Significance of serum CA125 and TPS antigen levels for determination of overall survival after three chemotherapy courses in ovarian cancer patients during long-term follow-up.

PURPOSE OF INVESTIGATION: To evaluate the prognostic significance for overall survival rate for the marker combination TPS and CA125 in ovarian cancer patients after three chemotherapy courses during long-term clinical follow-up. METHODS: The overall survival of 212 (out of 213) ovarian cancer patients (FIGO Stages I-IV) was analyzed in a prospective multicenter study during a 10-year clinical follow-up by univariate and multivariate analysis. RESULTS: In patients with ovarian cancer FIGO Stage I (34 patients) or FIGO Stage II (30 patients) disease, the univariate and multivariate analysis of the 10-year overall survival data showed that CA125 and TPS serum levels were not independent prognostic factors. In the FIGO Stage III group (112 patients), the 10-year overall survival was 15.2%; while in the FIGO Stage IV group (36 patients) a 10-year overall survival of 5.6% was seen. Here, the tumor markers CA125 and TPS levels were significant prognostic factors in both univariate and multivariate analysis (p < 0.0001). In a combined FIGO Stage III + FIGO Stage IV group (60 patients with optimal debulking surgery), multivariate analysis demonstrated that CA125 and TPS levels were independent prognostic factors. For patients in this combined FIGO Stage III + IV group having both markers below respective discrimination level, 35.3% survived for more than ten years, as opposed to patients having one marker above the discrimination level where the 10-year survival was reduced to 10% of the patients. For patients showing both markers above the respective discrimination level, none of the patients survived for the 10-year follow-up time. CONCLUSION: In FIGO III and IV ovarian cancer patients, only patients with CA 125 and TPS markers below the discrimination level after three chemotherapy courses indicated a favorable prognosis. Patients with an elevated level of CA 125 or TPS or both markers after three chemotherapy courses showed unfavorable prognosis.

Characterization of monoclonal antibodies directed against squamous cell carcinoma antigens: report of the TD-10 Workshop.

Thirteen monoclonal antibodies directed against squamous cell carcinoma antigens (SCCA1 and SCCA2) were obtained from five international collaborating laboratories participating in the ISOBM TD-10 Workshop. Native and recombinant forms of SCCA were used in a wide variety of approaches to determine the reactivity and specificity of these antibodies. Based on reactivity, the antibodies could be divided into three groups: the SCCA1-reactive group containing those that reacted only with recombinant SCCA1 (rSCCA1) and native SCCA1 (nSCCA1) antigens, the SCCA2-reactive group containing those that reacted only with recombinant SCCA2 (rSCCA2), and the pan-reactive group containing those antibodies that reacted with rSCCA1, nSCCA1, and rSCCA2. Binding to radioiodinated rSCCA1 showed that all reactive antibodies were of a high affinity (K(d) <2 x 10(-9) mol/l). Binding to labelled rSCCA2 demonstrated that five antibodies were of a high affinity (K(d) <2 x 10(-9) mol/l). Antibody reactivity on Western blots was tested with nonreduced and reduced native and recombinant SCCA1 and SCCA2. In general, these findings showed that reduction had little effect on binding to SCCA1, but often a strong effect on the binding to SCCA2. Binding of antibodies to rSCCA1 and rSCCA2 in complexes with cathepsin L and G, respectively, was used to assist in the localization of epitope regions in enzyme-complexed SCCA. Cross-inhibition experiments showed that SCCA1-reactive antibodies represent two different epitope groups, and this is supported by their ability to make SCCA1-specific assays by combining antibodies from the two epitope groups. The SCCA2-reactive group represents two related antibodies and one unique as seen in cross-inhibition, but they do not form successful assay combinations. Classification of the pan-reactive antibodies is more difficult, as some epitope groups differ when results from rSCCA1 are compared with rSCCA2 as the target. However, two antibodies are outstanding, SCC107 and SCC113, as they are high-affinity antibodies which react equally well with free and protease complexes of SCCA1 and SCCA2. The precise location of epitopes was further studied using sequential overlapping peptides and homology modelling. The findings from this workshop strongly indicate that the recombinant antigens (rSCCA1 and rSCCA2) are very similar in epitope structure to the native counterparts in saliva, and squamous epithelium from normal and cancer tissues. Therefore, it is reasonable to conclude that the specificities found are reliable and have application for antibody measurement of all forms of squamous cell carcinoma in serum except SCCA2 in complex with its protease.

