Showing papers by "Sven Mahner published in 2011"
Charité1, University of Marburg2, University of Freiburg3, The Catholic University of America4, Charles University in Prague5, University of Hamburg6, Ludwig Maximilian University of Munich7, Goethe University Frankfurt8, University of Bonn9, University of Ulm10, Royal Brisbane and Women's Hospital11
TL;DR: This score is the first prospectively validated instrument to positively predict surgical outcome in recurrent ovarian cancer and will be enrolled in the recently started randomized prospective DESKTOP III trial investigating the role of surgery in recurrent platinum-sensitive ovarian cancer.
Abstract: Purpose: The DESKTOP I trial proposed a score for the prediction of complete cytoreduction in recurrent ovarian cancer. Resectability was assumed if 3 factors were present: (1) complete resection at first surgery, (2) good performance status, and (3) absence of ascites. The DESKTOP II trial was planned to verify this hypothesis prospectively in a multicenter setting. Methods: Participating centers prospectively enrolled all consecutive patients with platinum-sensitive first or second relapse. The score was applied to all patients, but centers were free to decide on therapy. All further therapies were documented, and the outcome of patients was analyzed. A 75% complete resection rate in 110 prospectively classified patients had to be achieved to confirm a positive predictive value of 2 or higher of 3 with 95% probability. Results: A total of 516 patients were screened within 19 months; of these, 261 patients (51%) were classified as score positive, and 129 patients with a positive score and first relapse were operated on. The rate of complete resection was 76%, thus confirming the validity of this score regarding positive prediction of complete resectability in 2 or more of 3 patients. Complication rates were moderate including second operations in 11% and perioperative mortality in 0.8%. Conclusions: This score is the first prospectively validated instrument to positively predict surgical outcome in recurrent ovarian cancer. It can aid in the selection of patients who might benefit from secondary cytoreductive surgery and will be enrolled in the recently started randomized prospective DESKTOP III trial investigating the role of surgery in recurrent platinum-sensitive ovarian cancer.
222 citations
TL;DR: With regard to effectiveness in terms of response and PFS, Tc remains the standard of care in patients with platinum-resistant recurrent ovarian cancer, however, comparable OS rates and a favorable toxicity profile make Tw another viable treatment option in this setting.
Abstract: Purpose Weekly administration of topotecan (Tw) is less toxic and widely considered a better treatment option than conventional 5-day therapy (Tc) in women with platinum-resistant recurrent ovarian cancer. We conducted a randomized phase II trial (TOWER [Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer]) to better define the ratio between benefits and risks with either treatment approach. Patients and Methods Patients were randomly assigned to two independent two-stage protocols of Tw (4 mg/m2/wk administered on days 1, 8, and 15) or Tc (1.25 mg/m2/d on days 1 to 5). We evaluated risk ratios (RRs) for the primary end point of clinical benefit (complete response, partial response, and stable disease), the duration of progression-free survival (PFS) and overall survival (OS), associated hazard ratios (HRs), and RRs of toxicity with 95% CIs. Results In total, 194 patients were randomly assigned at 54 centers to Tw (n = 97) or Tc (n = 97). Clinical benefit...
87 citations
TL;DR: Criteria for the indication and performance of chemo/radiotherapy of the vulva/groins/pelvis are still not fully established and vary between different countries and institutions due to the low level of evidence.
87 citations
TL;DR: A tumor-free resection margin is essential for locoregional control in vulvar cancer, however, in this large, single-center study it could not demonstrate any prognostic impact of pathological margin distance.
Abstract: A tumor-free resection margin of at least 8 mm is considered state of the art in vulvar cancer. This standard is based on small and heterogeneous patient cohorts, and its implementation can result in mutilation. One hundred two consecutive patients with primary squamous cell vulvar cancer were analyzed. All patients received resection of the primary tumor and the inguinofemoral lymph nodes via three separate incisions, resulting in complete tumor resection. Median follow-up was 31 months. Minimal margin distances were pathologically determined in all dimensions after fixation. Median age of the patients was 62 years; 38.2% had International Federation of Gynecology and Obstetrics (FIGO) stage I, 17.6% stage II, 24.4% stage III, and 8.8% stage IV disease. The median minimal resection margin was 5 mm (range 0.5–25 mm). Sixteen patients (15.6%) developed disease recurrence, of whom 10 (62.5%) at the vulva. Margin distance had no significant impact on disease-free survival when analyzed continuously (p = 0.388). When cases were divided into three subgroups of <3 mm (28.4%), ≥3 to <8 mm (42.2%), and ≥8 mm (29.4%) resection margin, neither univariate nor multivariate analysis revealed a difference in disease-free survival. There was no significant difference between any of the subgroups regarding tumor stages and adjuvant radiotherapy of the vulva. These results were independent of the direction of the minimal margin distance and consistent when only vulvar recurrences were analyzed. A tumor-free resection margin is essential for locoregional control in vulvar cancer. However, in this large, single-center study, we could not demonstrate any prognostic impact of pathological margin distance.
