Ten years of live surgical broadcast at Charité-MAYO conferences (2010-2019): a systematic evaluation of the surgical outcome.

OBJECTIVE: The international Charité-MAYO Conference aims to promote international dialog on diagnostics, management, scientific breakthroughs, and state-of-the-art surgical procedures in gynecology and gynecologic oncology and senology. Live surgeries are a fundamental tool of interdisciplinary and international exchange of experts in their respective fields. Currently, there is a controversial and emotional debate about the true value, risks, and safety of live surgical broadcasts. The aim of the current study is to analyze peri-operative risks in patients who were operated live during the Charité-MAYO Conferences. METHODS: Live surgeries were performed by the core Charité team consisting of gynecologic oncologic surgeons, breast and plastic surgeons, partly in collaboration with visiting gynecologic oncologic surgeons. We performed a retrospective analysis of live surgeries performed during seven Charité-MAYO Conferences from 2010 to 2019 held in Berlin, Germany. Patients' files and tumor databases were analyzed as required and patients were contacted to update their long-term follow-up. RESULTS: Sixty-nine patients who were operated live were included. The types of surgery were as follows: urogynecologic procedures (n=13), breast surgery (n=21), and gynecologic oncology surgery for ovarian, uterine, vulvar or cervical cancer (n=35). Peri-operative complications were assessed according to the Clavien-Dindo classification. Despite a high rate of complete resection and the high frequency of multivisceral procedures, the rate of peri-operative complications was within the range published in the literature. Time of surgery and length of intensive unit care and hospital stay did not differ from data acquired at the home institution. CONCLUSIONS: Based on our analysis, live surgeries appear to be safe when performed within a multidisciplinary setting without an increase in surgical morbidity and mortality compared with historical controls and without compromise of patients' outcome. This is the first analysis of its kind to set the basis for patient information and consent for this type of surgeries.

Clinical Outcome of Neoadjuvant Radiochemotherapy in Locally Advanced Cervical Cancer: Results of an Open Prospective, Multicenter Phase 2 Study of the North-Eastern German Society of Gynecological Oncology.

OBJECTIVE: The aim of this study was to determine the response rate, toxicity, operability, and surgical complication rate of neoadjuvant concomitant radiochemotherapy (cRCH) (ifosfamide + carboplatin) followed by radical hysterectomy plus external-beam radiotherapy with curative intention in locally advanced primary inoperable stages IIB and IIIB squamous cell cervical cancer. METHODS: Patients with cervical cancer from 8 departments were enrolled. Patients received 3 cycles of ifosfamide 1.2 mg/m (+mesna 20%) plus carboplatin (area under the curve = 4), every 21 days, and concomitant external-beam radiotherapy (50.4 Gy [1.8 Gy/d]). Operability and remission were evaluated by clinical gynecological examination in general anesthesia (magnetic resonance imaging was optional), 4 weeks after the third cycle of cRCH. In case of achieved operability, a radical hysterectomy with pelvic lymphadenectomy was performed within 6 weeks after cRCH. If surgery was not performed because of incomplete remission or patient preferences, vaginal brachytherapy (15 Gy [5 Gy/d]) was given additionally. RESULTS: Forty-four patients were enrolled. Distribution of FIGO (International Federation of Gynecology and Obstetrics) tumor stage was as follows: IIB (19 patients) and IIIB (25 patients). All patients completed cRCH. Grade 3/4 hematologic toxicities (% of all cycles) were moderate: leukopenia, 7.3; thrombocytopenia, 2.4; and anemia, 3.2. In 13.8%, treatment cycles were delayed because of hematologic toxicity. Blood transfusions were given in 17.7% and granulocyte colony-stimulating factor in 39.5%. Overall, grade 3/4 nonhematologic toxicities were seldom (6.5%). Clinical overall response rate was 95.2%. Operability was achieved in 85.7%. Surgery was performed in 83.3%. Pathological response rates were as follows: pathological complete remission, 33.3%; partial remission, 63.3%; stable disease, 3.3%. CONCLUSIONS: Our study demonstrates that cRCH is an effective and tolerable regimen in locally advanced cervical cancer treatment.

CA27.29 as a tumour marker for risk evaluation and therapy monitoring in primary breast cancer patients.

