 were treated by resection and 321 by cryotherapy (with synchronous liver resection in 119). All of the cryotherapy was done through laparotomy. In patients who received this as their principal treatment, almost all had unresectable liver tumours (i.e. bilobar metastases, metastatic deposits close to major vessels or large number of metastases) and a minority of the patients were considered to be medically unfit for liver resection. In this study, we only included those with complete cryoablation, i.e. all of the liver metastases seen on intraoperative ultrasound were cryoablated. These patients were then retrospectively scored by Fong et al’s CRS,4 which were positive nodal status of the primary tumour, disease-free interval from primary diagnosis to detection of liver metastases
Table 1. Patient characteristics n (%) Dukes stage at presentation A B C D
0 (0) 10 (17) 22 (37) 28 (47)
Additional procedures Hepatic artery catheter Portal catheter Hepatic infusion pump Alcohol injection
58 (95) 1 (2) 5 (8) 3 (5)
< 12 months, multiple liver metastases, preoperative carcinoembryonic antigen (CEA) > 200 ng/mL and lesion diameter > 5 cm. Each criterion scored one point and the relationship to survival was studied by linear regression.
Results From 1990 to 2000, 61 patients received complete cryotherapy in our unit. Among them, 50 had bilobar diseases, 10 had distant metastases, seven had great vessel involvement and two were not fit for liver resection. There were 47 (77%) men and the mean age was 60 years (range, 31–74 years). The majority of these patients (95%) had simultaneous hepatic artery catheter insertion (Table 1) and 92% subsequently received regional chemotherapy (5-FU). The mean (median) diameter of liver metastases treated was 4 cm (3 cm) (range, 1–13 cm), and 19.6% of patients had tumours > 5 cm. The mean (median) number of liver metastases was 3.38 (3) (range, 1–9), and 19.6% of patients had one tumour. The mean (median) preoperative CEA level was 142 ng/mL (16.3 ng/mL) (range, 0.6–1,400 ng/mL). Fifty patients had lymph node involvement of the primary tumour, and the mean (median) interval between the primary diagnosis and liver cryotherapy was 11.3 months (5 months) (range, 0–108 months) (Table 2). Operative mortality rate was 1.6% (n = 1, myocardial infarction). The median survival was 26 months. The actual 1-, 2- and 3-year survival rates were 87% (53/61), 54% (33/61) and 36% (22/61), respectively. In the final calculation, only eight (13%) patients could not be classified according to the CRS. Among them, seven were due to unknown CEA level and one was due to unknown lymph node status. The median survivals in the five CRS groups are shown in Table 3 and varied from 37 months (CRS 1) to 15 months (CRS 5), with a R2 value of 0.81 (Figure).
Table 2. Fong et al’s4 prognostic factors in 61 patients who underwent hepatic cryotherapy for colorectal liver metastases
Nodal status of primary tumor — positive Disease-free interval from primary to detection of liver metastases < 12 mo Number of lesions > 1 Preoperative carcinoembryonic antigen > 200 ng/mL Size of largest tumour > 5 cm
ASIAN JOURNAL OF SURGERY VOL 29 • NO 4 • OCTOBER 2006
n (%)
3-yr survival, n (%)
50/60 (83) 39/61 (64) 49/61 (80.3) 10/54 (18.5) 12/61 (19.6)
19/50 (38) 13/39 (33) 17/49 (35) 2/10 (20) 2/12 (17)
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■ CHEN et al ■
Table 3. Clinical risk scores and survival Clinical risk score 0 1 2 3 4 5
Patients, n (%)
Median survival (mo)
Range (mo)
1-yr survival (%)
2-yr survival (%)
3-yr survival (%)
0 (0) 7/53 (13) 13/53 (25) 28/53 (53) 3/53 (6) 2/53 (4)
– 37 25 30 21 15
– 20–122 9–86 8–76 15–29 12–18
– 100 92 89 100 50
– 86 54 61 33 0
– 57 38 39 0 0
Series 1 Linear (series 1) y = –4.8x + 40 R2 = 0.8136
Median survival (mo)
40 35 30 25 20 15 10 5 0 0
2
4
6
CRS group Figure. Median survival versus clinical risk score (CRS).