59 citations
TL;DR: CAIX is associated with advanced tumor stages and lymph node metastases in cervical cancer, potentially representing a new target in this disease.
Abstract: Carbonic anhydrase IX (CAIX) is a membranous expressed metalloenzyme involved in pH homeostasis and cell adhesion. The protein is overexpressed in a variety of tumors and potentially associated with negative outcome. This study was designed to investigate the prognostic role of CAIX in serum and tumor tissue of patients with primary cervical cancer. Tumor samples of 221 consecutive patients with primary cervical cancer who underwent surgery between 1993 and 2008 were analyzed for CAIX expression by immunohistochemistry. Additionally, preoperative serum CAIX concentrations were determined by ELISA in a subset of patients. Correlation with intratumoral CAIX expression as well as clinicopathological factors and outcome was analyzed. CAIX expression was observed in 81.9% of the tumor specimens; 62.0% showed a moderate or strong staining intensity. Moderate/strong expression was associated with squamous histology (p = 0.024), advanced tumor stage (p = 0.001), greater invasion depth (p = 0.025), undifferentiated tumor grade (p < 0.001) and high preoperative SCC-Ag values (p = 0.042). Furthermore patients with moderate/strong intratumoral CAIX expression had a higher number of metastatic lymph nodes compared to those with none/weak intratumoral expression levels (p = 0.047) and there was a non-significant association between high intratumoral CAIX expression and shorter survival (p = 0.118). Preoperative serum concentrations of CAIX ranged between 23 and 499 pg/mL and did not correlate with intratumoral expression or other clinicopathological variables. CAIX is associated with advanced tumor stages and lymph node metastases in cervical cancer, potentially representing a new target in this disease. In contrast to other epithelial cancers we could not observe a correlation between serum CAIX and its intratumoral expression.
56 citations
TL;DR: Δ133p53 expression was associated with prognosis in the vast majority of ovarian cancer cases, that is, patients with p53 mutant advanced serous carcinomas, and underline the importance of considering the complex p53 regulatory network.
Abstract: We aimed to evaluate the clinical relevance of p53 and p73 isoforms that modulate the function of p53. This prospective multicentre study included 154 patients with stage III and IV serous ovarian cancer. A functional yeast-based assay and subsequent sequencing were performed to analyse the p53 mutational status. Expression of p53 and p73 isoforms was determined using RT–qPCR. Δ133p53 expression constituted an independent prognostic marker for recurrence-free (hazard ratio=0.571, P=0.016, 95% CI: 0.362–0.899) and overall survival (hazard ratio=0.365, P=0.004, 95% CI: 0.182–0.731) in patients with p53 mutant ovarian cancer (n=121). High Δ40p53 expression was associated with favourable tumour grading (P=0.037) and improved recurrence-free survival (33.4 vs 19.6 months, P=0.029), but not overall survival (43.1 vs 33.6 months, P=0.139), in patients with p53 wild-type cancer (n=33). Neither the p53 mutational status nor p73 isoform expression possessed prognostic significance in the examined ovarian cancer cases. Δ133p53 expression was associated with prognosis in the vast majority of ovarian cancer cases, that is, patients with p53 mutant advanced serous carcinomas. Thus, our findings underline the importance of considering the complex p53 regulatory network.
40 citations
TL;DR: CA-125 serum levels differ significantly before and after surgery in early and advanced-stage ovarian cancer and preoperative CA-125 values correlate with surgical outcome inAdvanced-stage disease, but it could not be determined a preoperative cutoff value for prediction of the surgical result.
Abstract: Introduction
Despite radical surgery and chemotherapy, most patients with ovarian cancer develop recurrence and die due to progressive disease. To stratify patients for optimal therapy, prognostic and predictive factors are needed. We examined the role of pre- and postoperative CA-125 in this context.
