Prognostic value of preoperative Ca125 and Tag72 serum levels and their correlation to disease relapse and survival in endometrial cancer.

OBJECTIVE: To evaluate preoperative serum levels of Ca125 and Tag72-4 tumour markers and investigate if abnormal levels correlate to mortality and disease-free survival. METHOD: Retrospective observational study of a cohort of 282 women (mean age 62.3, SD 10.5 years) with primary endometrial cancer included all consecutive cases treated in a tertiary Gynaecological oncology Center. Excluded cases with other cancer or previous cancer treatment, major abdominal pathology or inflammation, endometriosis. Preoperative serum Tag72 and Ca125 levels were determined and evaluated in relation to disease-free survival (DFS) and disease-specific overall survival (DOS). RESULTS: Raised Ca125 correlates to worse overall disease-specific survival (66.1 vs 87.8 months, p = 0.021) and Tag72 correlates to shorter disease-free survival (69.2 vs 67.3 months, p = 0.021) and higher recurrence rate (13.5 vs 6 %, p = 0.021). When both Ca125 and Tag72 are abnormal DFS and DOS are worse. 93.3 % (72.3 months) vs 82.4 %, (61.3 months) p = 0.018 and 96.3 % (74.8 months) vs 88.2 %, (65.9 months) p = 0.021, respectively. CONCLUSION: This study enhances the value of preoperative tumour markers and their prognostic value. Ca125 and Tag72 appear to be good predictors of poor prognosis in patients with endometrial cancer.

Improved survival trends in platinum-resistant patients with advanced ovarian, fallopian or peritoneal cancer treated with first-line paclitaxel/platinum chemotherapy: the impact of novel agents.

OBJECTIVE: The prognosis for patients with platinum-resistant advanced ovarian cancer remains poor. The impact of approved agents on survival has not been clarified during the last decade. We studied survival trends during the last 15 years in platinum-resistant patients treated with cytoreductive surgery followed by paclitaxel/platinum chemotherapy. METHODS: Patients with epithelial ovarian, fallopian or peritoneal cancer, stages III/IV and platinum-resistant disease after first-line chemotherapy with paclitaxel/platinum were included. They were grouped according to the period of chemotherapy: group A 31/3/1995-31/12/2001 (n = 56) and Group B 1/1/2002-24/12/2008 (n = 57). In order to compensate for the difference in follow-up between the 2 groups, we performed minimum follow-up (MFU) analyses by considering as cases only women who had an event within 3 years of follow-up. Patients with no events for up to 3 years were censored at that time. RESULTS: MFU analyses showed that median overall survival (OS) was significantly longer in group B: 12.3 vs. 17.5 months (p = 0.012). This was due to a doubling of the median OS after relapse: 5.7 vs. 10.9 months (p = 0.0180). Multivariate Cox regression indicated group and histology as factors statistically significantly associated with OS. Following relapse, patients in group B were predominantly treated with liposomal doxorubicin and gemcitabine, and patients in group A were treated with platinum compounds, docetaxel and oral etoposide (p < 0.001). CONCLUSIONS: The introduction of novel agents without cross-resistance to platinum or taxanes has improved the prognosis of platinum-resistant patients.

VEGF directly suppresses activation of T cells from ovarian cancer patients and healthy individuals via VEGF receptor Type 2.

The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis is well characterized; nevertheless, it is also a key element in promoting tumor evasion of the immune system by downregulating dendritic cell maturation and thus T cell activation. We sought to investigate the possible direct effect of VEGF on T cell activation and through which type of VEGF receptor (VEGFR) it exerts this effect. Circulating T cells from healthy donors and ovarian cancer patients were expanded in cultures with anti-CD3 and IL-2 with or without VEGF for 14 days, and the number of T cells was assessed. Cultured T cells were also tested for their cytotoxic activity in a standard 4-hr (51) Cr-release assay, and the expression of VEGFRs 1, 2 and 3 was assayed by flow cytometry, immunocytochemistry and Western blotting. To assess the ability of activated T cells to secrete VEGF, levels in culture supernatants were measured by enzyme linked immunosorbent assay. The addition of VEGF in cultures significantly reduced T cell proliferation in a dose-dependent manner. Protein expression studies demonstrated that CD3(+) T cells express VEGFR-2 on their surface upon activation. Experiments with anti-VEGFR-2 antibodies showed that the direct suppressive effect of VEGF on T cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells and that activated T cells secrete VEGF in the culture environment. Overall, our study shows that T cells secret VEGF and expresses VEGFR-2 upon activation. VEGF directly suppresses T cell activation via VEGF receptor type 2.

