The KORE-INNOVATION trial, a prospective controlled multi-site clinical study to implement and assess the effects of an innovative peri-operative care pathway for patients with ovarian cancer: rationale, methods and trial design.

BACKGROUND: Advanced ovarian cancer is managed by extensive surgery, which could be associated with high morbidity. A personalized pre-habilitation strategy combined with an 'enhanced recovery after surgery' (ERAS) pathway may decrease post-operative morbidity. PRIMARY OBJECTIVE: To analyze the effects of a combined multi-modal pre-habilitation and ERAS strategy on severe post-operative morbidity for patients with ovarian cancer (primary diagnosis or first recurrence) undergoing cytoreductive surgery. STUDY HYPOTHESIS: A personalized multi-modal pre-habilitation algorithm entailing a physical fitness intervention, nutritional and psycho-oncological support, completed by an ERAS pathway, reduces post-operative morbidity. TRIAL DESIGN: This is a prospective, controlled, non-randomized, open, interventional two-center clinical study. Endpoints will be compared with a three-fold control: (a) historic control group (data from institutional ovarian cancer databases); (b) prospective control group (assessed before implementing the intervention); and (c) matched health insurance controls. INCLUSION CRITERIA: Patients with ovarian, fallopian, or primary peritoneal cancer undergoing primary surgical treatment (primary ovarian cancer or first recurrence) can be included. The intervention group receives an additional multi-level study treatment: (1) standardized frailty assessment followed by (2) a personalized tri-modal pre-habilitation program and (3) peri-operative care according to an ERAS pathway. EXCLUSION CRITERIA: Inoperable disease or neoadjuvant chemotherapy, simultaneous diagnosis of simultaneous primary tumors, in case of interference with the overall prognosis (except for breast cancer); dementia or other conditions that impair compliance or prognosis. PRIMARY ENDPOINT: Reduction of severe post-operative complications (according to Clavien- Dindo Classification (CDC) III-V) within 30 days after surgery. SAMPLE SIZE: Intervention group (n=414, of which approximately 20% insure with the participating health insurance); historic control group (n=198); prospective control group (n=50), health insurance controls (for those intervention patients who are members of the participating health insurance). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The intervention phase started in December 2021 and will continue until June 2023. As of March 2023, 280 patients have been enrolled in the intervention group. The expected completion of the entire study is September 2024. TRIAL REGISTRATION: NCT05256576.

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.

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/m2 (OR 10.48, 95% CI 2.38-46.02, p = 0.002) along with the use of intraoperative norepinephrine > 0.11 µg/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/m2), are highly predictive factors for severe postoperative complications. The analysis of intraoperative data showed that the need for more than > 0.11 µg/kg/min of norepinephrine and transfusions of FFPs more than 17 units were strongly associated with severe postoperative complications.

Frailty Index for prediction of surgical outcome in ovarian cancer: Results of a prospective study.

BACKGROUND: Complete macroscopic tumor resection is the strongest prognostic factor for patients with ovarian cancer, which requires complex surgery for achievement. Based on the mostly advanced tumor stage and high symptom burden many patients are classified as frail which may limit optimal surgical outcome. Aim of this study is to evaluate the predictive ability of Frailty Index for surgical outcomes in patients with ovarian cancer. METHODS: This prospective study enrolled patients with ovarian cancer undergoing cytoreductive surgery. We classified frailty proposed by Mitnitski et al. regarding the cumulative deficit model of frailty. Utilizing Receiver Operator Characteristic (ROC) analysis and logistic regression, we determined predictive clinical factors for severe postoperative complications. The Kaplan-Meier method and log-rank test were used for overall survival analysis. RESULTS: Out of f 144 enrolled patients, the overall prevalence of frailty based on a Frailty Index >0.26 and Frailty Index >0.15 was 33% and 74%, respectively. The logistic regression shows that frail patients with a Frailty Index >0.26 (Odds ratio (OR): 3.64, 95% CI: 1.34-9.85, p = 0.01), ECOG PS > 1 (OR 6.33, 95% CI:1.31-30.51, p = 0.02) and high surgical complexity score (OR 8.86, 95% CI:1.88-41.76, p = 0.006) had a significant higher risk for severe postoperative complications. According to multivariable cox regression Frailty Index >0.15 (hazard ratio (HR) (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) resulted as significant parameters for poor overall survival. Resulted as significant parameters for poor overall survival. CONCLUSION: Next to surgical complexity score, ECOG PS > 1 and recurrent surgery, Frailty Index >0.26 is associated with severe postoperative complications in patients with ovarian cancer. Besides tumor residuals and low albumin levels a Frailty Index >0.15 predicts poor survival.

