BACKGROUND: Adjuvant chemotherapy (AC) is frequently considered in patients with stage II colon cancer who are considered to be at high risk. However, to the authors' knowledge, the survival benefits associated with AC in these patients remain largely unproven. In the current study, the authors sought to examine the use of AC in patients with AJCC stage II colon cancer and to compare the impact of AC on outcomes in patients with high-risk versus low-risk disease in a population-based setting. METHODS: Patients with stage II colon cancer who were evaluated at 1 of 5 regional cancer centers in British Columbia from 1999 to 2008 were analyzed. Kaplan-Meier and Cox regression methods were used to correlate high-risk versus low-risk status and receipt of AC with recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). RESULTS: A total of 1697 patients were identified: 1286 (76%) with high-risk and 411 (24%) with low-risk disease, among whom 373 (29%) and 51 (12%),respectively, received AC. Individuals with high-risk disease treated with AC were younger (median age, 62 years vs 72 years; P<.001) and had better Eastern Cooperative Oncology Group performance status (0/1: 47% vs 33%; P 5.001). . CONCLUSIONS: In this population-based analysis, AC was associated with an OS advantage in high-risk patients, most likely due to patient selection. RFS, DSS, and OS benefits were mainly observed in patients with T4 disease, suggesting a limited role for AC in patients deemed to be high risk by non-T4 features. Cancer 2015;121:527-34.
Recent studies have identified mutation signatures of homologous recombination deficiency (HRD) in over 20% of breast cancers, as well as pancreatic, ovarian, and gastric cancers. There is an urgent need to understand the clinical implications of HRD signatures. Whereas mutations confer sensitivity to platinum-based chemotherapies, it is not yet clear whether mutation signatures can independently predict platinum response. In this observational study, we sequenced tumor whole genomes (100× depth) and matched normals (60×) of 93 advanced-stage breast cancers (33 platinum-treated). We computed a published metric called HRDetect, independently trained to predict status, and assessed its capacity to predict outcomes on platinum-based chemotherapies. Clinical endpoints were overall survival (OS), total duration on platinum-based therapy (TDT), and radiographic evidence of clinical improvement (CI). HRDetect predicted status with an area under the curve (AUC) of 0.94 and optimal threshold of 0.7. Elevated HRDetect was also significantly associated with CI on platinum-based therapy (AUC = 0.89; = 0.006) with the same optimal threshold, even after adjusting for mutation status and treatment timing. HRDetect scores over 0.7 were associated with a 3-month extended median TDT ( = 0.0003) and 1.3-year extended median OS ( = 0.04). Our findings not only independently validate HRDetect, but also provide the first evidence of its association with platinum response in advanced breast cancer. We demonstrate that HRD mutation signatures may offer clinically relevant information independently of mutation status and hope this work will guide the development of clinical trials..
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.