ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease.

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.

A dramatic response to checkpoint inhibitor in a woman with small cell carcinoma of the hypercalcemic type of the ovary.

OBJECTIVE: We present the rare case of a 21 year old woman with small cell carcinoma of the right ovary of the hypercalcemic type with dramatic response to checkpoint inhibitor. METHODS: Case report. RESULTS AND CONCLUSIONS: Our patient, a 22-year old woman with small cell carcinoma of the hypercalcemic type with hepatic metastases, is currently 43 months under treatment with pembrolizumab. Last MRI revealed no viable liver metastases nor other signs of recurrence. This is the longest survival of a patient with small cell carcinoma of the ovary under therapy with checkpoint inhibitors reported in the literature so far. With this report we emphasize the importance of immunohistological testing for PD-L 1. Treating clinicians should keep off-label use of immune checkpoint blockade in mind when treating this highly aggressive tumor if all other treatment options fail.

Fertility-sparing strategy in a rare case of highly malignant Dicer-1-associated sarcoma of the cervix.

INTRODUCTION: We present the rare case of an 18-year-old patient with a Dicer-1 mutation-associated sarcoma of the cervix uteri. CASE: The patient presented with irregular vaginal bleeding in July 2022. The clinical examination showed an exophytic tumor of the cervix, uterus and ovaries were normal in sonogram. The tumor of the cervix was resected, followed by a diagnostic hysteroscopy and abrasion of the uterine cervix and cavity. Hysteroscopy showed normal findings of the cervix and uterus. After diagnosis of a highly malignant Dicer-1 mutation-associated sarcoma of the cervix, cryopreservation of oocytes was realized. Based on the principle of obtaining maximum oncological safety while preserving fertility in this 18-year-old patient, we recommended chemotherapy rather than radiation with its far severe implications on the patient´s reproductive organs. 4 cycles of chemotherapy consisting of doxorubicin and ifosfamide were applied until December 2022. After re-staging in December 2022 via CT scan and MRI, the abdomen and pelvis as well as control hysteroscopy and abrasion were unremarkable. Until now, the patient is tumor free. DISCUSSION: Primary sarcomas of the cervix are very rare. Recent literature hints towards a distinct DICER-1 sarcoma entity characterized by specific mutational clusters. Limited follow-up data suggested that DICER1-mutant tumors might exhibit a less aggressive clinical course than DICER1-wild-type tumors. CONCLUSION: Decision-making in case of rare histological entities with sparse recommendations in the literature poses a challenge to the treating physician. Treatment strategies should consider oncological safety as well as options of preserving fertility. Gonadotoxic potential of different strategies should be taken into consideration and discussed in detail with the affected patient.

INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line.

BACKGROUND: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). METHODS: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). RESULTS: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). CONCLUSIONS: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01379989.

Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial.

BACKGROUND: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. PATIENTS AND METHODS: Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis. RESULTS: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. CONCLUSIONS: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure.

Randomized phase II BGOG/ENGOT-cx1 study of paclitaxel-carboplatin with or without nintedanib in first-line recurrent or advanced cervical cancer.

OBJECTIVE: Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor. The aim was to establish the role of nintedanib in addition to paclitaxel and carboplatin in first-line recurrent/metastatic cervical cancer. METHODS: Double-blind phase II randomized study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin-paclitaxel with oral nintedanib 200 mg BID/placebo. The primary endpoint was progression-free survival (PFS) at 1.5 years and α = 0.15, ß = 80%, one sided. RESULTS: 120 patients (62 N, 58C) were randomized. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favor of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However, N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Global health status during and at the end of the study was similar in both arms. CONCLUSION: The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed.

Lymphedema after pelvic and para-aortic lymphadenectomy-results of a systematic evaluation in patients with cervical and endometrial carcinoma.

