ABSTRACT
BACKGROUND: Before the era of immunotherapies and antibody-drug conjugates, there were limited chemotherapeutic options for patients with recurrent and metastatic cervical cancer. Combination therapies with cisplatin have shown some superiority over monotherapy. This study examined platinum-free treatment regimens, comparing a combination of topotecan and paclitaxel (TP) with topotecan and cisplatin (TC) in patients with recurrent or metastatic cervical cancer, with or without prior platinum-based treatment. METHODS: The AGO-Zervix-1 Study (NCT01405235) is a prospective, randomized phase III study in which patients were randomly assigned at a 1:1 ratio to treatment within the control arm with topotecan (0.75 mg/m2) on days 1-3 and cisplatin (50 mg/m2) on day 1 every 3 weeks and in the study arm topotecan (1.75 mg/m2) and paclitaxel (70 mg/m2) on days 1, 8, and 15 every 4 weeks or treatment. The primary study aim was overall survival; progression-free survival, toxicity, and quality of life were secondary aims. The interim and final analysis is here reported after recruitment of 173 of 312 planned patients. RESULTS: Median overall survival in the TP arm was 9.6 months, compared with 12.0 months in the TC arm (log-rank test, P = 0.33). Median progression-free survival rates were 4.4 months with TP and 4.2 months with TC (log-rank test, P = 0.47). Leukopenia and nausea/vomiting were more frequent in the cisplatin-containing arm. Otherwise, toxicity profiles were comparable. There were no differences in FACT-G-assessed quality of life. CONCLUSION: Platinum-based combination chemotherapy remains the standard of care chemotherapy regimen for patients with recurrent or metastatic cervical cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cisplatin , Neoplasm Recurrence, Local , Paclitaxel , Topotecan , Uterine Cervical Neoplasms , Humans , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology , Female , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Topotecan/administration & dosage , Cisplatin/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Adult , Prospective Studies , Aged , Quality of Life , Progression-Free SurvivalABSTRACT
OBJECTIVE: Obesity is associated with worse survival and an increased risk of relapse in several malignancies. The influence of obesity on vulvar cancer recurrence has not been previously described. The primary objective of this study was to evaluate the association between obesity and tumor recurrence in patients with vulvar cancer. METHODS: This is an analysis of the AGO-CaRE-1 study. Patients diagnosed with squamous cell vulvar cancer (stage IB and higher), treated in 29 cancer centers between January 1998 and December 2008, were registered in a centralized database. The cohort was divided into two gropus depending on the body mass index (BMI) (<30 vs ≥30 kg/m²). Descriptive statistics, survival analyses, and multivariate Cox regression analyses were performed in order to evaluate the association between obesity and progression-free and overall survival. RESULTS: In 849 (52.4%) of 1618 patients in the database, the BMI was documented. Patients were grouped according to their BMI (<30 vs ≥30 kg/m²). There were 621 patients with a BMI <30 kg/m² and 228 patients with a BMI ≥30 kg/m². Besides age, there was no difference in baseline variables (tumor diameter, depth of infiltration, tumor stage, nodal metastasis, tumor grade). Treatment variables (R0 resection, chemotherapy, radiotherapy, continuation of adjuvant therapy) did not differ between groups. However, patients with BMI ≥30 kg/m² underwent radical vulvectomy more often (61.1% vs 51.8%, p=0.04). During follow-up there was a higher recurrence rate in the group with BMI ≥30 kg/m² (43.4% vs 28.3%, p<0.01) due to an increased rate of local recurrences (33.3% vs 18.5%, p<0.01). There was a significantly shorter time to recurrence in obese patients on univariate analysis (BMI ≥30 kg/m² vs <30 kg/m²: 43.8 months (95% CI 23.3 to 64.3) vs 102.3 months (95% CI 72.6 to 131.9), p=0.001) and on multivariate Cox regression analysis (HR 1.94 (95% CI 1.4 to 2.8), p<0.001). CONCLUSIONS: In this study a BMI ≥30 kg/m² was associated with a shorter time to recurrence in patients with vulvar cancer and this was mainly attributed to a higher risk of local recurrence.
