Has serum CA 125 assay at the time of relapse a prognostic relevance for patients with recurrent ovarian carcinoma after primary cytoreduction and platinum- and paclitaxel-based chemotherapy?

PURPOSE OF INVESTIGATION: To correlate serum CA125 at relapse with survival in ovarian cancer patients who achieved a complete response after primary cytoreduction and paclitaxel- and platinum-based chemotherapy. MATERIALS AND METHODS: The study was conducted in 104 patients. RESULTS: The 25%, 50%, and 75% quantiles of CA125 levels at relapse were 46, 118, and 190 U/ml. By log-rank test, survival after recurrence was related to consolidation treatment (p = 0.046), platinum-free interval (PFI) (p < 0.000005), number of recurrence sites (p = 0.03), treatment at recurrence (p = 0.002), and serum CA125 taking 118 U/ml as cut-off (p = 0.013). On multivariate analysis, consolidation treatment (p = 0.007), PFI (p = 0.0001), treatment at recurrence (p = 0.01), and serum CA125 taking 118 U/ml as cut-off (p = 0.04) were independent prognostic variables for survival. CONCLUSIONS: Serum CA125 at relapse was an independent prognostic variable. Patients with serum CA125 > 118 U/m had 1.943 higher risk of death than those with lower antigen value.

Prognostic value of lymph node status and number of removed nodes in patients with squamous cell carcinoma of the vulva treated with modified radical vulvectomy and inguinal-femoral lymphadenectomy.

PURPOSE OF INVESTIGATION: To assess the outcome of patients with squamous cell vulvar carcinoma treated with deep partial or total vulvectomy and inguinal-femoral lymphadenectomy. MATERIALS AND METHODS: The authors assessed 87 patients who underwent primary surgery. RESULTS: Tumor recurred in 34 patients, and the first relapse was local in 19, inguinal in ten, and distant in five. Five-year disease-free survival was 56.7% and was related to Stage (p < 0.0001), grade (p = 0.023), and node status (p < 0.0001). Groin failure occurred in 4.9% of node-negative patients compared with 29.6% of node-positive patients (p = 0.0096). Distant recurrences only developed in women with positive nodes. Among the 47 patients who underwent bilateral lymphadenectomy and who had negative nodes, groin recurrence occurred in 12% of those who had < or = 15 nodes removed and 0% of those who had > 15 nodes removed. CONCLUSIONS: Stage and node status were the most important prognostic variables. There was a trend favoring a better groin control in patients with node-negative disease who underwent extensive lymphadenectomy.

Analysis of the pattern of hypersensitivity reactions in patients receiving carboplatin retreatment for recurrent ovarian cancer.

The aim of this paper was to assess hypersensitivity reactions in 69 patients who received carboplatin (CBDCA) retreatment for recurrent ovarian cancer. Hypersensitivity reactions developed in 15 (21.7%) patients and occurred during the second cycle of retreatment in 13 (86.7%) of them. Reactions consisted of skin rash, flushing, itching, or abdominal cramping in eight (53.3%) and severe respiratory or cardiovascular events in seven patients (46.7%). One patient had a chest pain, without any other symptoms suggestive of hypersensitivity, followed by cardiac arrest unresponsive to standard resuscitative measures. All the other cases promptly recovered from symptoms. Logistic regression analysis showed that allergy history and CBDCA retreatment interval (interval time between the last cycle of first-line chemotherapy and CBDCA retreatment) were independent predictive variables for the risk of hypersensitivity, whereas patient age, first-line chemotherapy, total CBDCA dose given during first-line treatment, recurrence treated with CBDCA (first versus other), and CBDCA regimen at recurrence had no predictive value. Hypersensitivity reaction rate was higher in patients with CBDCA retreatment interval longer than 23.4 months compared to those with a shorter interval (36.3% versus 8.3%, P = 0.0132). Nine patients were subsequently treated with cisplatin, and two (22.2%) still developed allergic reactions. In conclusion, hypersensitivity reactions to CBDCA retreatment can occur in approximately one fifth of the cases, and a CBDCA retreatment interval longer than 2 years appears to be the strongest predictive variable for the development of allergic reactions.