Sample preparation of human serum for the analysis of tumor markers. Comparison of different approaches for albumin and gamma-globulin depletion.

LC-MS is a powerful method for the sensitive detection of proteins and peptides in biological fluids. However, the presence of highly abundant proteins often masks those of lower abundance and thus generally prevents their detection and identification in proteomic studies. In human serum the most abundant proteins are albumin and gamma-globulins. We tested several approaches to specifically reduce the level of these proteins based on either specific antibodies, dye ligands (for albumin) and protein A or G (for gamma-globulins). The resulting, depleted serum was analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis and LC-MS for the residual presence of these abundant proteins as well as for other serum proteins that should remain after depletion. To test the applicability of this method to real-life samples, depleted serum of a cervical cancer patient was analyzed for the presence of a specific tumor marker protein SCCA1 (squamous cell carcinoma antigen 1; P29508), which is present at ng/ml concentrations. The results demonstrate that SCCA1 can be detected by LC-MS in patient serum following depletion of albumin and gamma-globulins thus opening the possibility of screening patient sera for other, so far unknown, tumor markers.

Epitopes on CA 125 from cervical mucus and ascites fluid and characterization of six new antibodies. Third report from the ISOBM TD-1 workshop.

CA 125 is found in body fluids in a variety of molecular weight forms. The largest species are found in normal abdominal fluid and cervical mucus. The present study therefore incorporated CA 125 derived from these sources as well as ascites fluid to investigate if the source of CA 125 influenced epitope characterization. Ascites-derived CA 125 varied in size from about 190 to about 2,700 kD. Cervical mucus-derived CA 125 treated with ultrasound changed its apparent size from more than 20,000 to 700 kD. Epitope mapping of antibodies was not grossly influenced by the size or source of CA 125 used as target. However, low-molecular-weight CA 125, i.e. ascites fractions CA 17/E, CA 17/F and CA 10/7, did show differences in certain assay combinations and cross-inhibition patterns which probably can be explained by steric effects due to the smaller size compared with the most abundant forms of CA 125 present in serum and other body fluids. The specificity of six new monoclonal antibodies to CA 125 was tested by cross-inhibition and immunometric assay combinations and compared to reference antibodies. One antibody, X306, belonged to the OC125-like antibodies. Four antibodies, X52, X75, X325 and VK8, were M11-like. The sixth antibody, 7C12, reacted with an epitope which was difficult to define. This antibody was inhibited by M11-like antibodies and OV197. However, used as an inhibitor, 7C12 inhibited only itself. We grouped it as an OV197-like antibody, but clearly different from OV197. The topography of epitopes was studied by analyzing all antibody pairs in immunoradiometric assays. These results confirmed the grouping of antibodies described above and are in accordance with previous findings that the highest signal is obtained using an OC125-like antibody or OV197 on the solid phase and an M11-like antibody as tracer. The composition of the sample in terms of high- and low-molecular-weight species of CA 125 was measured, with different responses depending on the antibody pair used. This might be one reason for discrepancies between assay results for CA 125 using different assays.

OVX1, macrophage-colony stimulating factor, and CA-125-II as tumor markers for epithelial ovarian carcinoma: a critical appraisal.

