Primary results of the AGO-Zervix-1 Study: A prospective, randomized phase III study to compare the effects of paclitaxel and topotecan with those of cisplatin and topotecan in the treatment of patients with recurrent and persistent cervical cancer.

BACKGROUND: Before the era of immunotherapies and antibody-drug conjugates, there were limited chemotherapeutic options for patients with recurrent and metastatic cervical cancer. Combination therapies with cisplatin have shown some superiority over monotherapy. This study examined platinum-free treatment regimens, comparing a combination of topotecan and paclitaxel (TP) with topotecan and cisplatin (TC) in patients with recurrent or metastatic cervical cancer, with or without prior platinum-based treatment. METHODS: The AGO-Zervix-1 Study (NCT01405235) is a prospective, randomized phase III study in which patients were randomly assigned at a 1:1 ratio to treatment within the control arm with topotecan (0.75 mg/m2) on days 1-3 and cisplatin (50 mg/m2) on day 1 every 3 weeks and in the study arm topotecan (1.75 mg/m2) and paclitaxel (70 mg/m2) on days 1, 8, and 15 every 4 weeks or treatment. The primary study aim was overall survival; progression-free survival, toxicity, and quality of life were secondary aims. The interim and final analysis is here reported after recruitment of 173 of 312 planned patients. RESULTS: Median overall survival in the TP arm was 9.6 months, compared with 12.0 months in the TC arm (log-rank test, P = 0.33). Median progression-free survival rates were 4.4 months with TP and 4.2 months with TC (log-rank test, P = 0.47). Leukopenia and nausea/vomiting were more frequent in the cisplatin-containing arm. Otherwise, toxicity profiles were comparable. There were no differences in FACT-G-assessed quality of life. CONCLUSION: Platinum-based combination chemotherapy remains the standard of care chemotherapy regimen for patients with recurrent or metastatic cervical cancer.

Corrected Allele Frequency of BRCA1/2 Mutations Is an Independent Prognostic Factor for Treatment Response to PARP-Inhibitors in Ovarian Cancer Patients.

PARP inhibitors (PARPi) have increased treatment options in ovarian cancer, particularly in patients with BRCA1/2 mutations, although there are still marked differences in the duration of patients' response to this targeted therapy. BRCA testing is routinely performed in tumor tissue of ovarian cancer patients. The resulting molecular pathological findings include the genetic nomenclature of the mutation, the frequency of the mutated allele (variant allele frequency, VAF), and the tumor cell content. VAF measures the percentage of mutated alleles from the total alleles in the cells of the examined tissue. The aim of this study was to investigate the significance of VAF on the therapeutic response to PARPis in ovarian cancer patients. Epithelial ovarian cancer patients harboring BRCA1/2 tumor mutations, who underwent germline testing and received PARPi therapy at the Medical University of Vienna (n = 41) were included in the study. Corrected VAF (cVAF) was calculated based on VAF, tumor cell content, and germline mutation. Patients were divided into two groups based on their cVAF. Median PFS under PARPi in patients with low cVAF was 13.0 months (IQR [10.3-not reached]) and was not reached in the high cVAF group. High cVAF was significantly associated with longer PFS in the multivariate analysis (HR = 0.07; 95% CI [0.01-0.63]; p = 0.017). In conclusion, high cVAF was associated with a significantly better response to PARPi in this study population.

Austria-based real-world data on bevacizumab in newly diagnosed epithelial ovarian cancer.

BACKGROUND: Front-line maintenance therapy with bevacizumab demonstrates high efficacy and safety in epithelial ovarian cancer, as already shown in large phase III trials; however, the corresponding study populations are often not fully representative of patients in clinical routine. In this Austria-based multicenter study, we aimed to explore the real-world outcomes of bevacizumab use in front-line treatment of ovarian cancer, including patients with comorbidities and poor performance status. PATIENTS: This study is an open label single arm multicenter noninterventional trial and included patients with newly diagnosed advanced epithelial ovarian cancer, who were treated with platinum-based chemotherapy and were candidates for receiving bevacizumab according to the product label. Data collection started in the third quarter of 2012 and ended in the third quarter of 2018. RESULTS: In this study 50 patients were included and 575 adverse events were reported for 90% of the patients. The majority of the adverse events were mild (47%) or moderate (37%). The most common adverse events were hypertension (60%), anemia (48%), leukopenia (42%), thrombocytopenia (36%), neutropenia (36%) and proteinuria (26%). A relation to bevacizumab was documented only for 10.3% of all adverse events. In almost 50% of all adverse events, no intervention was needed and bevacizumab treatment had to be interrupted only in 3.3% of all adverse events. The median progression-free survival was 1.3 years (95% CI 1.1-1.8). CONCLUSION: The routine use of front-line bevacizumab for advanced ovarian cancer is associated with high efficacy comparable with that obtained in randomized phase III clinical trials; however, hypertension and proteinuria were reported significantly more often in our Austria-based real-world population.

