ECOG and BMI as preoperative risk factors for severe postoperative complications in ovarian cancer patients: results of a prospective study (RISC-GYN—trial)

Background: Accompanying co-morbidities in patients with ovarian cancer are of major relevance for scheduling debulking surgery, especially in the anesthesiological consultations. Aim of this study was to evaluate the impact of co-morbidities and patient characteristics on postoperative complications. Methods: Patients undergoing maximal cytoreductive surgery were prospectively enrolled from October 2015 to January 2017. Various variables were recorded, such as the Charlson comorbidity index, Eastern cooperative oncology group scale of performance status (ECOG PS) and the American society of anesthesiologists physical status classification system (ASA PS). Surgical complications were graded using the Clavien-Dindo criteria. Logistic regression models were used to analyze risk factors for severe postoperative complications. Results: Of 106 enrolled patients, 19 (17.9%) developed severe postoperative complications grade >= IIIb according to Clavien-Dindo criteria. In the multivariable regression analysis impaired (ECOG PS) > 1 (odds ratio OR) 13.34, 95% confidence interval (CI) 1.74-102.30, p = 0.01), body mass index (BMI) > 25 kg/m(2) (OR 10.48, 95% CI 2.38-46.02, p = 0.002) along with the use of intraoperative norepinephrine > 0.11 mu g/kg/min (OR 4.69, 95% CI 1.13-19.46, p = 0.03) and intraoperative fresh frozen plasma (FFP) > 17 units (OR 4.11, 95% CI 1.12-15.14, p = 0.03) appeared as significant predictors of severe postoperative complications. Conclusion: We demonstrated that neither the presence of a certain comorbidity nor the summation of the co-morbidities were associated with adverse outcome. Patient characteristics, such as ECOG PS > 1 and obesity (BMI > 25 kg/m(2)), are highly predictive factors for severe postoperative complications. The analysis of intraoperative data showed that the need for more than > 0.11 mu g/kg/min of norepinephrine and transfusions of FFPs more than 17 units were strongly associated with severe postoperative complications

The role of the epithelial marker EpCAM in ovarian cancer and small cell ovarian carcinoma of the hypercalcemic type