Subject(s)
Carcinoma, Squamous Cell/epidemiology , Neoplasm Recurrence, Local/epidemiology , Obesity/epidemiology , Vulvar Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , Body Mass Index , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Female , Germany/epidemiology , Humans , Middle Aged , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Vulvar Neoplasms/pathology , Vulvar Neoplasms/therapy , Young AdultABSTRACT
PURPOSE: Postmenopausal hormone therapy (HT) is known to affect the development of hormone-dependent endometrial carcinoma (type I EC). Several studies on breast and ovarian carcinoma have shown that HT influences the molecular profile and prognostic behavior of these tumors. This study aimed to investigate the influence of prior HT and other risk factors on the prognosis in a cohort of patients with invasive endometrial carcinoma (EC). METHODS: Among 525 patients diagnosed with EC between 1987 and 2010, 426 postmenopausal patients were identified. Information regarding HT was available in 287 of these patients, 78 of whom had a history of HT and 209 of whom did not. Both overall survival (OS) and progression-free survival (PFS) were analyzed. In addition to OS and PFS, risk factors such as age at diagnosis, postmenopausal HT, body mass index (BMI), diabetes mellitus, tumor stage, EC type (I or II), and recurrences were analyzed. RESULTS: Relative to HT alone, women with EC and a history of HT had a longer survival than those with no HT. However, the Cox proportional hazards model showed that it was not HT itself, but rather other characteristics in the HT group that were causally associated with longer survival. CONCLUSIONS: Age (the older, the worse) and tumor stage (the higher, the worse) were significant influences on overall survival. Patients with HT also had lower BMIs, less diabetes, more type I EC, and fewer recurrences in comparison with the non-HT group. With regard to the PFS, it made no difference whether the patient was receiving HT.
Subject(s)
Endometrial Neoplasms/drug therapy , Estrogen Replacement Therapy/adverse effects , Aged , Cohort Studies , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Humans , Neoplasm Recurrence, Local , Prognosis , Risk Factors , Survival RateABSTRACT
INTRODUCTION: Large translational research projects may contribute to further progress in cancer treatment by exploring molecular biology, immunologic approaches and identification of new prognostic and predictive factors. Therefore, the BRandOBio-project combines a clinical registry for collection of patient and tumor characteristics with a biobank comprising tumor and liquid biopsies. In addition, sociodemographic, environmental and lifestyle factors of included patients with primary newly diagnosed breast or ovarian cancer, other rare malignant ovarian tumors or gestational trophoblastic disease are prospectively collected. METHODS: The target population includes the German "Alb-Allgäu-Bodensee Region" which constitutes the outreach area of the University Hospital Ulm with affiliated academic centers and private practices. Clinical data combined with primary tumor tissue samples and longitudinal repeatedly collected blood samples [before, 6 (in high-risk situations), 12, 36 and 60 months after treatment and at relapse] will be acquired from more than 4000 patients within the next years. Standardized questionnaires are given to patients of the University Hospital Ulm and eight selected external sites for assessing life style and cancer risk factors. Concomitantly, storage of paraffin-embedded tumor samples as well as liquid biopsy samples will allow translational research projects, for example in terms of investigating circulating DNA and germ line DNA from cell pellets. RESULTS: Starting in January 2016 at the University Hospital Ulm, 19 additional external sites started recruiting patients in March 2017. As of September 15th 2019, 2151 patients with newly diagnosed cancers could be recruited (2044 breast cancer; 107 ovarian cancer). Nearly all patients provided biological samples (tumor and liquid biopsy) and about 80% returned the standardized questionnaire. After 1 year follow-up, blood samples were available from more than 80% of the participating patients. CONCLUSIONS: The BRandO BIO study is a large prospective cohort study with integrated comprehensive biobank and evaluation of sociodemographic and life style factors of gynecological cancer patients in a well-defined geographical area in the South West of Germany. Continuous high patient recruitment and stable rates over 80% for returned questionnaires as well as for repeated blood sampling show high acceptance of the BRandO study program and confirms feasibility of the project.
