AGO-OVAR 28/ENGOT-ov57. Niraparib alone versus niraparib in combination with bevacizumab in patients with carboplatin-taxane-based chemotherapy in advanced ovarian cancer: a multicenter randomized phase III trial.

BACKGROUND: Phase III trial data have shown a significant benefit by the addition of a maintenance treatment with niraparib, irrespective of BRCA or HRD status, in patients with advanced high-grade ovarian cancers; and, a significant benefit of the combination of olaparib and bevacizumab compared with bevacizumab monotherapy in HRD positive patients. However, it is unclear whether a PARP inhibitor monotherapy is sufficient, or if the addition of bevacizumab is needed. PRIMARY OBJECTIVES: This trial will investigate if the treatment strategy of carboplatin/paclitaxel/bevacizumab/niraparib is superior to the treatment of carboplatin/paclitaxel/niraparib in an all-comer population. STUDY HYPOTHESIS: Adding bevacizumab to chemotherapy followed by niraparib maintenance improves progression-free survival in patients with newly diagnosed advanced ovarian cancer. TRIAL DESIGN: AGO-OVAR 28/ENGOT-ov57 is an international, multicenter, randomized, prospective phase III trial within the the European Network for Gynecological Oncological Trial (ENGOT), led by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) study group. All patients should have completed the first cycle of chemotherapy (carboplatin and paclitaxel) as part of the Study Run-In-Period. Prior to day 1 of cycle 2, patients with a valid central tumor BRCA (tBRCA) test result were randomized in a 1:1 ratio into either: Arm 1, to receive five additional cycles of carboplatin and paclitaxel q21d, followed by niraparib for up to 3 years; or Arm 2, to receive five additional cycles of carboplatin and paclitaxel plus bevacizumab q21d, followed by bevacizumab q21d (for up to 1 year), and niraparib for up to 3 years. MAJOR INCLUSION/EXCLUSION CRITERIA: The trial population is composed of adult patients with newly diagnosed, advanced high-grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer FIGO III/IV (except FIGO IIIA2 without nodal involvement). Patients who are scheduled for neoadjuvant chemotherapy and interval debulking surgery are also eligible for the trial. PRIMARY ENDPOINT: The primary endpoint is progression-free survival. SAMPLE SIZE: The study plans to recruit 970 patients (485 patients in each arm). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The Last-Patient-In is expected to be enrolled in September 2024, with presentation of the primary endpoint in 2028. TRIAL REGISTRATION: NCT05009082; EudraCT Number: 2021-001271-16.

LION-PAW (lymphadenectomy in ovarian neoplasm) sexual function assessment: a prospective sub-study of the LION trial.

BACKGROUND: There is limited information about the impact of radical surgery including pelvic and para-aortic lymphadenectomy and subsequent platinum-based chemotherapy on sexuality in patients with advanced ovarian cancer. OBJECTIVE: To evaluate the impact of radical surgery including pelvic and para-aortic lymphadenectomy and subsequent platinum-based chemotherapy on sexuality in patients with advanced ovarian cancer as a sub-protocol of the prospectively randomized LION trial. METHODS: The Sexual Activity Questionnaire was applied to assess sexual function according to its sub-scales activity, pleasure, and discomfort. The 'orgasm' sub-scale from the Female Sexual Function Index was also added. The questionnaire was administered in combination with the EORTC QLQ-C30 questionnaire at baseline prior surgery, after 6, 12, and 24 months. The primary endpoint was changes in sexual function. RESULTS: Overall, 495 patients received the questionnaires. 254 (51%) responded at baseline. Of these, 55 (22%) patients were sexually active, 182 (72%) were sexually inactive, and for 17 (7%) patients' data were not available. There was a total of 55/495 (11%) patients at 6 months, 139 (28%) patients at 12 months, and 81 (16%) patients at 24 months. Median age was 60.5 years (range 21.4-75.8). At baseline, sexually active responders were significantly younger (median age 51.5 years,) than sexually inactive responders (median age 61.8 years) and tended to have a better performance status. Discomfort evaluated as dryness of the vagina and pain during sexual intercourse was significantly worse at 12 months than at baseline (p<0.001); however, the surgical variable, lymphadenectomy, did not have any impact on this. The orgasm sub-scale showed diverging results with a deterioration from baseline to 12 months in the lymphadenectomy group compared with the no-lymphadenectomy group (p=0.02). CONCLUSION: The majority of patients were sexually inactive; however, in those who were sexually active, pain during intercourse was worse at 12 months. In addition, the orgasm sub-scale demonstrated worse results in patients who underwent complete lymphadenectomy. The study suggests that surgery in the retroperitoneal space may influence sexual function.

Perioperative management of positioning in gynecological cancersurgery: a national NOGGO-AGO intergroup survey.

INTRODUCTION: The daily clinical routine in the operating room includes patient positioning. The number of perioperative positioning-related complications is growing, along with the legal proceedings concerning this topic, and only a few guidelines exist to provide specific recommendations. The aim of this survey was to assess perioperative positioning and associated adverse events during gynecological cancer surgery in Germany. METHODS: A total of 633 gynecological departments of primary, secondary, and maximum healthcare hospitals in Germany were invited to participate in this multiple-choice online questionnaire. The survey was conducted anonymously for a period of six months. The survey was divided into five different sections: descriptive information about the respondent department, pre- and postoperative management, management of positioning in the operating room based on two fictional case examples, and quality management. RESULTS: The response rate of our survey was 29.1 % (184/633). Nearly half of the departments (46.7 %) reported to have had one to five patients with positioning-related complications during the prior 12 months, and 29.1 % had experienced a legal dispute due to positioning-related complications. Departments with more than 50 gynecologic-oncological surgeries per year more often reported positioning-related complications (p=0.003). Standard operating procedures exist in almost every department for laparoscopic (97 %) and open surgery (95.1 %), respectively. DISCUSSION: The high number of positioning-related complications throughout all departments of different healthcare levels underlines the relevance of this issue and supports the need for a prospective European registry for further analysis. Training and education for all staff members should be routinely implemented to reduce and prevent positioning-related complications.

Association between obesity and vulvar cancer recurrence: an analysis of the AGO-CaRE-1 study.

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.

Is routine audiometric evaluation necessary in gynaecologic tumour patients undergoing chemotherapy?

BACKGROUND: Our objective was to assess the auditory function of gynaecological tumour patients who had received cytotoxic agents and to determine their associated risk of ototoxicity. PATIENTS AND METHODS: 87 patients who had undergone chemotherapy for gynaecological malignancies were investigated. Of these patients, 79% had breast cancer, and 14% ovarian cancer. All of the patients had a subjective assessment of their hearing function on a visual analogue scale. Audiometric tests were performed before and at 9 weeks, 18 weeks and 3 months after completion of chemotherapy. RESULTS: The age of the patients ranged from 32 to 71 years (mean age of 53.5 ± 10.5 years). The average subjective rating of the patients' hearing function was 83.0 ± 17.2 before and 84.8 ± 16.9 3 months after completion of chemotherapy. No significant audiometric change at either the speech hearing frequency range (0.5-2 KHz) or high frequencies was observed in the patients after chemotherapy. There was also no significant difference in the hearing threshold of the patients who had received platinum analogue-based chemotherapy compared to non-platinum analogue-based chemotherapy. CONCLUSION: Hearing loss is uncommon in patients treated with the typical gynaecological chemotherapy protocols. Hence, routine audiometric testing in these patients is not necessary.