Discussion This study is the first to apply Fong et al’s CRS4 to patients who underwent hepatic cryotherapy for unresectable colorectal liver metastases. Despite the small sample size, it is still one of the biggest studies in this area to date. It is clear that Fong et al’s CRS4 can be applied to cryotherapy. The 3-year survival in patients with CRS 1 reached 57%, while no one with CRS 5 survived more than 2 years. However, the difference between CRS groups 2, 3 and 4 is modest. While we used cryotherapy, it is likely that similar outcomes for Fong et al’s criteria would be seen with other ablation techniques such as radiofrequency ablation. Perhaps the most important issue with the use of the CRS is whether patients with high scores should be denied surgical treatment and offered adjuvant or palliative treatments. Cryotherapy has a median survival of 26–32 months.5–7 In our study, the median survivals of CRS 3, 4 and 5 were 30, 21 and 15 months, respectively, and there were only three and two patients with scores of 4 and 5, respectively. These results are not too different and are better than with regional8–10 or systemic chemotherapy.10–12 Even in the CRS 5 group, a 15-month
240
median survival is at least as good as, and more likely to be better than, that seen with systemic chemotherapy (median survival, 10–16 months)10–12 and definitely better than with palliative treatment only (median survival, 5–9 months).12–16 Therefore, we do not believe in denying all patients with high CRS cytoablative treatments. One of the major advantages of using CRS is that all of the parameters are easily assessable. Only eight (13%) patients from among the 61 could not be classified according to the CRS in our study, mostly due to lack of preoperative CEA. This is not an issue with increased recognition of CEA’s importance both as a prognostic tool and as one of the most important measures of treatment outcome.3,17–19 The differences between prognostic factors for liver resection and cryotherapy are probably not great. We would argue that the lesion diameter is even more important in cryotherapy, and that the number of lesions is not as important.5 In this paper, only 17% of the patients with tumour > 5 cm in diameter had 3-year survival compared to 35% of the patients with multiple metastases.
Conclusion This report confirms that CRS has clinical relevance in the preoperative evaluation of patients with colorectal liver metastases and that CRS is a useful prognostic tool. Significant survival difference exists between CRS 1 and 5 but the difference between CRS 2, 3 and 4 is modest.
References 1. Greenlee RT, Murray T, Bolden S, et al. Cancer statistics, 2000. Cancer J Clin 2000;50:7–33. 2. Ballantyne GH, Qin J. Surgical treatment of liver metastases in patients with colorectal cancer. Cancer 1993;71:4252–66. 3. Fusai G, Davidson BR. Management of colorectal liver metastases. Colorectal Dis 2003;5:2–23.
ASIAN JOURNAL OF SURGERY VOL 29 • NO 4 • OCTOBER 2006
■ COLORECTAL LIVER METASTASES TREATED BY CRYOTHERAPY ■
4. Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 1999;230:309–21. 5. Seifert KJ, Joachim K, Morris DL. Prognostic factors after cryotherapy for hepatic metastases from colorectal cancer. Ann Surg 1998;228:201–8. 6. Weaver ML, Ashton JG, Zemel R. Treatment of colorectal liver metastases by cryotherapy. Semin Surg Oncol 1998;14:163–70. 7. Ruers T, Joosten J, Jager GJ, et al. Long term results of treating hepatic colorectal metastases with cryosurgery. Br J Surg 2001; 88:855–9. 8. Lorenz M, Muller HN. Randomized, multicenter trial of fluorouracil plus leucovorin administered either via hepatic arterial or intravenous infusion versus fluorodeoxyuridine administered via hepatic arterial infusion in patients with nonresectable liver metastases from colorectal carcinoma. J Clin Oncol 2000;18:243–54. 9. Rougier P, Laplanche A, Huguier M, et al. Hepatic arterial infusion of fluoxuridine in patients with liver metastases from colorectal carcinoma: long term results of a prospective randomised trial. J Clin Oncol 1992;10:1112–8. 10. Kemeny N, Daly J, Reichman B, et al. Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal cancer. A randomised trial. Ann Intern Med 1987; 107:459–65. 11. Martin JK Jr, O’Connel MJ, Wieand HS, et al. Intra-arterial fluoxuridine vs systemic fluorouracil for hepatic metastases from colorectal cancer. A randomized trial. Arch Surg 1990;125:1022–7.
ASIAN JOURNAL OF SURGERY VOL 29 • NO 4 • OCTOBER 2006
12. Scheithaucer W, Rosen H, Kornek GV, Sebesta C, et al. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ 1993;306:752–5. 13. Gorog D, Toth A, Weltner J. Prognosis of untreated liver metastasis from rectal cancer. Acta Chir Hung 1997;36:106–7. 14. Goslin R, Steele G Jr, Zamcheck N, et al. Factors influencing survival in patients with hepatic metastases from adenocarcinoma of the colon or rectum. Dis Colon Rectum 1982;25: 749–54. 15. Colorectal cancer collaborative group. Palliative chemotherapy for advanced colorectal cancer: systematic review and metaanalysis. BMJ 2000;321:531–5. 16. Blanke CD, Shultz J, Cox J, et al. A double blind placebocontrolled randomized phase III trial of 5-FU and leucovorin plus or minus trimetrexate, in previously untreated patient with advanced colorectal cancer. Ann Oncol 2002;13:87–91. 17. Grem JL, Steinberg SM, Chen AP, et al. The utility of monitoring CEA during systemic therapy for advanced colorectal cancer. Oncol Rep 1998;5:559–67. 18. Quentmeier A, Schlog P, Hobenbergerr P, et al. Assessment of serial CEA: determinations to monitor the prognosis and prognosis of metastatic liver disease treatment by regional chemotherapy. J Surg Oncol 1989;40:112–8. 19. Preketes AP, King J, Caplehorn JRM, et al. CEA reduction after cryotherapy for liver metastases from colon cancer predict survival. Aust N Z J Surg 1994;64:612–4.
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