Introduction/Background Frailty is an underdiagnosed multidimensional age-related syndrome. Frail patients need to be identified preoperatively to reduce their risk of adverse surgical outcomes. We present first results of our systematic, preoperative two-step frailty screening algorithm of elderly ovarian cancer (OC) patients regarding their perioperative outcomes. Methodology All women with the diagnosis of OC regardless of the previous treatments or the histological type were screened preoperatively by the G8 geriatric screening tool (G8-Score). If a patient was considered to be G8-frail (cut-off:≤14points), various geriatric assessment tools followed. The main outcome measures were the relationship between perioperative laboratory results, intraoperative surgical parameters and the incidence of immediate postoperative in-hospital complications with the preoperatively evaluated frailty status. Results Till now, 37 consecutive patients with OC standardly treated with laparotomy for tumor debulking/extirpation at the University Medical Center Mainz between May 2020 and April 2023 were included. Mean age in the study cohort was 69.0 (±7.5) years. Most of the patients (72.9%) had advanced stage ovarian cancer ≥FIGOIIB. 35.1% of the patients were preoperatively identified as G8-frail (n=13). The G8-frail cohort had a significant longer hospital stay (p=0.005) and displayed a higher prevalence of polypharmacy than the G8-non-frail cohort (p=0.067). The G8-frail cohort showed a numerically but not statistically significant higher Clavien-Dindo-Score than the G8-non-frail cohort (grade≤2: 53.9% vs. 79.1%; grade≥3: 46.2% vs. 20.8%; p=0.402). Furthermore, the G8-frail cohort had significant more surgical revisions and readmitted more often to the hospital than the G8-non-frail cohort (revisions: 30.8% vs. 4%, p=0.042; readmission: 23.1% vs. 4%, p=0.115). One patient in each cohort died during the hospital stay. Conclusion The first interim-analysis shows that preoperative frailty assessment with the G8-Score can prospectively identify elderly women with OC associated with polypharmacy, a higher rate of postoperative in-hospital and a longer hospital stay. Further results will be expected in the near future. Disclosures The authors reports no potential conflict of interest.

Introduction/Background Frailty is an underdiagnosed multidimensional age-related syndrome. Preoperative frailty assessment is recommended in the guidelines for cancer patients. This study aims to investigate the impact of a standardized, two-step, multidisciplinary evaluation of frailty on complications and prognosis in women with gynecological malignancies, surgically treated. Methodology In this prospective clinical trial, women with all gynecological malignancies regardless of the previous treatments or the histological type who underwent surgery at the University Medical Centre Mainz from 02/2023 will be consecutively included. All participants undergo the two-step frailty assessment with selected screening tools (Screening I+II) and peripheral blood results and a comprehensive geriatric assessment (CGA). The main outcome measures will be the relationship between perioperative laboratory results, intraoperative surgical parameters and the incidence of immediate postoperative in-hospital complications and the oncological prognosis with the preoperatively evaluated frailty-status. Results This is an ongoing trail. So far, 133 patients were recruited for the study: 45 ovarian cancer (33.6%), 40 endometrial cancer (29.9%), cervical cancer 7 (5.2%), 31 vulvar and vaginal cancer (23.3%), as well as 10 others (7.5%). Conclusion Frailty is a multidimensional, difficult quantifiable complex. To ensure a possible operationalization, we developed the two-step frailty assessment. This two-step frailty assessment identifies a significant proportion of non-frail patients and women who received optimization of their global health status to realize the standard operation. Disclosures The authors declare no relevant conflict of interests.