A risk-adapted strategy of adjuvant paclitaxel/carboplatin in early-stage ovarian cancer: time-dependent effect of 4 versus 6 cycles on outcome.

OBJECTIVE: We investigated the efficacy of risk-adapted adjuvant paclitaxel/carboplatin chemotherapy in early-stage ovarian carcinoma. METHODS: Fifty-three patients were treated according to the risk of relapse: patients with stages IA or IB or with grade 1 (low risk) received 4 cycles of paclitaxel and carboplatin; patients with IC/IIA and grade 2 or 3 (high risk) received 6 cycles of chemotherapy. The outcome was compared with that of 95 patients who were all treated with 4 cycles. RESULTS: Median follow-up was 88, 113 and 42 months for the whole cohort, non-risk-adapted and risk-adapted treatment, respectively. Five-year relapse-free and disease-specific survival was 86 and 93% for the whole population, 96 and 97% for low-risk and 81 and 91% for high-risk patients. Risk classification was the only significant prognostic factor for relapse-free (p = 0.011) and disease-specific survival (p = 0.039). Among high-risk patients, the administration of 6 cycles was associated with a significantly lower relapse rate after censoring events, which occurred beyond 2 years (3 vs. 18%; p = 0.013), but this difference was diminished at 5 years (23 vs. 25%; p = 0.797). CONCLUSIONS: Six cycles of chemotherapy reduced the risk of relapse within 2 years, but the benefit from two additional cycles beyond this time is questionable.

Current use of impact models for agri-environment schemes and potential for improvements of policy design and assessment.

Agri-Environment Schemes (AES) to maintain or promote environmentally-friendly farming practices were implemented on about 25% of all agricultural land in the EU by 2002. This article analyses and discusses the actual and potential use of impact models in supporting the design, implementation and evaluation of AES. Impact models identify and establish the causal relationships between policy objectives and policy outcomes. We review and discuss the role of impact models at different stages in the AES policy process, and present results from a survey of impact models underlying 60 agri-environmental schemes in seven EU member states. We distinguished among three categories of impact models (quantitative, qualitative or common sense), depending on the degree of evidence in the formal scheme description, additional documents, or key person interviews. The categories of impact models used mainly depended on whether scheme objectives were related to natural resources, biodiversity or landscape. A higher proportion of schemes dealing with natural resources (primarily water) were based on quantitative impact models, compared to those concerned with biodiversity or landscape. Schemes explicitly targeted either on particular parts of individual farms or specific areas tended to be based more on quantitative impact models compared to whole-farm schemes and broad, horizontal schemes. We conclude that increased and better use of impact models has significant potential to improve efficiency and effectiveness of AES.

Paclitaxel- and platinum-based postoperative chemotherapy for primary fallopian tube carcinoma: a single institution experience.

BACKGROUND: Primary fallopian tube carcinoma (PFTC) is a rare gynecologic malignancy with very few data existing on the activity of the combination of paclitaxel with a platinum analogue as adjuvant chemotherapy. METHODS: We retrospectively analyzed 41 consecutive patients with PFTC who were treated postoperatively with paclitaxel- and platinum-containing chemotherapy regimens. RESULTS: We observed 12 (63.2%) complete and 6 (31.6%) partial responses among 19 patients with measurable disease. The median time to disease progression (TTP) for all patients was 68 months. The median overall survival (OS) for all patients has not been reached yet. The median TTP was 84 months for patients with stage I/II disease and 34 months for patients with advanced disease (p = 0.017). Median OS has not been reached yet for patients with stage I/II PFTC, while it was 63.8 months for patients with stage III/IV disease (p = 0.002). Furthermore, OS has not been reached yet for patients with optimally debulked tumors, while it was 34.1 months for patients with residual disease >2 cm (p < 0.0001). CONCLUSION: Adjuvant platinum- and paclitaxel-based chemotherapy should be regarded as the standard treatment in patients with PFTC. Early stage disease and optimal debulking are associated with improved TTP and OS.

