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Objective: To evaluate if exercise and sitting time during chemotherapy were associated with chemotherapy side-effects, completion of planned chemotherapy and survival., Methods: We used data from the Ovarian cancer Prognosis And Lifestyle (OPAL) Study, a national prospective cohort of adults with newly-diagnosed epithelial ovarian cancer. At 3-monthly questionnaires we asked about exercise and sitting time in the past week, and treatment-related side-effects. Details about treatment, toxicities, progression and death were abstracted from medical records. We used linear, logistic and Cox regression, respectively, to assess associations between both exercise and sitting time, and chemotherapy side-effects and completion (≥85% relative dose intensity) and survival., Results: 503 eligible participants were included in one or more analyses. Patients participating in higher-intensity exercise (≥30 min of moderate-vigorous exercise/week; 24%) reported significantly better Functional Assessment of Chronic Illness/Cancer Therapy (FACIT)-Fatigue (32.2 vs. 26.7) and FACT-Trial Outcome Index (69.4 vs. 61.7) scores, and were less likely to have clinician-reported moderate-severe neurotoxicity (odds ratio [OR]:0.50; 95% confidence interval [95%CI]:0.29-0.88), than minimal exercisers (<30 min moderate-vigorous exercise/week & <120 min walking/week; 52%). Participating in higher-intensity exercise was also possibly associated with greater chemotherapy completion (OR:1.70; 95%CI:0.90-3.20), particularly for paclitaxel. Sitting time was not associated with chemotherapy completion. For patients with advanced disease who underwent cytoreduction and received first-line carboplatin and paclitaxel, there was a suggestion higher-intensity exercise during chemotherapy may improve survival (HR:0.68; 95%CI:0.47-1.01)., Conclusions: Patients with ovarian cancer who carry out moderate-vigorous exercise during chemotherapy have fewer side-effects and potentially better completion of planned chemotherapy and overall survival., Competing Interests: Declaration of competing interest A DeFazio, PM Webb and ML Friedlander have received grant funding from AstraZeneca for an unrelated study of ovarian cancer. Outside of the submitted work PM Webb received a speaker's fee from AstraZeneca, A DeFazio's institution received honoraria from AstraZeneca and ML Friedlander received consulting/speakers fees from AstraZeneca, Novartis GSK and MSD as well as institutional research grants from AstraZeneca, Novartis and Beigene. All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Readily apparent cyclin E1 expression occurs in 50% of HGSOC, but only half are linked to 19q12 locus amplification. The amplified/cyclin E1 hi subset has intact BRCA1/2, unfavorable outcome, and is potentially therapeutically targetable. We studied whether non-amplified/cyclin E1 hi HGSOC has similar characteristics. We also assessed the expression of cyclin E1 degradation-associated proteins, FBXW7 and USP28, as potential drivers of high cyclin E1 expression in both subsets., Methods: 262 HGSOC cases were analyzed by in situ hybridization for 19q12 locus amplification and immunohistochemistry for cyclin E1, URI1 (another protein encoded by the 19q12 locus), FBXW7 and USP28 expression. Tumors were classified by 19q12 amplification status and correlated to cyclin E1 and URI1 expression, BRCA1/2 germline mutation, FBXW7 and USP28 expression, and clinical outcomes. Additionally, we assessed the relative genomic instability of amplified/cyclin E1 hi and non-amplified/cyclin E1 hi groups of HGSOC datasets from The Cancer Genome Atlas., Results: Of the 82 cyclin E1 hi cases, 43 (52%) were amplified and 39 (48%) were non-amplified. Unlike amplified tumors, non-amplified/cyclin E1 hi tumor status was not mutually exclusive with gBRCA1/2 mutation. The non-amplified/cyclin E1 hi group had significantly increased USP28, while the amplified/cyclin E1 hi cancers had significantly lower FBXW7 expression consistent with a role for both in stabilizing cyclin E1. Notably, only the amplified/cyclin E1 hi subset was associated with genomic instability and had a worse outcome than non-amplified/cyclin E1 hi group., Conclusions: Amplified/cyclin E1 hi and non-amplified/cyclin E1 hi tumors have different pathological and biological characteristics and clinical outcomes indicating that they are separate subsets of cyclin E1 hi HGSOC., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: Obesity is an increasing health problem that is reported to influence chemotherapy dosing. The extent to which this occurs and whether this affects outcomes in ovarian cancer was unclear. To describe chemotherapy dosing practices in normal, overweight and obese patients treated for FIGO Stage III/IV serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS). To evaluate the relationship between body mass index (BMI), dose intensity of chemotherapy received, overall survival (OS) and progression free survival (PFS)., Methods: Patient characteristics including age, height, weight, FIGO stage, serum creatinine, primary chemotherapy received and outcome data were extracted from medical records and entered into the AOCS database. Outcomes were analysed against BMI and relative dose intensity (RDI) received, based on calculations derived from a standard regimen (carboplatin AUC 5 and paclitaxel 175mg/m(2))., Results: 333 women were included in the analysis. 27% were overweight and 21% were obese. In cycle 1 66% of obese patients received carboplatin doses more than 5% below their optimal calculated dose, and 32% received sub-optimal paclitaxel doses, compared to 25% and 13% of normal weight patients respectively. Obese women were more likely to have received <85% RDI for carboplatin compared to normal weight women (p<0.001). BMI group and RDI of carboplatin and paclitaxel were not predictors of OS. Women who received less than 85% RDI for carboplatin had a worse PFS (univariate analysis, median PFS 11 versus 15 months; p=0.04). There was no significant association between RDI and OS or PFS in multivariate analysis., Conclusions: Obesity is common in ovarian cancer patients, and commonly results in lower chemotherapy dosing than recommended. Analysis of chemotherapy dosing from this study suggests that reduced dose intensity of carboplatin, which was more common in obese women, may impact on PFS in patients with advanced serous ovarian cancer., (Copyright © 2014 Elsevier Inc. All rights reserved.)