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Objectives: To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related moderators of these effects. Methods: Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics. Results: For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = −0.09, 95% CI [−0.16; −0.02]). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances. Conclusions: This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.

Objective: Despite being the most important prognostic factor for prolonged overall survival in epithelial ovarian cancer (EOC), the measurement of residual disease is hampered by its subjective character. Additional assessment tools are needed to establish the success of cytoreductive surgery in order to predict patients' prognosis more accurately. The aim of this study is to evaluate the independent prognostic value of perioperative CA125 change in advanced stage EOC patients.Study design: We identified all patients who underwent primary cytoreductive surgery for advanced stage (FIGO IIB-IV) EOC between 2008 and 2015, from the Netherlands Cancer Registry. The relative perioperative change in CA125 was categorized into four groups; increase, = 80% decline. Overall survival (OS) was analyzed using Kaplan-Meier survival curves and multivariable cox regression models.Results: We included 1232 eligible patients with known pre- and postoperative CA125 serum levels. Patients with a decline of >= 80% in CA125 levels experienced improved OS compared to those with a decline of = 80% 0.52(0.41-0.66)).Conclusions: This study shows that the perioperative change in CA125 is an independent prognostic factor for overall survival after primary surgery for EOC patients. This pleads for the use of a combined model, consisting of perioperative CA125 change and the outcome of residual disease, in order to predict the prognosis of EOC patients more accurately. (C) 2019 Elsevier B.V. All rights reserved.

Introduction: The care for patients with epithelial ovarian cancer(EOC) is organised in eight different geographical regions in the Netherlands. This situation allows us to study differences in practice patterns and outcomes between geographical regions for patients with FIGO stage IIIC and IV.Methods: We identified all EOC patients who were diagnosed with FIGO stage IIIC or IV between 01.01.2008 and 31.12.2015 from the Netherlands Cancer Registry. Descriptive statistics were used to summarize treatment and treatment sequence(primary cytoreductive surgery(PCS) or neoadjuvant chemotherapy and interval cytoreductive surgery(NACT-ICS)). Moreover, outcome of surgery was compared between geographical regions. Multilevel logistic regression was used to assess whether existing variation is explained by geographical region and case-mix factors.Results: Overall, 6,741 patients were diagnosed with FIGO IIIC or IV disease. There were no differences in the percentage of patients that received any form of treatment between the geographical regions(range 80-86%, P=0.162). In patients that received cytoreductive surgery and chemotherapy, a significant variation between the geographical regions was observed in the use of PCS and NACT-ICS(PCS: 24-48%, P <0.001). The percentage of complete cytoreductive surgeries after PCS ranged from 10 to 59%(P <0.001) and after NACT-ICS from 37 to 70%(P <0.001). Moreover, geographical region was independently associated with the outcome of surgery, also when adjusted for treatment sequence(P <0.001).Conclusion: We observed a significant variation in treatment approach for advanced EOC between geographical regions in the Netherlands. Furthermore, the probability to achieve no residual disease differed significantly between regions, regardless of treatment sequence. This may suggest that surgical outcomes can be improved across geographical regions. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer

Introduction. The ability to minimize residual disease during primary cytoreductive surgery is the strongest predictor for improved overall survival in advanced ovarian cancer. But while the probability to achieve a macroscopic complete resection increases if surgery is preceded by neoadjuvant chemotherapy (NACT), survival rates after NACT are similar to those observed after primary surgery. This may suggest that the prognostic effect of residual disease is altered after NACT. More specifically, randomized data suggest that there is no difference between optimal (0.1-1 cm) and suboptimal (>1 cm) cytoreductive surgery after NACT. Therefore, the aim of the current review is to establish the prognostic effect of the amount of residual disease after interval cytoreductive surgery (ICS) on overall survival.Methods. Potential articles for inclusion in the current review were systematically searched through Medline, Embase and Cochrane in September 2017. Median overall survival (mOS) was summarized by the outcome of ICS per study. In addition, mOS was summarized for all studies together stratified by the outcome of ICS, based on the principle of a weighted average.Results. In total, 3677 unique manuscripts were individually screened on title and abstract, which resulted in 11 individual studies that comprised a total of 2178 patients. MOS was 41 months for patients with no residual disease (range 33-54 months), 27 months for patients with 0.1-1 cm of residual disease (range 19-38 months) and 21 months with >1 cm of residual disease (range 14-27 months). Six studies showed significant differences between optimal and suboptimal ICS, while five studies showed no differences.Conclusion. The summary of the currently available literature showed that after NACT, patients with optimal cytoreductive surgery experience lengthened survival compared to patients with suboptimal cytoreductive surgery. Patients with no macroscopic residual disease have, howe