BACKGROUND: Ovarian carcinoma remains the leading cause of death from gynecologic malignancy in Australia, the Netherlands, and the United States. CA-125-II, the most widely used serum marker, has limited sensitivity and specificity for detecting small-volume, early-stage disease. Therefore, a panel of three serum tumor markers-OVX1, CA-125-II, and macrophage-colony stimulating factor (M-CSF)-has been used to evaluate the sensitivity and specificity of multiple markers for the detection of early-stage ovarian carcinoma. METHODS: Preoperative serum levels of OVX1, CA-125-II, and M-CSF were measured in 281 patients with primary ovarian epithelial tumors of different histotypes. Among these tumors, 175 were malignant, 29 were of borderline malignancy, and 77 were benign. The three markers also were measured in sera from 117 apparently healthy women. Marker levels were considered abnormal at CA-125-II > 35 U/mL, OVX1 > 7.2 U/mL, and M-CSF > 3.5 ng/mL. RESULTS: Among 175 women with malignant ovarian tumors, at least one of the three serum markers was elevated in 85%, whereas CA-125-II was elevated in 80% (P = 0.008). In 58 patients with Stage I ovarian carcinoma, at least one of the three serum markers was elevated in 76%, whereas CA-125 levels were elevated in 66% (P = 0.04). For patients with borderline and benign tumors, a combination of the three antigens had slightly higher sensitivity compared with CA-125-II, but the differences were not statistically significant. Among 117 apparently healthy women, CA-125-II was elevated in 4%, and one of the three markers was positive in 17%. CONCLUSIONS: The sensitivity of a combination of three serum markers was significantly greater than the sensitivity of the CA-125-II assay alone in patients with primary ovarian epithelial tumors of different histotypes. This was true for all stages, including early-stage, potentially curable disease. When used as single markers, however, only the CA-125-II assay could distinguish invasive Stage I tumors from apparently healthy women.

Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with early-stage cervical cancer.

PURPOSE: To investigate the contribution to recurrence detection and survival of serum squamous cell carcinoma antigen (SCC-ag) analysis in the follow-up of early-stage cervical cancer patients. PATIENTS AND METHODS: Follow-up data were evaluated in patients with early-stage squamous cell cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy with or without radiotherapy. Routine serum SCC-ag determination was performed at each follow-up visit. RESULTS: Recurrent disease occurred in 35 (16%) of 225 patients and was preceded or accompanied by serum SCC-ag elevation 26 times (sensitivity, 74%). In five (14%) of these 35 patients, elevated serum SCC-ag was the first measured clinical indicator. Desite salvage therapy, all five patients died of disease. In the other 31 patients (21 with serum SCC-ag elevation), either symptoms and/or positive signs led to recurrence detection. Median survival time after recurrence was worse (9 months; range, 2 to 112+) for patients with an elevated serum SCC-ag value at recurrence in comparison with patients with normal serum SCC-ag values (20 months; range, 4 to 96; P <.01). In 23 of the 190 patients without recurrences, serum SCC-ag values became falsely elevated. In 16 of these 23 patients, the repeat sample after 6 weeks showed a normal SCC-ag, and in seven patients benign (especially skin) disorders were found. CONCLUSION: Serum SCC-ag analysis results in earlier recurrence detection in a small proportion (14%) of patients but did not contribute to better survival. As long as treatment possibilities for recurrent cervical cancer patients are not improved, serum SCC-ag analysis should not be carried out in routine follow-up.

Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients.

OBJECTIVE: To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients. METHODS: We analyzed in a prospective multicenter study the 1- and 2-year overall survival (OS) in ovarian carcinoma patients. The prognostic significance of CA 125 and TPS levels above the discrimination value (25 kU/L and 100 U/L, respectively) was examined by univariate and multivariate analyses. RESULTS: Of the 213 cases included, 64 patients were staged as FIGO I + II and 149 patients were staged as FIGO III + IV. Tumor marker levels in stage I + II were not correlated with survival. However, stage III and IV patients with elevated levels of CA 125 or TPS after three chemotherapy courses had a worse 2-year OS (69% vs 26%, P < 0.0001 and 57% vs 20%, P < 0.0001, respectively) than patients with normal levels of the markers. In univariate analysis the result of operation (staging laparatomy and partial debulking) and advanced FIGO stage (IV) were also adverse prognostic factors. Independent factors predictive of low 2-year OS by multivariate analysis were staging laparotomy, TPS elevated, and CA 125 elevated. The only factors predictive of low 1-year OS were TPS elevated and staging laparotomy. CONCLUSIONS: Ovarian cancer patients with elevated CA 125 levels after three chemotherapy courses have a poor prognosis. However, the prognostic accuracy can be significantly increased by the parallel determination of serum TPS.