Effects of sarcopenia and malnutrition on morbidity and mortality in gynecologic cancer surgery: results of a prospective study.

BACKGROUND: Malnutrition and sarcopenia often occur simultaneously in cancer patients and are thought to have harmful effects on both surgical and oncological outcomes. Therefore, we want to evaluate the effects of sarcopenia and malnutrition on severe postoperative complications and overall survival in gynecologic cancer patients. METHODS: We assessed nutritional parameters and run a bioelectrical impedance analysis in 226 women. Extracellular mass to body cell mass index, phase angle alpha, muscle mass, and fat mass were evaluated. To determine if patients suffer from sarcopenia, we ran the Timed 'Up and Go' test, performed hand grip strength, and calculated a skeletal muscle index. Postoperative complications were categorized using Clavien-Dindo Classification. Utilizing ROC analysis and logistic regression, we determined predictive clinical factors for severe postoperative complications. Kaplan-Meier method and log-rank test were used for overall survival analysis. RESULTS: Of the 226 female patients, 120 (53%) had a BMI ≥ 25 kg/m2 , 56 (26%) had a phase angle < 4.75°, and 68 (32%) were sarcopenic according to skeletal muscle index < 27%. Within 30 days after surgery, 40 (18%) patients developed severe postoperative complications, and 4% had died. According to multivariable regression analysis, ECOG status > 1 (OR 4.56, 95% CI: 1.46-14.28, P = 0.009), BMI ≥ 25 kg/m2 (OR 8.22, 95% CI: 3.01-22.48, P < 0.001), phase angle < 4.75° (OR 3.95, 95% CI: 1.71-9.10, P = 0.001), and tumour stage ≥ III A (OR 3.65, 95% CI: 1.36-9.76, P = 0.01) were predictors of severe postoperative complications. During 59 months of follow-up, 108 (48%) patients had died. According to multivariable Cox regression ECOG status > 1 (HR 2.51, 95% CI: 1.25-5.03, P = 0.01), hypoalbuminemia (HR 2.15, 95% CI: 1.28-3.59, P = 0.004), phase angle < 4.5° (HR 1.76, 95% CI 1.07-2.90, P = 0.03), tumour stage ≥ III A (HR 2.61, 95% CI: 1.53-4.45, P < 0.001), and severe postoperative complications (HR 2.82, 95% CI: 1.80-4.41, P < 0.001) were predictors of overall mortality. CONCLUSIONS: We observed that preoperatively assessed ECOG status > 1, BMI > 25 kg, as well as phase angle alpha < 4.75° and FIGO stage ≥ III A are significantly associated with severe postoperative complications within the first month. Whereas ECOG status > 1, hypoalbuminemia, phase angle < 4.5° as well as FIGO stage ≥ III A and severe postoperative complications within 30 days correlate significantly with poor overall survival.

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

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 and >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.

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 < 70 (OR 5.08, 95% CI 2.23-11.59, p < 0.001). Regarding symptoms nausea/vomiting assessed as 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.

Can Fried Frailty Score predict postoperative morbidity and mortality in gynecologic cancer surgery? Results of a prospective study.

