Treatment strategies in patients with gynecological sarcoma: Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA-NOGGO RU1).

OBJECTIVE: Gynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus on optimal therapeutic strategies. This study's objective was to describe the treatment strategies used in patients with gynecological sarcomas in the primary course of disease. METHODS: The German prospective registry for gynecological sarcoma (REGSA) is the largest registry for gynecological sarcomas in Germany, Austria and Switzerland. Primary inclusion criteria for REGSA are histological diagnosis of sarcoma of the female genital tract, sarcoma of the breast or uterine smooth muscle tumors of uncertain malignant potential (STUMP). We evaluated data of the REGSA registry on therapeutic strategies used for primary treatment from August 2015 to February 2021. RESULTS: A total of 723 patients from 120 centers were included. Data on therapeutic strategies for primary treatment were available in 605 cases. Overall, 580 (95.9%) patients underwent primary surgery, 472 (81.4%) of whom underwent only hysterectomy. Morcellation was reported in 11.4% (n=54) of all hysterectomies. A total of 42.8% (n=202) had no further surgical interventions, whereas an additional salpingo-ophorectomy was performed in 54% (n=255) of patients. An additional lymphadenectomy was performed in 12.7% (n=60), an omentectomy in 9.5% (n=45) and intestinal resection in 6.1% (n=29) of all patients. Among 448 patients with available information, 21.4% (n=96) received chemo- or targeted therapies, more commonly as single-agent treatment than as drug combinations. Information about anti-hormonal treatment was available for 423 patients, among which 42 (9.9%) received anti-hormonal treatment, 23 (54.8%) of whom with low-grade endometrial stroma sarcomas. For radiotherapy, data of 437 patients were available, among which 29 (6.6%) patients underwent radiotherapy. CONCLUSION: Our study showed that treatment of patients with gynecologic sarcomas is heterogeneous. Further trials are needed along with more information on treatment modalities, therapy response and patient-reported outcomes to implement new treatment strategies.

Pattern of care of adjuvant radiotherapy in male breast cancer patients in clinical practice: an observational study.

BACKGROUND AND PURPOSE: Due to the rarity of male breast cancer (male BC), no consensus has been reached regarding the most appropriate curative treatment strategy. The objective of the present observational study was to identify patient and tumor characteristics and assess the role of radiotherapy (RT) in clinical practice. METHODS: Between 1998 and 2014, data of male BC patients treated at two breast centers were consecutively collected and retrospectively analyzed. Patients were stratified based on the addition of adjuvant RT. Data on overall survival (OS) and local recurrence-free survival (LRFS) were estimated with the Kaplan-Meier method and compared by the log-rank test. RESULTS: A consecutive cohort of 58 male BC patients was evaluated. Median follow-up was 56 months. Twenty-one patients (36.2%) received adjuvant RT. Overall, patients undergoing postoperative RT were characterized by more high-risk features. Patients receiving postoperative RT had significantly more frequently a high UICC stage (50 vs. 9.7% UICC III, p = 0.018) and positive lymph nodes as compared to patients undergoing surgery alone (65 vs. 34.4% pN+, p = 0.046). Accordingly, there was a higher proportion of patients receiving axillary lymph node dissection in the RT group (71.4 vs. 35.6%). Mastectomy was performed in 31/37 (86.1%) in the surgery group as compared to 14/21 (66.7%) in patients receiving postoperative RT. In addition, RT patients were more likely to receive endocrine therapy (78.9 vs. 39.3%, p = 0.016). Outcome was not significantly different between the groups (5-year LRFS: 89.8 vs. 80.0%, p = 0.471 and 5­year OS 88.4 vs. 88.9%, p = 0.819). CONCLUSION: The present observational study evaluated the pattern of care in male BC patients treated in clinical practice. Due to its rarity, randomized clinical trials are unlikely and male BC remains an entity with a poor evidence base. Nevertheless, RT remains a crucial component of the multidisciplinary treatment strategy in male BC.

Quality of life in breast cancer patients and surgical results of immediate tissue expander/implant-based breast reconstruction after mastectomy.