Is pretreatment hemoglobin level a predictor of complete response to salvage chemotherapy for recurrent platinum-pretreated ovarian carcinoma?

PURPOSE OF INVESTIGATION: The aim of this retrospective study was to correlate some patient characteristics at relapse, including also baseline hemoglobin levels, with complete response rate and survival following second-line chemotherapy for recurrent platinum-pretreated ovarian carcinoma. METHODS: The investigation was conducted on 63 patients who received salvage chemotherapy with different agents for clinically detectable recurrent ovarian carcinoma following initial surgery and first-line platinum-based chemotherapy. Some patient characteristics at relapse (patient age, serum CA 125 level, baseline hemoglobin level, number of recurrence sites, ascites, platinum-free interval, and treatment-free interval) were related to complete response rate to salvage chemotherapy and survival after recurrence. Median baseline hemoglobin level was 11.6 g/dl (range, 7.5-15.0 g/dl). RESULTS: Second-line chemotherapy obtained a complete response in 17 (27.0%) patients and a partial response in 11 (17.5%), whereas stable disease and progressive disease were detected in 19 (30.1%) and 16 (25.4%) patients, respectively. By univariate analysis, complete response rate was related to baseline hemoglobin level (p = 0.0019), platinum-free interval (p = 0.0012) and treatment-free interval (p = 0.0048). Multiple logistic regression showed that platinum-free interval (p = 0.0107) and baseline hemoglobin level (0.0312) were independent predictors of complete response. Patients with baseline hemoglobin levels >11.6 g/dl had a 5.338 higher chance of obtaining a complete response when compared to those with lower hemoglobin values. The platinum-free interval was the only independent prognostic variable for survival after recurrence (p = 0.0141), whereas baseline hemoglobin level was not related to survival at univariate nor at multivariate analysis. CONCLUSIONS: Baseline hemoglobin level is an independent predictor of complete response to salvage chemotherapy in patients with recurrent platinum-pretreated ovarian carcinoma. Attention must be paid to anemia correction in these patients, with the aim of improving both the chance of response to salvage treatment and the quality of life.

First-line chemotherapy with epidoxorubicin, paclitaxel, and carboplatin for the treatment of advanced epithelial ovarian cancer patients.

OBJECTIVE: A combination of carboplatin (CBDCA) and paclitaxel (TAX) is the standard treatment in advanced ovarian cancer (AOC) patients. Epidoxorubicin (EDX) is an active treatment in AOC and exhibits nonoverlapping toxicities with CBDCA and TAX; moreover, when added to platinum-based chemotherapy, it improves long-term survival. We have therefore conducted a phase II study to evaluate the tolerability and antitumor activity of an EDX/TAX/CBDCA (ETC) triplet in AOC patients. METHODS: Patients with histologically confirmed suboptimal stage III-IV ovarian cancer who had not previously received cytotoxic drugs were treated with TAX (175 mg/m(2) in a 3-h iv infusion), CBDCA (AUC 6, Calvert formula), and EDX (75 mg/m(2) iv bolus) all given on day 1 every 28 days for a maximum of six courses on an outpatient basis. EDX dosage was chosen after a pilot phase I study. RESULTS: Fifty-five patients were registered, of whom 5 were determined ineligible bacause of age. Forty-two of the 50 are evaluable for response; 27 (64%) achieved a clinical complete response (CR) and 9 (21%) a partial response (PR) for a response rate of 86% (95% CI 71-94%). Thirty-three patients underwent a secondary debulking procedure after a median of 6 courses (range 2-6). Pathological CR and PR were observed in 9 (27.3%) and 21 (63.6%), respectively; among patients with persistent disease a successful cytoreduction (<1 cm) was obtained in 53.8% of patients. At a median follow up of 35.6 months (range 0-55.5) median progression-free survival is 19.5 months and median overall survival is 36 months. The most common adverse effects were G3-4 leukopenia and thrombocytopenia which occurred in 59 and 37% of patients, respectively. CONCLUSIONS: The ETC combination given according to the outlined doses and schedule is highly active in AOC patients with poor prognostic factors and deserves further study.