BACKGROUND: Aim of this study is to evaluate the predictive ability of Fried Frailty Score for surgical outcomes in patients undergoing gynecologic cancer surgery. METHODS: This is a prospective cohort study at an academic gynecological cancer center from Oct 2015 through Jan 2017. We applied systematically numerous screening tools, geriatric questionnaires and single measurements which may provide predictions for surgical outcomes. We classified frailty according to the Fried definition and surgical complications were graded according Clavien-Dindo criteria. Using logistic regression analysis, we identified predictive clinical variables for postoperative complications (POC). RESULTS: Overall 226 patients were enrolled (median age 59 years, range 18-87 years). The prevalence of frailty based on the presence of three or more frailty criteria was 14.2%, the presence of one or two frailty criteria was classified as prefrail with 59.4% and without any presence as robust with 26.5%. Within 30 days of surgery, nine (3.8%) patients have died and 40 (18.3%) experienced a grade ≥ IIIb complication. In the regression analysis obesity (OR: 5.37, 95% CI 1.99-14.49, p = 0.001) as well as ECOG >1 (OR: 4.32, 95% CI 1.28-1.55, p = 0.018) and Albumin<3.6 g/dl (OR: 3.88, 95% CI 1.37-10.98, p = 0.011) emerged as significant predictors of postoperative complications (POC). Fried Frailty Score (OR: 2.41, 95% CI 0.91-6.41, p = 0.077) showed no significant additional predictive value. CONCLUSION: Fried Frailty Score could help the surgeon to estimate the risk for POC among patients undergoing gynecologic cancer surgery. But preoperatively determined ECOG, BMI and Albumin can predict severe POC in patients undergoing gynecologic surgery more precisely and should be assessed routinely.

Role of predictive markers for severe postoperative complications in gynecological cancer surgery: a prospective study (RISC-Gyn Trial).

BACKGROUND: Surgery for gynecological cancer involves highly invasive and complex procedures potentially associated with various complications, which can cause extended hospital stays and delay of subsequent therapy, with a detrimental effect on the prognosis. The aim of this study was to explore and define the predictors of severe postoperative complications in patients undergoing surgery for gynecologic cancer. METHODS: Patients undergoing surgery for gynecologic cancers were analyzed prospectively from October 2015 through January 2017. Using validated assessment tools preoperatively, we assessed comorbidities, performance status, quality of life, nutritional and body composition by bioelectrical impedance analysis, and the surgical data of each patient. Surgical complications were graded using the Clavien-Dindo criteria. Using stepwise logistic regression models, we identified predictive markers for postoperative complications. RESULTS: Of the 226 enrolled patients, 40 (17.7%) experienced a grade ≥IIIb complication according to the Clavien-Dindo criteria. In the regression analysis, overweight/obesity (body mass index >25) (OR 6.41, 95% CI 2.38 to 17.24; p<0.001) and impaired physical functioning defined by a quality of life questionnaire (OR 4.19, 95% CI 1.84 to 9.50; p=0.001) emerged as significant predictors of postoperative complications. Moreover, postoperative complications were predicted by phase angle of bioelectrical impedance analysis <4.75° (OR 3.11, 95% CI 1.35 to 7.16; p=0.008) and Eastern Cooperative Oncology Group (ECOG) performance status >1 (OR 2.51, 95% CI 1.06 to 5.92; p=0.04). Intraoperative factors associated with higher risk of postoperative complications were increased use of norepinephrine (>11 µg/kg/min) (OR 5.59, 95% CI 2.16 to 14.44; p<0.001) and performance of large bowel resection (OR 4.28, 95% CI 1.67 to 10.97; p=0.002). CONCLUSION: In patients undergoing surgery for gynecological cancer, preoperative evaluation of performance status according to ECOG, domains of quality of life and nutritional status, as well as intraoperative monitoring of risk factors, might help to identify patients at high risk for severe postoperative complications, and thus reduce surgical morbidity and mortality.