Subject(s)
Biological Specimen Banks/standards , Breast Neoplasms/diagnosis , Ovarian Neoplasms/diagnosis , Adult , Feasibility Studies , Female , Humans , Middle Aged , Prognosis , Prospective Studies , Risk Factors , Translational Research, BiomedicalABSTRACT
OBJECTIVE: Lymph node ratio (LNR) can predict treatment outcome and prognosis in patients with solid tumors. Aim of the present analysis was to confirm the concept of using LNR for assessing outcome in patients with vulvar cancer after surgery with inguinal lymphadenectomy in a large multicenter project. METHODS: The AGO-CaRE-1 study multicenter database was used for analysis. LNR was defined as ratio of number of positive lymph nodes (LN) to the number of resected. Previously established LNR risk groups were used to stratify patients. LNR was investigated with respect to clinical parameters. Univariate and multivariable survival analyses were performed to assess the value of LNR in order to predict overall (OS) and progression-free (PFS) survival. RESULTS: In total, 1047 patients treated with surgery including inguinal lymph node resection for squamous cell carcinoma of the vulva were identified from the database. Of these, 370 (35.3%) were found to have positive inguinal LN. In total, 677 (64.7%) had a LNR of 0% (N0), 255 (24.4%) a LNR of >0%â¯<â¯20%, and 115 (11%) a LNR of ≥20%. Patients with higher LNR were found to have larger tumor size (Pâ¯<â¯.001), advanced tumor stage (Pâ¯<â¯.001), high tumor grade (Pâ¯<â¯.001), and deep stromal invasion (Pâ¯<â¯.001), more frequently. Three-year PFS rates were 75.7%, 44.2%, and 23.1% and three-year OS rates were 89.7%, 65.4%, and 41.9%, in patients with LNRs 0%, >0%â¯<â¯20%, and ≥20%, respectively (Pâ¯<â¯.001, Pâ¯<â¯.001). On multivariable analyses LNR (HR 7.75, 95%-CI 4.01-14.98, Pâ¯<â¯.001), FIGO stage (HR 1.41, 95%-CI 1.18-1.69, Pâ¯<â¯.001), and patient's performance status (HR 1.59, 95%-CI 1.39-1.82, Pâ¯<â¯.001), were associated with PFS. In addition, LNR (HR 12.74, 95%-CI 5.64-28.78, Pâ¯<â¯.001), and performance status (HR 1.72, 95%-CI 1.44-2.07, Pâ¯<â¯.001) were also the only two parameters independently associated with OS. LNR generally showed stronger correlation than number of affected LN when comparing the two different multivariable models. CONCLUSIONS: In women with vulvar cancer LNR appears to be a consistent, independent prognostic parameter for both PFS and OS and allows patient stratification into three distinct risk groups. In survival analyses, LNR outperformed nodal status and number of positive nodes.
Subject(s)
Carcinoma, Squamous Cell/surgery , Lymph Node Excision/statistics & numerical data , Lymphatic Metastasis , Vulvar Neoplasms/surgery , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Female , Germany/epidemiology , Humans , Lymph Nodes/pathology , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Assessment/methods , Survival Analysis , Vulvar Neoplasms/mortality , Vulvar Neoplasms/pathologyABSTRACT
BACKGROUND: Daysy is a fertility monitor that uses the fertility awareness method by tracking and analyzing the individual menstrual cycle. In addition, Daysy can be connected to the application DaysyView to transfer stored personal data from Daysy to a smartphone or tablet (IOS, Android). This combination is interesting because as it is shown in various studies, the use of apps is increasing patients´ focus on their disease or their health behavior. The aim of this study was to investigate if by the additional use of an App and thereby improved usability of the medical device, it is possible to enhance the typical-use related as well as the method-related pregnancy rates. RESULT: In the resultant group of 125 women (2076 cycles in total), 2 women indicated that they had been unintentionally pregnant during the use of the device, giving a typical-use related Pearl-Index of 1.3. Counting only the pregnancies which occurred as a result of unprotected intercourse during the infertile (green) phase, we found 1 pregnancy, giving a method-related Pearl-Index of 0.6. Calculating the pregnancy rate resulting from continuous use and unprotected intercourse exclusively on green days, gives a perfect-use Pearl-Index of 0.8. CONCLUSION: It seems that combining a specific biosensor-embedded device (Daysy), which gives the method a very high repeatable accuracy, and a mobile application (DaysyView) which leads to higher user engagement, results in higher overall usability of the method.
Subject(s)
Fertility/physiology , Mobile Applications , Ovulation Detection/methods , Pregnancy Rate , Smartphone/statistics & numerical data , Adult , Female , Humans , Pregnancy , Retrospective StudiesABSTRACT
PURPOSE: Analyzing the large patient cohort of the multicenter AGO-CaRE-1 study, we compared isolated sentinel lymph node dissection (SLND) with radical lymph node dissection (LND) of the groin in relation to recurrence rates and survival. METHODS: The AGO-CaRE-1 study retrospectively collected data on treatment patterns and follow-up of vulvar cancer patients [International Federation of Gynecology and Obstetrics (FIGO) stage ≥1B] treated at 29 gynecologic cancer centers between 1998 and 2008. This subgroup analysis evaluated the influence of SLND alone on progression-free survival (PFS) and overall survival (OS). RESULTS: In 487 (63.1%) of 772 included patients with tumors smaller than 4 cm, an LND was performed and no metastatic lymph nodes were detected (LN0). Another 69/772 (8.9%) women underwent SLND alone, showing a negative SLN (SLN0). Tumors in the LN0 group were larger and showed a deeper invasion (LN0 vs. SLN0 tumor diameter: 20.0 vs. 13.0 mm, p < 0.001; depth of invasion: 4.0 vs. 3.0 mm, p = 0.002). After a median follow-up of 33 months (0-156), no significant differences in relation to isolated groin recurrence rates (SLN0 3.0% vs. LN0 3.4%, p = 0.845) were detected. Similarly, univariate 3-year PFS analysis showed no significant differences between both groups (SLN0 82.7% vs. LN0 77.6%, p = 0.230). A multivariate Cox regression analysis, including tumor diameter, depth of invasion, age, grading, and lymphovascular space invasion was performed: PFS [hazard ratio (HR) 0.970, 95% confidence interval (CI) 0.517-1.821] and OS (HR 0.695, 95% CI 0.261-1.849) did not differ significantly between both cohorts. CONCLUSION: This subgroup analysis of the large AGO-CaRE-1 study showed similar results for groin LND and SLND alone with regard to recurrence rates and survival in node-negative patients with tumors <4 cm.
