Farouk Safi

The value of the tumor marker CA 15‐3 in diagnosing and monitoring breast cancer. A comparative study with carcinoembryonic antigen

To estimate the utility of the tumor‐associated antigen CA 15‐3 in the diagnosis of patients with breast cancer, this tumor marker was measured preoperatively in 1342 patients. This group included 509 patients with malignant disease (134 breast cancer patients and 375 patients with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast and 738 patients with other benign diseases). The results were compared with those obtained for carcinoembryonic antigen (CEA) in the diagnosis of breast cancer. The CA 15‐3 level was above normal (25 U/ml) in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. The CEA level was elevated in 26% of patients with breast cancer (more than 3 ng/ml). There was a good correlation of CA 15‐3 levels with the tumor stage of breast cancer. Both CA 15‐3 and CEA also were determined in 671 patients who had received initial curative surgery of breast cancer and who regularly attended our follow‐up clinic. The CA 15‐3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the postcare period, carcinoma recurred in 205 patients. Of these, 73% had CA 15‐3 concentrations above 25 U/ml; only 50% had CEA values above 3 ng/ml (P less than 0.0001). Although neither CA 15‐3 nor CEA were sensitive enough for the screening and diagnosis of early breast cancer, CA 15‐3 was significantly better than CEA in the detection of breast cancer metastases.

Thymidylate synthase is a predictor for response and resistance in hepatic artery infusion chemotherapy

The value of intratumoral thymidylate synthase (TS) quantitation as a predictive parameter for hepatic artery infusion (HAI) chemotherapy in patients with colorectal liver metastases was investigated. Relative TS mRNA levels were determined in 29 tumor samples using a quantitative RT-PCR amplification method. The median level of expression was 3.0 x 10(-3) (no units) and varied considerably among the tumors over a range of 135-fold. Patients with low TS levels were 4.1-fold more likely to respond (P < 0.03) compared to patients with high TS levels. Our results indicate that TS quantitation is a valuable predictive marker for tumor response to HAI therapy.

Is follow-up of colorectal cancer patients worthwhile?

Between 1978 and 1989, 1,045 of 1,399 patients (580 male and 474 female) underwent curative surgery for colorectal carcinoma. Of these patients, 350 (33 percent) had recurrences, another 16 (1.5 percent) developed a metachronous colorectal cancer, and 23 (2 percent) had cancers of other organs. An isolated locoregional recurrence was found in 75/350 (21 percent). The remaining 275/350 patients (79 percent) showed systemic dissemination of the carcinoma. Reoperations with curative intent were performed on 56/350 patients (16 percent). Only 21 of the 56 resected patients (38 percent),i.e.,21/350 (6 percent), were without recurrence at the end of the follow-up period on December 31, 1990. Despite a curative reoperation, 62 percent of the patients again developed recurrent growths. There is an imbalance between the efforts invested in tumor follow-up and the benefits gained. Further follow-up programs should be investigated in a controlled, prospective fashion.

CA 19‐9 and pancreatic adenocarcinoma

The diagnostic place value of CA 19‐9, a tumor‐associated antigen, was tested in 611 patients. This group of patients included 273 patients who suffered from a malignant disease (48 patients with pancreatic carcinomas and 225 patients with extrapancreatic malignant growths) and 338 patients with benign diseases (66 patients with chronic pancreatitis, 36 patients with acute pancreatitis, and 236 patients with general surgical diseases). In 93% of the patients with pancreatic carcinoma (median value, 528 U/ml), in 37% and 19% of the patients with carcinoma of the stomach and colorectal carcinomas (median value 8 U/ml), respectively, the CA 19‐9 value was estimated as being above the normal limits of 6 to 37 U/ml. A sensitivity of 93% and a specificity of 85%, as well as a total accuracy of 82%, were established in pancreatic carcinoma during preoperative observation. The preoperatively raised CA 19‐9 concentration in patients with pancreatic carcinomas dropped after curative resection of the carcinoma to within normal limits. However, a serum concentration of less than 37 U/ml was not recorded in any CA 19‐9 estimation after a palliative surgical intervention, or in any case of inoperable carcinomas.