Several trials showed that tumour markers are associated with an impaired prognosis for breast cancer. Whether earlier treatment can improve the course of the disease remains controversial. The SUCCESS Trial compares FEC (500/100/500)-docetaxel (100) vs. FEC (500/100/500)-docetaxel/gemcitabine (75/2000) as well as 2 vs. 5 years of zoledronate in high-risk primary breast cancer patients. In 2669 patients, CA27.29 was measured before and after chemotherapy with the ST AIA-PACK CA27.29 reagent for the AIA-600II automated enzyme immunoassay (Tosoh Bioscience, Belgium). Values above 31 U/ml were considered positive. Of the patients, 7.6 % (n = 202, mean 19, range 3-410) and 19.1 % (n = 511, mean 21, range 3-331) had elevated marker levels before and after chemotherapy, respectively. Of the patients, 4.9 and 78 % showed elevated and low CA27.29, respectively, at both time points. After treatment, 35 % of the pre-therapy positive patients were negative, and 15 % of the initially negative patients became positive. The correlation between both time points was significant (p < 0.0001). No correlations among nodal status, grading, hormonal status, HER2 status and CA27.29 levels were found. However, tumour size (p = 0.02), older age (p < 0.001) and post-menopausal status (p = 0.006) were significantly associated with higher CA27.29 levels. Before treatment, the prevalence of elevated CA27.29 was equally distributed between both treatment arms, whereas after chemotherapy, 13.7 % of the patients in the FEC-doc arm showed an increased level vs. 25.4 % of the patients in the FEC-doc/gemcitabine arm (p < 0.0001). However, we could not show a significant association between the G-CSF application (yes vs. no) and CA27.29 status before/after chemotherapy (p = 0.75). These results indicate a close relationship between CA27.29 levels and tumour mass. Increased values after the completion of chemotherapy might be attributed to treatment effects and should be considered with caution.

Detection of circulating tumor cells using manually performed immunocytochemistry (MICC) does not correlate with outcome in patients with early breast cancer - Results of the German SUCCESS-A- trial.

BACKGROUND: Recently, the prognostic significance of circulating tumor cells (CTCs) in primary breast cancer as assessed using the Food-and-Drug-Administration-approved CellSearch® system has been demonstrated. Here, we evaluated the prognostic relevance of CTCs, as determined using manually performed immunocytochemistry (MICC) in peripheral blood at primary diagnosis, in patients from the prospectively randomized multicenter SUCCESS-A trial (EudraCT2005000490-21). METHODS: We analyzed 23 ml of blood from 1221 patients with node-positive or high risk node-negative breast cancer before adjuvant taxane-based chemotherapy. Cells were separated using a density gradient followed by epithelial cell labeling with the anti-cytokeratin-antibody A45-B/B3, immunohistochemical staining with new fuchsin, and cytospin preparation. All cytospins were screened for CTCs, and the cutoff for positivity was at least one CTC. The prognostic value of CTCs with regard to disease-free survival (DFS), distant disease-free survival (DDFS), breast-cancer-specific survival (BCSS), and overall survival (OS) was assessed using both univariate analyses applying the Kaplan-Meier method and log-rank tests, and using multivariate Cox regressions adjusted for other predictive factors. RESULTS: In 20.6 % of all patients (n = 251) a median of 1 (range, 1-256) CTC was detected, while 79.4 % of the patients (n = 970) were negative for CTCs before adjuvant chemotherapy. A pT1 tumor was present in 40.0 % of patients, 4.8 % had G1 grading and 34.6 % were node-negative. There was no association between CTC positivity and tumor stage, nodal status, grading, histological type, hormone receptor status, Her2 status, menopausal status or treatment. Univariate survival analyses based on a median follow-up of 64 months revealed no significant differences between CTC-positive and CTC-negative patients with regard to DFS, DDFS, BCSS, or OS. This was confirmed by fully adjusted multivariate Cox regressions, showing that the presence of CTCs (yes/no) as assessed by MICC did not predict DFS, DDFS, BCSS or OS. CONCLUSIONS: We could not demonstrate prognostic relevance regarding CTCs that were quantified using the MICC method at the time of primary diagnosis in our cohort of early breast cancer patients. Further studies are necessary to evaluate if the presence of CTCs assessed using MICC has prognostic relevance, or can be used for risk stratification and treatment monitoring in adjuvant breast cancer. TRIAL REGISTRATION: The ClinicalTrial.gov registration ID of this prospectively randomized trial is NCT02181101 ; the (retrospective) registration date was June 2014 (study start date September 2005).

Endometrial Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry Number 032/034-OL, September 2022). Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer, Geriatric Assessment and Supply Structures.

Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat women with endometrial cancer of low risk prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 1 of this short version of the guideline provides recommendations on epidemiology, screening, diagnosis, and hereditary factors. The epidemiology of endometrial cancer and the risk factors for developing endometrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer. The use of geriatric assessment is considered and existing structures of care are presented.

Clinical outcome of tertiary surgical cytoreduction in patients with recurrent epithelial ovarian cancer.

