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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.

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.

Apoptosis is a genetically regulated biological process that plays a major role in chemotherapy-induced tumor cell killing. It may be triggered by two major intracellular signaling cascades, the mitochondrial pathway and the death receptor pathway, both leading to caspase activation and cleavage of specific cellular substrates. The p53 gene is involved in the regulation of apoptosis. Caspase activation following wild-type p53 induction is associated with the release of the apoptogenic factors cytochrome c and Smac/DIABLO from the mitochondria, that is in turn controlled by the pro-apoptotic and anti-apoptotic Bcl-2 family proteins. In ovarian cancer p53 status is a strong predictor of response to platinum-based chemotherapy. Patients whose tumors have p53 mutations experience a lower chance of achieving a complete response following platinum-based regimens when compared to patients without p53 mutations. Conversely, experimental and clinical data seem to show that paclitaxel enhances apoptosis through a p53-independent pathway, that probably involves the Bax gene. Whereas patients with wild-type p53 tumors have a good chance to respond to platinum, patients with mutant p53 tumors may have a clinical benefit from the addition of paclitaxel to platinum-based chemotherapy. Therefore determining p53 status can be useful in predicting therapeutic response to specific drugs. Moreover the understanding of cellular mechanisms regulating apoptosis might offer a strong rationale for the combination of chemotherapy with other biological treatments.

Purpose of Investigation: The objective of this retrospective multicenter study was to assess the prognostic relevance of histologic type in uterine sarcomas., Methods: The hospital reports of 249 patients with uterine sarcomas were reviewed. Surgery was the initial therapy for all patients. Histologic type was leiomyosarcoma in 95 cases, low-grade endometrial stromal sarcoma (ESS) in 19, high-grade ESS in 34, and carcinosarcoma in 101. Postoperative treatment was given without well-defined protocols. Median follow-up of survivors was 97 months., Results: In the whole series 2-year, 5-year, and 10-year survival rates were 53.5%, 41.6%, and 35.8%, respectively, and median survival was 31 months. At univariate analysis survival was significantly related to stage (p = 0.0001), mitotic count (p = 0.0001), and histologic type (low-grade ESS vs leiomyosarcoma vs carcinosarcoma vs high-grade ESS, median: not reached vs 27 months vs 21 months vs 16.5 months, p = 0.0011), but not to postoperative therapy and patient age. The Cox model revealed that tumor stage, mitotic count and histologic type were independent prognostic variables for survival. In detail, the risk of death was significantly lower for low-grade ESS (risk ratio [RR] = 0.257; 95% confidence interval [CI] = 0.071-0.931) and carcinosarcoma (RR = 0.509; 955 CI = 0.324-0.799) when compared to leiomyosarcoma. Conversely, no significant difference in survival was found between leiomyosarcoma and high-grade ESS., Conclusions: Histologic type is an independent prognostic variable for survival in uterine sarcomas. Low-grade ESS has the best clinical outcome, whereas leiomyosarcoma has the poorest one. It is noteworthy that, when adjusting for stage and mitotic count, leiomyosarcoma has a significantly worse prognosis than carcinosarcoma.