OBJECTIVES: The purpose of this study was to analyze the effects of prior radiotherapy (RT) as well as postmastectomy radiotherapy (PMRT) on patient-reported quality of life (QoL) and on surgical/aesthetic outcomes in patients with expander-/implant-based delayed immediate reconstruction (EIBR) compared to patients that underwent EIBR without any RT. MATERIAL AND METHODS: QoL was assessed by BREAST-Q, the surgical/aesthetic outcome by a structured examination and a picture analysis (BCCT.CORE software) and subsequently compared between the three cohorts. RESULTS: Of 161 eligible patients, 97 followed the invitation (no RT n = 54, 9 of them with bilateral EIBR; PMRT n = 26; history of RT n = 15). The surgical/aesthetic results were better in the RT-naive cohort than in the PMRT cohort, but satisfaction with outcome and psychosocial well-being were better in the PMRT cohort. The RT-naive cohort showed (significantly) higher scores in satisfaction with breast, satisfaction with implant and sexual well-being compared to the history of RT cohort, although satisfaction with outcome was comparable. The PMRT cohort reached significantly more points in almost all categories and better BCCT.CORE and examination results than the history of RT cohort. Of all patients, 92.7%, 84.6% and 78.6% (RT naive, PMRT, history of RT) would agree to undergo EIBR again. CONCLUSION: EIBR results in acceptable QoL and surgical results. In patients with a prior RT, QoL is significantly lower and surgical results are significantly worse. However, high acceptance rates suggest EIBR being a justifiable option even for this group. Prospective studies and long-term follow-up are required for definitive conclusions.

Endometrial cancer-how many patients could benefit from sentinel lymph node dissection?

BACKGROUND: Sentinel lymph node dissection (SLND) may reduce morbidity in patients with endometrial cancer. The objective of this study is to estimate how many systematic lymph node dissections (LND) can be spared with an implementation of a SLN-procedure. METHODS: Retrospective, single-center study, SLND according to NCCN-Guidelines. RESULTS: In 109 patients of 154 consecutive patients, SLND was performed. The detection rate was 61% on both sides and 86% on at least one side. Classification of uterine risk factors is as follows: low risk 53, intermediate risk 25, high-intermediate risk 13, and high-risk 18. Stage IIIC: 0, 3, 7, 11, respectively. Under the assumption that 56 patients with "higher than low risk" factors would be treated by systematic LND, we spared 26 pelvic and paraaortic LND. After failures of SLN detection, unilateral pelvic LND was performed in 15 patients. Patients with "higher than low risk" factors and node-negative SLN are candidates for a randomized study to prove safety and efficacy. Only every third patient in our study met these criteria. CONCLUSIONS: In a cohort of patients with "higher than low risk" endometrial cancer, the implementation of SLND nearly divided the number of radical lymph node dissections in half. Further studies are required to define the best modalities for SLND.

Opportunistic salpingectomies for the prevention of a high-grade serous carcinoma: a statement by the Kommission Ovar of the AGO.

The detection of premalignant cells in the epithelium of the fallopian tube has resulted in revolutionary theories regarding the origin of epithelial ovarian cancer (EOC). Serous tubal intra-epithelial carcinomas (STIC) have been detected in patients with BRCA 1 or 2 mutations and are considered as the most likely precursors of the high-grade serous ovarian cancer (HGSOC), which is the most common histological subtype in patients with EOC. A bilateral salpingo-oophorectomy is associated with a significant reduction in risk of developing EOC. According to various national guidelines, prophylactic bilateral salpingo-oophorectomy should be performed in the age group 40-45 years. As in patients with BRCA mutations, the prophylactic removal of the fallopian tubes is also performed in women without an increased genetic risk, for example, in surgical treatments of benign conditions. There is a current debate as to whether prophylactic or so-called opportunistic salpingectomy will influence the overall incidence of EOC in the coming years. Opponents of this theory warn of a higher surgical morbidity and the higher risk of a premature menopause through impaired vascular supply to the ovaries. The value of opportunistic salpingectomies has not yet been clarified since there are currently no systematic risk-benefit evaluations. This review will attempt to give an overview of the current body of evidence regarding the risks and benefits of opportunistic salpingectomies.

Interval debulking surgery in patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC and IV ovarian cancer.