Topical imiquimod compared with conization to treat cervical high-grade squamous intraepithelial lesions: Multicenter, randomized controlled trial.

OBJECTIVE: In a previous phase II trial, we showed that topical imiquimod (IMQ) therapy is an efficacious treatment for high-grade squamous intraepithelial lesion (HSIL). Aim of the present study was to investigate the non-inferiority of a 16-week topical, self-applied IMQ therapy compared to large loop excision of the transformation zone (LLETZ) in patients diagnosed with HSIL. METHODS: Phase III randomized, controlled, multicenter, open trial performed by Austrian Gynecologic Oncology group. Patients with histologically proven cervical intraepithelial neoplasia (CIN)2 (30 years and older) or CIN3 (18 years and older) and satisfactory colposcopy were randomized to topical IMQ treatment or LLETZ. Successful treatment was defined as negative HPV high-risk test result 6 months after start of the treatment. Secondary endpoints were histological outcome and HPV clearance rates. RESULTS: Within 3 years 93 patients were randomized, received the allocated treatment and were available for ITT analysis. In the IMQ group negative HPV test at 6 months after treatment start was observed in 22/51 (43.1%) of patients compared to 27/42 (64.3%) in the LLETZ group on ITT analysis (rate difference 21.2%-points, 95% two-sided CI: 0.8 to 39.1). In the IMQ group histologic regression 6 months after treatment was observed in 32/51 (63%) of patients and complete histologic remission was observed in 19/51 (37%) of patients. Complete surgical resection was observed in 84% after LLETZ. CONCLUSION: In women with HSIL, IMQ treatment results in lower HPV clearance rates when compared to LLETZ. LLETZ remains the standard for women with HSIL when treatment is required. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01283763, EudraCT number: 2012-004518-32.

The Pretreatment Controlling Nutritional Status Score in Ovarian Cancer: Influence on Prognosis, Surgical Outcome, and Postoperative Complication Rate.

Introduction The Controlling Nutritional (CONUT) Status score is an established predictor of impaired prognosis in patients with solid tumors. The aim of this study was to investigate the prognostic value of the CONUT score for overall survival and perioperative complication rates in patients with epithelial ovarian cancer. Patients In this retrospective study we assessed the data of 337 consecutive patients with ovarian cancer. The CONUT score was associated with surgical outcome, postoperative complications and clinicopathological parameters. We used univariate log-rank test and multivariable Cox regression models to evaluate the association between pretreatment CONUT scores and survival. Results A low CONUT score (0 - 2) was associated with an early FIGO stage (p = 0.004), complete tumor resection (p < 0.001), less neoadjuvant chemotherapy (p = 0.017) and other histologies than serous cystadenocarcinoma (p = 0.006). Postoperative complications were observed in 51.4% and 60.5% of patients with a CONUT score of 0 - 2 and a score > 2, respectively (p = 0.161). A shorter overall survival was observed in patients with a CONUT score > 2 compared to patients with a low CONUT score, with 5-year overall survival rates of 31.5% and 58.7%, respectively (p < 0.001). In multivariable analysis, both advanced age (p < 0.001) and FIGO stage (p < 0.001), residual disease (p < 0.001) and a high CONUT score (p = 0.048) were independently associated with unfavorable overall survival. Conclusion Pretreatment CONUT score is an independent prognostic marker for overall survival and associated with successful surgery. Patients with a high CONUT score might benefit from pretreatment nutritional intervention.

Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer.