Background Patients with ovarian cancer who are diagnosed with Federation of Gynecology and Obstetrics (FIGO) stage IV disease are a highly heterogeneous group with possible survival differences. The FIGO staging system was therefore updated in 2014.Objective To evaluate the 2014 changes to FIGO stage IV ovarian cancer on overall survival.Methods We identified all patients diagnosed with FIGO stage IV disease between January 2008 and December 2015 from the Netherlands Cancer Registry. We analyzed the prognostic effect of FIGO IVa versus IVb. In addition, patients with extra-abdominal lymph node involvement as the only site of distant disease were analyzed separately. Overall survival was analyzed by Kaplan-Meier curves and multivariable Cox regression models.Results We identified 2436 FIGO IV patients, of whom 35% were diagnosed with FIGO IVa disease. Five-year overall survival of FIGO IVa and IVb patients (including those with no or limited therapy) was 8.9% and 13.0%, respectively (p=0.51). Patients with only extra-abdominal lymph node involvement had a significant better overall survival than all other FIGO IV patients (5-year overall survival 25.9%, hazard ratio 0.77 [95% CI 0.62 to 0.95]).Conclusion Our study shows that the FIGO IV sub-classification into FIGO IVa and IVB does not provide additional prognostic information. Patients with extra-abdominal lymph node metastases as the only site of FIGO IV disease, however, have a better prognosis than all other FIGO IV patients. These results warrant a critical appraisal of the current FIGO IV sub-classification.

Introduction: About 5% of ovarian tumours have a non-epithelial histology, including germ cell tumours (GCTs), sex cord-stromal tumours (SCSTs) and sarcomas. Because these non-epithelial ovarian tumours are rare and population-based studies are scarce, the aim of this population-based study is to describe trends in the incidence, treatment and survival of women with these tumours in the Netherlands.Methods: All women diagnosed with non-epithelial ovarian malignant tumours in the Netherlands between 1989 and 2015 were identified from the Netherlands Cancer Registry. Data on demographics, tumour characteristics and initial treatment were collected, and overall survival was analysed.Results: A total of 1258 non-epithelial ovarian tumours were identified comprising 752 GCTs (60%), 341 SCSTs (27%) and 165 sarcomas (13%). The European age-standardised incidence rate (ESR) was 0.4 per 100,000 persons per year for GCTs, 0.2 for SCSTs and 0.1 for sarcomas. Approximately 97% of patients underwent surgical resection for the primary tumour, 31% received systemic treatment and 3% radiotherapy. Between the late 1980s and 2015, five-year overall survival improved for all histologic subtypes: GCTs rose from 73% to 88% (p = 0.03), SCSTs from 64% to 81% (p = 0.57) and sarcomas from 20% to 29% (p = 0.14).Conclusion: Malignant GCTs and SCSTs are rare, and their incidence has not significantly changed over recent decades. They have a good prognosis, which also improved slightly during this period. Primary sarcomas of the ovary are extremely rare and still have a poor prognosis. (C) 2019 Elsevier Ltd. All rights reserved.

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.