BACKGROUND: The feasibility of neoadjuvant chemotherapy (NAC) and the outcome in patients with Federation of Gynecology and Obstetrics (FIGO) IIIC and IV ovarian cancer were assessed. PATIENTS AND METHODS: 67 patients undergoing interval debulking surgery (IDS) and ≥ 4 courses of platinum-based NAC were analyzed for survival, perioperative morbidity and mortality. RESULTS: The median follow-up was 30 months. The median progression-free survival (PFS) was 17 months, the overall survival (OS) 34 months. The PFS of patients without residual disease (n = 23; 34.3%) was 31 months (p = 0.003), the OS 65 months (p = 0.001). PFS and OS were significantly longer in patients with no residual disease than in patients with 1-10 mm (n = 34; 47.9%) (p = 0.005 and p = 0.0001, respectively) residual disease. No survival benefit was seen for patients with 1-10 mm compared to > 1 cm (n = 12; 16.9%) residual disease (PFS p = 0.518; OS p = 0.077). 1 patient (1.4%) died; 12 patients needed interventional treatment or operation (16.9%) within the first 30 days postoperatively. Out of these, 5 patients (7.0%) had residual or lasting disability. CONCLUSIONS: NAC and IDS are safe and feasible in this series of patients with unfavorable prognosis. IDS does not change the goal of complete cytoreduction and therefore does not compensate for a less radical surgical approach.

Adjuvant Therapy for Elderly Breast Cancer Patients after Breast-Conserving Surgery: Outcomes in Real World Practice.

We aimed to evaluate the standard of care of adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) in elderly female patients (≥65 years) treated outside of clinical trials and to identify potential factors related to the omission of RT and the interaction with endocrine therapy (ET). All women treated with BCS at two major breast centers between 1998 and 2014 were evaluated. Data were provided by the Tumor Registry Munich. Survival analyses were conducted using the Kaplan-Meier method. Prognostic factors were identified using multivariate Cox regression analysis. The median follow-up was 88.4 months. Adjuvant RT was performed in 82% (2599/3171) of patients. Irradiated patients were younger (70.9 vs. 76.5 years, p < 0.001) and were more likely to receive additional chemotherapy (p < 0.001) and ET (p = 0.014). Non-irradiated patients more often had non-invasive DCIS tumors (pTis: 20.3% vs. 6.8%, p < 0.001) and did not undergo axillary surgery (no axillary surgery: 50.5% vs. 9.5%, p < 0.001). Adjuvant RT was associated with improved locoregional tumor control after BCS in invasive tumors (10-year local recurrence-free survival (LRFS): 94.0% vs. 75.1%, p < 0.001, 10-year lymph node recurrence-free survival (LNRFS): 98.1% vs. 93.1%, p < 0.001). Multivariate analysis confirmed significant benefits for local control with postoperative RT. Furthermore, RT led to increased locoregional control even in patients who received ET (10-year LRFS 94.8% with ET + RT vs. 78.1% with ET alone, p < 0.001 and 10-year LNRFS: 98.2% vs. 95.0%, p = 0.003). Similarly, RT alone had significantly better locoregional control rates compared to ET alone (10-year LRFS 92.6% with RT alone vs. 78.1% with ET alone, p < 0.001 and 10-year LNRFS: 98.0% vs. 95.0%, p = 0.014). The present work confirms the efficacy of postoperative RT for breast carcinoma in elderly patients (≥65 years) treated in a modern clinical setting outside of clinical trials, even in patients who receive ET.

Immunogenic cell death of human ovarian cancer cells induced by cytosolic poly(I:C) leads to myeloid cell maturation and activates NK cells.