Subject(s)
Lymph Node Excision/methods , Neoplasm Recurrence, Local , Sentinel Lymph Node/surgery , Vulvar Neoplasms/surgery , Adult , Age Factors , Aged , Aged, 80 and over , Disease-Free Survival , Female , Follow-Up Studies , Humans , Inguinal Canal , Lymphatic Metastasis , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Retrospective Studies , Survival Rate , Tumor Burden , Vulvar Neoplasms/pathology , Young AdultABSTRACT
OBJECTIVES: To evaluate activity and toxicity of mTOR inhibitor temsirolimus in patients with platinum-refractory/resistant ovarian cancer (OC) or advanced/recurrent endometrial carcinoma (EC). METHODS: Women with epithelial ovarian, fallopian tube or primary peritoneal cancer were eligible, when they had progression during treatment with a platinum based regimen or within 6 months after receiving a platinum based regimen and a previous taxane treatment. Women with advanced/recurrent EC, no longer amenable to curative surgery and/or radiotherapy were eligible when they had no previous or only adjuvant chemotherapy. Preceding endocrine therapy for metastatic/recurrent disease was allowed. Patients received weekly IV infusions of 25mg temsirolimus. Primary endpoint was progression free survival rate after 4 months (OC) or 6 months (EC). A two stage design was applied. RESULTS: Forty-four patients (OC: n=22; EC: n=22) were enrolled and received temsirolimus treatment. Median age was 56 years (OC) or 63 years (EC). After eight weeks of treatment, 10 of 21 evaluable patients in the OC cohort and 8 of 20 evaluable patients in the EC cohort had progressive disease. Thus efficacy did not meet the predefined levels during the first stage of recruitment and the trial was stopped. Some patients in both cohorts had long lasting PFS (>7 months). Toxicity of temsirolimus was mild. CONCLUSIONS: Temsirolimus treatment was well tolerated in our patients, but did not meet the predefined efficacy criteria. In our study as in other trials on rapalogs in OC or EC, a few patients had long lasting disease stabilisations.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma/drug therapy , Endometrial Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Sirolimus/analogs & derivatives , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Disease-Free Survival , Drug Resistance, Neoplasm , Early Termination of Clinical Trials , Female , Humans , Middle Aged , Platinum Compounds/therapeutic use , Response Evaluation Criteria in Solid Tumors , Retreatment , Sirolimus/adverse effects , Sirolimus/therapeutic use , Young AdultABSTRACT
BACKGROUND AND OBJECTIVES: Chylous ascites, an accumulation of milky-white lymph fluid in the peritoneal cavity, is a rare complication following retroperitoneal lymphadenectomy. This study evaluated the appearance and management of chylous ascites following lymphadenectomy for gynecological malignancies. METHODS: A total of 931 patients who underwent lymphadenectomy for gynecological malignancies at Erlangen University Hospital between 2002 and 2013 were reviewed retrospectively. RESULTS: Chylous ascites occurred postoperatively in 28 of the 931 patients (3.0%). All patients with chylous ascites had undergone combined systematic para-aortic and pelvic lymphadenectomy (SAPL). Patients with chylous ascites had a larger mean number of lymph nodes removed (51.9 vs. 40.0, P = 0.002) and the proportion of laparoscopic SAPLs was significantly higher (20/28; 71.4%) in comparison with open surgery (8/28; 28.6%) (P < 0.0001). Additional parameters, such as the number of positive lymph nodes, were not significantly associated with the occurrence of chylous ascites. Conservative management was sufficient to resolve chylous ascites in all observed cases, with a mean time to resolution of 8 days. CONCLUSIONS: Postoperative chylous ascites was more frequently observed in patients with laparoscopic SAPL in comparison with open SAPL and was strongly associated with a larger mean number of removed lymph nodes. J. Surg. Oncol. 2016;114:613-618. © 2016 Wiley Periodicals, Inc.