BACKGROUND: The value of tertiary cytoreductive surgery (TCS) on overall survival (OS) of patients with relapsed epithelial ovarian cancer (ROC) is not well defined. Aim of the present study was to evaluate the operative and clinical outcome after TCS. METHODS: We systematically evaluated all consecutive patients undergoing TCS. Tumor dissemination pattern, operative morbidity, residual tumor, and survival are described based on a validated intraoperative documentation tool. Predictors of survival and complete tumor resection are analyzed with Cox regression or logistic regression models. RESULTS: Between October 2000 and December 2008, 135 patients (median age, 51 years; range, 22-80 years) of mainly initial FIGO stage ≥ III (106 patients, 78.5%) were evaluated. In 53 patients (39.3%) a complete tumor-resection was obtained. The 1-month operative mortality was 6%. During a median follow-up period of 9.6 months (range, 0.1-75 months), 78 patients (57.8%) died, while 52 patients (38.5%) experienced a further relapse. Median OS was 19.1 months for the total collective (95% confidence interval [95% CI], 14.84-23.35). Median OS was 37.8 months (95% CI, 12.7-62.7) for patients without residual tumor; versus 19.0 months (95% CI, 9.8-28.2) for residual tumor ≤ 1 cm and 6.9 months (95% CI, 3.05-10.7) for residual tumor > 1 cm (P < .001). The presence of peritoneal carcinomatosis did not seem to significantly affect OS. Complete tumor resection was identified as the strongest predictor of OS. Other independent predictors of OS were interval to primary diagnosis ≥ 3 years (hazard ratio [HR], 0.28; 95% CI, 0.14-0.59) and serous papillary histology (HR, 0.23; 95% CI, 0.09-0.56). A total of 42 patients (31.1%) presented at least 1 major complication. Multivariate analysis identified tumor involvement of the middle abdomen and peritoneal carcinomatosis as independent predictors of complete tumor resection. CONCLUSIONS: Postoperative tumor residual disease remains the strongest predictor of survival even in TCS setting. To identify the optimal candidates for TCS, the predictive value of ascites and peritoneal carcinomatosis should be confirmed by future prospective trials.

Impact of obesity on operative morbidity and clinical outcome in primary epithelial ovarian cancer after optimal primary tumor debulking.

BACKGROUND: Obesity is a common and increasing condition in Western countries and seems to be associated with increased carcinogenesis and tumor invasiveness. We evaluated operative and clinical outcome in patients operated to treat primary epithelial ovarian cancer (EOC) according to their body mass index (BMI). METHODS: All consecutive EOC patients who underwent cytoreductive surgery in our institution between September 2000 and April 2010 were systematically evaluated according to their BMI (kg/m(2)). Survival was calculated by Kaplan-Meier curves. Logistic regression and Cox regression analysis were performed to identify the impact of obesity on surgical outcome and survival. RESULTS: Three hundred six patients were evaluated. A total of 40.2% were classified as overweight; 87 (28.4%) had a BMI of 25-30 kg/m(2) and 36 (11.8%) had a BMI of ≥30 kg/m(2). No statistically significant differences regarding tumor-related characteristics and comorbidities existed between normal-weight and overweight patients. Median operation time was significantly longer (P = 0.024) in overweight versus normal-weight patients (280 min; range 40-529 vs. 257 min; range 32-592, respectively). Complete tumor resection rates were equivalent between the two patient groups (68.6% vs. 72.5%; P = 0.543) with similar median overall and progression-free survival in both groups (43 vs. 42 months and 21 vs. 17.8 months, respectively). Operative morbidity was also not significantly different between the two groups. By comparable morbidity, operative procedures were similar between normal-weight and overweight patients, apart from higher intestinal and diaphragmatic resection rates in the overweight patients (61% vs. 43.7%; P = 0.004 and 24.4% vs. 14.2%; P = 0.034). In multivariate analysis, BMI of ≥25 kg/m(2) did not reveal any prognostic significance in respect of survival, operative morbidity, and complete tumor resection. CONCLUSIONS: BMI does not appear to influence tumor stage, histology, differentiation grade, or tumor marker levels in patients with primary EOC. Also, BMI is not an independent predictive and prognostic marker of survival, operative outcome, or morbidity at the time of primary tumor debulking.

Prognosis of Patients With Early Breast Cancer Receiving 5 Years vs 2 Years of Adjuvant Bisphosphonate Treatment: A Phase 3 Randomized Clinical Trial.