We examined differences in HER2 expression between primary tumors and distant metastases, particularly within the HER2-negative primary breast cancer cohort (HER2-low and HER2-zero). The retrospective study included 191 consecutive paired samples of primary breast cancer and distant metastases diagnosed between 1995 and 2019. HER2-negative samples were divided into HER2-zero (immunohistochemistry [IHC] score 0) and HER2-low (IHC score 1+ or 2+/in situ hybridization [ISH]-negative). The main objective was to analyze the discordance rate between matched primary and metastatic samples, focusing on the site of distant metastasis, molecular subtype, and de novo metastatic breast cancer. The relationship was determined by cross-tabulation and calculation of Cohen's Kappa coefficient. The final study cohort included 148 paired samples. The largest proportion in the HER2-negative cohort was HER2-low [primary tumor 61.4% (n = 78), metastatic samples 73.5% (n = 86)]. The discordance rate between the HER2 status of primary tumors and corresponding distant metastases was 49.6% (n = 63) (Kappa -0.003, 95%CI -0.15-0.15). Development of a HER2-low phenotype occurred most frequently (n = 52, 40.9%), mostly with a switch from HER2-zero to HER2-low (n = 34, 26.8%). Relevant HER2 discordance rates were observed between different metastatic sites and molecular subtypes. Primary metastatic breast cancer had a significantly lower HER2 discordance rate than secondary metastatic breast cancer [30.2% (Kappa 0.48, 95%CI 0.27-0.69) versus 50.5% (Kappa 0.14, 95% CI -0.03-0.32)]. This highlights the importance of evaluating potentially therapy-relevant discordance rates between a primary tumor and corresponding distant metastases.

Abstract Background: Novel antibody-drug conjugates (ADCs) show activity in HER2-low advanced breast cancer. We examined differences in HER2 expression between primary tumors and distant metastases, particularly within the HER2-negative cohort (HER2-low and HER2-zero). Patients and Methods: The retrospective study included 191 consecutive paired samples of primary breast cancer (BC) and distant metastases diagnosed between 1995 and 2019. HER2-negative samples were divided into HER2-zero (immunohistochemistry [IHC] score 0) and HER2-low (IHC score 1+ or 2+/in situ hybridization [ISH]-negative). The main objective was to analyze the discordance rate between matched primary and metastatic samples, focusing on the site of distant metastasis, molecular subtype, and de novo metastatic BC. The relationship was determined by cross-tabulation and calculation of Cohen's kappa coefficient. Results: The final study cohort included 148 paired samples. The largest proportion in the HER2-negative cohort was HER2-low [primary tumor 61.4% (n=78), metastatic samples 73.5% (n=86)]. The discordance rate between HER2 status of primary tumors and corresponding distant metastases was 49.6% (n=63) (kappa -0.003, 95%CI -0.15 - 0.15). Development of a HER2-low phenotype occurred most frequently (n=52, 40.9%), mostly with a switch from HER2-zero to HER2-low (n=34, 26.8%). Relevant HER2 discordance rates were observed between different metastatic sites (with the exception of lung/pleural metastases) and molecular subtypes. Primary metastatic breast cancer had a significantly lower HER2 discordance rate than secondary metastatic breast cancer [30.2% (kappa 0.48, 95%CI 0.27 - 0.69) versus 50.5% (kappa 0.14, 95% CI -0.03 - 0.32)]. Conclusion: In HER2-negative BC, there is a significant discrepancy between primary tumor and distant metastases. In particular, for the HER2-low cohort, biopsy of metastases opens new therapeutic opportunities with novel ADCs such as trastuzumab-deruxtecan.

Introduction/Background Endometrial cancer (EC) is the most common malignancy of the female genital tract in developed countries and is normally treated by surgery. Frail EC patients should be identified preoperatively to reduce their risk of adverse surgical outcomes. These are the first results of a systematic, preoperative frailty screening of EC patients regarding perioperative complication rates. Methodology All EC patients with a standardized surgical treatment, regardless of their actual cancer stage and previous treatments, were screened preoperatively with the G8 geriatric screening tool. If a patient was considered to be G8-frail, multiple geriatric assessment tools followed. The main outcome measures were the relationship between perioperative laboratory results, intraoperative surgical parameters and the incidence of immediate postoperative in-hospital complications with the preoperative frailty status. Results 42 patients with EC were included at the University Medical Centre Mainz between May 2020 and April 2023. 23.8% (n=10) of the patients were classified as G8-frail. Mean age was 67.6 (± 7.9) years. The G8-frail cohort was slightly older (71 years; p=0.43). Polypharmacy (≥ 5 medication) was found more often in the G8-frail cohort (60 vs 18.8%; p=0.02). The G8-frail cohort showed a numerically but not statistically significant higher Clavien-Dindo-Score than the G8-non-frail cohort (grade ≤2 (70 vs. 87.5%), grade ≥3 (30 vs 12.6%); p=0.29). The G8-frail cohort seemed to have a longer mean hospital stay than the G8-non-frail cohort (27.9 (± 48.3) vs. 5.8 (±5.4) days; p=0.06). The surgical revision rate seemed to be comparable between these two cohorts. One patient in the G8-frail cohort died during the hospital stay. Conclusion Our first interim-analysis implies that preoperative frailty assessment with the G8 geriatric screening tool for elderly patients with EC might be associated with more severe postoperative complications and a longer hospital stay. Further results will be expected in the near future. Disclosures The authors have no conflicts of interest to declare that are relevant to the content of this article.