BACKGROUND: Treatment for patients with recurrent ovarian cancer has been mainly based on systemic therapy. The role of secondary cytoreductive surgery is unclear. METHODS: We randomly assigned patients with recurrent ovarian cancer who had a first relapse after a platinum-free interval (an interval during which no platinum-based chemotherapy was used) of 6 months or more to undergo secondary cytoreductive surgery and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Patients were eligible if they presented with a positive Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score, defined as an Eastern Cooperative Oncology Group performance-status score of 0 (on a 5-point scale, with higher scores indicating greater disability), ascites of less than 500 ml, and complete resection at initial surgery. A positive AGO score is used to identify patients in whom a complete resection might be achieved. The primary end point was overall survival. We also assessed quality of life and prognostic factors for survival. RESULTS: A total of 407 patients underwent randomization: 206 were assigned to cytoreductive surgery and chemotherapy, and 201 to chemotherapy alone. A complete resection was achieved in 75.5% of the patients in the surgery group who underwent the procedure. The median overall survival was 53.7 months in the surgery group and 46.0 months in the no-surgery group (hazard ratio for death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.02). Patients with a complete resection had the most favorable outcome, with a median overall survival of 61.9 months. A benefit from surgery was seen in all analyses in subgroups according to prognostic factors. Quality-of-life measures through 1 year of follow-up did not differ between the two groups, and we observed no perioperative mortality within 30 days after surgery. CONCLUSIONS: In women with recurrent ovarian cancer, cytoreductive surgery followed by chemotherapy resulted in longer overall survival than chemotherapy alone. (Funded by the AGO Study Group and others; DESKTOP III ClinicalTrials.gov number, NCT01166737.).

Olaparib plus bevacizumab as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer: Japan subset from the PAOLA-1/ENGOT-ov25 trial.

OBJECTIVE: The addition of maintenance olaparib to bevacizumab demonstrated a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the PAOLA-1/ENGOT-ov25 trial (NCT02477644). We evaluated maintenance olaparib plus bevacizumab in the Japan subset of PAOLA-1. METHODS: PAOLA-1 was a randomized, double-blind, phase III trial. Patients received maintenance olaparib tablets 300 mg twice daily or placebo twice daily for up to 24 months, plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total. This prespecified subgroup analysis evaluated investigator-assessed PFS (primary endpoint). RESULTS: Of 24 randomized Japanese patients, 15 were assigned to olaparib and 9 to placebo. After a median follow-up for PFS of 27.7 months for olaparib plus bevacizumab and 24.0 months for placebo plus bevacizumab, median PFS was 27.4 versus 19.4 months, respectively (hazard ratio [HR]=0.34; 95% confidence interval [CI]=0.11-1.00). In patients with tumors positive for homologous recombination deficiency, the HR for PFS was 0.57 (95% CI=0.16-2.09). Adverse events in the Japan subset were generally consistent with those of the PAOLA-1 overall population and with the established safety and tolerability profiles of olaparib and bevacizumab. CONCLUSION: Results in the Japan subset of PAOLA-1 support the overall conclusion of the PAOLA-1 trial demonstrating that the addition of maintenance olaparib to bevacizumab provides a PFS benefit in patients with newly diagnosed, advanced ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02477644.

The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer-A Study of the OVCAD Consortium.

INTRODUCTION: We previously reported the prognostic impact of circulating tumor cells (CTCs) in a multicenter study on minimal residual disease in primary ovarian cancer. With additional follow-up data, we evaluated the combined CTC approach (CTCscombo), in particular for the patients who had survived more than five years. MATERIAL AND METHODS: Blood samples taken at baseline and six months after adjuvant treatment (follow-up) were assessed by quantitative PCR (qPCR) measuring PPIC transcripts and immunofluorescent staining (IF). A positive result with either IF or qPCR was classified as CTCcombo-positive. Further, PPIC was assessed in the primary tumor tissue. RESULTS: The concordance of IF and qPCR was 65% at baseline and 83% after treatment. Results showed that 50.5% of the baseline and 29.5% of the follow-up samples were CTCcombo-positive. CTCscombo after treatment were associated with increased mortality after adjusting for FIGO stage (HR 2.574, 95% CI: 1.227-5.398, p = 0.012), a higher risk of recurrence after adjusting for peritoneal carcinosis (HR 4.068, 95% CI: 1.948-8.498, p < 0.001), and increased mortality after five survived years. DISCUSSION: The two-sided analytical approach revealed CTC subpopulations associated with ovarian cancer progression and may illuminate a potential treatment-related shift in molecular phenotypes. That approach can identify patients who have elevated risk of recurrence and death due to ovarian cancer and who may require risk-adapted treatment strategies.