Malnutrition and cachexia in ovarian cancer patients: pathophysiology and management.

In ovarian cancer patients the poor nutritional status and cachexia are caused by the metabolic effects of the enlarging tumor masses and bowel obstruction. These patients may have a high resting energy expenditure due to increase in Cori cycle activity, glucose and triglyceride-fatty acid cycling and gluconeogenesis. Biochemical mediators of cachexia include cytokines, such as tumor necrosis factor and interleukin-6, and tumor-produced catabolic factors, such as lipid-mobilizing factor, proteolysis-inducing factor, and anemia-inducing factor. Mechanisms involved in the pathogenesis of obstruction may include extrinsic occlusion of the bowel due to pelvic, mesenteric omental masses, or intestinal motility disorders due to infilor tration of the mesentery or bowel muscle and nerves. The relief of malnutrition and cachexia may be attempted through nutritional support, pharmacological approach (megestrol acetate, cyclooxygenase inhibitors) and palliative treatment of bowel obstruction. Very few agents have been demonstrated to have true anticachectic activity, so future research should be addressed to the identification of drugs able to block the activity of tumor-produced catabolic factors. The decision regarding optimum management of bowel obstruction should be individualized. Krebs' and Goplerud's score (based on age, nutritional status, tumor status, ascites, previous chemotherapy and irradiation) seems to offer reliable eligibility criteria for those patients who can benefit from surgery.

The clinical relevance of serum CYFRA 21-1 assay in patients with ovarian cancer.

CYFRA 21-1 assay, which detects serum fragments of cytokeratin 19, has been widely assessed as a serum marker of several malignancies. Preoperative serum CYFRA 21-1 levels were retrospectively measured in 60 patients with ovarian cancer and in 59 control patients with benign ovarian disease. CYFRA 21-1 levels were also serially measured in 90 serum samples drawn from patients with advanced (FIGO stage III-IV) ovarian cancer followed after surgery and chemotherapy. Preoperative serum CYFRA 21-1 levels were higher in patients with ovarian cancer compared with controls (median, range = 2.6, 0.1-51.4 ng/ml versus 0.4, 0.0-3.6 ng/ml, P < 0.0001), and among the former, antigen values were higher in the 39 patients with advanced-stage than in the 21 patients with early (FIGO stage I-II) disease (P < 0.0001). In advanced ovarian cancer patients, the 25%, 50%, and 75% quantiles of preoperative CYFRA 21-1 levels were 1.9, 4.8 and 14.4 ng/ml, respectively. Preoperative CYFRA 21-1 levels were lower in the 11 patients who achieved a pathologic complete response at second-look compared with those who had clinically or surgically detectable persistent disease after first-line chemotherapy (median, range 1.9, 0.6-9.2 ng/ml versus 10.2, 0.1-51.4 ng/ml, P = 0.007). The pathologic complete response rate was significantly greater in patients with low preoperative CYFRA 21-1 levels compared with those with elevated CYFRA 21-1 levels at any cut-off limit for the antigen (1.9, 4.8 and 14.4 ng/ml). However, Cox regression analysis failed to detect a significant association between preoperative CYFRA 21-1 assay and survival. As for the follow-up of advanced ovarian cancer patients, CYFRA 21-1 levels were higher in the 42 samples drawn from patients with clinically detectable disease compared with the 48 specimens collected from patients with no clinical evidence of disease (median, range = 1.15, 0.3-40.7 ng/ml versus 0.4, 0.1-9.1 ng/ml, P < 0.0001). In conclusion, preoperative serum CYFRA 21-1 assay appears to be predictive of response to chemotherapy, but not prognostic of survival, for patients with advanced ovarian cancer. Moreover, the serial measurement of CYFRA 21-1 levels might have a potential clinical relevance for the assessment of disease status in patients followed after surgery and chemotherapy.