Serum CA 125, carcinoembryonic antigen, and CA 19-9 as tumor markers in borderline ovarian tumors.

OBJECTIVES: The goals of this study were to analyze preoperative serum levels of CA 125, carcinoembryonic antigen (CEA), and CA 19-9 in patients with borderline ovarian tumors and to investigate if routine assessment of these markers in follow-up may lead to earlier detection of recurrence. METHODS: For patient identification a database was used, in which data from all patients treated for gynecologic malignancies in the Department of Gynecologic Oncology, University Hospital Groningen, The Netherlands, are compiled. Between 1982 and 1997, 44 patients with borderline ovarian tumors were identified. Clinical data and serum CA-125 and CEA levels were retrieved from the database. CA 19-9 levels were determined in retrospect in available stored preoperative (24 patients) and follow-up (43 patients) serum samples. RESULTS: Preoperative CA 125 levels were elevated in 8 of 33 (24%), CEA levels in 3 of 32 (9%), and CA 19-9 levels in 11 of 24 (46%) cases. In patients with mucinous tumors preoperative CA 19-9 was more frequently elevated (8/14, 57%) than CA 125 (3/20, 15%) (P = 0.02) or CEA (2/18, 11%) (P = 0.02). Complete follow-up serum CA 125, CEA, and CA 19-9 levels were available for 43 of 44 patients. Median follow-up was 84 months (range, 22-204). During follow-up two patients (5%) had recurrent disease. In one patient CA 125 became elevated at the time of recurrence; in the other patient (in retrospect) the CA 19-9 level did not return to normal after surgery, but kept rising, preceding clinical symptoms of recurrence for 13 months. CONCLUSIONS: If one chooses to use serum markers in follow-up of mucinous borderline ovarian tumors CA 19-9 should be included. Measurement of serum tumor markers in the follow-up of patients with borderline ovarian tumors may lead to earlier detection of recurrence in only a very small proportion of patients, while the clinical value of earlier detection of recurrence remains to be established.

Eosinophil derived neurotoxin (EDN) levels in commercial human urinary preparations of glycoprotein hormones.

Eosinophil derived neurotoxin (EDN) is a ubiquitous human ribonuclease, occurring not only in eosinophils, but also in many tissues and body fluids. It may be a contaminant of commercial human urinary preparations of chorionic gonadotropin (hCG) and other glycoprotein hormones. Here we describe the use of a fast commercial assay to quantify this contaminant and demonstrate that the content varies much between different commercial glycoprotein hormone preparations. As this ribonuclease may have a cytotoxic activity on certain cells, it is useful to be able to determine its quantity in a fast and reliable way in these preparations.

Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up.

To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the polymerase chain reaction were tested using in vitro translated proteins E6 and E7 in a radioimmunoprecipitation assay and in an E7 synthetic peptide enzyme immunoassay. Antibody levels against E6 and E7 as measured by radioimmunoprecipitation assay showed a nearly identical pattern. Seronegative patients remained seronegative throughout treatment and follow-up. Seropositive patients showed either a decrease in antibody level or stable antibody levels during treatment. In contrast to patients without evidence of disease at the end of the study, the majority of patients with recurrent disease showed increasing antibody levels during the follow-up period. These results indicate that, in patients who are seropositive before treatment antibody levels against E6 and E7 of human papillomavirus type 16 after treatment are closely linked to treatment response. The use of the more sensitive radioimmunoprecipitation assay did not lead to a better correlation of antibody levels with clinical disease status of the patients than the use of the enzyme immunoassay.

Ovarian cysts in women receiving tamoxifen for breast cancer.

