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Purpose: As previously shown, antibody treatment increased survival of patients with resected colorectal cancer of stage Dukes' C. Since the 5-year analysis was criticized because of the wide range (2.7 to 7.5 years) of follow-up time, we performed a 7-year analysis with only four of 189 patients monitored for less than 5 years., Patients and Methods: A total of 189 patients with resected Dukes' C colorectal cancer were randomly allocated to infusions of a total of 900 mg 17-1A antibody, 500 mg postoperatively followed by 4 monthly doses of 100 mg (n=99), or to observation only (n=90). Primary end points were overall survival and disease-free interval. Patients were stratified by a dynamic randomization according to center, sex, location of tumor, number of affected lymph nodes, and preoperative carcinoembryonic antigen concentration., Results: Randomization produced balanced distribution of risk factors. After 7 years of follow-up evaluation, treatment had reduced overall mortality by 32% (Cox's proportional hazard, P < .01; log-rank, P=.01) and decreased the recurrence rate by 23% (Cox's proportional hazard, P < .04; log-rank, P=.07). The intention-to-treat analysis gave a significant effect for overall survival (Cox's proportional hazard, P < .01; log-rank, P=.02) and disease-free survival (Cox's proportional hazard, P=.02; log-rank, P=.11 ). While distant metastases were significantly reduced (Cox's proportional hazard, P=.004; log-rank, P=.004), local relapses were not (Cox's proportional hazard, P=.65; log-rank, P=.52). This differential effect of 17-1A antibody on disseminated isolated tumor cells versus occult local satellites may explain the increased significance seen in the overall survival., Conclusion: The now-matured study shows that 17-1A antibody administered after surgery prevents the development of distant metastasis in approximately one third of patients. The therapeutic effect is maintained after 7 years of follow-up evaluation.

Purpose: In 1997, the immunocytologic detection of isolated tumor cells in bone marrow, termed micrometastasis, will be optionally included in the tumor-node-metastasis (TNM) classification indicated M1(i). In the present meta-analyses, 20 studies, which included 2,494 patients, regarding the prognostic influence of a positive bone marrow micrometastases (BMM) status on relapse-free and/or overall survival were analyzed., Materials and Methods: The literature search included the Medline and Current Contents bibliographic data bases from August 1980 to June 1997. The statistical evaluation considered the prognostic influence of the prevalence of micrometastatic cells in bone marrow on relapse-free and/or overall survival. The comparable effect estimate and its corresponding 95% confidence interval (CI) were calculated with the Mantel-Haenszel method using the originally published data of the retrieved studies., Results: The presence of epithelial cells in bone marrow was detectable in all carcinoma types, with a median prevalence of approximately 35%. Fourteen of 20 studies found a positive correlation between positive BMM status and reduced relapse-free survival by univariate analysis, but only five of 11 studies confirmed positive BMM status as an independent predictor of short disease-free survival. Regarding overall survival, positive BMM status was identified univariately in five of 12 studies, but multivariately in only two studies, as an independent factor of poor survival. Despite the heterogeneity of the studies, calculation of the relative risk (RR) for reduced relapse-free survival was possible for breast cancer, which resulted in a Mantel-Haenszel RR (RR(MH)) of 1.34 (95% CI, 1.27 to 1.42)., Conclusion: In conclusion, the results suggest that the prognostic impact of epithelial cells in bone marrow remains to be substantiated by further studies using standardized methodic protocols before its entrance in the TNM classification.

Background: Monoclonal antibodies (mabs) against components of the cytoskeleton such as cytokeratins allow single disseminated epithelial carcinoma cells to be detected in the bone marrow. The aim of this study was to examine the prognostic relevance of these cells in patients with gastric cancer and to evaluate by multivariate analysis their predictive value compared with conventional risk factors., Patients and Methods: A total of 1 x 10(6) cells from bone marrow aspirates were screened immunoctochemically for the presence and absolute number of disseminated tumor cells using mab CK2 to cytokeratin component no. 18. Patients were monitored prospectively for 30.6 +/- 15.2 months., Results: Between one and 122 CK2-positive cells per 1 million mononuclear bone marrow cells were present in 95 of 180 patients (53%). A similar prevalence of 51% was found in curatively operated patients (55 of 109). Comparison with conventional prognostic risk factors showed a correlation of cell dissemination with pathohistologic tumor (pT) stage (P = .07) and Bormann classification (P = .022). Tumor-cell content in the bone marrow predicted disease-free and overall survival in curatively resected patients (P = .007 and P = .049, respectively). Multivariate analysis, which included established risk factors, showed that extent of tumor-cell dissemination was an independent prognostic parameter for disease-free survival in T1/2 tumors (P = .014; relative risk [RR], 1.84; 95% confidence interval [CI], 1.35 to 2.52), in intestinal type carcinomas according to Laurén (P = .008; RR, 1.62; 95% CI, 1.23 to 2.12), and in patients without lymph node involvement (P = .004; RR, 2.43; 95% CI, 1.22 to 4.82)., Conclusion: Presence of disseminated tumor cells in bone marrow is indicative of systemic disease even in early-stage gastric cancer. The extent of tumor-cell presence in bone marrow correlates with prognosis in curatively resected patients. Therefore, a positive bone marrow finding may be a selection criteria for adjuvant treatment because of minimal residual tumor load.

A monoclonal antibody (mAb) directed against the cytokeratin (CK) polypeptide no. 18 specifically expressed in cells derived from simple epithelia was used to detect epithelial tumor cells in bone marrow aspirates. Of 156 patients with colorectal carcinoma, 42 presented with cells at the time of primary surgery. The incidence of positive findings varied considerably with the size and the localization of the primary tumor, the involvement of regional lymph nodes, and the presence of clinically manifest metastases. Applying a sensitive double-staining procedure, we could demonstrate that epithelial cells in bone marrow showed a heterogeneic expression of receptors for epidermal growth factor (EGF-R) and transferrin (Tf-R) as well as of the proliferation-associated Ki67 antigen. Also human leukocyte antigen (HLA) class I antigens differed widely in their expression on the CK-positive cells. Clinical follow-up studies on 85 patients showed a significantly higher relapse rate in patients presenting with CK-positive cells in their bone marrow at the time of primary surgery. Twenty-three patients were monitored for the presence or absence of CK-positive cells in bone marrow over time. The majority of monitored patients (18 of 23) exhibited a constant pattern of immunocytochemical findings during the time of observation. Thus, the technique may be useful in identifying high-risk patients as well as in monitoring adjuvant therapeutic trials.