Advanced epithelial ovarian cancer in the elderly: chemotherapy tolerance and outcome.

BACKGROUND: The prognostic significance of age in ovarian cancer has not been clarified. We investigated the characteristics of ovarian cancer presenting in ages > 70 years and assessed the prognostic significance of advanced age. PATIENTS AND METHODS: Four hundred and fifty-three patients with stage IIC-IV ovarian cancer (age>70 years n=106 [23%]), treated postoperatively with platinum-based chemotherapy were retrospectively reviewed. RESULTS: Median overall survival (OS) of patients 570 years old (52.3 months, 95% CI: 43.2-61.3) was longer than that of older patients (38.8 months, 95% CI: 29.9-47.7) (p =0.005), but this difference was not significant in a multivariate analysis (p=0.978). Age >70 years was correlated with worse performance status (PS) (p=0.019), higher tumor grade (p=0.033), residual disease >2 cm (p=0.006) and less frequent paclitaxel administration (p<0.001). Toxicity from chemotherapy was similar between the two age groups, but the relative dose intensity of paclitaxel was lower among elderly patients. CONCLUSION: The worse outcome of ovarian cancer in elderly patients may be attributed to other associated adverse prognostic factors, but advanced age was not an independent prognostic factor.

Mucinous but not clear cell histology is associated with inferior survival in patients with advanced stage ovarian carcinoma treated with platinum-paclitaxel chemotherapy.

BACKGROUND: Mucinous and clear cell histology have been associated with adverse prognosis in ovarian carcinomas. The authors compared the outcome of these subtypes with that of serous tumors in patients who were treated with combination paclitaxel/platinum at their center. METHODS: Four hundred twenty patients with histologically confirmed, serous (n = 367), mucinous (n = 24), or clear cell (n = 29) ovarian carcinomas, International Federation of Gynecology and Obstetrics stage III or IV disease, and who were treated with paclitaxel/platinum after cytoreductive surgery were included in this analysis. RESULTS: The median overall survival for each histological subtype was 47.7 months (95% confidence interval [CI], 37.7-57.7 months) for serous, 15.4 months (95% CI, 4.2-26.6 months) for mucinous, and 36.6 months (95% CI, 22.7-50.5 months) for clear cell carcinomas. Cox regression analysis showed that mucinous histology was an independent predictor of poor prognosis compared with serous tumors (hazard ratio, 0.360; 95% CI, 0.215-0.603; P = .001). In contrast, such a difference between clear cell and serous carcinomas was not found (P = .337). Median survival of patients with mucinous tumors and residual disease >2 cm was poor, averaging 7.1 months (95% CI, 4.6-9.6 months). CONCLUSIONS: Mucinous but not clear cell histology is associated with significantly worse prognosis in advanced ovarian cancer treated with combination platinum/paclitaxel. Different therapeutic strategies should be studied in this entity.

Young age is associated with favorable characteristics but is not an independent prognostic factor in patients with epithelial ovarian cancer: a single institution experience.

BACKGROUND: Young age has been reported to be a favorable prognostic factor in ovarian cancer. The aim of the present study was to investigate the characteristics of ovarian cancer presenting in patients aged < or =40 and assess the prognostic significance of young age. METHODS: Data from 591 consecutive ovarian cancer patients, including 37 subjects (6.3%) aged < or =40, who were treated postoperatively with platinum-based chemotherapy in our institution were retrospectively reviewed. RESULTS: In our series, age < or =40 did not show an independent association with overall (p = 0.542) or progression-free survival (p = 0.334). Nonetheless, it was correlated with low tumor grade (p = 0.009) and small volume of residual disease after primary surgery (p = 0.020), while there was a nonsignificant trend for correlation with performance status 0 (p = 0.052). Stratified analysis showed that age < or =40 was associated with improved overall survival in the subgroups of serous histology and stage IIC-IV disease; however, multivariate analyses failed to identify age as an independent predictor of survival within either subgroup (p = 0.079 and p = 0.585, respectively). CONCLUSIONS: Age < or =40 was not an independent prognostic factor in our analysis. The survival advantage of young patients may be attributed to the association with low tumor grade, more complete surgical debulking and better performance status.