Tamoxifen is a nonsteroidal anti-oestrogen with gynaecological side-effects. Only recently, ovarian cyst formation during tamoxifen treatment has been reported. The present study aimed to evaluate patient-related parameters that determine ovarian cyst formation in women using tamoxifen for breast cancer. A cross-sectional study was performed in 142 breast cancer patients using tamoxifen. Forty-five patients were also examined prior to tamoxifen treatment. Gynaecological assessment, transvaginal ultrasonography (TVU) and serum oestradiol (E2) and follicle stimulating hormone (FSH) analysis were performed. Follow-up assessments were performed twice a year. Uni- or bilateral ovarian cysts were detected by TVU in 24 tamoxifen-using patients and in one patient before tamoxifen treatment. Multiple regression analysis showed that cyst development is related (multiple R = 0.73) to high E2 (P < 0.001), younger age (P < 0.001) and absence of high-dose chemotherapy (P = 0.007). Patients with ovarian cysts had higher serum E2 levels compared to patients without cysts (1.95 vs 0.05 nmol l(-1); P < 0.001). All patients after high-dose chemotherapy or older than 50 years had E2 < 0.10 nmol l(-1) and/or amenorrhoea > 1 year and did not develop ovarian cysts. Patients still having a menstrual cycle during tamoxifen had a high chance (81%) of developing ovarian cysts. Breast cancer patients receiving tamoxifen only develop ovarian cysts if their ovaries are able to respond to FSH stimulation as shown by E2 production.

The clinical value of squamous cell carcinoma antigen in cancer of the uterine cervix.

A review is given of the clinical use and interpretation of serum tumor marker levels during the treatment of patients with cancer of the uterine cervix. Pretreatment serum squamous cell carcinoma (SCC) antigen provides a new prognostic factor in early stage squamous cell carcinoma of the uterine cervix. Elevated serum values of SCC antigen at the time of diagnosis of stage IB and IIA cervical cancer indicate a 3 x increased risk of tumor recurrence, independent of tumor diameter, grade or the presence of lymph node metastases. High pretreatment SCC antigen levels could therefore be used to select 'high-risk' patients for adjuvant therapy. Measurement of the serum SCC antigen levels provides a means of monitoring the effect of therapy. During the postoperative follow-up of patients with localized cancer of the uterine cervix the measurement of SCC antigen can lead to the early detection of recurrent disease when curative therapy is still an option. The profile of serum SCC antigen parallels the response to radiotherapy and provides a way of evaluating the effectiveness of chemotherapy. Serial measurements after surgery and during radio- and chemotherapy demonstrate that SCC antigen is a more sensitive marker for recognizing tumor progression or recurrence than CYFRA-21.1, TPS or CEA. When following up patients with a pure adenocarcinoma of the cervix measurements of serum CA 125 and CEA are preferred over SCC antigen measurements.

Serum and cystic fluid levels of soluble interleukin-2 receptor-alpha in patients with epithelial ovarian tumors are correlated.

At the diagnosis of ovarian cancer, patients have higher serum levels of soluble interleukin-2 receptor-alpha (IL-2R alpha) compared to patients with benign ovarian tumors or healthy blood donors (means of 750 vs. 469 and 390 U/ml, respectively, p < 0.001). Serum levels were positively related to the extent of the disease. Disease progression was associated with rising serum levels of IL-2R alpha in 13 of the 15 patients but no advantage was recognized over serum CA 125 measurements when following the effect of therapy. We measured higher levels of IL-2R alpha in cystic fluids from epithelial ovarian cancers compared to benign ovarian tumors (means of 1,620 and 616 U/ml, respectively, p = 0.0002). In ovarian cancer patients, serum levels at diagnosis were positively correlated to cystic fluid levels (p < 0.0001). The presence of high IL-2R alpha levels in cystic fluids from epithelial ovarian cancer may provide a biochemical signal of lymphocyte activation at the tissue level.

Effect of low-dose oral etoposide on serum CA-125 in patients with advanced epithelial ovarian cancer.

