Brown, Justin C.

PURPOSECurrent tools in predicting survival outcomes for patients with colon cancer predominantly rely on clinical and pathologic characteristics, but increasing evidence suggests that diet and lifestyle habits are associated with patient outcomes and should be considered to enhance model accuracy.METHODSUsing an adjuvant chemotherapy trial for stage III colon cancer (CALGB 89803), we developed prediction models of disease-free survival (DFS) and overall survival by additionally incorporating self-reported nine diet and lifestyle factors. Both models were assessed by multivariable Cox proportional hazards regression and externally validated using another trial for stage III colon cancer (CALGB/SWOG 80702), and visual nomograms of prediction models were constructed accordingly. We also proposed three hypothetical scenarios for patients with (1) good-risk, (2) average-risk, and (3) poor-risk clinical and pathologic features, and estimated their predictive survival by considering clinical and pathologic features with or without adding self-reported diet and lifestyle factors.RESULTSAmong 1,024 patients (median age 60.0 years, 43.8% female), we observed 394 DFS events and 311 deaths after median follow-up of 7.3 years. Adding self-reported diet and lifestyle factors to clinical and pathologic characteristics meaningfully improved performance of prediction models (c-index from 0.64 [95% CI, 0.62 to 0.67] to 0.69 [95% CI, 0.67 to 0.72] for DFS, and from 0.67 [95% CI, 0.64 to 0.70] to 0.71 [95% CI, 0.69 to 0.75] for overall survival). External validation also indicated good performance of discrimination and calibration. Adding most self-reported favorable diet and lifestyle exposures to multivariate modeling improved 5-year DFS of all patients and by 6.3% for good-risk, 21.4% for average-risk, and 42.6% for poor-risk clinical and pathologic features.CONCLUSIONDiet and lifestyle factors further inform current recurrence and survival prediction models for patients with stage III colon cancer.

AbstractBackgroundEnergy balance-related biomarkers are associated with risk and prognosis of various malignancies. Their relationship to survival in metastatic colorectal cancer (mCRC) requires further study.MethodsBaseline plasma insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGFBP-7, C-peptide, and adiponectin were measured at time of trial registration in a prospective cohort of patients with mCRC participating in a National Cancer Institute–sponsored trial of first-line systemic therapy. We used Cox proportional hazards regression to adjust for confounders and examine associations of each biomarker with overall survival (OS) and progression-free survival (PFS). P values are 2-sided.ResultsMedian follow-up for 1086 patients was 6.2 years. Compared with patients in the lowest IGFBP-3 quintile, patients in the highest IGFBP-3 quintile experienced an adjusted hazard ratio (HR) for OS of 0.57 (95% confidence interval [CI] = 0.42 to 0.78; Pnonlinearity < .001) and for PFS of 0.61 (95% CI = 0.45 to 0.82; Ptrend = .003). Compared with patients in the lowest IGFBP-7 quintile, patients in the highest IGFBP-7 quintile experienced an adjusted hazard ratio for OS of 1.60 (95% CI = 1.30 to 1.97; Ptrend < .001) and for PFS of 1.38 (95% CI = 1.13 to 1.69; Ptrend < .001). Plasma C-peptide and IGF-1 were not associated with patient outcomes. Adiponectin was not associated with OS; there was a nonlinear U-shaped association between adiponectin and PFS (Pnonlinearity = .03).ConclusionsAmong patients with mCRC, high plasma IGFBP-3 and low IGFBP-7 were associated with longer OS and PFS. Extreme levels of adiponectin were associated with shorter PFS. These findings suggest potential avenues for prognostic and therapeutic innovation.

This article presents a clinical screening and referral framework to enable health care professionals to guide individuals with cancer to safe and effective exercise programs.