Einleitung: Das epitheliale Zelladhäsionsmolekül EpCAM ist auf Karzinomen, wie z.B. Ovarialkarzinomen, überexprimiert. Es wurde als Prognosemarker bei Mammakarzinomen identifi¬ziert, die prognostische Bedeutung bei Ovarialkarzinomen ist jedoch weitgehend unbekannt. Zunächst wurde EpCAM daher als potentieller Prognosemarker untersucht. Darüber hinaus wurde analysiert, ob EpCAM auch im Verlauf der Erkrankung überexprimiert wird, da EpCAM- spezifische Therapien im Rezidiv eingesetzt werden, die Expression in der Rezidivsituation je¬doch unzureichend geklärt ist. Weiterhin wurde die Erfahrung unserer Klinik mit dem sehr selte¬nen hyperkalzämischen Ovarialkarzinom evaluiert. Methodik: Klinische Daten und Tumorge¬webe wurden innerhalb des Projektes „Tumor Bank Ovarian Cancer“ gesammelt. Die EpCAM- Expression wurde mithilfe der Avidin-Biotin-Komplex-Methode immunhistochemisch unter¬sucht. EpCAM-Überexpression wurde definiert als Anfärbung von 76-100 % der Tumorzellen. Für die Evaluation der hyperkalzämischen Ovarialkarzinome wurden Therapie und Verlauf der Patientinnen analysiert, die am Europäischen Kompetenzzentrum für Eierstockkrebs behandelt wurden. Ergebnisse: In der Untersuchung von EpCAM als Prognosemarker zeigten 65 von 74 eingeschlossenen Patientinnen eine EpCAM-Überexpression. Mit dem progressionsfreien Über¬leben und dem Ansprechen auf eine platinhaltige Chemotherapie korrelierte die Überexpression von EpCAM signifikant (p=0,040 und p=0,048). EpCAM wurde zudem als unabhängiger Mar¬ker für das Gesamtüberleben identifiziert (p=0,022). Für die Analyse der EpCAM-Expression in der Rezidiv- im Vergleich zur Primärsituation wurden 19 Patientinnen identifiziert. EpCAM war in 89 % in der Primär- und in 84 % in der Rezidivsituation überexprimiert. Es konnte kein signi¬fikanter Unterschied in der EpCAM-Expression im Verlauf der Erkrankung gefunden werden (p=1.0). Vier Patientinnen mit hyperkalzämischem Ovarialkarzinom konnten in die Analyse ein¬geschlossen werden. Alle wurden operiert, drei feritilitätserhaltend, und erhielten eine adjuvante Chemotherapie. Drei der Patientinnen leben rezidivfrei während einer medianen Nachbeobach¬tungszeit von 22 Monaten (Range: 8-47), während eine Patientin 15 Monate nach Diagnosestel¬lung verstarb. Schlussfolgerung: Wir konnten zeigen, dass eine EpCAM-Überexpression mit einem signifikant besseren Überleben beim Ovarialkarzinom assoziiert ist. Dies muss nun in größeren Studien bestätigt werden, um EpCAM als Prognosemarker etablieren zu können. Un¬sere Ergebnisse hinsichtlich der stabilen Expression von EpCAM auch im Verlauf der Erkran¬kung unterstützen den Einsatz EpCAM-spezifischer Therapien in der Rezidivsituation. In frühen Stadien des hyperkalzämischen Ovarialkarzinoms kann eine fertilitätserhaltende Operation in Betracht gezogen werden. Für definitive Therapieempfehlungen sind höhere Fallzahlen und die Einrichtung von Registern nötig.Introduction: The epithelial cell adhesion molecule EpCAM is overexpressed by many carcinomas such as ovarian cancer. It was identified as prognostic marker e.g. in breast cancer; its prognostic significance in ovarian cancer is not clear. Initially, EpCAM was investigated as prognostic marker in ovarian cancer. Furthermore, it was analyzed if EpCAM is also overexpressed throughout the disease, because EpCAM-targeted therapies are used in recurrent ovarian cancer although EpCAM expression has not been studied sufficiently in recurrent disease. Moreover, the experience of our hospital with the very rare small cell ovarian cancer of the hypercalcemic type (OSCCHT) was evaluated. Methods: Clinical data and tissues were collected within the project “Tumor Bank Ovarian Cancer”. EpCAM expression was assessed by immunohistochemistry using the avidin biotin complex method. EpCAM overexpression was defined as 76-100 % of tumor cells being positively stained for EpCAM. Treatment and clinical course were evaluated in patients with OSCCHT who had been treated in the European Competence Center for Ovarian Cancer. Results: In our investigation of EpCAM as prognostic marker EpCAM was overexpressed in 65 out of 74 included patients. EpCAM overexpression was associated with better progression free survival and response to platinum based chemotherapy (p=0.040 and p=0.048). Moreover, EpCAM was identified as independent marker for overall survival (p=0.022). The analysis of EpCAM expression in the course of the disease involved 19 patients with both primary and corresponding recurrent tumor tissue. EpCAM overexpression was noted in 89 % in the primary and in 84 % in the recurrent situation without any significant change of expression throughout the disease (p=1.0). Four patients with OSCCHT were identified. All underwent surgery, in three cases fertility-sparing, and all received adjuvant chemotherapy. One patient died 15 months after initial diagnosis while three patients are alive without relapse in a median follow-up time of 22 months (range: 8-47). Conclusion: EpCAM overexpression was associated with significant better survival in ovarian cancer. To establish EpCAM as prognostic marker, larger studies are warranted. Our results, that show a stable expression pattern of EpCAM throughout the course of the disease, support the use of EpCAM targeted therapy in recurrent ovarian cancer. In early stages of OSCCHT fertility-sparing surgery can be considered; more cases should be evaluated for definite therapeutic recommendations

Preoperative quality of life as prediction for severe postoperative complications in gynecological cancer surgery: results of a prospective study

Purpose: The aim of this study was to investigate preoperative quality of life (QoL) as a predictive tool for severe postoperative complications (POC) in gynecological cancer surgery. Methods: This is a prospective study of patients undergoing gynecologic cancer surgery at an academic center in Germany. QoL was assessed by the EORTC Quality of Life Questionnaire (QLQ-C30) and the NCCN Distress Thermometer (DT). Several geriatric assessment tools have been applied. POC were graded using Clavien–Dindo criteria. Using multivariable logistic regression models, we identified predictive clinical characteristics for postoperative complications. Results: Within 30 days of surgery, 40 patients (18%) experienced grade ≥ 3b complications including 9 patients (4%) who died. The dominant complication was anastomosis insufficiency with 13 patients (5.8%). In the multivariable stepwise logistic regression through all univariate significant variables, we found that impaired physical functioning was predictive of POC, defined by an EORTC score  20 (OR 3.08, 95% CI 1.15–8.26, p = 0.025) indicated a significant predictive value. Being overweight or obese (BMI > 25) were also identified as predictive factors (OR 5.44, 95% CI 2.04–14.49, p = 0.001) as were reduced Mini Mental State Examination (MMSE) results < 27 (OR 7.94, 95% CI 1.36–45.46, p = 0.02). Conclusion: Preoperative QoL measurements could help to predict postoperative complications in patients with gynecological cancer. Patients with limitations of mobility, debilitating symptoms and cognitive impairment have an increased risk for developing severe POC