The effect of oral etoposide on CA-125 serum levels was evaluated in 17 patients with epithelial ovarian cancer and progressive disease during, or relapsing after, prior chemotherapy. Only three patients had measurable lesions at extraperitoneal sites. Five had no measurable lesions. The oral etoposide dose was 50 mg b.d. for 7 days every 3 weeks, escalating to 10 or 14 days and continued until clinical progression. CA-125 after 4 courses was compared to baseline (CA-125 ratio). The rate of change of CA-125 (s, slope of the exponential regression curve) during the first 4 courses was compared to s over a similar period before treatment. One patient had a clinical partial response. Two other patients had a biochemical response (CA-125 ratio <0.5). Although the biochemical response rate was modest (12.5%), a decrease of s was observed in 14/16 patients (P = 0.02). The mean change of s represented an increase of mean doubling time from 52 to 693 days. No patients were withdrawn because of toxicity. General malaise, nausea, diarrhea, and anemia were the most important side effects. At the given dose schedule, oral etoposide shows activity in advanced ovarian cancer if the rate of change of CA-125 is used as a measure of activity.

Relation between HPV-16 serology and clinico-pathological data in cervical carcinoma patients: prognostic value of anti-E6 and/or anti-E7 antibodies.

To investigate the clinical significance of the enhanced sensitivity of antibody detection by radio immunoprecipitation assays (RIPA), using in vitro translated HPV-16 E6 and E7 proteins, over synthetic-peptide enzyme-linked immunosorbent assay (ELISA), RIPA for HPV-16 E6 and E7 were performed. The results obtained with E6 and E7 RIPA were related to clinico-pathological data from cervical carcinoma patients positive for HPV type 16 DNA in their primary tumour. The data obtained with E6 and E7 RIPA were then compared to the results obtained using the E7/6-35 synthetic-peptide ELISA. The prevalence of antibodies to E6, E7, E6 and/or E7 and E6 and E7, as determined by RIPA, was significantly higher in cervical cancer patients than in both controls and cervical intraepithelial neoplasia patients. Odds ratios, calculated for cervical carcinoma patients versus controls, ranged from 7.4 to 15.4. Antibodies to E6 and/or E7 were largely restricted to patients with HPV DNA in their primary tumour. Analysis of the relation between prevalence of antibodies to E6 and E7 and clinico-pathological parameters was limited to 85 patients positive for HPV-16 DNA. The strongest relation with clinico-pathological data, such as lesion size, lymph node involvement, and prognosis, was found for E7 synthetic-peptide ELISA, whereas E6 and E7 RIPA did not reach significance. The significance of these findings is discussed.

The value of cancer antigen 125 (CA 125) during treatment and follow-up of patients with ovarian cancer.

Although the nature of the cancer antigen 125 leaves many questions unanswered, the use of serum measurements as a means to assess the response to surgery and chemotherapy in ovarian cancer is now well documented. Good prognostic significance is attributed to a rapid decline in cancer antigen 125 levels after chemotherapy in patients with advanced ovarian cancer. Pre-operative serum cancer antigen 125 levels may successfully discriminate benign from malignant adnexal masses in postmenopausal women, but in women in their reproductive years the specificity is low. In stage I ovarian cancer patients, high preoperative cancer antigen 125 levels are reported to lead to a sixfold increase in the risk of dying from the disease. Low expectations on the specificity and outcome of cancer antigen 125-based screening of asymptomatic women are contradicted by the first results of screening programmes for postmenopausal women. Large, randomized, controlled studies will assess if survival can be improved by early detection of ovarian cancer. Experimental immunotherapy by activation of the idiotypic network directed against cancer antigen 125 may offer new possibilities to prolong survival in advanced ovarian cancer.

Quantification of vascular density and of lumen and vessel morphology in endometrial carcinoma. Evaluation of their relation to serum levels of tissue polypeptide-specific antigen and CA-125.