Subject(s)
Carcinoma/surgery , Chylous Ascites/etiology , Genital Neoplasms, Female/surgery , Laparoscopy/adverse effects , Lymph Node Excision/adverse effects , Postoperative Complications/etiology , Adult , Aged , Aged, 80 and over , Carcinoma/pathology , Female , Genital Neoplasms, Female/pathology , Humans , Middle Aged , Retrospective Studies , Risk Factors , Young AdultABSTRACT
PURPOSE: There is low evidence regarding the optimal treatment in patients with uterine sarcomas and malignant mixed Mullerian tumors (MMMTs). This study provides an overview of experience at our center with patients diagnosed with uterine sarcoma and MMMT, in relation to the clinical management and outcome. METHODS: The medical records for 143 patients with low-grade endometrial stromal sarcoma (ESS), leiomyosarcoma (LMS), and high-grade (undifferentiated) endometrial sarcoma (UES) and MMMT were reviewed. All available clinical and pathological data were collected and analyzed. Putative prognostic factors were entered into a multivariate analysis using a Cox proportional hazards ratio model, and survival data were calculated. RESULTS: The 5-year overall survival rates were significantly different between patients with ESS, LMS, and UES and MMMT (86 vs. 40 vs. 57 vs. 45 %; P < 0.001). The multivariate analysis showed that the patients' age, higher FIGO stage (III-IV), a history of smoking, prior pelvic radiation, diabetes, and residual tumor after surgery were associated with a poorer overall survival. Histological subtypes of LMS (HR 4.68; 95 % CI 1.35-16.17), UES (HR 1.21; 95 % CI 0.26-5.77) and MMMT (HR 1.63; 95 % CI 0.42-6.43) were also associated with a poorer overall survival than ESS (P = 0.008). Adjuvant therapies showed no associations with overall survival. CONCLUSIONS: Adjuvant therapy has so far not shown any overall survival benefit, and the focus is therefore on primary surgery. In future studies, the entities should be investigated separately in relation to prognostic factors and effective therapeutic management.
Subject(s)
Endometrial Stromal Tumors/pathology , Leiomyosarcoma/pathology , Mixed Tumor, Mullerian/pathology , Sarcoma, Endometrial Stromal/pathology , Uterine Neoplasms/pathology , Adult , Aged , Combined Modality Therapy , Disease-Free Survival , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Endometrial Neoplasms/therapy , Endometrial Stromal Tumors/mortality , Endometrial Stromal Tumors/therapy , Female , Humans , Kaplan-Meier Estimate , Leiomyosarcoma/mortality , Leiomyosarcoma/therapy , Middle Aged , Mixed Tumor, Mullerian/mortality , Mixed Tumor, Mullerian/therapy , Multivariate Analysis , Prognosis , Proportional Hazards Models , Sarcoma/pathology , Sarcoma, Endometrial Stromal/mortality , Sarcoma, Endometrial Stromal/therapy , Survival Rate , Uterine Neoplasms/mortality , Uterine Neoplasms/surgeryABSTRACT
BACKGROUND: Medical research studies are becoming increasingly important for optimizing the prevention, diagnosis and treatment of illnesses. Participation in research studies can have many benefits for patients. In randomized and controlled clinical studies, they can receive the best possible medical care currently available. However, only a small proportion of patients nowadays are treated within the framework of medical research. The primary endpoint of this study was to discover what level of knowledge patients have about clinical studies and how they currently perceive them, in order to identify ways of optimizing the information provided about studies from the patients' point of view. METHODS: The study included 2546 patients (breast cancer 21.6%, gynecological cancer 8.3%, obstetrics 32.7%, endometriosis 7.8%, fertility treatment 3.2%, other benign gynecological illnesses 19.2%, no information for 7.2%) in the outpatient clinic (45.2%) and in the in-patient sector (54.8%) at the Department of Gynecology at Erlangen University Hospital and associated centers. In the single-center study, conducted between January 2011 and January 2012, the patients were asked about their level of knowledge regarding the background to medical research studies and the ways in which they are carried out and used. The patients were also asked how they perceived medical studies and how they thought study conditions might be optimized. The three-page questionnaire was included in the feedback sheet received by patients as part of the hospital's quality management system. RESULTS: As a whole, the group only had moderate knowledge about clinical studies. A majority of the respondents considered that studies were valuable (91.6%), but only a few were also willing to take part in them (58.4%). Knowledge and willingness to participate strongly depended on age (P < 0.001), educational level (P < 0.001) and patient group (P < 0.001). Most patients would prefer to decide about participating in studies through a discussion with their outpatient physicians. CONCLUSIONS: The information that patients have about clinical studies affects whether they participate in them. It is therefore extremely important for patients to be well informed, for their anxieties about participation to be relieved, and for the benefits of participation to be explained to them.