Tumor Growth Rate Estimates Are Independently Predictive of Therapy Response and Survival in Recurrent High-Grade Serous Ovarian Cancer Patients.

This study aimed to assess the predictive value of tumor growth rate estimates based on serial cancer antigen-125 (CA-125) levels on therapy response and survival of patients with recurrent high-grade serous ovarian cancer (HGSOC). In total, 301 consecutive patients with advanced HGSOC (exploratory cohort: n = 155, treated at the Medical University of Vienna; external validation cohort: n = 146, from the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium) were enrolled. Tumor growth estimates were obtained using a validated two-phase equation model involving serial CA-125 levels, and their predictive value with respect to treatment response to the next chemotherapy and the prognostic value with respect to disease-specific survival and overall survival were assessed. Tumor growth estimates were an independent predictor for response to second-line chemotherapy and an independent prognostic factor for second-line chemotherapy use in both univariate and multivariable analyses, outperforming both the predictive (second line: p = 0.003, HR 5.19 [1.73-15.58] vs. p = 0.453, HR 1.95 [0.34-11.17]) and prognostic values (second line: p = 0.042, HR 1.53 [1.02-2.31] vs. p = 0.331, HR 1.39 [0.71-2.27]) of a therapy-free interval (TFI) < 6 months. Tumor growth estimates were a predictive factor for response to third- and fourth-line chemotherapy and a prognostic factor for third- and fourth-line chemotherapy use in the univariate analysis. The CA-125-derived tumor growth rate estimate may be a quantifiable and easily assessable surrogate to TFI in treatment decision making for patients with recurrent HGSOC.

PD-1 and PD-L1 expression on TILs in peritoneal metastases compared to ovarian tumor tissues and its associations with clinical outcome.

The therapeutic potential of immune checkpoint inhibitors is currently being investigated in epithelial ovarian cancer (EOC), but immunological effects of the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis in EOC still remain poorly understood. The aim of this study was thus to compare infiltration rates of PD-1 and PD-L1 expressing tumor infiltrating leucocytes (TILs) in primary ovarian tumor tissue and metastatic intraperitoneal implants and to investigate its impact on overall survival (OS). Tumor specimens (ovarian tumor tissues and intraperitoneal metastases) of 111 patients were used to investigate the PD-1, PD-L1 and CD8 expression rates on TILs and PD-L1 expression rate of tumor cells. The percentages of CD8, PD-1, and PD-L1 expressing subpopulations of TILs differ in primary ovarian tumor tissues and metastatic intraperitoneal implants. High PD-1 among TILs in peritoneal metastases were associated with favorable OS. High PD-L1 expression in TILs was associated with poor OS. Combining both factors in peritoneal metastases revealed an unfavorable prognosis. Primary ovarian tumor tissue and intraperitoneal metastatic tissues in EOC might have different strategies to evade immune control. Those findings are of importance for the process of biomarker assessment to predict patients' response to immunotherapy.

Risk Reclassification of Patients with Endometrial Cancer Based on Tumor Molecular Profiling: First Real World Data.

Recently, guidelines for endometrial cancer (EC) were released that guide treatment decisions according to the tumors' molecular profiles. To date, no real-world data regarding the clinical feasibility of molecular profiling have been released. This retrospective, monocentric study investigated the clinical feasibility of molecular profiling and its potential impact on treatment decisions. Tumor specimens underwent molecular profiling (testing for genetic alterations, (immune-)histological examination of lymphovascular space invasion (LVSI), and L1CAM) as part of the clinical routine and were classified according to the European Society for Medical Oncology (ESMO) classification system and to an integrated molecular risk stratification. Shifts between risk groups and potential treatment alterations are described. A total of 60 cases were included, of which twelve were excluded (20%), and eight of the remaining 48 were not characterized (drop-out rate of 16.7%). Molecular profiling revealed 4, 6, 25, and 5 patients with DNA polymerase-epsilon mutation, microsatellite instability, no specific molecular profile, and TP53 mutation, respectively. Three patients had substantial LVSI, and four patients showed high L1CAM expression. Molecular profiling took a median of 18.5 days. Substantial shifts occurred between the classification systems: four patients were upstaged, and 19 patients were downstaged. Molecular profiling of EC specimens is feasible in a daily routine, and new risk classification systems will change treatment decisions substantially.