Fatigue is a very common side effect during intravenous chemotherapy. Unfortunately, only few effective therapeutic options are available, mostly based on daily activity. In our pilot trial we were able to demonstrate that intermittent fasting can reduce fatigue in healthy people, thus we aimed to assess the effects of the fasting dietary on quality of life during chemotherapy in patients with gynecological cancer, especially on the domain of fatigue. The IFAST trial is designed as a prospective, randomized-controlled, multi-center trial. Participation will be offered to women with gynecological cancers (breast cancer, ovarian cancer including peritoneal and fallopian tube cancers, endometrial cancer and cervical cancer) who are planned to receive intravenous chemotherapy for at least three months. Eligible patients will be randomized 1:1, stratified by tumor type and study center. Primary endpoint is the difference in mean change in fatigue, assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT- FS©). Exploratory secondary endpoints will include general Quality of Life impairment, tolerance of chemotherapy, immunological changes, peripheral cell damage in blood cells, as well as tumor response to chemotherapy. There is new evidence that prolonged fasting periods of 46-96 hours during chemotherapy can positively influence the quality of life during chemotherapy. However, these fasting regiments are not feasible for many patients. Intermittent fasting could be a feasible (manageable) option for many patients to actively improve their quality of life and tolerance to chemotherapy and possibly even enhance the effectiveness of chemotherapy.Trial Registrationhttps://drks.de, identifier DRKS00031429.

Background: Lymph node involvement is the most important prognostic factor for recurrence and survival in vulvar cancer. Sentinel node (SN) procedure can be offered in well-selected patients with early vulvar cancer. This study aimed to assess current management practices with respect to the sentinel node procedure in women with early vulvar cancer in Germany. Methods: A Web-based survey was conducted. Questionnaires were e-mailed to 612 gynecology departments. Data were summarized as frequencies and analyzed using the chi-square test. Results: A total of 222 hospitals (36.27%) responded to the invitation to participate. Among the responders, 9.5% did not offer the SN procedure. However, 79.5% evaluated SNs by ultrastaging. In vulvar cancer of the midline with unilateral localized positive SN, 49.1% and 48.6% of respondents, respectively, would perform ipsilateral or bilateral inguinal lymph node dissection. Repeat SN procedure was performed by 16.2% of respondents. For isolated tumor cells (ITCs) or micrometastases, 28.1% and 60.5% of respondents, respectively, would perform inguinal lymph node dissection, whereas 19.3% and 23.8%, respectively, would opt for radiation without further surgical intervention. Notably, 50.9% of respondents would not initiate any further therapy and 15.1% would opt for expectant management. Conclusions: The majority of German hospitals implement the SN procedure. However, only 79.5% of respondents performed ultrastaging and only 28.1% were aware that ITC may affect survival in vulvar cancer. There is a need to ensure that the management of vulvar cancer follows the latest recommendations and clinical evidence. Deviations from state-of-the-art management should only be after a detailed discussion with the concerned patient.

Introduction: Metronomic chemotherapy (MCT) is increasingly used in oncology due to its favorable therapeutic index. There is still a lack of evidence for MCT in metastatic breast cancer (MBC). In this retrospective unicenter study, we demonstrated real-word data on MCT in MBC. Methods: MBC patients who received metronomic oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day), CTX and capecitabine (CAPE) (500 mg thrice daily), CTX, or vinorelbine (VRL) (30 mg daily) alone for at least 4 weeks between 2009 and 2021 were included. The primary endpoint was disease control rate (DCR) ≥24 weeks. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Patient characteristics and therapy response were analyzed using χ2 test. For survival analyses, Kaplan-Meier estimator and log-rank test were used. Results: Seventy-two patients were identified. Sixty-two patients received CTX/MTX, three CTX/CAPE, two CTX, and five VRL. Median age at diagnosis MBC and at start of MCT was 59.0 years and 64.5 years, respectively. 72.2% tumors were hormone receptor positive and 27.8% were triple-negative. 54.2% patients had more than two different metastases. 80.6% patients showed visceral involvement. 31.9% patients achieved DCR ≥24 weeks. Median PFS was 17.0 weeks (95% CI 14.5–19.5) and median OS was 58.0 weeks (95% CI 29.0–87.0). MCT showed similar DCR ≥24 weeks and clinically meaningful but not statistically significant shorter median PFS compared to prior therapy (31.9% versus 32.8% [p = 0.570] and 17.0 weeks versus 20.0 weeks [p = 0.093], respectively) and statistically significant higher DCR ≥24 weeks and longer median PFS compared to subsequent therapy (31.9% versus 17.4% [p = 0.038] and 17.0 weeks versus 12.0 weeks [p = 0.006], respectively). Three (4.2%) patients terminated MCT because of toxicity. Conclusion: In this real-world retrospective study, MCT was effective and well tolerated and may thus represent a valuable treatment option in selected MBC patients.