BACKGROUND: Lymphedema is a frequent complication after surgical treatment in gynecological oncology with substantial impact on patients´ Quality of Life (QoL). Little is known about screening instruments and prevention. Primary objective was to develop and validate the German version of a 13 items screening questionnaire (SQ) developed by Yost et al. to provide a valid instrument for early diagnosis of lower extremity lymphedema (LEL). METHODS: After translation the SQ was used in pt. with cervical or endometrial cancer who underwent pelvic/paraaortic Lymphadenectomy. Sensitivity and specifity were analysed regarding possible prediction and influencing factors of LEL. RESULTS: 67 pt. had LEL (N = 128). Nearly 50% of women in each group (38 in LEL + e 30 in LEL - ) had a body mass index (BMI) > 30 kg/m2. Number of removed lymphnodes, radiotherapy and were significantly associated with development of LEL. Translated Mayo Clinic questionnaire can be used with reliable specifity and sensitivity. Four additional questions improved the diagnostic accuracy of the SQ. CONCLUSIONS: The translated SQ is a valuable and predictive tool for screening and early detection of LEL in Gynecological cancer surgery and can even improved by adding simple questions.

Surgery due to mechanical bowel obstruction in relapsed ovarian cancer: clinical and surgical results of a bicentric analysis of 87 patients.

INTRODUCTION: Mechanical bowel obstruction is a frequent acute and life-threatening event in relapsed ovarian cancer. Salvage surgery after failure of all conservative approaches, resulting in short bowel syndrome (SBS) constitutes a therapeutic dilemma. Our aim was to evaluate patients' surgical and clinical outcome in these highly palliative situations. Previous, limited, data reported a high morbidity and mortality. However, recent surgical and therapeutical improvements in relapsed ovarian cancer (ROC) offer better identification of patients who might benefit from surgery in an effort to extend the window of opportunity to subsequently offer these patients novel systemic therapeutic approaches. MATERIAL AND METHODS: All subsequent ROC patients between 2012 and 2017 with acute mechanical bowel obstruction who underwent salvage extraperitoneal en bloc intestinal resection were retrospectively identified. Data were collected from two ESGO certified Ovarian Cancer Centers of Excellence (Charité Berlin and Imperial College London) and systematically evaluated regarding surgical and clinical outcomes. RESULTS: Overall, 87 ROC patients were included in the analysis (median age 56 years, range 24-88), 47% were platinum resistant. High grade serous was the most common histology (76%) while most of the patients (67%) had at least two previous lines of treatment. Mean observed OS was 7.8 months. After salvage surgery, 46% of the patients had a residual small bowel length < 180 cm and 18% > 180 cm resulting in 41% in need of total parental nutrition. In 80% of the patients a permanent stoma was necessary. 30d morbidity and mortality was 74% and 10%, respectively. More than half of the patients were able to receive further courses of chemotherapy after surgery. DISCUSSION: Salvage surgery for bowel obstruction in ROC patients needs careful consideration and identification of optimal surgical candidates to have the maximal therapeutic benefit. Despite the challenging morbidity profile, most patients managed to proceed to subsequent novel and conventional systemic treatment and so have their window of therapeutic opportunity extended.

Impact of COVID-19 on gynaecological patient care: results of patient's survey with 327 patients.

PURPOSE: The pandemic SARS-CoV-2 poses new and unprecedented challenges for health care systems on a national and global level. Although the current situation has been going on for more than 1 year, there is limited data on the impact of the pandemic on general hospital and medical practice care. This survey captures the perspective of patients with gynaecological diseases of this impact. METHODS: Using a paper-based questionnaire, 327 patients were asked about medical care and their experiences during the pandemic at the University Hospital Bonn and the University Hospital Charité Berlin. The study was performed from the 1st June to 30th September 2020. RESULTS: A total of 327 patients participated in the study: 156 stated to have been tested for coronavirus, and 1 patient reported a positive test. 41.3% of the patients felt insecure about the current situation, 30.4% were concerned about the risk of infection during the hospital stay. The pandemic-specific measures in hospitals and medical practices unsettled 6.8% of patients. 18.1% of patients feared that their gynaecological disease would not be treated adequately due to the pandemic. 55.7% of patients reported that their confidence in their physicians has increased during the pandemic. CONCLUSION: The results show that patients' confidence in the healthcare system and the physicians acting significantly increased during the COVID-19 crisis. Transparent and comprehensive information policy regarding actions and restrictions within the COVID-19 crisis eases patients concerns and improves patients' confidence in their physicians, which is crucial for a successful treatment's outcome.

