RESUMO
OBJECTIVE: Elevated allostatic load (AL), an integrated, cumulative marker of physiologic damage due to socioenvironmental stress, is associated with increased mortality in patients with breast, lung, and other cancers. The relationship between allostatic load and mortality in ovarian cancer patients remains unknown. We examined the relationship between allostatic load and overall survival in ovarian cancer patients. METHODS: This cross-sectional study used data from 201 patients enrolled in a prospective observational ovarian cancer cohort study at a National Cancer Institute-designated Comprehensive Cancer Center from October 2012 through June 2022. All patients underwent debulking surgery and completed a full course of standard-of-care platinum-based chemotherapy. Follow-up was completed through January 2024. Allostatic load was calculated as a summary score by assigning one point to the worst sample quartile for each of ten biomarkers measured within 45 days before the ovarian cancer diagnosis. High allostatic load was defined as having an allostatic load in the top quartile of the summary score. A Cox proportional hazard model with robust variance tested the association between allostatic load and overall survival. RESULTS: There were no associations between allostatic load and ovarian cancer clinical characteristics. After accounting for demographic, clinical, and treatment factors, high allostatic load was associated with a significant increase in mortality (hazard ratio 2.17 [95%CI, 1.13-4.15]; P = 0.02). CONCLUSION: Higher allostatic load is associated with worse survival among ovarian cancer patients. Allostatic load could help identify patients at risk for poorer outcomes who may benefit from greater socioenvironmental support during treatment.
Assuntos
Alostase , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/fisiopatologia , Pessoa de Meia-Idade , Alostase/fisiologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Idoso , Estudos Transversais , Estudos Prospectivos , Adulto , Estudos de Coortes , Modelos de Riscos ProporcionaisRESUMO
Ovarian cancer continues to have a high mortality rate despite therapeutic advances. Traditionally, treatment has focused on surgery followed by systemic platinum- based chemotherapy. Unfortunately, most patients develop resistance to platinum agents, highlighting the need for targeted therapies. PARP inhibitors and anti-angiogenic agents, such as bevacizumab, have more recently changed upfront therapy. Unfortunately, other targeted therapies including immunotherapy have not seen the same success. Emerging therapeutic targets and modalities such as small molecule tyrosine kinase inhibitors, lipid metabolism targeting agents, gene therapy, ribosome targeted drugs as well as several other therapeutic classes have been and are currently under investigation. In this review, we discuss targeted therapies in high grade serous ovarian cancer from preclinical studies to phase III clinical trials.