IMPORTANCE: Bisphosphonate treatment in patients with early breast cancer has become part of care, but the optimal treatment duration is still unclear. OBJECTIVE: To compare 2 vs 5 years of zoledronate treatment following adjuvant chemotherapy in patients with early breast cancer. DESIGN, SETTING, AND PARTICIPANTS: The SUCCESS A phase 3 multicenter randomized open-label clinical trial with a 2 × 2 factorial design enrolled 3754 patients from September 21, 2005, to March 12, 2007 (last patient out, May 7, 2014). Final data analysis was conducted from September 2019 to October 2020. In 250 German study centers, patients were eligible for participation in the SUCCESS A trial if they had either node-positive or high-risk node-negative (defined as at least 1 of the following: tumor size ≥ pT2, histologic grade 3, negative hormone receptor status, or age ≤35 years) primary invasive breast cancer. INTERVENTIONS: Patients were first randomized to adjuvant chemotherapy with 3 cycles of fluorouracil, epirubicin, and cyclophosphamide followed by 3 cycles of docetaxel with or without gemcitabine (not presented in this report). After chemotherapy, patients underwent a second randomization of 5 years of zoledronate treatment (4 mg intravenously every 3 months for 2 years, followed by 4 mg intravenously every 6 months for 3 years) vs 2 years of zoledronate treatment (4 mg intravenously every 3 months for 2 years). MAIN OUTCOMES AND MEASURES: The primary end point of the study was disease-free survival; secondary end points were overall survival, distant disease-free survival, and the incidence of skeletal-related adverse events. Survival times were measured from 2 years after the start of zoledronate treatment (landmark analysis). RESULTS: Overall, data on 2987 patients were available for analysis; median age was 53 (range, 21-86) years. Disease-free survival, overall survival, and distant disease-free survival did not differ significantly between the 2 treatment arms (5 vs 2 years) as shown by adjusted multivariable Cox proportional hazards regression models (disease-free survival: hazard ratio [HR], 0.97; 95% CI, 0.75-1.25; P = .81; overall survival: HR, 0.98; 95% CI, 0.67-1.42; P = .90; distant disease-free survival: HR, 0.87; 95% CI, 0.65-1.18; P = .38). Adverse events were observed more often in the 5-year (46.2%) vs 2-year (27.2%) zoledronate treatment arm, which was particularly true for the skeletal-related events bone pain (5 years, 8.3% vs 2 years, 3.7%) and arthralgia (5 years, 5.1% vs 2 years, 3.1%). CONCLUSIONS AND RELEVANCE: The results of this phase 3 randomized clinical trial indicate that extending the zoledronate treatment beyond 2 years does not improve the prognosis of high-risk patients with early breast cancer receiving chemotherapy, suggesting that the currently recommended bisphosphonate treatment duration of 3 to 5 years could be reduced. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02181101.

Role of secondary cytoreductive surgery in ovarian cancer relapse: who will benefit? A systematic analysis of 240 consecutive patients.

BACKGROUND AND OBJECTIVES: In contrast to primary ovarian cancer, the value of surgery in relapsed-OC (ROC) remains unclear. We evaluated surgical and clinical outcome of secondary cytoreduction in ROC. METHODS: All consecutive ROC patients who underwent secondary tumor-debulking surgery were systematically analyzed as based on a validated intraoperative documentation tool. Tumor dissemination pattern, operative and clinical outcome were evaluated. Cox-regression analysis was performed to identify independent predictors of mortality. RESULTS: Between 09/2000 and 10/2008, 240 operations were evaluated; 184 patients (81.1%) were platinum-sensitive and 43 (20%) platinum-resistant. 47.5% of the patients had ascites, while 85.8% presented a multifocal tumor dissemination pattern. In 53.8% a complete tumor resection was achieved; in another 24.2%, postoperative tumor residuals were < 1 cm. In multivariate analysis, no tumor resection (HR: 7.6; 95% CI: 2.9-19.9), ascites > 500 ml (HR: 6.76; 95% CI: 3.77-12.1), platinum resistance (HR: 3.1; 95% CI: 1.26-7.7), and initial FIGO stage IV (HR: 2.86; 95% CI: 1.16-7) were the most significant risk factors for mortality. Median OS was 42.3 months (95% CI: 24.37-60.2); 17.7 months (95% CI: 12.27-23.13); and 7.7 months (95% CI: 3.1-12.3) for patients with complete tumor resection, tumor residuals ≤ 1 and > 1 cm, respectively (trend P-value < 0.001). CONCLUSIONS: Absence of ascites, platinum-sensitivity, initial FIGO stage < IV, and complete tumor resection correlate with a significantly better long-term prognosis after ROC surgery. However, a significant trend of continuously improving survival associated with increasing tumor reduction rates could be identified even in patients where a complete tumor resection is not achievable.