Analysis of treatment failures and survival of patients with fallopian tube carcinoma: a cooperation task force (CTF) study.

OBJECTIVE: The objective of this retrospective multicenter study was to assess the pattern of failures and survival of patients with primary carcinoma of the fallopian tube. METHODS: The hospital records of 88 patients with primary carcinoma of the fallopian tube were reviewed. Surgery was the initial therapy for all patients. Tumor stage was I in 21 (23.9%), II in 21 (23.9%), III in 43 (48.8%), and IV in 3 (3.4%) patients. Postoperative treatment was given without well-defined protocols. The median follow-up of survivors was 55 months (range, 7-182). RESULTS: Of the 21 patients with stage I disease, 10 had no postoperative treatment and 11 had platinum-based chemotherapy. Five (23.8%) patients recurred after a median of 29 months (range, 8-93) from initial surgery. Of the 21 patients with stage II disease, 2 had no postoperative treatment, 2 underwent external pelvic irradiation, 16 received platinum-based chemotherapy, and 1 patient had oral melphalan. Eight (38.1%) patients recurred after a median of 25.5 months (range, 7-57). Of the 46 patients with stage III-IV disease, 1 patient refused chemotherapy and died after 19 months and 45 patients received platinum-based chemotherapy. A clinical complete response was obtained in 29 (64.4%) patients and a partial response in 8 (17.8%). A second-look laparotomy was performed in 14 of the 29 clinically complete responders: 12 patients were found to be in pathological complete response and 2 had persistent disease. Six (50.0%) of the former recurred after a median of 22 months (range, 13-101) from initial surgery. The two patients with persistent disease developed tumor progression after 15 and 11 months, respectively. Fifteen clinically complete responders did not undergo second-look, and 7 (46.7%) of them had a recurrence after a median of 18 months (range, 9-41). For the whole series, 5-year survival was 57%. By log-rank test, survival was related to FIGO stage (III-IV vs I-II, P = 0.0001), tumor grade (G3 vs G1 + G2, P = 0.0038), and patient age (>58.5 years vs <58.5 years, P = 0.0069), but not to histological type. The Cox model showed that FIGO stage (P = 0.0018) and patient age (P = 0.0290) were independent prognostic variables for survival. Among the patients with stage III-IV disease, 5-year survival was 55% for the patients who had residual tumor <1 cm compared with 21% for those who had larger residuum (P = 0.0169). CONCLUSIONS: Primary carcinoma of the fallopian tube shares several biological and clinical features with ovarian carcinoma. However, when compared with the latter, fallopian tube carcinoma more often tends to recur in retroperitoneal nodes and distant sites. Stage, patient age, and, among patients with advanced disease, residual tumor after initial surgery represent important prognostic variables for survival.

Complete salvage surgical cytoreduction improves further survival of patients with late recurrent ovarian cancer.

OBJECTIVE: The aim of this study was to assess the clinical benefit of salvage surgical cytoreduction in patients with late recurrent ovarian cancer. METHODS: Thirty patients with recurrent ovarian cancer who underwent salvage surgical cytoreduction were retrospectively reviewed. All had been initially treated by primary surgery and platinum-based chemotherapy and had a period of clinical remission of at least 6 months. Median time to recurrence was 17.5 months (range, 6-76 months). RESULTS: A macroscopically complete salvage cytoreduction was obtained in 17 (56.7%) patients, whereas 8 patients were left with macroscopic residual disease <2 cm and 5 patients with a larger residuum. Logistic regression showed that the probability of achieving a complete cytoreduction was significantly related to the residual disease after initial surgery (<2 cm versus >2 cm, P = 0.0027, odds ratio = 36.000, 95% confidence interval = 3. 473-373.176), but not to FIGO stage, tumor grade, histologic type, patient age at recurrence, and time to recurrence. In the whole series median survival following salvage surgery was 21 months. Survival was significantly longer in patients who were completely cytoreduced compared to those who were not (median: 37 months versus 19 months, P = 0.04). Moreover, survival was significantly related to time to recurrence (>17.5 months versus <17.5 months, median: 25 months versus 15 months, P = 0.039), number of recurrence sites (single versus multiple, median: 40 months versus 19 months, P = 0. 009), and residual disease after initial surgery (<2 cm versus >2 cm, median: 37 months versus 19 months, P = 0.01), but not to patient age, recurrence site with the largest size, FIGO stage, tumor grade, and histologic type. CONCLUSIONS: The present data seem to show that complete salvage surgical cytoreduction significantly improves further survival of ovarian cancer patients who recur at least 6 months after the completion of primary therapy.