Impact of frailty on the management of patients with gynecological cancer aged 80 years and older.

PURPOSE: To assess the impact of frailty on compliance of standard therapy, complication, rate and survival in patients with gynecological malignancy aged 80 years and older. METHODS: In total, 83 women with gynecological malignancy (vulva, endometrial, ovarian or cervical cancer) who underwent primary treatment between 2007 and 2017 were retrospectively analyzed. Frailty index was calculated and its association with compliance of standard treatment, peri- and postoperative mortality and morbidity, and survival was evaluated. RESULTS: Frailty was observed in 24.1% of cases. Both frail and non-frail patients were able to receive standard therapy in most cases - 75.0% and 85.7%, respectively (p = 0.27). Frail patients did not show an increased postoperative complication rate. Frail patients had shorter 3 years overall survival rates (28%) when compared to non-frail patients (55%) (p = 0.02). In multivariable analysis high frailty index (Hazard Ratio [HR] 12.15 [1.39-106.05], p = 0.02) and advanced tumor stage (HR 1.33 [1.00-1.76], p = 0.05) were associated with poor overall survival, but not age, histologic grading, performance status, and compliance of standard therapy. CONCLUSION: Majority of patients was able to receive standard therapy, as suggested by the tumor board, irrespective of age and frailty. Nonetheless, frailty is a common finding in patients with gynecological malignancy aged 80 years and older. Frail patients show shorter progression-free, and overall survival within this cohort.

The systemic immune-inflammation index (SII) is an independent prognostic parameter of survival in patients with invasive vulvar cancer / 부인종양

Objective@#To assess the prognostic value of the systemic immune-inflammation index (SII) in patients with vulvar cancer. @*Methods@#Data of 130 consecutive patients who underwent primary surgical resection for vulvar cancer at the Medical University of Vienna between 1999 and 2018 was retrospectively analyzed. The SII was defined as platelets × neutrophils/lymphocytes as previously described. Its prognostic value on disease-specific survival (DSS) and overall survival (OS) was evaluated by univariate log-rank tests and multivariable cox regression models. Prediction accuracy was assessed by receiver operating characteristics curves and Youden's J statistics. A HosmerLemeshow test was performed to confirm the model's goodness of fit. @*Results@#A pre-therapeutic high serum SII (>866.4) was associated with advanced International Federation of Gynecology and Obstetrics (FIGO)-stage. In univariate survival analysis, a high SII was associated with both DSS (p<0.001) and OS (p=0.001). A multivariate cox regression model confirmed the prognostic value of SII regarding DSS (p<0.001) and OS (p=0.014) independently from patients' age and FIGO stage. @*Conclusions@#Pretherapeutic SII may serve as a promising predictor for survival in patients with vulvar cancer. After clinical validation, the SII may be used to improve both pretreatment patient risk stratification and patient counseling.

Decrease in gynecological cancer diagnoses during the COVID-19 pandemic: an Austrian perspective.

BACKGROUND: On March 16, 2020, the federal government of Austria declared a nationwide lockdown due to the COVID-19 pandemic. Since the lockdown, screening examinations and routine checkups have been restricted to prevent the spread of the virus and to increase the hospitals' bed capacity across the country. This resulted in a severe decline of patient referrals to the hospitals. OBJECTIVE: To assess the impact of the COVID-19 pandemic on the rate of newly diagnosed gynecological and breast cancers in Austria. METHODS: Data of 2077 patients from 18 centers in Austria with newly diagnosed gynecological or breast cancer between January and May 2019 and January and May 2020 were collected. Clinical parameters, including symptoms, performance status, co-morbidities, and referral status, were compared between the time before and after the COVID-19 outbreak. RESULTS: Our results showed a slight increase of newly diagnosed cancers in January and February 2020 as compared with 2019 (+2 and +35%, respectively) and a strong decline in newly diagnosed tumors since the lockdown: -24% in March 2020 versus March 2019, -49% in April 2020 versus April 2019, -49% in May 2020 versus May 2019. Two-thirds of patients diagnosed during the pandemic presented with tumor-specific symptoms compared with less than 50% before the pandemic (p<0.001). Moreover, almost 50% of patients in 2020 had no co-morbidities compared with 35% in 2019 (p<0.001). Patients, who already had a malignant disease, were rarely diagnosed with a new cancer in 2020 as compared with 2019 (11% vs 6%; p<0.001). CONCLUSIONS: The lockdown led to a decreased number of newly diagnosed gynecological and breast cancers. The decreased accessibility of the medical services and postponed diagnosis of potentially curable cancers during the COVID-19 pandemic may be a step backwards in our healthcare system and might impair cancer treatment outcomes. Therefore, new strategies to manage early cancer detection are needed to optimize cancer care in a time of pandemic in the future.