Long-term clinical outcome of pelvic exenteration in patients with advanced gynecological malignancies.

BACKGROUND AND OBJECTIVES: We evaluated the outcome of pelvic exenteration in women with locally advanced primary or recurrent gynecological malignancies. METHODS: All pelvic exenteration procedures performed between 01/2003 and 06/2009 were evaluated. Extent of surgical radicality, operative techniques, and outcome were evaluated. Kaplan-Meier curves were calculated for Overall (OS) and progression-free survival (PFS). RESULTS: Forty-seven patients (median age: 52.5 years) were evaluated. Ten of 47 patients (21.3%) had a primary and 37(78.7%) a relapsed cancer. Most common (80.8%) site of origin was the cervix. Patients (80.8%) had undergone previous pelvic irradiation. A total exenteration was performed in 32/47 patients (68%). A complete tumor resection was obtained in 23 patients (49%). Thirty-three patients (70.2%) had at least one major complication, including ileus (8.5%), intestinal-fistula (29.8%), ureteral anastomotic insufficiency (6.4%), abscess (6.4%), and cardiothrombotic events (23.4%). At a median follow-up of 7 months (range: 1-42), 22/47 patients (46.8%) died and 22/47 (46.8%) experienced a relapse. Median OS was 4 months (range: 0.1-16) and 22 months (range: 6-42) for patients with versus without postoperative tumor residuals, respectively (P = 0.0006), while median PFS was 4 months (range:0.1-16) versus 12 months (range: 6-42) (P < 0.0001). CONCLUSIONS: Radical pelvic exenteration due to advanced pelvic malignancies may be associated with a high morbidity. Complete tumor resection is associated with a significantly higher overall and PFS.

Development of the Berlin Symptom Checklist Ovary (BSCL-O) for the measurement of quality of life of patients with primary and recurrent ovarian cancer: results of a phase I and II study.

GOALS OF WORK: Quality of life (Qol) represents a relevant end point in the clinical management of advanced ovarian cancer (AOC). However, there exist only a few specific instruments which have been designed for patients with ovarian cancer. The aim of this study was to develop a systematic checklist (Berlin Symptom Checklist Ovary (BSCL-O)) as an instrument of Qol for patients with AOC and to discriminate between the frequency and the importance of symptoms. PATIENTS AND METHODS: The main symptoms were identified in a phase I study via free interviews of five patients with ovarian cancer (OC) as well as five medical doctors, family dependent, and care workers. In the phase II study, the capability of BSCL-O was evaluated by questionnaire-guided interviews of 200 patients with primary OC, recurrent OC, metastasized breast cancer, and benign ovarian tumors. MAIN RESULTS: In phase I, 36 main symptoms were identified. In phase II, 7,200 answers from 98.5% of all patients were evaluable. Of the 36 symptoms of the BSCL-O, 23 revealed clinical relevance. There was a correlation of frequency and importance of symptoms (p < 0.05). The symptoms of the BSCL-O were deemed twice as strenuous in patients with recurrent OC. CONCLUSIONS: The BSCL-O can measure Qol of patients with OC. The BSCL-O is being validated in a phase III study.

Primary versus interval debulking surgery in advanced ovarian cancer: results from a systematic single-center analysis.

OBJECTIVE: To evaluate the difference in operative and clinical outcome for patients with primary advanced ovarian cancer (AOC) after optimal primary debulking surgery (PDS) versus interval debulking surgery (IDS). METHODS: Tumor dissemination pattern and surgical outcome, as defined by morbidity, progression-free (PFS) survival and overall survival (OS) were systematically analyzed in AOC patients who underwent surgery in our institution between September 2000 and August 2009. Overall survival and PFS were calculated by Kaplan-Meier curves. Univariate and Cox regression analysis were performed to identify the impact of IDS on surgical outcome and survival. RESULTS: Overall, 372 consecutive patients with histologically proven AOC (FIGO [International Federation of Gynecology and Obstetrics] stage III/IV) were evaluated. Forty patients (10.8%) underwent IDS after a median of 5 cycles (range, 2-6 cycles) platinum- and taxane-based chemotherapy, and 332 patients (89.2%) underwent PDS. Patients who underwent IDS had a significantly lower rate of tumor involvement of the lower (78.9% vs 98.8%; P < 0.001) and middle abdomen (68.4% vs 83.1%; P = 0.044) compared with PDS patients. During IDS, a significantly higher probability for complete tumor resection occurred when compared with PDS (85% vs 58.7%; P = 0.02) by equivalent rates of operative complications (36.4% vs 36.5%; P = 1.00). However, mean PFS was significantly reduced in IDS patients (14.6 vs 33.2 months; P < 0.001). Mean OS was also higher in PDS patients, but this reached a statistical significance only when complete tumor resection was obtained (65.4 vs 37.9 months; P = 0.005). Multivariate analysis identified that IDS was associated with an unfavorable OS and PFS. CONCLUSIONS: : It seems that PDS has a more favorable outcome than IDS on both OS and PFS in AOC patients, even though IDS leads to significantly higher rates of complete tumor resection.