Owing to high rates of tumor relapse, ovarian cancer remains a fatal disease for which new therapeutic approaches are urgently needed. Accumulating evidence indicates that immune stimulation may delay or even prevent disease recurrence in ovarian cancer. In order to elicit proinflammatory signals that induce or amplify antitumor immune reactivity, we mimicked viral infection in ascites-derived ovarian cancer cells. By transfection or electroporation we targeted the synthetic double-stranded RNA poly(I:C) intracellularly in order to activate melanoma differentiation-associated gene-5 (MDA-5), a sensor of viral RNA in the cytosol of somatic cells. Cancer cells reacted with enhanced expression of HLA-class I, release of CXCL10, IL-6, and type I IFN as well as tumor cell apoptosis. Monocytes and monocyte-derived DCs (MoDCs) engulfed MDA-5-activated cancer cells, and subsequently upregulated HLA-class I/II and costimulatory molecules, and secreted CXCL10 and IFN-α. Further, this proinflammatory milieu promoted cytolytic activity and IFN-γ secretion of NK cells. Thus, our data suggest that the engagement of MDA-5 in a whole tumor cell vaccine is a promising approach for the immunotherapy of ovarian cancer.

Detection of lymphovascular invasion by D2-40 (podoplanin) immunoexpression in endometrial cancer.

BACKGROUND: Lymph node involvement is a major feature in tumor spread of endometrial cancer and predicts prognosis. Therefore, evaluation of lymph vessel invasion (LVI) in tumor tissue as a predictor for lymph node metastasis is of great importance. Immunostaining of D2-40 (podoplanin), a specific marker for lymphatic endothelial cells, might be able to increase the detection rate of LVI compared with conventional hematoxylin-eosin (H-E) staining. The aim of this retrospective study was to analyze the eligibility of D2-40-based LVI evaluation for the prediction of lymph node metastases and patients' outcome. PATIENTS AND METHODS: Immunohistochemical staining with D2-40 monoclonal antibodies was performed on paraffin-embedded tissue sections of 182 patients with primary endometrioid adenocarcinoma treated in 1 gynecologic cancer center. Tumors were screened for the presence of LVI. Correlations with clinicopathological features and clinical outcome were assessed. RESULTS: Immunostaining of D2-40 significantly increased the frequency LVI detection compared with conventional H-E staining. Lymph vessel invasion was identified by D2-40 in 53 (29.1%) of 182 tumors compared with 34 (18.3%) of 182 carcinomas by routine H-E staining (P = 0.001). D2-40 LVI was detectable in 81.0% (17/21) of nodal-positive tumors and significantly predicted lymph node metastasis (P = 0.001). Furthermore, D2-40 LVI was an independent prognostic factor for patients overall survival considering tumor stage, lymph node involvement, and tumor differentiation (P < 0.01). D2-40-negative tumors confined to the inner half of the myometrium showed an excellent outcome (5-year overall survival, 97.8%). CONCLUSIONS: D2-40-based LVI assessment improves the histopathological detection of lymphovascular invasion in endometrial cancer. Furthermore, LVI is of prognostic value and predicts lymph node metastasis. D2-40 LVI detection might help to select endometrial cancer patients who will benefit from a lymphadenectomy.

Validation of the 21-Gene Recurrence Score Assay in Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer and 0 to 3 Positive Lymph Nodes: Risk Pattern and Outcomes on a Community Level.

Introduction: The aim of the present study was to analyze the performance of Oncotype DX® multigene assay (ODX®) in patients with 0-3 lymph nodes in a high-volume community hospital. Methods: Patients with non-metastatic HR*/HER2- EBC and 0-3 positive lymph nodes, who underwent primary surgery at the Red Cross Hospital Munich, Germany and consecutively had ODX® testing were included in this retrospective study. The distribution of clinicopathologic characteristics, recurrence score (RS) risk, and use of systemic therapy were compared among patients without positive lymph nodes (N0) and patients with micrometastases or 1 to 3 positive lymph nodes (N1). Disease-free survival (DFS) and overall survival (OS) were estimated. Results: From 2012 to 2017 ODX® was consecutively performed in 575 (16.4%) of 3,492 women with HR*/HER- EBC, of which 553 were eligible for this analysis (N0: 60.8%; N1: 39.2%). Among the patients included, 441 (79.7%) had an RS of 0 to 25 and 112 (20.3%) had an RS of 26 or higher. In patients with RS 0 to 25 the rate of chemotherapy use was low, independent from nodal status (N0: 17.1% and N1: 19.1%) and 5-year DFS was 90.5% and 91.7% for N0 and N1 patients, respectively. There was no significant difference in DFS (90.5% vs. 93.3%; p = 0.101) or OS (97.2% vs. 96.0%; p = 0.737) for patients with an RS of 0 to 25 when treated with chemo-endocrine therapy or endocrine therapy alone, independent from nodal status. Conclusions: The results of the study confirm the observations from randomized studies on the use of the ODX® in a real-world population in terms of risk distribution and patient outcome. Adjuvant chemotherapy could be safely omitted in patients with HR*/HER2- breast cancer with 0-3 positive lymph nodes and RS <25.

