Abstract Background Disparities in colon cancer outcomes have been reported across race and socioeconomic status, which may reflect, in part, access to care. We sought to assess the influences of race and median household income (MHI) on outcomes among colon cancer patients with similar access to care. Methods We conducted a prospective, observational study of 1206 stage III colon cancer patients enrolled in the CALGB 89803 randomized adjuvant chemotherapy trial. Race was self-reported by 1116 White and 90 Black patients at study enrollment; MHI was determined by matching 973 patients’ home zip codes with publicly available US Census 2000 data. Multivariate analyses were adjusted for baseline sociodemographic, clinical, dietary, and lifestyle factors. All statistical tests were 2-sided. Results Over a median follow-up of 7.7 years, the adjusted hazard ratios for Blacks (compared with Whites) were 0.94 (95% confidence interval [CI] = 0.66 to 1.35, P = .75) for disease-free survival, 0.91 (95% CI = 0.62 to 1.35, P = .65) for recurrence-free survival, and 1.07 (95% CI = 0.73 to 1.57, P = .73) for overall survival. Relative to patients in the highest MHI quartile, the adjusted hazard ratios for patients in the lowest quartile were 0.90 (95% CI = 0.67 to 1.19, Ptrend = .18) for disease-free survival, 0.89 (95% CI = 0.66 to 1.22, Ptrend = .14) for recurrence-free survival, and 0.87 (95% CI = 0.63 to 1.19, Ptrend = .23) for overall survival. Conclusions In this study of patients with similar health-care access, no statistically significant differences in outcomes were found by race or MHI. The substantial gaps in outcomes previously observed by race and MHI may not be rooted in differences in tumor biology but rather in access to quality care.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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Abstract Background: MR fingerprinting (MRF) is a novel imaging method proposed for the diagnosis of Multiple Sclerosis (MS). This study aims to determine if MR Fingerprinting (MRF) relaxometry can differentiate frontal normal appearing white matter (F-NAWM) and splenium in patients diagnosed with MS as compared to controls and to characterize the relaxometry of demyelinating plaques relative to the time of diagnosis.Methods: Three-dimensional (3D) MRF data were acquired on a 3.0T MRI system resulting in isotropic voxels (1x1x1mm3) and a total acquisition time of 4min 38s. Data were collected on 18 subjects paired with 18 controls. Regions of interested were drawn over MRF-derived T1 relaxometry maps encompassing selected MS lesions, F-NAWM and splenium. T1 and T2 relaxometry features from those segmented areas were used to classify MS lesions from F-NAWM and splenium with T-distributed stochastic neighbor embedding algorithms (T-SNE). Partial least squares discriminant analysis (PLS-DA) was performed to discriminate NAWM and Splenium in MS compared with controls. Results: Mean out-of-fold machine learning prediction accuracy for discriminant results between MS patients and controls for F-NAWM was 65% and approached 90% for the splenium. There was significant positive correlation between time since diagnosis and MS lesions mean T2 (p=0.015), minimum T1 (p=0.03) and negative correlation with splenium uniformity (p=0.04). Perfect discrimination (AUC=1) was achieved between selected features from MS lesions and F-NAWM.Conclusions: 3D-MRF has the ability to differentiate between MS and controls based on relaxometry properties from the F-NAWM and splenium. Whole brain coverage allows the assessment of quantitative properties within lesions that provide chronological assessment of the time from MS diagnosis.
Association of Diet Quality With Survival Among People With Metastatic Colorectal Cancer in the Cancer and Leukemia B and Southwest Oncology Group 80405 Trial
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.
TURBINE‐MRE: A 3D hybrid radial‐Cartesian EPI acquisition for MR elastography
PurposeTo develop a novel magnetic resonance elastography (MRE) acquisition using a hybrid radial EPI readout scheme (TURBINE), and to demonstrate its feasibility to obtain wave images and stiffness maps in a phantom and in vivo brain.MethodThe proposed 3D TURBINE‐MRE is based on a spoiled gradient‐echo MRE sequence with the EPI readout radially rotating about the phase‐encoding axis to sample a full 3D k‐space. A polyvinyl chloride phantom and 6 volunteers were scanned on a compact 3T GE scanner with a 32‐channel head coil at 80 Hz and 60 Hz external vibration, respectively. For comparison, a standard 2D, multislice, spin‐echo (SE) EPI‐MRE acquisition was also performed with the same motion encoding and resolution. The TURBINE‐MRE images were off‐line reconstructed with iterative SENSE algorithm. The regional ROI analysis was performed on the 6 volunteers, and the median stiffness values were compared between SE‐EPI‐MRE and TURBINE‐MRE.ResultsThe 3D wave‐field images and the generated stiffness maps were comparable between TURBINE‐MRE and standard SE‐EPI‐MRE for the phantom and the volunteers. The Bland–Altman plot showed no significant difference in the median regional stiffness values between the two methods. The stiffness measured with the 2 methods had a strong linear relationship with a Pearson correlation coefficient of 0.943.ConclusionWe demonstrated the feasibility of the new TURBINE‐MRE sequence for acquiring the desired 3D wave‐field data and stiffness maps in a phantom and in‐vivo brains. This pilot study encourages further exploration of TURBINE‐MRE for functional MRE, free‐breathing abdominal MRE, and cardiac MRE applications.