Surgical cytoreduction during second-look laparotomy in patients with advanced ovarian cancer.

BACKGROUND: The impact of surgical cytoreduction performed during second-look on the survival of patients with advanced ovarian cancer is still under debate. MATERIALS AND METHODS: The present retrospective investigation assessed 81 patients with advanced ovarian cancer who underwent second-look laparotomy after initial cytoreductive surgery and six cycles of platinum-based chemotherapy. RESULTS: At the beginning of the second-look, 31 patients were in pathological complete response, 7 had microscopic residual disease, 22 had macroscopic residual disease < 2 cm and 21 had a larger residuum. Twenty-two (51.2%) of the 43 patients with macroscopic disease underwent surgical cytoreduction during the second-look: 11 patients were completely cytoreduced, whereas 11 were debulked from residuum > 2 cm to macroscopic residuum < 2 cm. Patients with microscopic residual disease after the second-look had improved survival when compared to those with macroscopic residuum after re-exploration (median survival, 43 months versus 19.5 months, p = 0.002). Among the former, no difference in survival was detected between the patients who had microscopic disease at the beginning of the second-look and those who were surgically cytoreduced to microscopic disease. Moreover, the patients with macroscopic residuum < 2 cm after the second-look had a better survival than those with a larger residuum after re-exploration (median survival, 24 months versus 10 months, p = 0.0001). Among the former, no difference in survival was seen between the patients who had residual disease < 2 cm at the beginning of the second-look and those who were surgically cytoreduced to < 2 cm. However, ovarian cancer recurred in all the patients with small or large macroscopic residuum after the second-look. CONCLUSION: The complete resection of macroscopic persistent tumor seems to give ovarian cancer patients the highest likelihood of long-term survival and should represent the goal of surgical cytoreduction during second-look laparotomy.

An intensive follow-up does not change survival of patients with clinical stage I endometrial cancer.

BACKGROUND: The clinical benefit of an intensive follow-up protocol in endometrial cancer patients is still uncertain. MATERIALS AND METHODS: One hundred and thirty-three patients underwent initial abdominal surgery for clinical stage I endometrial cancer between January 1988 and December 1997 and were periodically followed-up until April 1999 or until death. After surgery, 89 patients received postoperative adjuvant treatment. Periodical surveillance included physical examination, vaginal smear and abdominal-pelvic ultrasound every 3-4 months for the first 2 years from surgery, every 6 months for the next 3 years and yearly thereafter. Chest X-ray was performed every 6 months for the first 2 years, every year for the next 3 years and with individually increasing intervals afterwards. An abdominal-pelvic CT scan was carried out yearly for 5 years. RESULTS: Twenty-four patients (18.0%) developed recurrent disease after a median time of 17.5 months (range, 6-64 months). Five-year actuarial disease-free survival was 81.2% in the whole series, and in detail 94.2% in the subset of patients with FIGO stage Ia grade 1 or 2 endometrioid adenocarcinoma, or stage Ib grade 1 endometrioid adenocarcinoma (low-risk), compared to 76.0 (p = 0.0472) in the subset of patients with stage Ia grade 3 endometrioid adenocarcinoma, stage Ib grade 2 or 3 endometrioid adenocarcinoma, stage equal to or greater than Ic endometrioid adenocarcinoma any grade, and aggressive histologies (high-risk). The site of recurrent disease was local in 6 (25.0%) patients, distant in 17 (70.8%), and local plus distant in 1 (4.2%). Eleven (45.8%) recurrences were symptomatic and 13 (54.2%) were asymptomatic. The median survival after recurrence was 10 months. Survival was longer in patients who relapsed after 17.5 months from initial surgery when compared to those who relapsed earlier (p = 0.02). Conversely, survival after recurrence was not related to patient characteristics at diagnosis, such as FIGO stage, tumor grade, myometrial invasion, histologic type, and lymph node status. It is noteworthy that survival was similar in asymptomatic women, in whom the relapse was occasionally detected by follow-up examinations, and in symptomatic ones. CONCLUSION: An intensive surveillance protocol seems to have no significant impact on the outcome of patients with clinical stage I endometrial cancer. Simplified follow-up programs tailored for patient subsets with different recurrence risk are required.