Prospective validation study of a predictive score for operability of recurrent ovarian cancer: the Multicenter Intergroup Study DESKTOP II. A project of the AGO Kommission OVAR, AGO Study Group, NOGGO, AGO-Austria, and MITO.

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.

Application of T cell-based transcriptomics to identify three candidate biomarkers for monitoring anti-TGFbetaR therapy.

OBJECTIVES: The development of targeted drugs would greatly benefit from the simultaneous identification of biomarkers to determine the aspects of bioactivity, drug safety and efficacy, particularly when affecting receptor-signaling pathways. However, the establishment of appropriate systems to monitor drug-induced events requires an accessible surrogate tissue for functional read out. METHODS: Therefore we present a universal platform based upon T cell-based gene expression profiling for the identification of biomarkers using the antitransforming growth factor beta receptor inhibitor LY2109761 as an example. RESULTS: Our initial screen revealed 12 candidate genes specifically regulated in T cells by the inhibitor. In subsequent in-vitro and in-vivo analyses, the combined monitoring of independent gene regulation of three genes was established in peripheral blood mononuclear cells as novel pharmacodynamic candidate biomarkers for antitransforming growth factor beta receptor based therapies. CONCLUSION: Overall, the proposed concept of biomarker identification can be easily adapted towards other drug candidates for whom gene regulation can be established in cellular components of peripheral blood.

Foxp3(+) cell infiltration and granzyme B(+)/Foxp3(+) cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma.

Preoperative neoadjuvant chemotherapy (NAC) can significantly reduce tumour burden in patients with primarily unresectable chemosensitive tumours, allowing a more complete cytoreduction during debulking surgery and facilitating evaluation of tumour chemosensitivity, identification of appropriate treatment options and improvement of intervention protocols. In this study, we investigate, using immunohistochemistry, the impact of platinum/taxane-based NAC (NAC) on tumour-infiltrating lymphocytes (TILs) in advanced epithelial ovarian cancer (EOC) and their relationship with clinical outcome. All patients had clinical response, as shown by ascites volume and CA125 levels compared to pre-treatment findings. NAC intervention significantly increased CD4(+), CD8(+) and granzyme B(+) infiltration while Foxp3(+) accumulation remained unaffected. TILs were prognostically neutral for both progression-free survival (PFS) and overall survival (OS) before NAC. In contrast, after NAC, elevated granzyme B(+) infiltration displayed a tendency for improved PFS (log-rank 0.064). Further, low Foxp3(+) cell density was associated with longer PFS, as compared with strong Foxp3(+) infiltration (median 20.94 vs. 11.24 months; log-rank 0.0001) and with improved OS (median 30.75 vs. 16.04 months, respectively; log-rank 0.056), demonstrating clear prognostic significance for PFS. In addition, high granzyme B(+)/Foxp3(+) ratio post-NAC strongly correlated with improved PFS compared to low granzyme B(+)/Foxp3(+) cell ratio (median 17.88 vs. 11.24 months, respectively), and showed to be a favourable prognostic factor for PFS (log-rank 0.014). Our findings indicate that NAC elicited an immunologic profile in which low immunosuppressive Foxp3(+) infiltration and elevated numbers of activated granzyme B(+) cells were significantly associated with EOC-specific PFS, suggesting a contribution of immunologic effects to improved clinical outcome.

In vivo intratumor angiogenic treatment effects during taxane-based neoadjuvant chemotherapy of ovarian cancer.

