Recreational physical inactivity and mortality in women with invasive epithelial ovarian cancer: evidence from the Ovarian Cancer Association Consortium

Background: Little is known about modifiable behaviours that may be associated with epithelial ovarian cancer (EOC) survival. We conducted a pooled analysis of 12 studies from the Ovarian Cancer Association Consortium to investigate the association between pre-diagnostic physical inactivity and mortality. Methods: Participants included 6806 women with a primary diagnosis of invasive EOC. In accordance with the Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. We utilised Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) representing the associations of inactivity with mortality censored at 5 years. Results: In multivariate analysis, inactive women had significantly higher mortality risks, with (HR=1.34, 95% CI: 1.18–1.52) and without (HR=1.22, 95% CI: 1.12–1.33) further adjustment for residual disease, respectively. Conclusion: In this large pooled analysis, lack of recreational physical activity was associated with increased mortality among women with invasive EOC

Prognostic impact of adjuvant chemotherapy treatment intensity for ovarian cancer.

OBJECTIVE:We aimed to investigate the prognostic impact of duration of first-line chemotherapy administration in patients with epithelial ovarian cancer (EOC). METHODS:Chemotherapy records were abstracted from the electronic medical record. Patients with on-time completion (105 days) were compared to patients finishing early (4 weeks. For 222 women with stage IIIC/IV, stage-stratified estimates of progression-free survival (PFS) and overall survival (OS) were compared. A delay sub-study was performed with outliers removed. Each week of delay was correlated with the change in PFS and OS to identify time points associated with change in outcome. RESULTS:Most women had on-time completion of chemotherapy (23.6%) or a treatment delay of ≤4 weeks (21.8%); 21.6% of women experienced a delay longer than 4 weeks. R0 resection at initial debulking (OR = 1.99, 95%CI: 1.18-3.36, p = 0.010) and RECIST complete response (OR = 4.88, 95%CI: 2.47-10.63, p1 month delay had decreased median survival of 18.1 months (14.7-24.9 months), while women with short intervals survived 35.0 months (95%CI: 21.8-49.8 months). Short-term delays lead to progressively decreasing OS. This was significantly different from the on-schedule survival estimate after 6 weeks of delay. CONCLUSIONS:On-time completion of chemotherapy correlates with increased survival and higher complete response rates. Increasing delays in chemotherapy completion were associated with decreased survival

Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian cancer

WOS: 000404945600010PubMed ID: 28495239Objective. The presence of miliary disease during initial ovarian cancer debulking may reflect a distinct mode of peritoneal spread independent from size-based tumor staging and may explain variation in response to treatment and survival outcomes. To infer the prevalence, presentation and clinical implications of miliary disease we reviewed existing surgical records. Methods. Reports were available for 1008 primary debulking surgeries for ovarian, primary peritoneal or fallopian tube cancer between 2001 and 2015 (685 reports from 2005 to 2015). Clinical outcome data was available for 938 patients. We analyzed a high-stage sub-cohort for survival (N = 436). Results. Most records were evaluable for miliary disease (761/938); for these, the miliary phenotype was highly prevalent (249/761, 32.7%) and often accompanied by ascites (185/249, 74%). While optimal debulking rates were unaffected by miliary disease, total resection (RO) rates were poorer. Liver, stomach, spleen or bladder appeared to be sporadically involved while the omentum, mesentery, bowel, peritoneum and diaphragm were affected simultaneously (Spearman rho > 0.5). Overall, miliary disease was associated with worse progression free survival, overall survival, and time from relapse to death independent of stage. Survival effects were particularly strong for Stage IV disease where median overall survival varied by over 30 months (log-rank p = 0.002). Conclusions. Miliary disease is an identifiable surgical phenotype reflecting a distinct clinical trajectory that adds prognostic information to standard disease burden-based staging. These findings should permit further retrospective investigation in a wider cohort and prompt the consideration of prospective structured operative reporting standards and treatment strategies. (C) 2017 The Authors. Published by Elsevier Inc.National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [K01LM012100, T32CA108456, P30CA016056]; RPCI-UPCI Ovarian Cancer SPORE [P50CA159981-01A1]; Roswell Park Alliance Foundation; Roswell Park Cancer InstituteThis work was supported by the National Institutes of Health (K01LM012100, T32CA108456, P30CA016056), RPCI-UPCI Ovarian Cancer SPORE (P50CA159981-01A1) and the Roswell Park Alliance Foundation, Roswell Park Cancer Institute. The authors report no conflicts of interest

Paternal lineage early onset hereditary ovarian cancers: A Familial Ovarian Cancer Registry study

<div><p>Given prior evidence that an affected woman conveys a higher risk of ovarian cancer to her sister than to her mother, we hypothesized that there exists an X-linked variant evidenced by transmission to a woman from her paternal grandmother via her father. We ascertained 3,499 grandmother/granddaughter pairs from the Familial Ovarian Cancer Registry at the Roswell Park Cancer Institute observing 892 informative pairs with 157 affected granddaughters. We performed germline X-chromosome exome sequencing on 186 women with ovarian cancer from the registry. The rate of cancers was 28.4% in paternal grandmother/granddaughter pairs and 13.9% in maternal pairs consistent with an X-linked dominant model (Chi-square test X2 = 0.02, p = 0.89) and inconsistent with an autosomal dominant model (X2 = 20.4, p<0.001). Paternal grandmother cases had an earlier age-of-onset versus maternal cases (hazard ratio HR = 1.59, 95%CI: 1.12–2.25) independent of BRCA1/2 status. Reinforcing the X-linked hypothesis, we observed an association between prostate cancer in men and ovarian cancer in his mother and daughters (odds ratio, OR = 2.34, p = 0.034). Unaffected mothers with affected daughters produced significantly more daughters than sons (ratio = 1.96, p<0.005). We performed exome sequencing in reported BRCA negative cases from the registry. Considering age-of-onset, one missense variant (rs176026 in <i>MAGEC3</i>) reached chromosome-wide significance (Hazard ratio HR = 2.85, 95%CI: 1.75–4.65) advancing the age of onset by 6.7 years. In addition to the well-known contribution of BRCA, we demonstrate that a genetic locus on the X-chromosome contributes to ovarian cancer risk. An X-linked pattern of inheritance has implications for genetic risk stratification. Women with an affected paternal grandmother and sisters of affected women are at increased risk for ovarian cancer. Further work is required to validate this variant and to characterize carrier families.</p></div

Age-of-onset by genotype and familial pattern.

<p>Age-of-onset by genotype and familial pattern.</p

Representative registry pedigrees.

<p>Ovarian cancers are represented by teal circles, breast cancers by pink circles, prostate cancers by blue squares and prophylactic oophorectomies by grey circles. The earliest of age of onset, prophylaxis, death or last follow up is indiciated below individuals as well as oophorectomies (ooph.) and one heterozygous variant carrier (A/G).</p