The systemic treatment of recurrent ovarian cancer revisited.

Treatment approaches for relapsed ovarian cancer have evolved over the past decade from a calendar-based decision tree to a patient-oriented biologically driven algorithm. Nowadays, platinum-based chemotherapy should be offered to all patients with a reasonable chance of responding to this therapy. The treatment-free interval for platinum is only one of many factors affecting patients' eligibility for platinum re-treatment. Bevacizumab increases the response to chemotherapy irrespective of the cytotoxic regimen and can be valuable in patients with an urgent need for symptom relief (e.g. pleural effusion, ascites). For patients with recurrent high-grade ovarian cancer, which responds to platinum-based treatment, maintenance therapy with a poly(ADP-ribose) polymerase inhibitor can be offered, regardless of the BRCA mutation status. Here we review contemporary decision-making processes in the systemic treatment of relapsed ovarian cancer.

Influence of migrant background on patient preference and expectations in breast and gynecological malignancies (NOGGO-expression V study): results of a prospective multicentre study in 606 patients in Germany.

BACKGROUND: An effective cross-cultural doctor-patient communication is vital for health literacy and patient compliance. Building a good relationship with medical staff is also relevant for the treatment decision-making process for cancer patients. Studies about the role of a specific migrant background regarding patient preferences and expectations are lacking. We therefore conducted a multicentre prospective survey to explore the needs and preferences of patients with a migrant background (PMB) suffering from gynecological malignancies and breast cancer to evaluate the quality of doctor-patient communication and cancer management compared to non-migrants (NM). METHODS: This multicentre survey recruited patients with primary or recurrence of breast, ovarian, peritoneal, or fallopian tube cancer. The patients either filled out a paper form, participated via an online survey, or were interviewed by trained staff. A 58-item questionnaire was primarily developed in German and then translated into three different languages to reach non-German-speaking patients. RESULTS: A total of 606 patients were included in the study: 54.1% (328) were interviewed directly, 9.1% (55) participated via an online survey, and 36.8% (223) used the paper print version. More than one quarter, 27.4% (166) of the participants, had a migrant background. The majority of migrants and NM were highly satisfied with the communication with their doctors. First-generation migrants (FGM) and patients with breast cancer were less often informed about participation in clinical trials (p < 0.05) and 24.5% of them suggested the help of an interpreter to improve the medical consultation. Second and third-generation migrants (SGM and TGM) experienced more fatigue and nausea than expected. CONCLUSIONS: Our results allow the hypothesis that training medical staff in intercultural competence and using disease-related patient information in different languages can improve best supportive care management and quality of life in cancer patients with migrant status.

Results of TRIO-14, a phase II, multicenter, randomized, placebo-controlled trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-ganitumab in newly diagnosed epithelial ovarian cancer.