Primary radical surgery in elderly patients with epithelial ovarian cancer: analysis of surgical outcome and long-term survival.

OBJECTIVE: Geriatric population life expectancy is increasing and so is the incidence of epithelial ovarian cancer (EOC) in elderly women. The aim of our study was to determine the impact of radical cytoreductive surgery, the cornerstone of clinical management in primary EOC, in this population with special regard to the associated morbidity. METHODS: Through a pooled data analysis, cancer-related patient characteristics, intraoperative tumor pattern, and surgical and clinical outcomes were evaluated according to a validated documentation data collection tool. Kaplan-Meier curves were calculated for overall survival (OS). The Cox regression analysis was performed to identify independent predictors of mortality. RESULTS: One hundred one EOC patients older than 69 years (mean [SD] age, 75.54 [4.49] years) were evaluated. The mean (SD) follow-up period was 22.63 (22.92) months. Advanced International Federation of Gynecology and Obstetrics stage III (60.4%) was the most common tumor stage. A complete tumor resection was achieved in 45 patients (44.6%) with an associated complication rate of 40.6%. The postoperative mortality was 6%. The mean OS was 47.29 months (95% confidence interval, 36.24-58.34). The multivariate analysis identified age older than 75 years, incomplete tumor resection, and absence of adjuvant chemotherapy to negatively affect OS. CONCLUSIONS: Radical surgery for primary EOC obtaining complete tumor resection is associated with a significantly prolonged OS in elderly patients (> or =70 years). The increased postoperative morbidity must be considered, underlining the high requirement for special interdisciplinary postoperative management in this special collective.

Regional abdominal hyperthermia combined with systemic chemotherapy for the treatment of patients with ovarian cancer relapse: Results of a pilot study.

PURPOSE: Due to the poor prognosis of patients with ovarian cancer relapse (OCR), newer strategies are warranted to improve the therapeutic index. We performed a prospective phase I/II-study of regional abdominal hyperthermia (RHT) combined with systemic chemotherapy in OCR patients in order to evaluate outcome, efficacy and tolerance. MATERIALS AND METHODS: OCR patients with an Eastern Cooperative Oncology Group status <2, without any thromboembolic disease or severe cardiovascular co-morbidities, and pre-treated with at least one systemic chemotherapy regimen due to epithelial ovarian cancer were enrolled into the present study. RHT was applied using a SIGMA 60 applicator and a Hybrid-System SIGMA-Eye/MRT composed of a 1.5T-MRT and a Sigma-Eye-applicator. RESULTS: Overall, 36 OCR patients were enrolled. The majority of the patients (>80%) were classified as platinum resistant. The most common chemotherapeutic agent applied was pegylated-liposomal-doxorubicin (47.2%) followed by carboplatin (16.6%) and topotecan (13.9%). One patient (2.8%) achieved a complete remission (CR), 12 patients (33.3%) yielded a partial remission (PR) and 16 patients (44.4%) developed a progressive disease (PD). In platinum-sensitive patients we observed higher response (57.1% versus 31%) and lower progression rates (28.6% versus 48.3%) than in platinum-resistant patients. Eleven patients (30.5%) discontinued treatment due to toxicity. The main toxicity was a haematological one with grade 3/4 anaemia, leucopenia and thrombocytopenia occurring in 13.9%, 5.6% and 8.3%, respectively. Median overall survival was 12 months (range: 1-48), while median progression-free survival was 5 months (range: 0.5-34). CONCLUSIONS: Our results demonstrate the feasibility of RHT combined with systemic treatment. Prospective phase III trials are warranted to evaluate the benefit and efficacy in heavily pre-treated patients with OCR.

Monitoring of IL-10 in the serum of patients with advanced ovarian cancer: results from a prospective pilot-study.

