ABSTRACT
OBJECTIVE: Homologous recombination (HR) is frequently impaired in sporadic high-grade serous ovarian carcinoma (sHGSOC) due to deficiencies in BRCA1/2 genes, a situation associated with hypersensitivity to platinum compounds. Alterations in other genes can also cause HR deficiency. Preclinical data show that RAP80 is an HR-pathway-related gene that influences BRCA1 activity. RAP80 has been reported to affect outcome in some solid neoplasms. This study investigates the role of RAP80 in sHGSOC survival. METHODS: mRNA expression of RAP80 was analyzed in tumor samples from 35 patients who postoperatively received standard platinum-based chemotherapy. The effects of RAP80 expression on progression-free survival (PFS) and overall survival (OS) were examined by means of Cox regressions. The clinical variables known to have prognostic value (FIGO stage, residual disease at surgery, and debulking surgery) were included as covariates in the analysis. BRCA1 was analyzed given the moderate correlations with RAP80. RESULTS: Median follow-up, PFS and OS were 61.3, 20.2 and 62.8 months, respectively. Low RAP80 expression levels were associated with shorter PFS (HR = 1.449, p = 0.007) and OS (HR = 1.331, p = 0.047). CONCLUSIONS: This is the first study to show a potential prognostic role of RAP80 expression in patients with HGSOC. The results suggest that HR deficiency due to low RAP80 expression is not associated with hypersensitivity to platinum compounds in sHGSOC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/genetics , Carrier Proteins/genetics , Cystadenocarcinoma, Serous/mortality , Nuclear Proteins/genetics , Ovarian Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/therapy , DNA-Binding Proteins , Female , Follow-Up Studies , Histone Chaperones , Humans , Middle Aged , Neoplasm Grading , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Survival RateABSTRACT
BACKGROUND: Chronic obstructive pulmonary disease (COPD) generates a high burden on health care, and hospital admissions represent a substantial proportion of the overall costs of the disease. Integrated care (IC) has shown efficacy to reduce hospitalisations in COPD patients at a pilot level. Deployment strategies for IC services require assessment of effectiveness at the health care system level. AIMS: The aim of this study was to explore the effectiveness of a community-based IC service in preventing hospitalisations and emergency department (ED) visits in stable frail COPD patients. METHODS: From April to December 2005, 155 frail community-dwelling COPD patients were randomly allocated either to IC (n=76, age 73 (8) years, forced expiratory volume during the first second, FEV1 41(19) % predicted) or usual care (n=84, age 75(9) years, FEV1 44 (20) % predicted) and followed up for 12 months. The IC intervention consisted of the following: (a) patient's empowerment for self-management; (b) an individualised care plan; (c) access to a call centre; and (d) coordination between the levels of care. Thereafter, hospital admissions, ED visits and mortality were monitored for 6 years. RESULTS: IC enhanced self-management (P=0.02), reduced anxiety-depression (P=0.001) and improved health-related quality of life (P=0.02). IC reduced both ED visits (P=0.02) and mortality (P=0.03) but not hospital admission. No differences between the two groups were seen after 6 years. CONCLUSION: The intervention improved clinical outcomes including survival and decreased the ED visits, but it did not reduce hospital admissions. The study facilitated the identification of two key requirements for adoption of IC services in the community: appropriate risk stratification of patients, and preparation of the community-based work force.