PURPOSE: Insulin-like growth factor (IGF) signaling is implicated in pathogenesis and chemotherapy resistance of epithelial ovarian cancer (EOC). We explored efficacy and safety of adding ganitumab, a monoclonal antibody targeting IGF-1R, to carboplatin/paclitaxel (CP) chemotherapy in patients with primary EOC. DESIGN: Patients were randomly assigned to receive CP/ganitumab (18 mg/kg q3w) or CP/placebo for 6 cycles followed by 6 cycles of single agent ganitumab/placebo maintenance therapy as front-line therapy. Primary endpoint was progression free survival. Secondary endpoints were time to progression and overall survival. Pretreatment samples were prospectively collected for retrospective biomarker analyses. RESULTS: 170 patients enrolled. 165 patients assessable for toxicity. Median PFS was 15.7 months with CP/ganitumab and 16.7 months with CP/placebo (HR 1.23; 95% CI 0.82-1.83, P = 0.313). All grade neutropenia (84.1% vs 71.4%), thrombocytopenia (75.3% vs 57.1%) and hyperglycemia (15.9% vs 2.6%) were more common in the ganitumab group compared to the placebo group. Ganitumab/placebo related serious adverse events were reported in 26.1% of the patients with ganitumab and in 6.5% with placebo. Non-progression related fatal events were more common with ganitumab (5 versus 2 patients). The ganitumab group experienced more dose delays which resulted in lower relative dose intensity of chemotherapy in the experimental group. In an exploratory model IGFBP2 expression was predictive of ganitumab response (treatment interaction; PFS, P = 0.03; OS, P = 0.01). CONCLUSION: Addition of ganitumab to CP chemotherapy in primary EOC did not improve PFS. Our results do not support further study of ganitumab in unselected EOC patients.

When and how should peritoneal endometriosis be operated on in order to improve fertility rates and symptoms? The experience and outcomes of nearly 100 cases.

PURPOSE: To analyze the follow-up results of patients suffering from symptomatic early-stage endometriosis after a consistent laparoscopic peritoneal stripping of the altered peritoneum (peritoneal endometriosis and surrounding inflamed tissue) was performed. This type of endometriosis is resistant to medical therapy and/or impairs fertility. METHODS: Using our prospectively maintained database, we were able to identify all symptomatic women with the suspicion of only peritoneal endometriosis who underwent laparoscopy at our endometriosis center over a period of 5 years. All procedures were carried out in a standardized fashion by one single surgeon, who is highly experienced in minimal invasive surgery, and included a suspended hormonal pretreatment for 2 months. Postoperative outcomes including complications, fertility and recurrence rates were analysed. RESULTS: Laparoscopic peritonectomy was performed on 94 women. Follow-up data were available in 87% of these cases. At the time of surgery, almost all patients tested showed signs of stage I or II endometriosis (44.7 and 48.9%, respectively). More than three-quarters of the women reported pain relief, inter alia, due to the post-surgical hormonal therapy. About one-third of the patients wanted to have children after the procedure. 62% of them became pregnant and the majority did so without the need for assisted reproductive therapy. In seven women a re-operation was performed. CONCLUSION: According to our data, a consistent excision of altered peritoneum followed by adjuvant hormonal therapy and multimodal concepts results in better outcomes for the patient, particularly in regards to pregnancy and recurrence rates.

The prognostic and predictive role of pain before systemic chemotherapy in recurrent ovarian cancer: an individual participant data meta-analysis of the North-Eastern German Society of Gynecological Oncology (NOGGO) of 1226 patients.

BACKGROUND: Aim of this study was to analyze the impact of pain on quality of life and survival in recurrent OC patients. METHODS: Raw data including the QLQ-C30 questionnaire from three phase II/III trials ("Topotecan phase III," "Hector," and "TRIAS") conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) were synthesized and analyzed using logistic and Cox regression analyses. RESULTS: Data on pain was available for 952 patients out of 1226. Moderate to severe pain, which was defined as pain ≥ 50 in the QLQ-C30 symptom scale, was experienced by more than one-third of patients (36.6%). A total of 31% were taking non-opioid pain medication and 16% opioids. Median age at randomization was 61 years (range 25-84). Most patients (84.7%) were diagnosed in FIGO III/IV. Pain was independent from age, FIGO stage, grading, amount of recurrences, and chemotherapy-free interval. ECOG was significantly worse in patients with pain (p < 0.001). Fatigue, nausea/vomiting, sleeping disorders, and abdominal symptoms such as loss of appetite, diarrhea, and constipation were more frequently found in patients with pain (all p < 0.001). Quality of life was significantly diminished (p < 0.001). Pain was also an independent marker for overall survival (OS). Median OS was 18.2 months in patients with pain compared with 22.0 months in patients without pain (p = 0.013, HR 1.25, 95% confidence interval 1.05-1.48). OS was shorter in patients with pain and without pain medication compared with those on sufficient pain medication, whereas OS was mostly decreased in patients having pain despite pain medication (18.5, 19.6, and 15.0 months respectively; p = 0.026). Progression-free survival and prior treatment discontinuation were not associated with pain. CONCLUSION: Best supportive care including sufficient pain medication should be delivered as early as possible because effective pain management is crucial for both quality of life and overall survival in patients with recurrent ovarian cancer.