OBJECTIVES: The fact that ovarian cancer remains confined to the peritoneal cavity even in advanced stages has allowed us to surmise that local immunosuppressive factors could be involved in the tumor biology of ovarian cancer. In this context, IL-10 can be one of the key factors. By studying the kinetics of IL-10 concentrations prior to and after surgery, this study attempts to reveal once more the ability of tumor micro-environment to produce IL-10. Some studies indicate that IL-10 concentration correlates with the tumor burden and can thus predict the surgical outcome. Data concerning this aim from patients with ovarian cancer do not seem to exist. METHODS: In this prospective study, serum blood was collected from 27 patients, one day prior to surgery as well as 24h, 4 and 8 days after surgery. The concentration of IL-10 was determined using ELISA. RESULTS: While IL-10 levels rise within the first day post-OP, they are found to be reduced significantly when measured at later time points. IL-10 levels also correlate statistically significantly with the tumor grade, with lower IL-10 levels observed in well-differentiated and higher IL-10 levels in undifferentiated or only poorly differentiated tumors. CONCLUSION: IL-10 expression levels appear to be a good surrogate marker for tumor grading. If validated, this may in future contribute to the understanding of the biology stage cancers.

Prognostic value of serum and ascites levels of estradiol, FSH, LH and prolactin in ovarian cancer.

UNLABELLED: The aim of this study was to investigate the influence of sex hormone levels on tumor biology and patients' outcome in ovarian cancer. PATIENTS AND METHODS: One hundred and six patients with ovarian cancer were enrolled into this prospective study. Serum and ascites samples were obtained intraoperatively. Concentrations of estradiol, FSH, LH and prolactin were measured and correlated with parameters of tumor biology, such as FIGO stage, tumor spread and postoperative tumor residual mass. Patients with primary ovarian cancer were compared to patients with recurrent disease. Influence factors on progression-free survival and overall survival were analyzed using the Kaplan-Meyer method. RESULTS: Serum FSH concentrations were significantly higher and estradiol concentrations in ascites were significantly lower in patients with recurrent disease. According the multivariate analysis, only FSH level in ascites was seen to be an independent prognostic factor for patients' survival. CONCLUSION: High level of FSH in the ascites provides prognostic information in patients with ovarian cancer and is inversely correlated with patients' survival.

Circulating vascular endothelial growth factors and their soluble receptors in pre-invasive, invasive and recurrent cervical cancer.

AIM: To study the impact of circulating vascular endothelial growth factors (VEGF) -A, -C and -D and their soluble receptors VEGFR-1/-2 on disease invasion and progression in patients with pre-invasive (CIN), invasive (PCC) and recurrent (RCC) cervical cancer. PATIENTS AND METHODS: Blood samples were obtained from 125 women, including 50 cases of CIN, 51 of PCC and 24 of RCC, before treatment. Soluble (s) biomarker levels were determined by ELISA and tested for correlation with histopathological factors. RESULTS: With disease progression, sVEGF-A (p = 0.007) and sVEGFR-2 (p = 0.014) significantly increased, while sVEGF-D (p = 0.046) decreased. sVEGFR-2 levels were increased in node+ patients (p = 0.024) and in metastatic disease (p = 0.003). sVEGF-A values were higher in HPV+ cases (p = 0.019). In detecting disease invasiveness, sensitivity and specificity were 76% and 48% for sVEGF-A, 52% and 32% for sVEGF-D, 25% and 94% for sVEGF-C, 93% and 6% for sVEGFR-1 and 73% and 34% for sVEGFR-2, respectively. CONCLUSION: In cervical neoplasia, a switch from a lymphangiogenic phenotype towards a hemangiogenic phenotype occurs with disease invasion and progression. The sensitivity and specificity values, however, seem not convincing enough to establish these factors as clinical markers for disease invasiveness in cervical cancer.

Systematic evaluation of the intraoperative tumor pattern in patients with borderline tumor of the ovary.

OBJECTIVE: Borderline ovarian tumors (BOTs) are rare entities with excellent prognosis depending on tumor stage and presence of invasive implants. There are limited data regarding the intraoperative tumor pattern, the actual base of optimal treatment planning. We conducted a systematic evaluation of the macroscopic and microscopic tumor spreads in patients with BOTs with special focus on the diagnosis of invasive and noninvasive lesions. METHODS: Between January 2001 and July 2008, data of patients with BOTs were evaluated using a systematic and validated documentation tool (intraoperative mapping of ovarian cancer). Surgical outcome and pathological findings were analyzed. RESULTS: Fifty-one patients underwent surgery for BOT. Mean (SD) age was 47.76 (15.9) years. In 6 patients (11.8%), surgery was performed for recurrence. Complete tumor resection was achieved in 47 patients (92.15%), whereas mean (SD) operative time was 126.34 (73.4) minutes. Pathologic evaluation identified 12 patients (23.53%) with mucinous and 39 patients (76.47%) with serous histologic diagnoses. Twenty-nine (56.86%) and 22 patients (43.13%) were found to have unilateral and bilateral ovarian involvements, respectively. Sixteen patients (31.37%) presented extraovarian involvement into the peritoneum (23.5%), omentum (17.7%), uterus (7.84%), sigmoid (7.8%), lymph nodes (7.8%), ileum (3.9%), mesentery (5.9%), and appendix (1.96%). Twenty patients (39.2%) had implants; of those, 9 (17.64%) and 11 patients (21.6%) have invasive and noninvasive lesions, respectively. Eight of the 9 patients with positive peritoneal cytology were associated with the presence of peritoneal implants; 3 of them with invasive character. CONCLUSIONS: Borderline ovarian tumors require a systematic surgical evaluation to verify or exclude extrapelvic tumor lesions and allow further clinical relevant differentiation between invasive and noninvasive implants.