Introduction/Background First-evidence exists that fasting during chemotherapy (CHT) reduces peripheral blood immunosuppressive myeloid cells while increasing cytotoxic cells. Furthermore, it might protect healthy cells from damage and increase quality of life (QoL) during CHT. However, fasting periods of 60–90h are not feasible for many patients. We aim to assess the effects of short-term intermittent fasting on QoL, immunological changes and peripheral cell damage during CHT. Methodology In this multicenter, randomized-controlled trial 110 female patients with breast/cervical/endometrial or ovarian cancer, planned to receive intravenous CHT are recruited. The intervention group will follow a 16:8h fasting regimen with a 24h fast on the day of CHT. The control group is encouraged to follow a healthy, mediterranean diet. Both groups will receive a dietary counselling session. Primary endpoint is the change in fatigue during 3 months of CHT. Secondary endpoints will assess the distribution of peripheral blood mononuclear cells collected at baseline, after 1 week, 7 weeks and 13 weeks of CHT and peripheral DNA cell damage (measured by yH2AX concentration) at week 0, 6 and 12 of CHT. Changes of the insulin-like growth factor 1 (IGF-1) are also measured over the course of the trial. Results This is an ongoing trial. So far, 10 patients (2 with ovarian cancer, 8 with breast cancer) have been recruited for the study. Compliance with the intermittent fasting regiment is high. Conclusion Intermittent fasting is a generally feasible dietary concept and has shown to reduce IGF-1 and fatigue in healthy patients, highlighting its great potential for patients receiving CHT. Should this trial be able to demonstrate reduced fatigue during CHT, or to protect healthy cells and promote the antitumor activity of the immune system, intermittent fasting could truly be a beneficial option for patients wanting to actively effect their oncological treatment and outcome. Disclosures The authors declare no conflict of interest regarding this trial.

Purpose Despite the growing understanding of the carcinogenesis of pelvic high-grade serous carcinoma (HGSC) of the ovary and peritoneum and its precursor lesion serous tubal intraepithelial carcinoma (STIC), evidence-based proven recommendations on the clinical management of patients with STIC are lacking so far. Methods A questionnaire containing 21 questions was developed to explore the clinical experience with patients with the diagnosis of STICs and the diagnostic, surgical and histopathological approaches in Germany. Overall, 540 clinical heads of department in all German gynaecological centres were asked to participate. Results 131 questionnaires (response rate 24.3%) were included in this survey. 45.8% of the respondents had treated one to three STIC patients during their career. 75.6% of the respondents performed opportunistic bilateral salpingectomies during other gynaecological surgeries. Most of the participants (31.3%) started with the SEE-FIM (Sectioning and Extensively Examining the FIMbria) protocol in 2014. It was requested by 39.7% centres for prophylactic salpingectomies, by 13.7% for both prophylactic and opportunistic salpingectomies and by 22.1% for neither of both. 38.2%, 1.5% and 24.4% of the participants would use the laparoscopic, transverse and midline laparotomic approach for a surgical staging procedure, respectively. 25.6% (54.7%) of the respondents recommended a hysterectomy in premenopausal (versus postmenopausal) patients with a STIC, 24.4% (88.4%) a bilateral oophorectomy and 50.0% (4.7%) an affected side oophorectomy (all p values < 0.001). Omentectomy, pelvic and para-aortic lymphadenectomy would be performed by 60.5% (64.0%), 9.3% (11.6%) and 9.3% (11.6%) of respondents in premenopausal (versus postmenopausal) patients (all p values > 0.05). Conclusion Our survey highlights significant inconsistency in the management of patients with STIC. Prospective data are urgently needed to elucidate the clinical impact of a STIC lesion and its clinical management.