p53 status is neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen.

BACKGROUND: The aim of this study was to assess the relationship between p53 status and the clinical outcome of patients with advanced ovarian cancer treated with a paclitaxel-based regimen. PATIENTS AND METHODS: The investigation was conducted on 38 patients with FIGO stage III-IV ovarian cancer from whom tumor tissue samples for p53 protein immunostaining were obtained during initial cytoreductive surgery. All these patients subsequently received six cycles of first-line combination chemotherapy with paclitaxel 175 mg/m2 (3-hour infusion) plus carboplatin AUC 6 with or without epidoxorubicin 75 mg/m2. RESULTS: Positive p53 immunostaining was detected in tissue samples collected from 24 (63.2%) ovarian cancers. A clinical complete response was obtained in 14 (58.3%) of the 24 patients with positive p53 immunostaining compared to 9 (64.3%) of the 14 patients with negative p53 immunostaining (p = 0.717). A pathological complete response was found in 6 (25.0%) of the former compared to 4 (28.6%) of the latter (p = 0.956). Similarly, survival did not correlate with p53 status (p = 0.1271). DISCUSSION: p53 status seems to be neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen. These results are consistent with experimental data showing that paclitaxel cytotoxicity in ovarian cancer is likely to be mediated by a p53-independent pathway.

Combination of cisplatin, epirubicin, and cyclophosphamide (PEC regimen) in advanced or recurrent endometrial cancer: a retrospective clinical study.

The combination of cisplatin (50 mg/m2), epirubicin (60 mg/m2), and cyclophosphamide (600 mg/m2) (PEC regimen) was given every 4 weeks to 19 patients with advanced (n.2) or recurrent (n.17) endometrial cancer. The median number of cycles delivered to each patient was 5 (range, 2-8). All patients were evaluable for toxicity and 16 for response. Two (12.5%) patients experienced a complete response and 5 (31.2%) had a partial response, for an overall objective response rate of 43.7%. The median duration of objective response was 10 months (range, 3-28 months). Median survival was 10 months (range, 3-68+ months) in the whole series. According to response to chemotherapy, median survival was 12 months (range, 3-68+ months) for responders and 9 months (range, 6-17 months) for nonresponders. Hematologic toxicity was relatively frequent but it could be easily managed, and significant nonhematologic toxicities were not found except for nausea and vomiting. In conclusion, PEC regimen has a good activity in advanced or recurrent endometrial cancer, but the short duration of responses limits the impact of the treatment on survival time.

Serum preoperative vascular endothelial growth factor (VEGF) in epithelial ovarian cancer: relationship with prognostic variables and clinical outcome.