miR-181a overexpression predicts the poor treatment response and early-progression of serous ovarian cancer patients.

Ovarian cancer (OC) remains a leading cause of gynecological cancer-related death worldwide, characterized by poor 5-year survival. Molecular markers could serve as crucial tools of personalized prognosis and therapy. Herein, we present miR-181a as novel predictor of OC prognosis, using five independent OC cohorts. In particular, a screening (n = 81) and an institutionally independent validation (n = 100, OVCAD multicenter study) serous OC (SOC) cohorts were analyzed. Bagnoli et al (2016) OC179 (n = 124) to OC133 (n = 100) and TCGA (n = 489) served as external validation cohorts. Patients' survival and disease progression were assessed as clinical endpoint events. Bootstrap analysis was performed for internal validation and decision curve analysis was utilized to evaluate clinical benefit. miR-181a overexpression was unveiled as powerful and independent molecular predictor of patients' poor survival and higher risk for disease progression after debulking surgery and platinum-based chemotherapy. Analysis of the OVCAD institutionally independent cohort, as well as of Bagnoli et al. and TCGA external cohorts further confirmed the unfavorable prognostic nature of miR-181a overexpression in SOC. Strikingly, multivariate prognostic models incorporating miR-181a with established disease markers clearly improved patients' risk-stratification and offered superior clinical benefit in OC prognostication. Conclusively, miR-181a evaluation could augment prognostic accuracy and support precision medicine decisions in OC.

Molecular Guided Treatments in Gynecologic Oncology: Analysis of a Real-World Precision Cancer Medicine Platform.

INTRODUCTION: Advanced gynecologic cancers have a poor prognosis and constitute a major challenge for adequate treatment strategies. By analyzing and targeting molecular alterations, molecular guided treatments may be a viable option for the treatment of advanced gynecologic cancers. PATIENTS AND METHODS: In this single-center, real-world retrospective analysis of our platform for precision cancer medicine (PCM), we describe the molecular profiling of 72 patients diagnosed with different types of advanced gynecologic malignancies. Tumor samples of the patients were examined by next-generation sequencing panel and immunohistochemistry (IHC). RESULTS: In total, we identified 209 genetic aberrations in 72 patients. The ten most frequent alterations were TP53 (n = 42, 20%), KRAS (n = 14, 6.6%), PIK3CA (n = 11, 5.2%), PIK3R1 (n = 9, 4.3%), ATR (n = 8, 3.8%), PTEN (n = 8, 3.8%), BRCA1 (n = 6, 2.8%), NF1 (n = 4, 1.9%), NOTCH1 (n = 4, 1.9%), and POLE (n = 4, 1.9%), which account for more than half of all molecular alterations (52.6%). In 21 (29.1%) patients only one mutation could be detected, and 44 (61.1%) patients had more than one mutation. No molecular alterations were detected in seven (9.7%) patients. IHC detected expression of phosphorylated mammalian target of rapamycin and epidermal growth factor receptor in 58 (80.6%) and 53 (73.6%) patients, respectively. In over two thirds (n = 49, 68.1%), a targeted therapy was suggested, based on the identified genetic aberrations. The most frequently recommended specific treatment was the combination of everolimus with exemestane (n = 18, 25 %). CONCLUSION: Based on our observations, it seems that PCM might be a feasible approach for advanced gynecologic cancers with limited treatment options. IMPLICATIONS FOR PRACTICE: Nowadays molecular profiling of advanced gynecologic malignancies is feasible in the clinical routine. A molecular portrait should be done for every patient with an advanced therapy-refractory gynecologic malignancy to offer molecular-based treatment concepts.

