ABSTRACT
BACKGROUND AND AIMS: Left main (LM) coronary artery disease is associated with greater myocardial infarction-related mortality, however, coronary artery calcium (CAC) scoring does not account for disease location. We explored whether LM CAC predicts excess mortality in asymptomatic adults. METHODS: Cause-specific cardiovascular and all-cause mortality was studied in 28,147 asymptomatic patients with non-zero CAC scores in the CAC Consortium. Multivariate regression was performed to evaluate if the presence and burden of LM CAC predict mortality after adjustment for clinical risk factors and the Agatston CAC score. We further analyzed the per-unit hazard associated with LM CAC in comparison to CAC in other arteries. RESULTS: The study population had mean age of 58.3⯱â¯10 years and CAC score of 301⯱â¯631. LM CAC was present in 21.7% of the cases. During 312,398 patient-years of follow-up, 1,907 deaths were observed. LM CAC was associated with an increased burden of clinical risk factors and total CAC, and was independently predictive of increased hazard for all-cause (HR 1.2 [1.1, 1.3]) and cardiovascular disease death (HR 1.3 [1.1, 1.5]). The hazard for death increased proportionate to the percentage of CAC localized to the LM. On a per-100 Agatston unit basis, LM CAC was associated with a 6-9% incremental hazard for death beyond knowledge of CAC in other arteries. CONCLUSIONS: The presence and high burden of left main CAC are independently associated with a 20-30% greater hazard for cardiovascular and total mortality in asymptomatic adults, arguing that LM CAC should be routinely noted in CAC score reports when present.
Subject(s)
Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Coronary Artery Disease/complications , Vascular Calcification/complications , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk FactorsABSTRACT
PURPOSE: To determine whether pathologic colorectal tumor KRAS mutation status is correlated with progression-free survival (PFS) by imaging after selective internal radiation therapy with Yttrium-90 (SIRT Y90) for metastatic colorectal cancer in the liver (mCRC). MATERIALS AND METHODS: This was an IRB approved, HIPAA compliant retrospective cohort study. Consecutive patients with unresectable mCRC with documented KRAS mutation status treated at a single center from 2002 to 2013 with SIRT Y90 were investigated. Treatment response was compared between KRAS wild-type (wt) and mutant (mut) using an anatomic tumor response criteria based on RECIST 1.0. Kaplan-Meier estimation and Cox regression analysis were used to measure progression-free survival (PFS) and to assess independent prognostic factors for PFS. RESULTS: 82 of 186 patients met review criteria. 33 (40.2%) patients were identified as KRAS mut. PFS was longer in KRAS wt (median 166 days [95% CI 96-258 days]) vs. mut (median 91 days [95% CI 79-104 days], p = 0.002). KRAS mut patients were 1.48 times more likely to progress at first follow-up imaging than wt (95% CI 1.06-2.08, p = 0.024). Univariate analysis identified high pre-SIRT Y90 INR, KRAS wt, any use of anti-EGFR therapy, and post-SIRT Y90 chemotherapy as prognostic factors for longer PFS. In multivariate analysis, only KRAS wt was an independent prognostic factor for longer PFS (RR: 1.80 [95% CI 1.08-2.99], p = 0.024). CONCLUSION: Longer PFS is associated with KRAS wt vs. mut following SIRT Y90.
Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/radiotherapy , Liver Neoplasms/genetics , Liver Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Contrast Media , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Magnetic Resonance Imaging , Male , Middle Aged , Mutation , Prognosis , Proto-Oncogene Proteins p21(ras) , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome , Yttrium RadioisotopesABSTRACT
PURPOSE: To evaluate Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status as a prognostic factor for survival after yttrium-90 ((90)Y) radioembolization for colorectal cancer (CRC) liver metastases. MATERIALS AND METHODS: Consecutive patients with unresectable CRC liver metastases and documented KRAS mutation status who were treated with (90)Y radioembolization during the period 2007-2014 were investigated. Patient demographics, disease characteristics, therapy regimens, and overall survival (OS) from first (90)Y radioembolization were compared between patients with KRAS wild-type (wt) and mutant status. Kaplan-Meier estimation and Cox regression were used for survival analysis and to assess independent prognostic factors for OS. RESULTS: Of 186 patients, 104 underwent KRAS mutation analysis before (90)Y radioembolization, with 45 (43.3%) identified as mutant. The wt and mutant groups were similar in demographics, liver status, overall performance status, and tumor characteristics (all P > .05). Mean time from liver metastasis to (90)Y radioembolization was greater in patients with KRAS wt status (P = .033). A greater percentage of wt patients received anti-epidermal growth factor receptor therapies before (90)Y radioembolization (66.1% vs 8.9%; P < .001). Median OS from first (90)Y radioembolization was significantly greater in KRAS wt patients (9.5 mo vs 4.8 mo; P = .041). Univariate analysis identified Child-Pugh class, carcinoembryonic antigen (CEA), chemotherapy after (90)Y radioembolization, KRAS status, and treatment-induced toxicity as prognostic factors for OS. Multivariate Cox regression analysis demonstrated Child-Pugh class, CEA, and KRAS status to be independent prognostic factors for OS, even when correcting for the effect of chemotherapy after (90)Y radioembolization. CONCLUSIONS: Patients with CRC and KRAS wt may derive greater survival benefit from (90)Y radioembolization therapy than patients with KRAS mutant.