Abstract Background Diabetes is a prognostic factor for some malignancies, but its association with outcome in patients with advanced or metastatic colorectal cancer (CRC) is less clear. Methods This cohort study was nested within a randomized trial of first-line chemotherapy and bevacizumab and/or cetuximab for advanced or metastatic CRC. Patients were enrolled at 508 community and academic centers throughout the National Clinical Trials Network. The primary exposure was physician-documented diabetes at the time of enrollment. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS) and adverse events. Tests of statistical significance were two-sided. Results Among 2326 patients, 378 (16.3%) had diabetes. The median follow-up time was 6.0 years. We observed 1973 OS events and 2173 PFS events. The median time to an OS event was 22.7 months among those with diabetes and 27.1 months among those without diabetes (HR = 1.27, 95% CI = 1.13 to 1.44; P < .001). The median time to a PFS event was 9.7 months among those with diabetes and 10.8 months among those without diabetes (HR = 1.16, 95% CI = 1.03 to 1.30; P = .02). Patients with diabetes were more likely to experience no less than grade 3 hypertension (8.1% vs 4.4%; P = .054) but were not more likely to experience other adverse events, including neuropathy. Conclusions Diabetes is associated with an increased risk of mortality and tumor progression in patients with advanced or metastatic CRC. Patients with diabetes tolerate first-line treatment with chemotherapy and monoclonal antibodies similarly to patients without diabetes.

114 Background: We evaluated baseline differences in arm tissue composition (fat mass, lean mass, bone mineral content [BMC] and bone mineral density [BMD]) between the affected and unaffected arms in women with breast cancer-related lymphedema (BRCL). We compared changes in arm tissue composition and self-reported lymphedema symptoms after one-year of weight-lifting vs. usual-care. Methods: We utilized data from the PAL trial that included 141 women with BRCL. Arm tissue composition was quantified using dual-energy x-ray absorptiometry. The severity of lymphedema was quantified using self-report survey. Weight-lifting was performed at community fitness facilities. Results: At baseline, the affected arm had more fat (D= 89.7±21.0g; P < 0.001) and lean mass (D= 149.1±25.3g; P < 0.001), but less BMC (D= -3.2±0.9g; P < 0.001) than the unaffected arm. No difference was observed in BMD. After 12-months of weight-lifting, composition of the affected arm was improved: lean mass (71.2±27.9g; P = 0.01) and BMD (0.01±0.01g; P = 0.02) increased, arm fat percentage decreased (0.01±0.01; P = 0.003). No changes observed in fat mass and BMC. Baseline body mass index and BCRL grade modified the relationship between weight-lifting and tissue composition changes. Increases in lean mass were associated with less severe BCRL symptoms. With every one-percent decrease in arm fat percentage, affected limb volume reduced 13.81mL. Conclusions: Among women with BRCL, affected and unaffected arms differ in tissue composition. These differences may be improved with weight-lifting. Changes in arm tissue composition correlate with improved BCRL symptoms. Investigating the combined effects of exercise and weight-loss on arm tissue composition and BCRL symptoms may provide additional insight to the benefits of lifestyle modification on lymphedema biology. Clinical trial information: NCT00194363.

Introduction. High BMI is a risk factor for upper body breast cancer-related lymphedema (BCRL) onset. Black cancer survivors are more likely to have high BMI than White cancer survivors. While observational analyses suggest up to 2.2 times increased risk of BCRL onset for Black breast cancer survivors, no studies have explored race or other social factors that may affect BCRL severity, operationalized by interlimb volume difference (ILD).Materials and Methods. ILD was measured by perometry for 296 overweight (25 > BMI < 50) Black (n=102) or White (n=194) breast cancer survivors (>6 months from treatment) in the WISER Survivor trial. Multivariable linear regression examined associations between social and physical factors and ILD.Results. Neither Black race (−0.26,p=0.89) nor BMI (0.22,p=0.10) was associated with ILD. Attending college (−4.89,p=0.03) was the strongest factor associated with ILD, followed by having more lymph nodes removed (4.75,p=0.01), >25% BCRL care adherence (4.10,p=0.01), and years since treatment (0.55,p<0.001).Discussion. Neither race nor BMI was associated with ILD among overweight cancer survivors. Education, a proxy for resource level, was the strongest factor associated with greater ILD. Tailoring physical activity and weight loss interventions designed to address BCRL severity by resource rather than race should be considered.