BACKGROUND: The aim of our study was to analyze the effect of taxane-based chemotherapy on tumor angiogenesis in patients with advanced epithelial ovarian cancer. METHODS: Within a prospective phase II trial, 32 patients with stage IIIC and IV ovarian cancer were treated with either two or three cycles of neoadjuvant chemotherapy prior to cytoreductive surgery. Carboplatin (AUC5) and docetaxel (75 mg/m2) were administered intravenously in a 3-weekly schedule. Changes in intratumor microvessel density (MVD) were assessed with immunohistochemistry by staining pre- and posttreatment surgical tumor specimens with panendothelial, neovascular and lymphatic vessel markers. RESULTS: Mean values of MVD defined by CD31, CD34, CD105 and D2-40 antibodies showed 12.3, 21.0, 2.7 and 3.1 vessels per high power field (HPF) before chemotherapy and increased after treatment to 15.3, 21.8, 4.8 and 3.6 per HPF, respectively. These changes were significant for CD31 (p = 0.04) and for CD105 (p = 0.02). CONCLUSION: Taxane-based chemotherapy appears to promote tumor vascularization when administered every 3 weeks. A possible explanation is the secondary recovery of MVD in response to immediate cytotoxic and antiangiogenic effects of the chemotherapy. If confirmed prospectively, these findings favor shorter treatment intervals of taxane-based chemotherapy to counteract proangiogenic recovery.

Changes in Ki-67 labeling indices during neoadjuvant chemotherapy for advanced ovarian cancer are associated with survival.

OBJECTIVE: To evaluate changes in Ki-67 expression during neoadjuvant chemotherapy (NACT) in advanced ovarian cancer. MATERIALS AND METHODS: Patients with International Federation of Gynecology and Obstetrics stage IIIC or IV and large-volume ascites were treated with NACT within a phase 2 trial. The expression of Ki-67 was evaluated by immunohistochemistry on paraffin-embedded tissue samples and classified by percentage of stained cells. Survival curves were plotted using the Kaplan-Meier method. RESULTS: Comparison of 40 individual paired results from pretreatment and posttreatment samples revealed a median difference of -0.11 in the Ki-67 index (95% confidence interval, -0.20 to -0.01; P = 0.005, signed rank test). Univariate analysis identified a high Ki-67 index as well as an increasing Ki-67 index after NACT as significant prognostic markers for progression-free survival (P = 0.004 and P = 0.001; log-rank test). Six of 12 patients with an increased Ki-67 index after NACT developed recurrence within 6 months after therapy. CONCLUSIONS: Changes of the Ki-67 index during NACT are associated with progression-free survival. If confirmed in prospective trials, an increasing Ki-67 index during preoperative treatment may serve as an indicator for resistance to chemotherapy.

Neoadjuvant chemotherapy with carboplatin and docetaxel in advanced ovarian cancer--a prospective multicenter phase II trial (PRIMOVAR).

Early response criteria and surgical outcome were evaluated in patients with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy. Patients with FIGO stage IIIC or IV ovarian cancer and an ascites volume of >or=500 ml were randomly assigned to receive preoperatively 3 (A1) or 2 (A2) of 6 cycles of carboplatin and docetaxel intravenously. Response was monitored by measuring target lesions, ascites volumes and serum CA 125 levels. The primary outcome measure was the preoperative reduction of ascites volume. Secondary outcome measures were the evaluation of residual tumor and perioperative morbidity and mortality. Eighty-three patients underwent cytoreductive surgery, 40 after 3 cycles and 43 patients after 2 cycles of neoadjuvant chemotherapy. 'Optimal debulking' (or=500 ml. A decrease of the CA 125 level from baseline of less than 50% was observed in 7 (A1) and 9 patients (A2). Computed tomography scan results showed progressive disease in 6 patients (3 A1; 3 A2). Any amount of residual disease after cytoreductive surgery, persistent ascites, and a less pronounced decrease of CA 125 were associated with poor progression-free survival rates. In conclusion, ascites volume reduction and CA 125 decline appear to be appropriate response criteria. A treatment schedule with two preoperative cycles is a reasonable option for neoadjuvant chemotherapy in advanced ovarian cancer. High surgical standards are mandatory, even after neoadjuvant chemotherapy.

Detection of lymphovascular invasion in vulvar cancer by D2-40 (podoplanin) as a predictor for inguinal lymph node metastases.