ECOG and BMI as preoperative risk factors for severe postoperative complications in ovarian cancer patients: results of a prospective study (RISC-GYN—trial)

Background!#!Accompanying co-morbidities in patients with ovarian cancer are of major relevance for scheduling debulking surgery, especially in the anesthesiological consultations. Aim of this study was to evaluate the impact of co-morbidities and patient characteristics on postoperative complications.!##!Methods!#!Patients undergoing maximal cytoreductive surgery were prospectively enrolled from October 2015 to January 2017. Various variables were recorded, such as the Charlson comorbidity index, Eastern cooperative oncology group scale of performance status (ECOG PS) and the American society of anesthesiologists physical status classification system (ASA PS). Surgical complications were graded using the Clavien-Dindo criteria. Logistic regression models were used to analyze risk factors for severe postoperative complications.!##!Results!#!Of 106 enrolled patients, 19 (17.9%) developed severe postoperative complications grade ≥ IIIb according to Clavien-Dindo criteria. In the multivariable regression analysis impaired (ECOG PS) &amp;gt; 1 (odds ratio OR) 13.34, 95% confidence interval (CI) 1.74-102.30, p = 0.01), body mass index (BMI) &amp;gt; 25 kg/m!##!Conclusion!#!We demonstrated that neither the presence of a certain comorbidity nor the summation of the co-morbidities were associated with adverse outcome. Patient characteristics, such as ECOG PS &amp;gt; 1 and obesity (BMI &amp;gt; 25 kg/

Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HR-QoL) in Patients with Ovarian Cancer: What Is Different Compared to Healthy Women?

Simple Summary: The aim of this analysis was to evaluate the health-related quality of life (HR-QoL) in patients with ovarian cancer using a questionnaire based on patient-reported outcomes (PROs). The HR-QoL for 155 enrolled patients with ovarian cancer was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) prior to surgery and compared with 501 healthy females in Germany, as well as to the previously published European Organization for Research and Treatment of Cancer (EORTC) reference data for 917 patients with ovarian cancer worldwide. The HR-QoL for the emotional, cognitive, and social functioning scales was lower in patients with ovarian cancer than the healthy female population. Interestingly, the patients with ovarian cancer had no significant differences in the physical functioning scale when compared with the healthy women. Furthermore, the younger patients with ovarian cancer had an even lower HR-QoL for the emotional, social, and cognitive functioning scales, and additionally had more fatigue and financial difficulties. Abstract: Introduction: The aim of this analysis was to evaluate the health-related quality of life (HR-QoL) in patients with ovarian cancer using a patient-reported outcome (PRO) based questionnaire and to compare it to the healthy female population in Germany and to other ovarian cancer patients worldwide. Additionally, we looked for differences in the HR-QoL with respect to the patients' ages in our cohort. Methods: The HR-QoL for 155 enrolled patients with ovarian cancer was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) prior to surgery and then compared with 501 healthy females in Germany, as well as to the previously published European Organization for Research and Treatment of Cancer (EORTC) reference data for 917 patients with ovarian cancer worldwide. Moreover, we grouped our cohort by ages 65 years and analyzed them for further differences. To identify the differences, T-tests were applied. Results: Overall, 155 patients were enrolled, and 126 patients had advanced-stage ovarian cancer (FIGO III-IV) (82.4%). Fifty-five (36%) patients were >65 years. Except for the physical functioning scale, all other domains of the functioning scales were significantly lower in our patients with ovarian cancer than in the healthy female population. The emotional (50 points versus 60 points, p = 0.02), cognitive (76 points versus 88 points, p = 0.005), and social functioning scales (68 points versus 81 points, p = 0.006) were lower in the younger subgroup. Further, the younger subgroup exhibited significantly more fatigue (40 points versus 29 points, p = 0.03) and financial difficulties (20 points versus 2 points, p < 0.001) than the older subgroup. Discussion: Interestingly, the patients with ovarian cancer had no significant differences in the physical functioning scale when compared with the healthy women. In contrast, the patients, especially in the younger group, needed special support for the emotional and social areas of their daily lives