Regional chemotherapy for hepatic metastases of colorectal carcinoma (continuous intraarterial versus continuous intraarterial/intravenous therapy): results of a controlled clinical trial

Sixty‐four patients with a biopsy diagnosis of colorectal cancer with liver metastases were treated with 5‐fluorodeoxyuridine (FUDR) infusions. In a pilot study, the first 20 patients were given hepatic artery infusions of FUDR by implanted pumps. The remaining 44 patients were then randomized prospectively to compare the effectiveness of continuous hepatic artery and intravenous infusion of FUDR (IA/IV group; 21 patients) with hepatic artery infusion alone (IA group; 23 patients). A continuous 14‐day infusion regimen of FUDR was applied each month. The dosage was 0.2 mg/kg/d of FUDR for the IA group and 0.3 mg/kg/d for the IA/IV group. The complete and partial response rates were each 50% in the pilot study and 52% and 48% in the IA and IA/IV randomized groups, respectively. Drug toxicities in the 64 patients included gastroenteritis (21%), chemical hepatitis (57%), and biliary sclerosis (25%). There was no difference in the toxicity of FUDR in the two randomized groups (P > 0.1). Extrahepatic spread of cancer during therapy was found in 61% (n = 14) of the IA group and 33% (n = 7) of the IA/IV group. There was no difference in survival between the randomized groups. The 64 patients were categorized into the following two groups according to their response to therapy: (1) responders (patients with complete or partial remission [n = 32]) or nonresponders (patients with stable disease or progression of metastases [n = 32]). The median survival time was 31 months for responders and 16 months for nonresponders (P < 0.0001). Intraarterial FUDR infusion provided control of liver metastases. The combination of intraarterial and intravenous therapy seemed to prevent extrahepatic spread during therapy in most of the patients, Survival appeared to be significantly prolonged in patients with a regression of metastases.

Diagnostic value of CA 19-9 in patients with pancreatic cancer and nonspecific gastrointestinal symptoms

Serum expression of the tumor marker CA 19-9 was studied in 2119 patients. The discriminating capacity between benign and malignant disease was high for CA 19-9, especially in patients, with pancreatic cancer (n=347). The sensitivity of CA 19-9 was 85%. In patients who were Lewis blood type positive, the sensitivity increased to 92%. CA 19-9 levels were significantly lower in patients with resectable tumors (n=126) than in those with unresectable tumors (n=221,P<0.0001; sensitivity 74% vs. 90%). CA 19-9 levels dropped sharply after resection but normalized in only 29%, 13%, and 10% of patients with stage I, II, and III tumors, respectively. In unresectable tumors no significant decrease in CA 19-9 levels after laparotomy or bypass surgery was found. Among patients with the same tumor stage, the median survival time in those whose CA 19-9 levels returned to normal after resection was significantly longer than in those who had postoperative CA 19-9 levels that decreased but did not return to normal (stage I, 33 months vs. 11.3 months; stage II, 41 months vs. 8.6 months; and stage III, 28 months vs. 10.8 months). In patients with recurrent disease, 88% had an obvious increase in CA 19-9 levels. CA 19-9 measurement is a simple test that can be used for diagnosis, for evaluation of resectability, and for prediction of survival after surgery and recurrences.

Ca 19-9 serum course and prognosis of pancreatic cancer

ConclusionCA 19-9 measurement is a simple test that can be used for diagnosis as well as for prediction of resection, survival rate after surgery, and recurrences.AbstractMethodsSerum expression of the tumor marker CA 19-9 was studied in 2119 patients.AbstractResultsThe discriminating capacity between benign and malignant disease was high for CA 19-9, especially in patients with pancreatic cancer (n=347). The sensitivity of CA 19-9 was 85%. In patients who were Lewis blood type positive, the sensitivity increased to 92%. CA 19-9 levels were significantly lower in patients with resectable tumors (n=126) than in those with unresectable tumors (n=221,p<0.0001) (sensitivity 74 vs 90%). CA 19-9 dropped sharply after resection, but normalized only in 29, 13, and 10% in patients with stage I, II, and III, respectively. In unresectable tumors no significant decrease of CA 19-9 after laparotomy or bypass operation was found. In patients of the same tumor stage, the median survival time in those whose CA 19-9 levels returned to normal after resection was significantly longer than in those with postoperative CA 19-9 levels that decreased, but did not return to normal (in stage I, 33 vs 11.3 mo, in stage II, 41 vs 8.6 mo, and in stage III, 28 vs 10.8 mo). In patients with recurrent disease, 88% had an obvious rise in CA 19-9 levels.

