Factors determining ultra-short-term survival and the commencement of active treatment in high-grade serous ovarian cancer: a case comparison study.

BACKGROUND: Despite improvements in median survival some patients with advanced ovarian cancer die within 100 days of diagnosis; the reasons for which remain poorly understood. Here we investigate if ultra short-term survival can be explained by patient characteristics or treatment pathways. METHODS: A nested case comparison study was used to examine differences between patients with high grade serous ovarian/fallopian tube cancer who died within 100 days (n = 28) compared to a comparison group of patients matched for histology and including any survival greater than 100 days (n = 134). RESULTS: Cases and comparison patients had similar ages, BMI, ACE-27, deprivation indices, and distribution of disease on CT. There were no significant delays in time to diagnosis or treatment (p = 0.68) between the groups. However, cases had lower serum albumin, haemoglobin and higher platelet counts than matched comparison patients (p < 0.0001) and a worse performance score (P = 0.006). CONCLUSION: Patients who die rapidly after a diagnosis of ovarian cancer are only slightly older and have similar pre treatment frailty compared to patients whose survival approaches the median. However they do appear to undergo greater physiological compromise as a result of their disease.

DNA damage repair in ovarian cancer: unlocking the heterogeneity.

Treatment for advanced ovarian cancer is rarely curative; three quarters of patients with advanced disease relapse and ultimately die with resistant disease. Improving patient outcomes will require the introduction of new treatments and better patient selection. Abrogations in the DNA damage response (DDR) may allow such stratifications.A defective DNA-damage response (DDR) is a defining hallmark of high grade serous ovarian cancer (HGSOC). Indeed, current evidence indicates that all HGSOCs harbour a defect in at least one major DDR pathway. However, defective DDR is not mediated through a single mechanism but rather results from a variety of (epi)genetic lesions affecting one or more of the five major DNA repair pathways. Understanding the relationship between these pathways and how these are abrogated will be necessary in order to facilitate appropriate selection of both existing and novel agents.Here we review the current understanding of the DDR with regard to ovarian, and particularly high grade serous, cancer, with reference to existing and emerging treatments as appropriate.