Sexuality as a Prognostic Factor—Results of an Individual Patient Data NOGGO (North-Eastern German Society of Gynecological Oncology)-Meta-Analysis of 644 Recurrent Ovarian Cancer Patients Prior to Chemotherapy

Background: The aim of this study was to analyze the associations between sexuality, quality of life, treatment discontinuation, and survival in recurrent ovarian cancer (OC). Methods: Raw data from various phase II/III studies, including the questionnaires EORTC-QLQ-C30 and QLQ-OV28, were included. Data from the meta-analysis were calculated using logistic and Cox regression. Results: Data on sexuality were available for 644 patients. A total of 162 patients had an interest in sex and were sexually active (Group A). A total of 45 patients had an interest in sex and were sexually not active (Group I) and 437 patients had no interest in sex and were not sexually active (Group N). Group A was younger in median age (age at randomization), at 57 years, than Group I, at 60 years, and Group N, at 65 years (p p p p p = 0.012). In addition, Group A reported less pain, less peripheral neuropathy, and less fatigue (all p p < 0.001). Conclusions: Physicians should routinely address the topic of sexuality with ovarian cancer patients. Sexuality appears to be a marker for quality of life as well as overall survival

Frailty Index for Prediction of Surgical Outcome in Ovarian Cancer: Results of a Prospective Study [Editorial Material]

Surgical complete tumor resection is the strongest prognostic factor for patients with ovarian cancer; however, frailty is common among this population, which raises concerns for surgical outcomes and recovery. Alternative therapies such as neoadjuvant therapy are available, and identification of the frail patient can assist with identification of the appropriate treatment. Frailty index is a deficit accumulation model that uses symptoms, signs, current disease status, and disabilities in activities of daily life to evaluate frailty. Very few prospective studies have evaluated frailty index among a population of patients with ovarian cancer. This prospective study aimed to evaluate the frailty index as a predictor of surgical outcomes among patients with ovarian cancer. Patients older than 18 years with histologically confirmed or strongly suspected ovarian cancer and a surgery with an expected minimal duration of 60 minutes were included. Recruitment occurred between October 2015 and January 2017. Validated questionnaires and screening tools were used to assess the medical, physical, cognitive, and psychological state of each patient prior to surgery. Frailty index was calculated based on previously published studies, with a cutoff calculated by performing receiver operating characteristic curve analyses to differentiate women with severe complications from those without. Further receiver operating characteristic analyses were used to evaluate predictive outcomes of continuous variables, and a multivariable Cox proportional hazards model was used to obtain independent risk factors for overall survival. Postoperative complications were graded using validated Clavien-Dindo criteria. A 3-month follow-up call was conducted to record late postoperative complications following discharge and follow-up for overall mortality continued until September 2020. A total of 144 patients undergoing surgery for ovarian cancer were included in this analysis, with 27 (19%) experiencing severe postoperative complications and 3 (2%) dying within 30 days of surgery. The overall prevalence of frailty defined by a frailty index >0.26 and frailty index >0.15 was 33% and 74%, respectively. Frailty index >0.26 (odds ratio [OR], 3.64; 95% confidence interval [CI], 1.34-9.85; P = 0.01), Eastern Cooperative Oncology Group performance status >1 (OR, 6.33; 95% CI, 1.31-30.51; P = 0.02), recurrent surgery (OR, 3.05; 95% CI, 0.98-9.47; P = 0.05), and high surgical complexity score (OR, 8.86; 95% CI, 1.88-47.76; P = 0.006) were significant predictors of severe postoperative complications. Patients with frailty index 0.15 had a mean survival of 54 months, whereas those with 0.15 frailty index had a mean survival of 34 months (P = 0.02). Frailty index >0.15 (hazard ratio [HR], 1.87; 95% CI, 1.01-3.47; P = 0.048), residual tumor 1 cm (HR, 2.75; 95% CI, 1.53-4.99; P = 0.001), residual tumor >1 cm (HR, 5.00; 95% CI, 2.74-9.13; P 0.001), and albumin 35.5 g/dL (HR, 1.92; 95% CI, 1.08-3.43; P = 0.03) were significant parameters for reduced overall survival. This study demonstrates a robust association between frailty index and major postoperative complications and overall survival among women with ovarian cancer. Frailty index and also surgical complexity score, ECOG performance status >1, and recurrent surgery were predictors of postoperative complications, whereas frailty index, tumor residual sizes, and albumin levels were predictors of overall survivalYYYYY