Subject(s)
Breast Neoplasms/epidemiology , Breast Neoplasms/psychology , Clinical Studies as Topic/psychology , Genital Diseases, Female/epidemiology , Genital Diseases, Female/psychology , Health Knowledge, Attitudes, Practice , Adolescent , Adult , Aged , Aged, 80 and over , Biomedical Research , Cross-Sectional Studies , Female , Humans , Middle Aged , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: No screening programs are available for ovarian or endometrial cancer. One reason for this is the low incidence of the conditions, resulting in low positive predictive values for tests, which are not very specific. One way of addressing this problem might be to use risk factors to define subpopulations with a higher incidence. The aim of this study was to investigate the extent to which a medical history of endometriosis can serve as a risk factor for ovarian or endometrial cancer. METHODS: In a hospital-based case-control analysis, the cases represented patients with endometrial or ovarian cancer who were participating in studies aimed at assessing the risk for these diseases. The controls were women between the age of 40 and 85 who were invited to take part via a newspaper advertisement. A total of 289 cases and 1016 controls were included. Using logistic regression models, it was tested whether self-reported endometriosis is a predictor of case-control status in addition to age, body mass index (BMI), number of pregnancies and previous oral contraceptive (OC) use. RESULTS: Endometriosis was reported in 2.1 % of the controls (n = 21) and 4.8 % of the cases (n = 14). Endometriosis was a relevant predictor for case-control status in addition to other predictive factors (OR 2.63; 95 % CI, 1.28 to 5.41). CONCLUSION: This case-control study found that self-reported endometriosis may be a risk factor for endometrial or ovarian cancer in women between 40 and 85 years. There have been very few studies addressing this issue, and incorporating it into a clinical prediction model would require a more precise characterization of the risk factor of endometriosis.
Subject(s)
Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/etiology , Endometriosis/complications , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/etiology , Adult , Aged , Aged, 80 and over , Body Mass Index , Case-Control Studies , Female , Humans , Middle Aged , Odds Ratio , Pregnancy , Risk FactorsABSTRACT
Small cell carcinoma of the ovary, hypercalcemic type is a very rare aggressive neoplasm of unknown histogenesis, affecting mainly girls and young women. Recently, inactivating mutations in SMARCA4 (BRG1), a member of the switch/sucrose nonfermenting chromatin remodeling complex, has been identified as driver events in most cases. We herein describe 3 cases in 34, 34, and 37-year-old women. Symptoms were mainly abdominal pain and mass. One patient was normocalcemic, and the other 2 had no preoperative serum calcium values available. All patients received radical hysterectomy with salpingo-oophorectomy, lymphadenectomy, and variable multimodality therapy. Two developed abdominal recurrences/metastases and died of disease at 4 and 12 months. One patient was alive without disease 17 months after surgery and radiochemotherapy. Histologic examination showed undifferentiated neoplasms composed of diffuse sheets, nests and cords of noncohesive monomorphic small blue/basaloid cells (classic variant, 1 case), and large undifferentiated/rhabdoid cells with abundant cytoplasm (large cell/rhabdoid variant, 2 case) admixed with minor small cell areas. One case contained rare isolated goblet cells, but true glandular component was absent. All tumors expressed vimentin and variably pancytokeratin and WT1. Nuclear SMARCB1 was intact in all cases (1 case showed small foci with mosaic loss). All tumors showed complete loss of SMARCA4. In conclusion, SMARCA4 immunohistochemistry represents a highly valuable emerging tool in identifying small cell carcinoma of the ovary, hypercalcemic type in routine practice. Distinguishing this aggressive neoplasm from juvenile granulosa cell tumor and other undifferentiated ovarian cancers is mandatory in selecting appropriate chemotherapeutic regimens and would allow better characterization of this entity, for which targeted molecular therapy still remains to be established.