Prognostic role of chemotherapy-induced nausea and vomiting in recurrent ovarian cancer patients: results of an individual participant data meta-analysis in 1213.

BACKGROUND: The aim of this study was to analyze the potential impact of chemotherapy-induced nausea and vomiting (CINV) on dose reductions, discontinuation of chemotherapy, and survival. PATIENTS AND METHODS: This study was designed as individual participant data meta-analysis with the original study data of three phase II/III trials that were conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) including 1213 patients with recurrent ovarian cancer. Logistic and Cox regression analyses were used to estimate odds and hazard ratios after adjusting for age, ECOG, amount of delivered cycles, amount of recurrences, and amount of comedications and study. RESULTS: The majority of patients developed nausea (58.1%) and almost one third experienced vomiting (31.0%). CINV was not associated with FIGO stage, grading, histology, and number of recurrences. The necessity of dose reduction and discontinuation of chemotherapy did not correlate to nausea and vomiting (p = 0.88, p = 0.39 and p = 0.25, p = 0.54 respectively). Progression-free survival was shorter in patients with grade III/IV nausea and vomiting (p = 0.02; hazard ratio (HR) for grade III/IV nausea 1.58, 95% CI 1.14-2.20, and p = 0.02; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CINV grade III/IV was also associated with poorer overall survival (p < 0.001; HR for grade III/IV nausea 2.35, 95% CI 1.64-3.37, and p < 0.001; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CONCLUSION: CINV is significantly associated with poorer prognosis in recurrent ovarian cancer patients while there was no correlation found with the necessity of dose reduction and prior discontinuation of treatment. This study underlines the importance of prevention and treatment of CINV as part of early best supportive care.

Prehabilitation programs and ERAS protocols in gynecological oncology: a comprehensive review.

PURPOSE: The "Enhanced recovery after surgery" (ERAS) concept has been continuously developed for many surgical disciplines. Shorter length of stay (LOS) and associated cost savings have been achieved without an increase in the complication or readmission rate. Current guidelines helped to support an increasing standardisation of care. One innovation of the recently published update is the proposal to integrate prehabilitation (PREHAB) into the ERAS concept. On this basis, the authors provide an overview of the current data on ERAS concepts in gynecological oncology and review the evidence of prehabilitation concepts. METHODS: Systematic literature review of all comparative studies on ERAS concepts in gynecological oncology and prehabilitation undergoing abdominal cancer surgery was performed using the standard databases. Outcomes of interest included prehabilitation program composition (exercise, nutritional, and psychological interventions), duration and outcome measures used to determine impact of prehabilitation vs. standard care. RESULTS: Five studies reported on PREHAB programs in gynecology (three RCTs, one study protocol, one pilot study). There is no trial evaluating a pathway for patients with extensive ovarian or cervical cancer. Study protocols were heterogenous, but showed improvements in both physical and psychological parameters. ERAS protocols in ovarian cancer patients were investigated in 12 observational studies, mostly single center and only 1 RCT, in 4 studies patients with ovarian cancer or patients. Most studies showed improvement in complication rate and shorter LOS. DISCUSSION: PREHAB programs seem feasible in abdominal cancer surgery and may improve surgical outcome. However, there is no prospective trial in gynecological oncology so far. Furthermore, there is no concept combining ERAS and PREHAB interventions. Therefore, the authors encourage the further development of both by describing in a novel treatment algorithm.

Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study.

BACKGROUND: Advanced recurrent ovarian cancer (ROC) is the leading cause of gynecologic cancer-related death in developed countries and new treatments are needed. Previous studies of immune checkpoint blockade showed low objective response rates (ORR) in ROC with no identified predictive biomarker. PATIENTS AND METHODS: This phase II study of pembrolizumab (NCT02674061) examined two patient cohorts with ROC: cohort A received one to three prior lines of treatment with a platinum-free interval (PFI) or treatment-free interval (TFI) between 3 and 12 months and cohort B received four to six prior lines with a PFI/TFI of ≥3 months. Pembrolizumab 200 mg was administered intravenously every 3 weeks until cancer progression, toxicity, or completion of 2 years. Primary end points were ORR by Response Evaluation Criteria in Solid Tumors version 1.1 per blinded independent central review by cohort and by PD-L1 expression measured as combined positive score (CPS). Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Cohort A enrolled 285 patients; the first 100 served as the training set for PD-L1 biomarker analysis. Cohort B enrolled 91 patients. ORR was 7.4% for cohort A and 9.9% for cohort B. Median DOR was 8.2 months for cohort A and not reached for cohort B. DCR was 37.2% and 37.4%, respectively, in cohorts A and B. Based on the training set analysis, CPS 1 and 10 were selected for evaluation in the confirmation set. In the confirmation set, ORR was 4.1% for CPS <1, 5.7% CPS ≥1, and 10.0% for CPS ≥10. PFS was 2.1 months for both cohorts. Median OS was not reached for cohort A and was 17.6 months for cohort B. Toxicities were consistent with other single-agent pembrolizumab trials. CONCLUSIONS: Single-agent pembrolizumab showed modest activity in patients with ROC. Higher PD-L1 expression was correlated with higher response. CLINICAL TRIAL NUMBER: Clinicaltrials.gov, NCT02674061.

Survival and prognostic factors in patients with recurrent low-grade epithelial ovarian cancer: An analysis of five prospective phase II/III trials of NOGGO metadata base.

OBJECTIVE: Low-grade epithelial ovarian cancers (EOC), constitute the minority among all epithelial cancers. Our study objective was to focus on low-grade recurrent EOC and compare the survival with high-grade disease, as well as in regard to "platinum-sensitive" and "-resistant" recurrences according to platinum-free interval. METHODS: This is an exploratory analysis within the North-Eastern German Society of Gynecological Oncology (NOGGO) database including five randomized phase II/III trials comparing different chemotherapy regimens in recurrent EOC. We conducted survival analyses and cox-proportional regression models. RESULTS: Out of 1050 patients having the first recurrence, 42 (4%) patients had low-grade and 1008 (96%) patients had high-grade disease. In the subgroup of platinum-sensitive recurrences, progression-free survival (PFS) (8.7 m vs 9.7 m, p = 0.7) and overall survival (OS) (23.9 m vs 24.8 m, p = 0.9) did not differ between low-grade and high-grade diseases. In platinum-resistant recurrences, patients with low-grade ovarian cancer had significantly better PFS (7.6 m vs 3.6 m, p = 0.03) and OS (41.9 m vs 9.5 m p = 0.002) in comparison to those with high-grade cancer. At low-grade EOC, there were no significant PFS (p = 0.91) and OS (p = 0.25) differences between platinum-sensitive and -resistant recurrences. Patients with low-grade non-serous histology had lower PFS with compared to those with low-grade serous histology (p = 0.004). At cox regression analysis presence of ascites and residual disease after secondary cytoreductive surgery were independently associated with poor PFS within low-grade recurrent EOC. CONCLUSION: Our study indicates, platinum-free interval does not have any prognostic significance at recurrent low-grade EOC and non-serous histology is associated with poorer outcome in recurrence. Secondary surgical cytoreduction to no-gross residual disease and ascites are independently associated with disease progression.

