Ou, Fang‐Shu

Abstract Background: Higher intake of long-chain ω-3 polyunsaturated fatty acids and nuts, rich plant sources of unsaturated fats, after colon cancer diagnosis are associated with improved survival. It is not known whether the amount or the distribution of other types of fat is associated with survival after colon cancer. Methods: We prospectively examined postdiagnostic total, animal, and vegetable fats, as well as the saturated, monounsaturated, polyunsaturated, and trans fat in relation to disease-free survival among 1,011 patients with stage III colon cancer. Patients were enrolled between 1999 and 2001 at the onset of adjuvant chemotherapy and followed for recurrence or death through 2009. Results: During median follow-up of 7 years, we observed 305 deaths and 81 recurrences (total events: 386). Neither total nor any specific type of dietary fat examined was statistically significantly associated with risk of cancer recurrence or death from any cause (disease-free survival) after stage III colon cancer. Conclusions: The amount and type (animal, vegetable, saturated, monounsaturated, polyunsaturated, and trans) of dietary fat consumed after colon cancer does not appear to be substantially associated with risk of recurrence or survival. Impact: Neither total nor major types (animal, vegetable, saturated, monounsaturated, polyunsaturated, and trans) of dietary fat consumed after colon cancer was associated with cancer recurrence or survival. Cancer Epidemiol Biomarkers Prev; 27(10); 1227–30. ©2018 AACR.

Purpose Overall survival (OS) is the definitive and best-established primary efficacy end point to evaluate diffuse large B-cell lymphoma (DLBCL) therapies, but it requires prolonged follow-up. An earlier end point assessed post-treatment would expedite clinical trial conduct and accelerate patient access to effective new therapies. Our objective was to formally evaluate progression-free survival (PFS) and PFS at 24 months (PFS24) as surrogate end points for OS in first-line DLBCL. Patients and Methods Individual patient data were analyzed from 7,507 patients from 13 multicenter randomized controlled trials of active treatment in previously untreated DLBCL, published after 2002, with sufficient PFS data to predict treatment effects on OS. Trial-level surrogacy examining the correlation of treatment effect estimates of PFS/PFS24 and OS was evaluated using both linear regression ( R2WLS) and Copula bivariable ( R2Copula) models. Prespecified criteria for surrogacy required either R2WLS or R2Copula ≥ 0.80 and neither < 0.7, with lower-bound 95% CI > 0.60. Results Trial-level surrogacy for PFS was strong ( R2WLS = 0.83; R2Copula = 0.85) and met the predefined criteria for surrogacy. At the patient level, PFS strongly correlated with OS. The surrogate threshold effect had a hazard ratio of 0.89. Surrogacy was consistent across comparisons with or without rituximab and with rituximab maintenance trials. Trial-level surrogacy for PFS24 was relatively strong ( R2WLS = 0.77; R2Copula = 0.78) but did not meet prespecified criteria. At the patient level, PFS24 significantly correlated with OS. The surrogate threshold effect had an odds ratio of 1.51. Conclusion This large pooled analysis of individual patient data supports PFS as a surrogate end point for OS in future randomized controlled trials evaluating chemoimmunotherapy in DLBCL. Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before OS results are mature.

757 Background: Progression free survival (PFS) and overall survival (OS) appear to differ across trials, even when pts receive the same regimen (REG). This analysis aimed to benchmark the clinical outcomes in the 2nd line treatment of metastatic colorectal cancer (mCRC). Methods: Individual patient (pt) data was available on 6,462 pts with mCRC enrolled in 7 2ndline clinical trials (8 REGs) in the ARCAD database. Regimens used in at least two trials included FOLFIRI +/- an EGFR inhibitor (EGFRi), FOLFOX +/- a VEGF inhibitor (VEGFi), and irinotecan (IRI). Descriptive statistics were used to describe pt demographics. Multivariable Cox models were used to assess differences (DIFFs) in PFS and OS, while p-value <0.05 were considered statistically significant (SS). Results: 500-1400 pts received each REG (see Table). Median OS and PFS differed by 0.2 to 4.6 months (mo) and 0.8 to 2.5 mo across trials within the same REG. These DIFFs were SS except for PFS in REGs containing FOLFIRI +/- EGFRi. After multivariable adjustment, all DIFFs in OS were attenuated and non-significant. DIFFs in PFS attenuated for most REGs but remained SS for FOLFOX and IRI. Conclusions: After multivariable adjustment, there were no SS DIFFs in outcomes across trials within the same REG, with the exception of PFS in FOLFOX and IRI. The initial observed DIFFs in outcomes could be due to confounding factors and the remaining SS DIFFs in PFS in FOLFOX and IRI may be due to variation in definition of progression across trials. Therefore, caution is warranted when using historical data to design future trials.[Table: see text]

Background— Temporal trends and contemporary data characterizing the impact of patient age on in-hospital outcomes of percutaneous coronary interventions are lacking. We sought to determine the importance of age by assessing the in-hospital mortality of stratified age groups in the National Cardiovascular Data Registry. Methods and Results— In-hospital mortality after percutaneous coronary intervention on 1 410 069 patients was age stratified into 4 groups—group 1 (age <40, n=25 679), group 2 (40 to 59, n=496 204), group 3 (60 to 79, n=732 574), and group 4 (≥80, n=155 612)—admitted from January 1, 2001, to December 31, 2006. Overall in-hospital mortality was 1.22%; in-hospital mortality was 0.60%, 0.59%, 1.26%, and 3.16% in groups 1 to 4, respectively, P <0.0001. Overall temporal improvement per calendar year in the adjusted in-hospital mortality after percutaneous coronary intervention was noted in most groups; however, this finding was significant only in the 2 older age groups, group 3 (odds ratio, 0.94; 95% CI, 0.92 to 0.96) and group 4 (odds ratio, 0.95; 95% CI, 0.92 to 0.97). The absolute mortality reduction was greatest in the most elderly group, those over the age of 80 years. Conclusions— In-hospital mortality after percutaneous coronary intervention has fallen for all age groups over the past 6 years. However, the largest absolute reduction was seen among patients 80 years of age or older.