OBJECTIVE: To determine whether differences in tumor vessel architecture influence the entry of tumor-associated antigens into the circulation. STUDY DESIGN: Using an image analysis system, nine vascular parameters in samples of endometrial carcinomas stained for factor VIII-related antigen were evaluated. These were related to groups with, respectively, normal and elevated serum values for two different serum tumor markers: one with low tissue polypeptide-specific antigen (TPS) and one with high molecular weight (CA-125). RESULTS: Lumen area, lumen perimeter and maximum lumen diameter appeared to differentiate between the normal and elevated TPS group; the higher lumen values occurred in the latter (Mann and Whitney U test: P = .021, .013 and .014, respectively). For CA-125 a higher number of vessels per square millimeter after correction for the epithelium-stroma ratio was found to differentiate between the normal and elevated group (P = .011). The other parameters did not show differentiation between the groups. CONCLUSION: Distension of vessels appears to be related to the TPS serum level; that might be explained by the presence of endothelial gaps, permitting passive passage of the small TPS molecules. Vascular density appears to be related to the CA-125 serum level. However, whether this relation is real remains to be determined.

Rising serum values of beta-subunit human chorionic gonadotrophin (hCG) in patients with progressive vulvar carcinomas.

Elevated serum levels of the beta-subunit of human chorionic gonadotrophin (hCG) were measured in 50% of patients with locoregional recurrences or progressive vulvar carcinoma (n = 14). At diagnosis of vulvar cancer, however, the incidence of elevated serum levels was low (5%) in 104 patients. The rising serum levels during progression of disease indicate that the synthesis of the beta-subunit hCG can be increased in vulvar carcinoma.

Concurrent chemo- and radiotherapy in patients with locally advanced carcinoma of the cervix.

BACKGROUND: The feasibility of concurrent chemotherapy and radiotherapy for advanced primary carcinoma of the cervix was evaluated and the results were compared to historical controls. PATIENTS AND METHODS: In a single institution study, patients (n = 74) with primary cervical carcinoma received 3 cycles carboplatin/5-fluorouracil concurrent with radiotherapy followed by salvage hysterectomy (group I). Treatment results were compared with those of a historical control group (n = 39) (group II), treated similarly but without chemotherapy. RESULTS: In group I median follow-up is 28 months (12-68+) and in group II 23 months (14-90+ months). The 5-year overall survival, progression-free survival and local recurrence free survival for group I and II are, respectively, 69% versus 38% (P < 0.003), 67% versus 38% (P < 0.005) and 84% versus 43% (P < 0.0001). Two patients in each group developed posttreatment enteritis. CONCLUSIONS: Radiotherapy with concurrent carboplatin and 5-fluorouracil resulted in a better overall survival, disease free survival and local disease free survival compared to historical controls. The toxicity of this schedule did not exceed that of radiation alone in historical controls.

Pretreatment serum squamous cell carcinoma antigen: a newly identified prognostic factor in early-stage cervical carcinoma.

PURPOSE: To investigate the prognostic value of pretreatment serum squamous cell carcinoma antigen (SCC-ag) levels in patients with cervical squamous cell carcinoma in relation to well-established conventional risk factors. PATIENTS AND METHODS: Sera from 653 women treated for squamous cervical cancer between 1978 and 1994 were analyzed for the presence of SCC-ag and related to clinicopathologic characteristics and patient outcome using univariate and multivariate analyses. RESULTS: Increased pretreatment SCC-ag levels correlated strongly with unfavorable clinicopathologic characteristics (International Federation of Gynecology and Obstetrics [FIGO] stages IB to IV [P < or = .00005]; stages IB and IIA: tumor size [P = .0236], deep stromal infiltration [P = .00009], and lymph node metastasis [P = .0001]). After multivariate analysis, elevated pretreatment serum SCC-ag levels (P = .001), lesion size (P = .043), and vascular invasion by tumor cells (P = .001) were independent predictors for the presence of lymph node metastases. In Cox regression analysis, controlling for SCC-ag, lesion size, grade, vascular invasion, depth of stromal infiltration, and lymph node status only the initial SCC-ag level had a significant independent effect on survival (P = .0152). Even in node-negative patients, the risk of recurrence was three times higher if the SCC-ag level was elevated before therapy. CONCLUSION: The determination of pretreatment serum SCC-ag level provides a new prognostic factor in early-stage disease, particularly in patients with small tumor size. In future trials to assess the value of new treatment strategies, pretreatment serum SCC-ag levels can be used to help identify patients with a poor prognosis.