Effect of Viewing Disney Movies During Chemotherapy on Self-Reported Quality of Life Among Patients With Gynecologic Cancer: A Randomized Clinical Trial.

Importance: In addition to treatment efficacy, evaluation of adverse effects and quality of life assessments have become increasingly relevant in oncology. Objective: To evaluate the association of watching Disney movies during chemotherapy with emotional and social functioning and fatigue status. Design, Setting, and Participants: This randomized clinical trial was performed from December 2017 to December 2018 at a cancer referral center in Vienna, Austria. A consecutive sample of women with gynecologic cancers was recruited through July 2018. Inclusion criteria included age older than 18 years, written informed consent, and planned 6 cycles of chemotherapy with either carboplatin and paclitaxel or carboplatin and pegylated liposomal doxorubicin. Exclusion criteria were inadequate knowledge of the German language or receipt of other chemotherapy regimens. Data analysis was performed from February 2019 to April 2019. Intervention: Participants were either shown Disney movies or not during 6 cycles of chemotherapy. Before and after every cycle, they completed standardized questionnaires from the European Organisation for Research and Treatment of Cancer (EORTC). Main Outcomes and Measures: Primary outcomes were change of quality of life, as defined by the EORTC Core-30 (version 3) questionnaire, and fatigue, as defined by the EORTC Quality of Life Questionnaire Fatigue, during 6 cycles of chemotherapy. Results: Fifty-six women entered the study, and 50 completed it, including 25 women in the Disney group (mean [SD] age, 59 [12] years) and 25 women in the control group (mean [SD] age, 62 [8] years). In the course of 6 cycles of chemotherapy, patients in the Disney group felt less tense and worried less than patients in the control group according to their responses to the questions about emotional functioning (mean [SD] score, 86.9 [14.3] vs 66.3 [27.2]; maximum test P = .02). Furthermore, watching Disney movies was associated with less encroachment on patients' family life and social activities, as evaluated by the social functioning questions (mean [SD] score, 86.1 [23.0] vs 63.6 [33.6]; maximum test P = .01). Moreover, this intervention led to fewer fatigue symptoms (mean [SD] score, 85.5 [13.6] vs 66.4 [22.5]; maximum test P = .01). Perceived global health status was not associated with watching Disney movies (mean [SD] score, 75.9 [17.6] vs 61.0 [25.1]; maximum test P = .16). Conclusions and Relevance: These findings suggest that watching Disney movies during chemotherapy may be associated with improvements in emotional functioning, social functioning, and fatigue status in patients with gynecologic cancers. Trial Registration: ClinicalTrials.gov Identifier: NCT03863912.

Low anterior resection syndrome (LARS) in ovarian cancer patients - A multi-centre comparative cohort study.

BACKGROUND: Low anterior resection syndrome (LARS) is a common functional disorder after low anterior resection impacting the quality of life. Data on LARS derives nearly exclusively from rectal cancer studies. Therefore, the study was designed to assess LARS in advanced epithelial ovarian cancer (EOC) patients, who underwent rectal resection and to compare it with a female rectal cancer cohort. MATERIAL AND METHODS: A cross-sectional multi-centre analysis was performed on female patients suffering from either rectal or EOC who received a low anterior resection as part of their therapy regimen. None of the patients received pre- or postoperative radiotherapy. LARS was defined by using the validated LARS score and its severity was divided into "no", "minor" and "major LARS". RESULTS: In total, 125 female patients (44.8% (n = 56) EOC vs. 55.2% (n = 69) rectal cancer patients) met the final inclusion criteria and were retrospectively analyzed. Baseline characteristics were comparable between the groups. Median follow-up was 22 (IQR 12-56) months. In total, 30.4% (n = 38) of the patient group reported bowel dysfunction after surgery. Rates of LARS were not significantly different between EOC and rectal cancer patients (major LARS 16.1% (n = 9) vs. 15.9% (n = 11); minor LARS 17.9% (n = 10) vs. 11.6% (n = 8); p = 0.984). The time interval between surgery and final assessment had no impact on the postoperative bowel function (p = 0.820). CONCLUSION: LARS is a frequent and highly underreported postoperative disorder in EOC patients who require cytoreductive surgery with rectal resection. The functional outcome is comparable to female patients with rectal cancer who underwent low anterior resection without receiving radiotherapy.