Neoadjuvant letrozole in postmenopausal estrogen and/or progesterone receptor positive breast cancer: a phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy.

BACKGROUND: In recent years, preoperative volume reduction of locally advanced breast cancers, resulting in higher rates of breast-conserving surgery (BCS), has become increasingly important also in postmenopausal women. Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors (AIs), including letrozole, for such neoadjuvant endocrine treatment. This usually lasts 3-4 months and has been extended to up to 12 months, but optimal treatment duration has not been fully established. METHODS: This study was designed as a multicenter, open-label, single-arm, exploratory phase IIb/III clinical trial of letrozole 2.5 mg, one tablet daily, for 4-8 months. The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration. Tumor regression (by clinical examination, mammography, and ultrasound), shift towards BCS eligibility, and safety assessments were the main outcome measures. Standard parametric and nonparametric descriptive statistics were performed. RESULTS: Letrozole treatment was received by 32 of the enrolled 33 postmenopausal women (median (range): 67.0 (56-85) years) with unilateral, initially BCS-ineligible primary breast cancer (clinical stage > or = T2, N0, M0). Letrozole treatment duration in the modified intent-to-treat (ITT; required 4 months' letrozole treatment) analysis population (29 patients) was 4 months in 14 patients and > 4 months in 15 patients. The respective per-protocol (PP) subgroup sizes were 14 and 11. The majority of partial or complete responses were observed at 4 months, though some beneficial responses occurred during prolonged letrozole treatment. Compared with baseline, median tumor size in the ITT population was reduced by 62.5% at Month 4 and by 70.0% at final study visit (Individual End). Similarly, in the PP population, respective reductions were 64.0% and 67.0%. Whereas initially all patients were mastectomy candidates, letrozole treatment enabled BCS (lumpectomy) in 22 ITT (75.9%) and 18 PP (72.0%) patients. CONCLUSION: Over half of patients become BCS-eligible within 4 months of preoperative letrozole treatment. While prolonged treatment for up to 8 months can result in further tumor volume reduction in some patients, there is no clear optimum for treatment duration. Letrozole has a favorable overall safety and tolerability profile. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00535418.

Long-term effects of neovaginal reconstruction with sigmoid loop technique on sexual function and self image in patients with gynecologic malignancies: results of a prospective study.

OBJECTIVE: We evaluated the long-term results of sigmoid vaginoplasty in women with gynecologic malignancies after radical pelvic surgery, with specific focus on safety and effects of the procedure on patients' sexuality and self image. METHODS: This prospective study included women with gynecologic malignancies who underwent partial or complete colpectomy as part of the cancer treatment. In all cases a pedicled sigmoid loop was used for the neovaginal reconstruction. Systematic clinical examination was performed and validated questionnaires about sexuality (Female Sexual Function Index), quality of life (SF-12) and susceptibility to depression (ADSk-15) were answered by all patients at the earliest 6 months after vaginoplasty. RESULTS: Seven patients with sigmoid vaginoplasty, recruited between 11/2003 and 02/2008, were evaluated in the present analysis. Mean patients age was 48+/-8.49 years. Mean neovaginal length was 6.4 cm (range: 2-12 cm). The mean Female Sexual Function Index (FSFI)-score of all patients was 16.6+/-12.6. In the subset of sexually active patients the mean FSFI-score was 22.5+/-9.4 higher. Regarding early operative morbidity and complications, sigmoid vaginal reconstruction appears to be a safe procedure, though in a long-term assessment 85% of the patients developed a vaginal stenosis with the need for operative bougienage. CONCLUSIONS: The vaginal reconstruction using a sigmoid loop is a safe and well accepted procedure in patients with gynecologic malignancies. However lower sexuality scores seem to be achieved than in non-cancer patients after equivalent vaginoplasty. Cancer-related physical and psychological comorbidity seem to have negative effects on the overall outcome and patient's satisfaction.