Introduction: Primary debulking surgery (PDS) followed by adjuvant chemotherapy is historically recommended as first line treatment for advanced stage ovarian cancer. Two randomized controlled trials, however, showed similar efficacy and reduced toxicity with neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS). Nevertheless, uptake of NACT-IDS varies widely between hospitals, which cannot be explained by difference in patient populations. In this survey, we therefore aimed to evaluate the views on NACT-IDS among all Dutch gynaecologists and medical oncologists involved in the treatment of ovarian cancer. Study design: An e-mail link to the online questionnaire was sent to all medical oncologists and gynaecologists in the Netherlands, regardless of their (sub)specializations. The data was analysed using descriptive statistics and chi-square tests were used to analyse differences between groups. Results: Three-hundred-forty physicians were invited to fill out the questionnaire. After two reminders, 167 of them responded (49%). Among the responders, 82% of the gynaecologists versus 93% of the medical oncologists considered the available evidence sufficiently convincing to treat advanced stage ovarian cancer patients with NACT-IDS (p = 0.076). Moreover, 33% of gynaecologists and 62% of medical oncologists preferred NACT-IDS to PDS as first line treatment (p = 0.001). While most responders (86%) indicated that selecting the right patients for NACT-IDS is difficult, those with bulky disease, FIGO stage IV or metastases near the porta hepatica were most likely to undergo NACT-IDS. Conclusion: The majority of Dutch gynaecologists and medical oncologists adopted NACT-IDS as an alternative treatment approach for advanced stage primary ovarian cancer. About two-thirds of medical oncologists and one-third of gynaecologists prefer NACT-IDS to PDS as first line treatment in this setting. Improving patient selection is considered of paramount importance. (C)

Aim: This study investigates changes in therapy and long-term survival for patients with epithelial ovarian cancer (EOC) in the Netherlands. Methods: All patients with EOC, including peritoneal and fallopian tube carcinoma, diagnosed in the Netherlands between 1989 and 2014 were selected from the Netherlands Cancer Registry. Changes in therapy were studied and related to overall survival (OS) using multivariable Cox regression models. Results: A total of 32,540 patients were diagnosed with EOC of whom 22,047 (68%) had advanced stage disease. In early stage, lymph node dissection as part of surgical staging procedures increased over time from 4% in 1989-1993 to 62% in 2009-2014 (P < 0.001). In advanced stage, the number of patients receiving optimal treatment with surgery and chemotherapy increased from 55% in 1989-1993 to 67% in 2009-2014 (P < 0.001). Five-year survival rates improved in both early stage (74% versus 79%) and advanced stage (16% versus 24%) as well as in all patients combined (31% versus 34%). Ten-year survival rates, however, slightly improved in early stage (62% versus 67%) and advanced stage (10% versus 13%) but remained essentially unchanged at 24% for all patients combined. Conclusion: Despite intensified treatment and staging procedures, long-term survival for women with EOC has not improved in the last 25 years. The observed improvements in 5-year OS reflect a more prolonged disease control rather than better chances for cure. Furthermore, the apparent better long-term outcome, when early and advanced stage patients are analysed separately, is largely due to improved staging procedures and the ensuing stage migration. These effects disappear in a combined analysis of all patients. (C) 2017 Elsevier Ltd. All rights reserved.

3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib in relapsed disease has been well established, but the benefit of olaparib as maintenance therapy in newly diagnosed disease is uncertain. METHODS We conducted an international, randomized, double-blind, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients with newly diagnosed advanced (International Federation of Gynecology and Obstetrics stage III or IV) high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-Tube cancer (or a combination thereof) with a mutation in BRCA1, BRCA2, or both (BRCA1/2) who had a complete or partial clinical response after platinumbased chemotherapy. The patients were randomly assigned, in a 2:1 ratio, to receive olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival. RESULTS Of the 391 patients who underwent randomization, 260 were assigned to receive olaparib and 131 to receive placebo. A total of 388 patients had a centrally confirmed germline BRCA1/2 mutation, and 2 patients had a centrally confirmed somatic BRCA1/2 mutation. After a median follow-up of 41 months, the risk of disease progression or death was 70% lower with olaparib than with placebo (Kaplan-Meier estimate of the rate of freedom from disease progression and from death at 3 years, 60% vs. 27%; hazard ratio for disease progression or death, 0.30; 95% confidence interval, 0.23 to 0.41; P<0.001). Adverse events were consistent with the known toxic effects of olaparib. CONCLUSIONS The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression-free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, with a 70% lower risk of disease progression or death with olaparib than with placebo. (Funded by AstraZeneca and Merck; S

Bernard, P., Savard, J., Steindorf, K., Sweegers, M. G., Courneya, K. S., Newton, R. U., ... Buffart, L. M., (2019). Effects and moderators of exercise on sleep in adults with cancer: Individual patient data and aggregated meta-analyses. Journal of Psychosomatic Research, 124, Article 109746. Available here