BACKGROUND: Lymphatic vessel invasion (LVI) plays a major role in the spread of vulvar cancer and predicts regional lymph node metastasis. D2-40, a monoclonal immunohistochemical marker might be able to increase the detection rate of LVI compared to conventional hematoxylin-eosin (HE) staining. The aim of the study was to evaluate the suitability of D2-40 for the prediction of regional lymph node metastases. PATIENTS AND METHODS: Immunohistochemical staining with D2-40 was performed on formalin-fixed, paraffin-embedded tissue sections of 32 patients with squamous cell carcinoma of the vulva. Slides were screened for the presence of LVI. Correlation with clinico-pathological features including LVI as retrieved by routine HE-stained sections was assessed. RESULTS: Immunostaining with D2-40 significantly (p = 0.019) increased the frequency of detection of lymphatic invasion compared to conventional HE staining. LVI was correctly identified by D2-40 (D2-40+ LVI) in 65.6% of tumor specimens as compared to 40.6% by routine HE staining (HE+ LVI). D2-40+ LVI significantly (p = 0.026) predicted inguinal lymph node metastases. CONCLUSIONS: Immunostaining with D2-40 significantly increased the frequency of detection of lymphatic invasion compared to conventional HE staining in squamous cell carcinomas of the vulva. D2-40+ LVI is a strong predictor for inguinal lymph node metastases.

Detection of early breast cancer beyond mammographic screening: a promising biomarker panel.

Aim: We assessed the suitability of a biomarker panel to improve early detection and individual risk assessment in breast cancer (BC) patients. Materials & methods: PENK, pro-SP, hGH and CA15-3 of 204 BC patients and 68 healthy controls were measured. Results: PENK and human growth hormone concentrations were significantly lower and pro-SP values higher in BC patients compared with controls. C-index increased from 0.628 for CA15-3 alone to 0.754 when all three biomarkers were added to the model. Conclusion: This biomarker panel may improve early detection of BC and influence the assessment of breast imaging. It might be useful for a risk-adapted cancer surveillance or primary prevention program by a more precise determination of an individualized BC risk.

Detection of lymphovascular invasion in early breast cancer by D2-40 (podoplanin): a clinically useful predictor for axillary lymph node metastases.

PURPOSE: The aim of this study was to investigate the use of D2-40 for the detection of lymphovascular invasion (LVI) in node positive and negative early breast cancer. LVI is associated with axillary lymph node metastases (ALNM) and a long-term prognostic factor. A precise identification of LVI would have a strong clinical impact for breast cancer patients. METHODS: Immunohistochemical staining with D2-40 and CD34 was performed on formalin-fixed, paraffin-embedded tissue sections of 254 invasive breast tumors of 247 patients with node negative and node positive early breast cancer. All slides were screened for the presence of LVI. Correlation with clinico-pathological factors including LVI as retrieved by routine haematoxylin and eosin (H.E.) stained sections and the eligibility for the prediction of ALNM was assessed. RESULTS: Using the D2-40 antibody for immunostaining, our results demonstrate a significant higher detection (P < 0.001) of LVI as compared with routine H.E.-staining in early breast cancer. LVI was correctly identified by D2-40 (D2-40+) in 70 out of 254 tumors (28%) as compared to 40 tumors (16%) by routine HE staining (HE+). There was a significant correlation between D2-40 + LVI and age, t-stage, nodal status, grading and hormonreceptor-status. Correlation between D2-40 + LVI and menopausal-status, HER2-status and histological type was not significant, while there was a significant correlation of D2-40 and so called "triple negative" tumors (ER/PR and HER2neu-negative). In a multivariate analysis D2-40+ was the strongest predictor for ALNM with an odds ratio of 3.489 and a P-value of P = 0.0003, followed only by T-stage and grading with odds ratios of 3.167 and 1.953 and P-values P = 0.0003 and P = 0.0352. CONCLUSION: Immunostaining with D2-40 significantly increased the frequency of detection of lymphatic invasion compared to conventional H.E.-staining in early breast cancer. As LVI is a strong predictive and prognostic marker, the monoclonal antibody D2-40 has the potential to play a significant role in pathological routine workup of breast tumors. Further prospective studies are needed to prove the clinical impact of D2-40.