Association of Somatic Mutations of ADAMTS Genes With Chemotherapy Sensitivity and Survival in High-Grade Serous Ovarian Carcinoma.
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ABSTRACT:
SUBMITTER: Liu Y
PROVIDER: S-EPMC4608536 | biostudies-literature | 2015 Jul
REPOSITORIES: biostudies-literature
Publications
Association of Somatic Mutations of ADAMTS Genes With Chemotherapy Sensitivity and Survival in High-Grade Serous Ovarian Carcinoma.
Liu Yuexin Y Yasukawa Maya M Chen Kexin K Hu Limei L Broaddus Russell R RR Ding Li L Mardis Elaine R ER Spellman Paul P Levine Douglas A DA Mills Gordon B GB Shmulevich Ilya I Sood Anil K AK Zhang Wei W
JAMA oncology 20150701 4
<h4>Importance</h4>Chemotherapy response in the majority of patients with ovarian cancer remains unpredictable.<h4>Objective</h4>To identify novel molecular markers for predicting chemotherapy response in patients with ovarian cancer.<h4>Design, setting, and participants</h4>Observational study of genomics and clinical data of high-grade serous ovarian cancer cases with genomic and clinical data made public between 2009 and 2014 via the Cancer Genome Atlas project.<h4>Main outcomes and measures< ...[more]
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Project description:ObjectiveTo examine clinicopathologic variables associated with survival among women with low-grade (grade 1) serous ovarian carcinoma enrolled in a phase III study.MethodsThis was an ancillary data analysis of Gynecologic Oncology Group protocol 182, a phase III study of women with stage III-IV epithelial ovarian carcinoma treated with carboplatin and paclitaxel compared with triplet or sequential doublet regimens. Women with grade 1 serous carcinoma (a surrogate for low-grade serous disease) were included in the analysis.ResultsAmong the 3,686 enrolled participants, 189 had grade 1 disease. The median age was 56.5 years and 87.3% had stage III disease. The median follow-up time was 47.1 months. Stratification according to residual disease after primary surgery was microscopic residual in 24.9%, 0.1-1.0 cm of residual in 51.3%, and more than 1.0 cm of residual in 23.8%. On multivariate analysis, only residual disease status (P=.006) was significantly associated with survival. Patients with microscopic residual had a significantly longer median progression-free (33.2 months) and overall survival (96.9 months) compared with those with residual 0.1-1.0 cm (14.7 months and 44.5 months, respectively) and more than 1.0 cm of residual disease (14.1 months and 42.0 months, respectively; progression-free and overall survival, P<.001). After adjustment for other variables, patients with low-grade serous carcinoma with measurable residual disease had a similar adjusted hazard ratio for death (2.12; P=.002) as their high-grade serous carcinoma counterparts with measurable disease (2.31; P<.001).ConclusionsSurgical cytoreduction to microscopic residual was associated with improved progression-free and overall survival in women with advanced-stage low-grade serous ovarian carcinoma.Clinical trial registrationClinicalTrials.gov, www.clinicaltrials.gov, NCT00011986.Level of evidenceII.
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