Early tumor regrowth is a contributor to impaired survival in patients with completely resected advanced ovarian cancer. An exploratory analysis of the Intergroup trial AGO-OVAR 12.

OBJECTIVE: Surgical assessment of residual tumor provides the strongest prognostic information in advanced ovarian cancer (AOC), with the best outcome observed after complete resection. Postoperative radiological assessment before initiation of chemotherapy can supplement the information obtained by surgical assessment; however, it may also reveal conflicting findings. METHODS: Patients with AOC enrolled in the AGO-OVAR 12 trial underwent baseline imaging before the first chemotherapy cycle. The findings from surgical and radiologic assessment for disease extend were compared. Additionally, an integrated approach was assessed. RESULTS: Complete data from all 3 assessment methods were available for 1345 patients. Of 689 patients with complete resection, tumor was observed in 28% and 22% of patients undergoing radiologic and integrated assessment, respectively. Patients with surgical- radiological and surgical-integrated concordant findings showed a 5-year overall survival (5Y-OS) of 72% and 71%, whereas patients with surgical-radiological and surgical-integrated discordant results showed inferior 5Y-OS of 47% and 49%, respectively. Patients with surgically assessed residual disease had a 5-YOS of 37%. The interval between surgery and baseline assessment was independently associated with discordance between assessment methods, which might reflect early tumor regrowth. CONCLUSIONS: Baseline tumor assessment before chemotherapy provides information that stratifies patients with complete resection into different prognostic groups. Integrating the data from different assessment methods might lead to improved definitions of prognostic groups. Further investigation to determine if earlier initiation of chemotherapy after debulking surgery could increase survival of patients with early tumor regrowth is warranted.

Impact of brief prewarming on anesthesia-related core-temperature drop, hemodynamics, microperfusion and postoperative ventilation in cytoreductive surgery of ovarian cancer: a randomized trial.

BACKGROUND: General (GA)- and epidural-anesthesia may cause a drop in body-core-temperature (BCTdrop), and hypothermia, which may alter tissue oxygenation (StO2) and microperfusion after cytoreductive surgery for ovarian cancer. Cell metabolism of subcutaneous fat- or skeletal muscle cells, measured in microdialysis, may be affected. We hypothesized that forced-air prewarming during epidural catheter placement and induction of GA maintains normothermia and improves microperfusion. METHODS: After ethics approval 47 women scheduled for cytoreductive surgery were prospectively enrolled. Women in the study group were treated with a prewarming of 43 °C during epidural catheter placement. BCT (Spot on®, 3 M) was measured before (T1), after induction of GA (T2) at 15 min (T3) after start of surgery, and until 2 h after ICU admission (TICU2h). Primary endpoint was BCTdrop between T1 and T2. Microperfusion-, hemodynamic- and clinical outcomes were defined as secondary outcomes. Statistical analysis used the Mann-Whitney-U- and non-parametric-longitudinal tests. RESULTS: BCTdrop was 0.35 °C with prewarming and 0.9 °C without prewarming (p < 0.005) and BCT remained higher over the observation period (ΔT4 = 0.9 °C up to ΔT7 = 0.95 °C, p < 0.001). No significant differences in hemodynamic parameters, transfusion, arterial lactate and dCO2 were measured. In microdialysis the ethanol ratio was temporarily, but not significantly, reduced after prewarming. Lactate, glucose and glycerol after PW tended to be more constant over the entire period. Postoperatively, six women without prewarming, but none after prewarming were mechanical ventilated (p < 0.001). CONCLUSION: Prewarming at 43 °C reduces the BCTdrop and maintains normothermia without impeding the perioperative routine patient flow. Microdialysis indicate better preserved parameters of microperfusion. TRIAL REGISTRATION: ClinicalTrials.gov ; ID: NCT02364219 ; Date of registration: 18-febr-2015.