Substantial experimental and clinical evidence links tumor growth, progression and metastatic potential with neoangiogenesis. This process is modulated by several angiogenic growth factors, such as vascular endothelial growth factor (VEGF). Little data are currently available on serum VEGF levels in cancer patients. In the present retrospective investigation preoperative serum VEGF was higher in 53 patients with epithelial ovarian cancer than in 25 patients with benign ovarian disease as controls (median, range: 229.7, 23.5-1807.5 pg/ml versus 140.3, 14.7-1038.7 pg/ml, p = 0.034). With regard to FIGO stage, antigen values were significantly elevated in stage III-IV (p = 0.027) but not in stage I-II ovarian cancer patients when compared to controls. In patients with advanced disease preoperative serum VEGE was significantly related to the presence of ascites (p = 0.013), but not to common prognostic variables, response to chemotherapy and survival. In conclusion, preoperative serum VEGF assay reflects tumor progression and ascites generation in epithelial ovarian cancer, but it seems to have a limited predictive and prognostic value in patients with advanced disease.

Assessment of the prognostic relevance of serum anti-p53 antibodies in epithelial ovarian cancer.

The objective of this study was to assess the prognostic relevance of preoperative serum anti-p53 antibodies in epithelial ovarian cancer. These autoantibodies were detected with a new generation enzyme-linked immunosorbent assay in blood samples preoperatively drawn from 86 patients with this malignancy. Serum anti-p53 antibodies were found in 3 (10.0%) of the 30 patients with stage I-II and 15 (26.8%) of the 56 patients with stage III-IV epithelial ovarian cancer (P = 0.09). We assessed in detail 44 patients with stage III-IV disease who underwent six cycles of first-line platinum-based chemotherapy. A pathological complete response at second-look was achieved by none of the 15 patients with serum anti-p53 antibodies compared to 24.1% of the 29 patients without autoantibodies (P = 0.09). However, the preoperative serum anti-p53 antibody status had no prognostic relevance for progression-free survival and survival. In conclusion, the assessment of preoperative serum anti-p53 antibodies seems to have a limited clinical value in the management of patients with advanced epithelial ovarian cancer.

Serum anti-p53 antibodies in the follow-up of patients with advanced ovarian carcinoma.

Serum anti-p53 antibodies have been detected in different human malignancies, including ovarian carcinoma. In the present investigation these autoantibodies were retrospectively measured with a new ELISA (Immunotech, Marseilles, France) before first surgery and subsequently at different times during the course of disease from 40 patients with advanced ovarian carcinoma. Anti-p53 antibodies were preoperatively found in 15 (37.5%) patients. With regard to the follow-up of these 15 patients, anti-p53 antibodies were detected in 87.8% of the 41 samples drawn when there was clinical evidence of disease compared to 57.1% of the 14 samples collected when there was no clinical evidence of tumor (p = 0.037). As for the 25 patients whose serum originally scored negative, the autoantibodies were found only in 1.8% of the 113 samples obtained during the follow-up, independently of the status of disease. In conclusion, anti-p53 antibodies are often detected in serum from patients with advanced ovarian carcinoma. However, the serial measurement of these autoantibodies does not seem to give useful clinical information for the follow-up of these patients.

The serum assay of soluble CD44 standard (sCD44-st), CD44 splice variant 5 (sCD44-v5), and CD44 splice variant 6 (sCD44-v6) in patients with cervical cancer.

The pretreatment serum levels of soluble CD44 standard (sCD44st), CD44 splice variant 5 (sCD44-v5), and CD44 splice variant 6 (sCD44-v6) were retrospectively measured in 37 patients with untreated cervical cancer and in 36 patients with benign gynecological diseases as controls. Median sCD44-st levels were significantly higher in patients with cervical cancer than in controls (547 ng/ml, range 244-880 ng/ml versus 400.5 ng/ml, range 217-723 ng/ml, p = 0.004), whereas sCD44-v5 and sCD44-v6 concentrations were significantly lower in the former (34 ng/ml, range 0-140 ng/ml versus 44 ng/ml, range 11-109 ng/ml, p = 0.038; and 37 ng/ml, range 1-191 ng/ml versus 52.5 ng/ml, range 11-173 ng/ml, p = 0.007, respectively). sCD44-st, sCD44-v5, and sCD44-v6 levels were not related to FIGO stage and histologic type. Moreover, among patients with stage Ib-IIa cervical cancer, the preoperative levels of these glycoproteins correlated with neither the common prognostic variables nor the clinical outcome. Therefore, the serum assay of sCD44-st, sCD44-v5, and sCD44-v6 seems to have no clinical relevance for the management of patients with cervical cancer.