Comparison of CA 15-3 and CEA in diagnosis and monitoring of breast cancer.

In order to assess the utility of the tumor-associated antigen CA15-3 in the diagnosis of breast cancer, this new tumor marker was measured pre-operatively in 1342 patients. This group comprised 509 patients with malignant disease (134 with breast cancer and 375 with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast, 738 with other benign diseases). The results were compared with those for carcino-embryonic antigen (CEA) in the diagnosis of breast cancer. CA15-3 was above the normal limits of 25 U/ml in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. CEA was elevated in 26% of patients with breast cancer (> 3ng/ml). CA15-3 levels were above 50 U/ml in 13% of the breast cancer patients, in 6%) of patients with other malignancies, and in 0.2% of the patients with benign diseases. There was a good correlation between CA 15-3 level and tumor stage in breast cancer. CA 15-3 serum levels were over 50 U/ml in respectively 0%, 2%, 13%, and 73% of the patients with stages I, II, III, and IV. CA 15-3 and CEA were also determined in 671 patients who had received initial curative surgery of breast cancer, and who regularly attended our follow-up clinic. CA15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the post-care period, carcinoma recurred in 205 patients. Of these 73% had CA15-3 concentrations above 25 U/ml, whereas only 50% had CEA values above 3 ng/ml (p< 0.0001). Although neither CA15-3 nor CEA are sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 is superior to CEA in the detection of breast cancer metastases.

Comparison of CA 72-4, CA 19-9 and CEA in the diagnosis and monitoring of gastric cancer

In order to assess the utility of the tumor-associated antigen CA 72-4 in the diagnosis and monitoring of gastric cancer, this tumor marker was measured preoperatively in 718 patients. This group comprised 282 patients with malignant disease (115 with gastric cancer and 167 with other malig-nancies not involving the stomach) and 476 patients with benign surgical diseases. The results were compared with those for carcinoembryonic antigen (CEA) and the tumor-associated antigen CA 19-9. CA 72-4 was above the normal limit of 2.5 U/ml in 61% of the patients with gastric cancer, in 35% of the patients with other malignancies, and in 7% of the patients with benign diseases. CEA and CA 19-9 were elevated in 37% of the patients with gastric cancer (>3 ng/mlfor CEA and >37 U/ml for CA 19-9). CA 72-4 levels were above 10 U/ml in 26% of the gastric cancer patients, in 15% of patients with other malignancies, and in 0.4% of the patients with benign diseases. There was a good correlation between CA 72-4 level and tumor stage in gastric cancer. CA 72-4 serum levels were over 2.5 U/ml in 31%, 48%, 68% and 88% of patients with stage I, II, III and IV disease, respectively. CA 72-4 was found to be more sensitive than CEA and CA 19-9 in detecting recurrences of gastric cancer. In the postoperative-care period, carcinoma recurred in 29 patients. Of these 93% had CA 72-4 concentrations above 2.5 U/ml, whereas only 59% and 35% had pathological CEA and CA 19-9 serum levels (p<0.002, p<0.0001). Although neither CA 72-4 nor CEA and CA 19-9 are sensitive enough for screening and diagnosis of early gastric cancer, CA 72-4 is superior to CEA and CA 19-9 in the detection of gastric cancer recurrences.

The Value of CA 19-9 in Gastric and Colorectal Carcinoma

We have conducted a prospective study of 441 patients, to investigate the utility of a new tumor marker CA 19-9 for the diagnosis and monitoring of patients with cancer of the gastrointestinal tract (93 patients with colorectal carcinoma, 57 with carcinoma of the stomach, 10 with esophageal carcinoma, 45 with malignancies outside the gastrointestinal tract, and 236 with benign general surgical disease). Results were compared to those obtained for carcinoembryonic antigen (CEA) in the diagnosis of carcinoma of the stomach and colon/rectum. CEA is more sensitive than CA 19-9 in all stages of carcinoma of the stomach and colon/rectum. During treatments of gastrointestinal carcinomas, CEA and CA 19-9 were determined at the same time in 66 and 165 patients with surgically treated carcinoma of the stomach and colorectal carcinoma, respectively. It was noted that CEA is more sensitive than CA 19-9 in detecting recurrence. However, CA 19-9 is more specific. The best results were obtained when both markers were used together.