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial.

BACKGROUND: State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin-paclitaxel or carboplatin-gemcitabine) or the most active non-bevacizumab regimen: carboplatin-pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin-pegylated liposomal doxorubicin combined with bevacizumab. METHODS: This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK. Eligible patients (aged ≥18 years) had histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with first disease recurrence more than 6 months after first-line platinum-based chemotherapy, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were stratified by platinum-free interval, residual tumour, previous antiangiogenic therapy, and study group language, and were centrally randomly assigned 1:1 using randomly permuted blocks of size two, four, or six to receive six intravenous cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (area under the concentration curve [AUC] 4, day 1) plus gemcitabine (1000 mg/m2, days 1 and 8) every 3 weeks or six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (AUC 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m2, day 1) every 4 weeks, both followed by maintenance bevacizumab (15 mg/kg every 3 weeks in both groups) until disease progression or unacceptable toxicity. There was no masking in this open-label trial. The primary endpoint was investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy data were analysed in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug. This completed study is registered with ClinicalTrials.gov, NCT01837251. FINDINGS: Between Aug 1, 2013, and July 31, 2015, 682 eligible patients were enrolled, of whom 345 were randomly assigned to receive carboplatin-pegylated liposomal doxorubicin-bevacizumab (experimental group) and 337 were randomly assigned to receive carboplatin-gemcitabine-bevacizumab (standard group). Median follow-up for progression-free survival at data cutoff (July 10, 2018) was 12·4 months (IQR 8·3-21·7) in the experimental group and 11·3 months (8·0-18·4) in the standard group. Median progression-free survival was 13·3 months (95% CI 11·7-14·2) in the experimental group versus 11·6 months (11·0-12·7) in the standard group (hazard ratio 0·81, 95% CI 0·68-0·96; p=0·012). The most common grade 3 or 4 adverse events were hypertension (88 [27%] of 332 patients in the experimental group vs 67 [20%] of 329 patients in the standard group) and neutropenia (40 [12%] vs 73 [22%]). Serious adverse events occurred in 33 (10%) of 332 patients in the experimental group and 28 (9%) of 329 in the standard group. Treatment-related deaths occurred in one patient in the experimental group (<1%; large intestine perforation) and two patients in the standard group (1%; one case each of osmotic demyelination syndrome and intracranial haemorrhage). INTERPRETATION: Carboplatin-pegylated liposomal doxorubicin-bevacizumab is a new standard treatment option for platinum-eligible recurrent ovarian cancer. FUNDING: F Hoffmann-La Roche.

Precision Medicine Tumor Boards: Clinical Applicability of Personalized Treatment Concepts in Ovarian Cancer.

BACKGROUND: Treating cancer according to its molecular alterations (i.e., targeted treatment, TT) is the goal of precision medicine tumor boards (PTBs). Their clinical applicability has been evaluated for ovarian cancer patients in this analysis. METHODS: All consecutive ovarian cancer patients discussed in a PTB at the Medical University of Vienna, Austria, from April 2015 to April 2019 were included (n = 44). RESULTS: In 38/44 (86%) cases, at least one mutation, deletion or amplification was detected. The most frequently altered genes were p53 (64%), PI3K pathway (18%), KRAS (14%), BRCA1 (11%) and BRCA2 (2%). In 31 patients (70%) a TT was recommended. A total of 12/31 patients (39%) received the recommended therapy. Median time from indication for PTB to TT start was 65 days (15-216). Median time to treatment failure was 2.7 months (0.2-13.2). Clinical benefit rate (CBR) was 42%. Reasons for treatment discontinuation were disease progression (42%), poor performance status (PS > 2; 25%), death (17%) or treatment related side effects (8%). In 61% the TT was not administered-mainly due to PS > 2. CONCLUSION: Even though a TT recommendation can be derived frequently, clinical applicability remains limited due to poor patients' general condition after exploitation of standard treatment. However, we observed antitumor activity in a substantial number of heavily pretreated patients.