The Diet of Higher Insulinemic Potential Is Not Associated with Worse Survival in Patients with Stage III Colon Cancer (Alliance)
Abstract Background: Hyperinsulinemia is considered to be important in the development of colon cancer, but few studies have investigated the associations of hyperinsulinemia with colon cancer survival via dietary scores. Methods: Empirical dietary index for hyperinsulinemia (EDIH) was derived to assess the insulinemic potential of daily diets reflecting the long-term insulin exposure, with higher (more positive) scores indicating higher insulinemic diets. We prospectively estimated the HRs and 95% confidence intervals (CI) to investigate the association of EDIH with disease-free, recurrence-free, and overall survival among patients with stage III colon cancer (1999–2009) enrolled in a randomized adjuvant chemotherapy trial (CALGB 89803). Results: Of 1,024 patients (median follow-up: 7.3 years), 311 died, 350 had recurrences, and 394 had events for disease-free survival. Compared with patients in the lowest quintile of EDIH, the corresponding HRs of patients in the highest quintile for disease-free survival events, cancer recurrence, and overall mortality were 0.80 (95% CI, 0.56–1.15), 0.76 (95% CI, 0.51–1.11), and 0.77 (95% CI, 0.52–1.14). Conclusions: Higher EDIH was not associated with the risk of colon cancer recurrence or mortality in this population of patients with stage III colon cancer. Impact: EDIH, as a measure of dietary insulinemic potential, may be associated with colon cancer risk but not survival in patients with late-stage colon cancer.
A Preliminary Report of a Phase I Study of Zevalin® Using a Modified Treatment Regimen for Relapsed or Refractory CD20+ B-Cell Follicular or Transformed Non-Hodgkin’s Lymphoma (NHL).
Abstract Rationale Escalation of the Zevalin dose is limited by hematologic toxicity associated with marrow B-cells ± tumor cells. Rituxan treatment before Zevalin may reverse marrow infiltration with malignant and normal B-cells allowing an increase in the dosage of Zevalin with enhanced radiation delivery to lymphoma tumor sites. Since NHL is radiation sensitive, a substantial increase in radiation dose delivered should increase the ORR and CR rates. Design Low-grade follicular/transformed NHL patients receive 4 weekly dose of Rituxan (375mg/m2) before the corresponding Zevalin dose. Bilateral bone marrow biopsies/aspirates as well as biodistribution and dosimetry studies using 111In-2B8 were obtained before and after Rituxan. The trial was schedule to escalate the Zevalin dose (from 0.4 to 0.7 mCi/Kg). After completion of the 0.4 mCi/kg cohort an additional cohort of Rituxan sensitive patients using 0.3 mCi/kg was completed. Safety, pharmacokinetics, dosimetry and preliminary responses are presented. Results 5 pts were enrolled in the 0.4mCi/kg cohort and 6 pts in the 0.3 mCi/kg cohort. In the 10 Rituxan sensitive patients the plasma T ½ and the AUC of 111In-2B8 increased after the administration of Rituxan, with a reduction in the plasma clearance (T½ from 45 ± 4.5 hours to 54 ± 1.9 hours, AUC from 60 ± 10 hrs/μCi/ml to 85 ± 14 hrs/μCi/ml, and the clearance from 1.4 ± 0.3 ml/hrs/kg to 0.9 ± 0.2 ml/hrs/kg). Dosimetry showed no differences in the radiation-absorbed dose for major normal organs (whole body, liver, kidneys) except for the spleen in which a reduction was observed in 7 out of 10 patients. The radiation-absorbed dose to the marrow increased after Rituxan; from 3.6 rads/mCi to 4.28 rads/mCi. In the 0.4 mCi/kg cohort 3 out of 4 evaluable patients for response had a complete response, and 1 patient had progression documented at initial evaluation six weeks post-Zevalin (patient refractory to previous Rituxan). No non-hematological toxicity was observed. One patient had a grade 4 thrombocytopenia, 3 patients had grade 3 thrombocytopenia, and 4 patients had grade 4 WBC and ANC. All patients recovered within two weeks after the nadir. Two out of 6 patients treated in the 0.3 mCi/kg cohort had complete response by physical evaluation, and 4 had partial response; no early progressions were seen in this cohort. No non-hematological toxicity was observed. Only one patient had a grade 4 WBC and ANC, and 2 patients had a grade 3; 3 patients had grade 3 thrombocytopenia; all patients recovered. Conclusions The administration of high doses of Rituxan before Zevalin prolongs the circulation time of the radiolabeled antibody and increases the bone marrow exposure to the radioisotope. Additionally, the increased amount of the radiolabeled antibody available after Rituxan therapy with the prolonged circulation time may explain the unusual high complete response rate observed in this small number of patients despite extensive chemotherapy failures. Although this is very provocative data, the number of patients is very limited to generate a strong conclusion. The trial continues at this time.
Diabetes and Clinical Outcome in Patients With Metastatic Colorectal Cancer: CALGB 80405 (Alliance)
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.