Subject(s)
Carcinoma, Small Cell/pathology , Carcinoma/pathology , DNA Helicases/deficiency , Hypercalcemia/pathology , Nuclear Proteins/deficiency , Ovarian Neoplasms/pathology , Transcription Factors/deficiency , Adult , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma/drug therapy , Carcinoma/metabolism , Carcinoma/surgery , Carcinoma, Small Cell/drug therapy , Carcinoma, Small Cell/metabolism , Carcinoma, Small Cell/surgery , Chromosomal Proteins, Non-Histone/genetics , Chromosomal Proteins, Non-Histone/metabolism , DNA Helicases/genetics , DNA Helicases/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Female , Humans , Hypercalcemia/metabolism , Immunohistochemistry , Mutation , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , SMARCB1 Protein , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
PURPOSE: To analyze reoperation rates and perioperative outcomes after long-term follow-up of two surgical approaches in the treatment of endometrial cancer when the standard of care shifts from open surgery to laparoscopy at a university hospital. METHODS: In this retrospective monocenter study a total of 267 patients with endometrial cancer were included; 107 women underwent laparoscopy and 160 laparotomy. All of the patients received total hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy, depending on individual pathological features (e.g. high risk for positive lymph nodes) and the expertise of the surgeon. RESULTS: Repeat surgery was needed significantly more often in the laparotomy group in comparison with the laparoscopy group (11.9 vs. 0.9 %, respectively; P < 0.001). Hospital stays were longer in the laparotomy group in comparison with laparoscopy (16.2 vs. 9.5 days; P < 0.000001). Postoperative complications were significantly more frequent in the laparotomy group in comparison with laparoscopy (25.0 vs. 10.3 %; P < 0.01). Operating times and preoperative and postoperative hemoglobin differences were similar in the two groups (193.9 vs. 190.6 min, 2.0 vs. 1.8 g/dl). Intraoperative complication rates were similar in the two groups (3.8 vs. 5.6 %). CONCLUSIONS: Laparoscopy is a safe alternative to laparotomy for low risk endometrial cancer patients and offers markedly improved perioperative outcomes with a lower reoperation rate and fewer postoperative complications when the standard of care shifts from open surgery to laparoscopy in a university hospital.
Subject(s)
Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Hysterectomy , Laparoscopy/methods , Reoperation/statistics & numerical data , Standard of Care , Aged , Aged, 80 and over , Animals , Female , Follow-Up Studies , Humans , Laparotomy/adverse effects , Length of Stay , Lymph Node Excision , Middle Aged , Neoplasm Staging , Outcome Assessment, Health Care , Ovariectomy , Perioperative Period , Postoperative Complications/etiology , Retrospective Studies , Second-Look SurgeryABSTRACT
PURPOSE: Ectopic pregnancy is an acute, potentially life-threatening condition. The aim of this study was to compare the results of surgery and methotrexate treatment in women with ectopic pregnancy, along with a review of the literature. METHODS: 164 women with ectopic pregnancy, treated from 2000 to 2008 at the university gynecology department, were examined in a retrospective analysis. Patients with diagnosed ectopic pregnancy underwent one of the following treatments: Salpingotomy, salpingectomy or administration of a single dose of 30 mg methotrexate. The main outcome measures were treatment success rate, rate of patients wishing to have children after the ectopic pregnancy, and rates of pregnancy, live births, recurrent ectopic pregnancy, miscarriage, use of assisted reproduction and side effects. RESULTS: There were no significant differences in success rates between the groups (methotrexate 83.9 %, salpingotomy 88.2 %, salpingectomy 96.8 %). Significantly more patients in the salpingotomy group wished to become pregnant afterward than in the salpingectomy group. No significant differences were observed between the groups in the rates of intrauterine pregnancy, live births, recurrences, miscarriages, or side effects. CONCLUSIONS: With defined inclusion criteria, similar results can be achieved with low-dose single administration of 30 mg methotrexate in comparison with surgical treatment for ectopic pregnancy. On the basis of the data presented here, further research to establish optimal dosages for methotrexate is needed.
Subject(s)
Folic Acid Antagonists/administration & dosage , Methotrexate/administration & dosage , Pregnancy, Ectopic/drug therapy , Adult , Fallopian Tubes/surgery , Female , Humans , Pregnancy , Pregnancy, Ectopic/surgery , Retrospective Studies , Salpingectomy , Treatment OutcomeABSTRACT
Prediction of the prognosis for metastatic breast cancer patients depends on molecular subtypes similar to those found in patients with primary breast cancer. Several studies have shown that estrogen receptor (ER) and progesterone receptor (PR) status determine the course of the disease and the prognosis. As Ki-67 helps to differentiate molecular subtypes in patients with primary breast cancer, the aim of this study was to assess the prognostic relevance of Ki-67 in the primary tumor in relation to its prognostic relevance for patients with metastatic breast cancer. A total of 467 patients with invasive breast cancer were identified in the database of a single breast cancer center, in whom Ki-67 had been assessed in tumor material from the breast at the time of the primary diagnosis and who had developed a metastasis at any time during the subsequent course. For these patients, tumor and patient characteristics were used to determine prognostic factors relative to overall survival after the diagnosis of distant metastases. Ki-67 was added to this model to investigate whether this might improve the prediction of overall survival. In the multivariate Cox model, age at diagnosis, body mass index, nodal status, tumor size, ER and PR status, and time from diagnosis to metastasis were identified as relevant prognostic factors. Adding Ki-67 to the model improved the prediction of overall survival. There was also a significant and relevant interaction with the PR status. In patients with a low-proliferation primary tumor, a high level of PR expression would indicate an extraordinarily good prognosis (HR 0.39; 95 % CI, 0.23-0.66). In patients with higher-proliferation primary tumors, PR status was not capable of differentiating prognostic groups. Ki-67 is useful in addition to known prognostic factors for breast cancer. It is able to indicate a group of women with a poorer prognosis, specifically in the group of patients with PR-positive breast cancer.