33 citations
TL;DR: Serum CAIX might be an easily assessable marker to stratify patients for adjuvant therapy and potentially monitor response, and elevated preoperative serum values are associated with unfavorable prognosis.
Abstract: Introduction: Therapeutic options in advanced or recurrent vulvar cancer are limited. The identification of new prognostic factors and markers for therapy stratification is therefore highly desirable. Carbonic anhydrase IX (CAIX) is up-regulated in various solid tumors and a promising new target. We therefore determined CAIX serum concentration and its prognostic relevance in correlation to intratumoral CAIX expression in patients with primary vulvar cancer. Methods: Thirty-one serum samples of patients with primary vulvar cancer were prospectively collected before surgery and analyzed for CAIX by enzyme-linked immunosorbent assay. In addition, intratumoral CAIX expression was determined by immunohistochemistry and correlation with serum CAIX and clinicopathological factors, and outcome was analyzed. Results: Preoperative serum concentration of CAIX ranged between 56 and 879 pg/mL (median, 147 pg/mL; mean, 237.29) and was significantly higher in patients with high intratumoral expression (median, 269 pg/mL vs 126 pg/mL, P = 0.03). High serum CAIX was not associated with any of the analyzed clinicopathological parameters. However, disease-free survival was shorter in patients with high preoperative serum CAIX (above median; P = 0.012). By immunohistochemistry, 26% of the tumors showed a moderate or strong expression of CAIX, whereas 74% showed weak or no expression. High intratumoral expression of CAIX was also associated with unfavorable disease-free survival (P = 0.043). Conclusions: Carbonic anhydrase IX serum concentration is higher in patients with high intratumoral expression, and elevated preoperative serum values are associated with unfavorable prognosis. Serum CAIX might therefore be an easily assessable marker to stratify patients for adjuvant therapy and potentially monitor response. Carbonic anhydrase IX is differentially expressed in vulvar cancer and potentially associated with negative outcome.
26 citations
TL;DR: Topical clobetasol is of potential therapeutic benefit for patients with vulvar LS and might therefore improve quality of life.
Abstract: Background: This study investigates the health-related quality of life in patients with vulvar lichen sclerosus (LS) and the patient-defined therapeutic benefit of clobetasol.
25 citations
TL;DR: The combination of pegylated liposomal doxorubicin and carboplatin is active in this indication and the safety profile seems to be favourable compared to other widely used combination therapies for these diseases.
Abstract: 5093 Background: There are only limited data on treatment options in patients with malignant mixed epithelial mesenchymal and mesenchymal gynecologic tumors. An internationally accepted treatment s...
6 citations
TL;DR: In this article, further recent data regarding surgery for recurrent ovarian cancer are going to be discussed and the advantages of incorporating patients into randomized trials are highlighted.
Abstract: Cytoreductive surgery is accepted as a major treatment of primary ovarian cancer. The role in recurrent ovarian cancer remains a field of discussion and controversy, mainly owing to missing data from prospective randomized trials and lack of universal definitions. Retrospective data indicate that complete resection of recurrent tumor formations should be aimed for, since survival prolongation is mainly seen for patients with no residual disease. Thus, it is most important to find predictors of complete resection, on the one hand to offer the best therapeutic chances to patients, but on the other hand to protect patients with limited life expectancy from additional surgical burden. The first prospective surgical trial in recurrent ovarian cancer, AGO-DESKTOP II validated a score ('AGO score') for complete resection. It was shown that patients with a good general condition (ECOG 0), no residual disease after surgery for primary ovarian cancer and absence of ascites in presurgical diagnostics have a 76% likelihood of undergoing complete resection. In this article, further recent data regarding surgery for recurrent ovarian cancer are going to be discussed and the advantages of incorporating these patients into randomized trials are highlighted.
TL;DR: Carbanatin-PLD and carboplatin-paclitaxel are equieffective in patients with very platinum-sensitive relapsed ovarian cancer previously treated with platinum and paclitaxe, however, carboplATLD has a superior risk/benefit profile compared to carboplati-pac Litaxel which is of particular importance in this subgroup of patients with favourable prognosis.
Abstract: 5059 Background: CALYPSO is a randomized trial that showed superiority of carboplatin-pegylated liposomal doxorubicin (C-PLD) over carboplatin-paclitaxel (C-P) in relapsed ovarian cancer (ROC). Bec...