Introduction/Background The omission of state of the art (SOTA) surgery results in lower survival rates in the elderly. Here, we report an interim-analysis of a prospective observational cohort study on the impact of a praeoperative, multidisciplinary, two-step frailty assessment in gynecological malignancies. Methodology Women were included meeting one of the following criteria 1) age 60 years and older, 2) BMI>30kg/m2 or 3) subjective frail impression. The screening step uses the G8-Score accompanied by the Lee-Index and various laboratory values. If the G8-Score was impaired, a complete geriatric assessment (CGA) was performed accompanied by the history of falls, MiniCoq, Barthel-Index and Geriatric Depression Scale. Here, we report an interim-analysis after a recruiting period of 33 months. Results 133 women (median age 69.9 years) were included. 45 (33.6%) patients were affected by ovarian cancer, 40 (29.9%) by endometrial cancer, 28 (20.9%) by vulva cancer, 7 (5.2%) by cervical cancer and 13 (9.7%) by other malignancies. The first screening step identified 36 (27.1%) patients out of them 20 (15.0%) were regarded as frail by the CGA. 16 (12.0%) patients received an individualized operative strategy. Therefore, 117 patients (88.0%) underwent SOTA surgery. Impaired G8 score was associated with a higher rate of individualized operative surgery (24.2% vs. 8.5%), revision procedures (20.0% vs. 6.4%) and re-admission (20.0% vs. 4.0%) (all p-values <0.05). 21 (15.8%) recurrences and 11 (8.3%) deaths were recorded during the median follow-up time of 13.2 months. Conclusion Our two-step frailty-assessment algorithm is feasible and identifies a substantial portion of patients who safely underwent SOTA surgery. Contrastingly, patients with an impaired G8 score were faced with an unfavorable perioperative outcome. Whether our two-step frailty-assessment algorithm stratifies patients in terms of prognosis will be addressed by this ongoing trial and should be answered with a larger number of events and an adequate follow-up time. Disclosures The authors declare, that there do not exist any financial conflicts with the submitted abstract.

Introduction/Background Epidural anaesthesia is a standard procedure to mitigate pain during endometrial cancer (EC) surgery. Little data exist about the influence of epidural anaesthesia on the oncological outcome in elderly patients with EC. This retrospective study aims to investigate potential correlations between epidural anaesthesia and cancer recurrence in patients with EC. Methodology We screened the archives of patients treated surgically for EC at the University Medical Centre Mainz between January 2008 and December 2019. All women underwent general anaesthesia (GA) alone or combined with epidural anaesthesia (EGA). Cox regression as well as the Kaplan-Meier method were used to analyse the prognostic influence of this aesthetical technique on survival. Results A total of 152 women with EC were included. 29 patients (19.1%) formed the EGA cohort. The median time of follow-up was 31 months (interquartile range (IQR): 8–67.5). 26 patients (17.1%) developed recurrence in the follow-up (FU) at a median of 13 months (IQR: 7.75–29.5). 32 patients died during FU (21.1%). The EGA cohort showed higher FIGO-stages and a higher histological grading than the GA cohort. Regarding anaesthesiologic scores, such as the Charlson Comorbidity Index and the ASA Physical Status Classification System, no differences were recorded between the two cohorts (p>0.05). EGA showed a significantly reduced 5-year recurrence-free survival (RFS) (36.5% vs. 72.6%, p<0.001) and overall survival (OS) (58.6% vs. 79.9%, p=0.008). However, in multivariate cox regression analysis including FIGO stages und the histological grading, EGA was not associated with improved or decreased RFS (HR: 1.89, 95%- CI [0.90–3.98], p=0.093), nor with OS (HR: 1.22, 95%-CI [0.51–2.92], p=0.649). Conclusion Though in our heterogeneous cohort EGA showed a decreased 5-year RFS and OS in elderly patients with standardized EC surgery, this effect could not be reproduced in multivariate analysis considering tumour characteristics. Prospective randomized trials are warranted. Disclosures The authors have no conflicts of interest to declare that are relevant to the content of this article.