Subject(s)
Breast Neoplasms/mortality , Breast Neoplasms/pathology , Ki-67 Antigen/analysis , Aged , Body Mass Index , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Bone Neoplasms/secondary , Breast Neoplasms/metabolism , Female , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Lymphatic Metastasis/pathology , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective StudiesABSTRACT
OBJECTIVES: The aim of this study is to evaluate the activity and toxicity of fulvestrant, a pure estrogen receptor antagonist in patients with advanced or recurrent endometrial cancer, expressing estrogen and/or progesterone receptors (ER/PR). METHODS: Eligible patients with advanced or recurrent endometrial cancer not amenable to curative surgery and/or radiotherapy were treated with fulvestrant at a dose of 250 mg by IM injection every 4 weeks for at least 12 weeks. Therapy was continued until disease progression, death, intolerable side effects or end of study. Response was assessed in patients with at least one target lesion according to WHO-criteria. RESULTS: Thirty-five patients were enrolled in this study and received at least one injection of fulvestrant (intention to treat-population, ITT). Twenty six patients received the intended 3 injections of fulvestrant (per protocol population, PP). There was no complete response but 4 partial responses (11.4% ITT) and 8 stable diseases. The median time to progression was 2.3 months (ITT). Overall survival was 13.2 months (ITT). Treatment was well tolerated. CONCLUSIONS: Fulvestrant at a dose of 250 mg IM every 4 weeks has marginal activity and good tolerability in patients with ER and/or PR positive advanced or recurrent endometrial cancer. A loading dose strategy and the use of 500 mg/4 weeks might improve the efficacy of this treatment.
Subject(s)
Antineoplastic Agents, Hormonal/administration & dosage , Endometrial Neoplasms/drug therapy , Estradiol/analogs & derivatives , Estrogen Antagonists/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Aged , Aged, 80 and over , Antineoplastic Agents, Hormonal/adverse effects , Drug Administration Schedule , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Estradiol/administration & dosage , Estradiol/adverse effects , Estrogen Antagonists/adverse effects , Female , Fulvestrant , Humans , Injections, Intramuscular , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Receptors, Estrogen/biosynthesis , Receptors, Progesterone/biosynthesisABSTRACT
INTRODUCTION: Although care in certified breast centers is now established throughout Germany, numerous services are still not being reimbursed. This also affects other centers involved in the specialty of gynecology such as gynecological cancer centers, perinatal centers, and endometriosis centers. Although a certified center is entitled to charge additional fees, these are in most cases not reimbursed. Calculation of additional costs is limited by the fact that data from the Institute for the Hospital Reimbursement System (Institut für das Entgeltsystem im Krankenhaus, InEK) do not reflect interdisciplinary services and procedures. For decision-makers, society's willingness to pay is an important factor in guiding decisions on the basis of social priorities. A hypothetical maximum willingness to pay can be calculated using a willingness-to-pay analysis, making it possible to identify deficiencies in the arbitrary setting of health budgets at the macro-level. MATERIALS AND METHODS: In a multicenter study conducted between November 2009 and December 2010, 2,469 patients at a university hospital and at a non-university hospital were asked about the extent of their awareness of certified centers, the influence of centers on hospital presentation, and about personal attitudes toward quality-oriented reimbursement. A subjective assessment of possible additional charges was calculated using a willingness-to-pay analysis. RESULTS: In the overall group, 53.4 % of the patients were aware of what a certified center is and 27.4 % had specific information (obstetrics 40.0/32.3 %; mastology 66.8/23.2 %; gynecological oncology 54.7/27.3 %; P < 0.001). For 43.8 %, a certified center was one reason or the major reason for presentation (obstetrics 26.2 %; mastology 66.8 %; gynecological oncology 46.6 %; P < 0.001). A total of 72.6 % were in favor of quality-oriented reimbursement and 69.7 % were in favor of an additional charge for a certified center amounting to 538.56 (mastology 643.65, obstetrics 474.67, gynecological oncology 532.47). In all, 33.9 % would accept an increase in health-insurance fees (averaging 0.3865 %), and 28.3 % were in favor of reduced remuneration for non-certified centers. CONCLUSIONS: The existence of certified centers is being increasingly recognized by patients. Additional charges for certified centers are generally supported. There is therefore a clear demand for them-from patients as well. This may be useful when negotiations are being conducted.