Analysis of failures after negative second-look in patients with advanced ovarian cancer: an Italian multicenter study.

This multicenter retrospective study is based on 192 patients with advanced ovarian cancer in pathological complete response at second-look surgery. Ninety-four (48.9%) patients developed recurrent disease after a median time of 18 months (range, 4-89 months) from surgical reassessment. The recurrence involved the pelvis in 45 (47.9%) cases, the abdomen in 42 (44.7%), the retroperitoneal lymph nodes in 13 (13.8%), and distant sites in 20 (21.2%). On the whole series, 5- and 7-year disease-free survival rates after negative second-look were 47.4 and 44.5%, respectively. By log-rank test the disease-free survival rate was related to FIGO stage (P = 0.008), tumor grade (P = 0.0021), size of residual disease after initial surgery (P = 0.0038), and type of second-look (laparoscopy vs laparotomy, P = 0.0061), but not to histological type and first-line chemotherapy. Cox proportional hazard model showed that tumor grade, size of residual disease, and type of second-look were independent prognostic variables for disease-free survival. The risk ratio of relapse was 2.386 (95% CI, 1.140-4.990) for grade 2 and 3.118 (95% CI, 1.515-6.416) for grade 3 compared to grade 1 disease. For patients with residual disease 1-2 cm and > 2 cm the risk ratio was, respectively, 1.877 (95% CI, 1.117-3.156) and 2.156 (95% CI, 1.324-3.511) compared to patients with residual disease < 1 cm. The risk ratio was 1.826 (95% CI, 1.121-2.973) for patients who were submitted to a laparoscopic second-look compared to those who underwent a laparotomic reassessment. Poorly differentiated grade and large residual disease after initial surgery are the strongest prognostic variables for recurrence after a negative second-look.

Preoperative D-dimer plasma assay is not a predictor of clinical outcome for patients with advanced ovarian cancer.

D-dimer (DD) plasma levels are significantly higher in patients with ovarian cancer than in those with benign ovarian masses. The aim of this paper is to assess whether preoperative DD plasma assay has a prognostic relevance for 35 patients with advanced ovarian cancer receiving platinum-based chemotherapy. Preoperative DD levels ranged from 162 to 3720 ng/ml. The 25, 50, and 75% quartiles of DD levels were 1600, 1894, and 2069 ng/ml, respectively. Preoperative DD levels correlated neither with the common clinicopathological prognostic variables nor with the disease status at the end of first-line chemotherapy. Survival was related to residual disease after initial surgery (> or =2 cm vs <2 cm, P = 0.003), but not to preoperative DD levels. In conclusion, the present data seem to show that preoperative DD plasma assay is not a predictor of clinical outcome for patients with advanced ovarian cancer.

Hormone replacement therapy and gynecological cancer.

The aim of this paper is to report the risk of development of gynecological cancer in women receiving hormone replacement therapy and to review the current knowledge on the administration of hormone replacement therapy following treatment of gynecological cancer. Estrogens alone may act as promoting factors for endometrial carcinogenesis. However, the addition of progestins reduces the risk of endometrial cancer to that of nonusers. Hormone replacement therapy could be given to selected patients following treatment for endometrial cancer. However, we think that this therapy should be reserved only for patients enrolled in controlled clinical trials. Ovarian cancer does not seem to be sensitive to estrogens, even if current literature does not allow firm conclusions to be drawn. Hormone replacement therapy should be offered to patients previously treated for ovarian cancer and cervical cancer.