Advanced Imaging Modalities in Early Stage Breast Cancer: Preoperative Use in the United States Medicare Population

Background

Guidelines for breast cancer staging exist, but adherence remains unknown. This study evaluates patterns of imaging in early stage breast cancer usually reserved for advanced disease.

Methods

Surveillance Epidemiology, and End Results data linked to Medicare claims from 1992–2005 were reviewed for stage I/II breast cancer patients. Claims were searched for preoperative performance of computed tomography (CT), positron emission tomography (PET), bone scans, and brain magnetic resonance imaging (MRI) (“advanced imaging”).

Results

There were 67,874 stage I/II breast cancer patients; 18.8 % (n = 12,740) had preoperative advanced imaging. The proportion of patients having CT scans, PET scans, and brain MRI increased from 5.7 % to 12.4 % (P < 0.0001), 0.8 % to 3.4 % (P < 0.0001) and 0.2 % to 1.1 % (P = 0.008), respectively, from 1992 to 2005. Bone scans declined from 20.1 % to 10.7 % (P < 0.0001). “Breast cancer” (174.x) was the only diagnosis code associated with 62.1 % of PET scans, 37.7 % of bone scans, 24.2 % of CT, and 5.1 % of brain MRI. One or more symptoms or metastatic site was suggested for 19.6 % of bone scans, 13.0 % of CT, 13.0 % of PET, and 6.2 % of brain MRI. Factors associated (P < 0.05) with use of all modalities were urban setting, breast MRI and ultrasound. Breast MRI was the strongest predictor (P < 0.0001) of bone scan (odds ratio [OR] 1.63, 95 % confidence interval [CI] 1.44–1.86), Brain MRI (OR 1.74, 95 % CI 1.15–2.63), CT (OR 2.42, 95 % CI 2.12–2.76), and PET (OR 5.71, 95 % CI 4.52–7.22).

Conclusions

Aside from bone scans, performance of advanced imaging is increasing in early stage Medicare breast cancer patients, with limited rationale provided by coded diagnoses. In light of existing guidelines and increasing scrutiny about health care costs, greater reinforcement of current indications is warranted.     

Considering pharmacy workflow in the context of Australian community pharmacy: A pilot time and motion study

Background

Given time pressures on primary care physicians, utilising pharmacists for chronic disease management is of great interest. However, limited data are available on the current workflow in community pharmacies to guide these discussions.

Use of a linearization approximation facilitating stochastic model building

The objective of this work was to facilitate the development of nonlinear mixed effects models by establishing a diagnostic method for evaluation of stochastic model components. The random effects investigated were between subject, between occasion and residual variability. The method was based on a first-order conditional estimates linear approximation and evaluated on three real datasets with previously developed population pharmacokinetic models. The results were assessed based on the agreement in difference in objective function value between a basic model and extended models for the standard nonlinear and linearized approach respectively. The linearization was found to accurately identify significant extensions of the model’s stochastic components with notably decreased runtimes as compared to the standard nonlinear analysis. The observed gain in runtimes varied between four to more than 50-fold and the largest gains were seen for models with originally long runtimes. This method may be especially useful as a screening tool to detect correlations between random effects since it substantially quickens the estimation of large variance–covariance blocks. To expedite the application of this diagnostic tool, the linearization procedure has been automated and implemented in the software package PsN.     

Risk of Positive Nonsentinel Nodes in Women with 1–2 Positive Sentinel Nodes Related to Age and Molecular Subtype Approximated by Receptor Status

We examine risk of positive nonsentinel axillary nodes (NSN) and ≥4 positive nodes in patients with 1–2 positive sentinel nodes (SN) by age and tumor subtype approximated by ER, PR, and Her2 receptor status. Review of two institutional databases demonstrated 284 women undergoing breast conservation between 1997 and 2008 for T1‐2 tumors and 1 (229) or 2 (55) positive SN followed by completion dissection. The median number of SN and total axillary nodes removed were 2 (range 1–10) and 14 (range 6–37), respectively. The rate of positive NSNs (p = 0.5) or ≥4 positive nodes (p = 0.6) was not associated with age. NSN were positive in 36% of luminal A, 26% of luminal B, 21% of TN and 38% of Her2+ (p = 0.4). Four or more nodes were present in 17% of luminal A, 13% luminal of B, 0% of TN and 29% of Her2+ (p = 0.1). Microscopic extracapsular extension was significantly associated with having NSNs positive (55% versus 24%, p < 0.0001) and with having total ≥4 nodes positive (33% versus 7%, p < 0.0001). In a population that was largely eligible for ACOSOG Z0011, the risk of positive NSN or ≥4 positive nodes did not vary significantly by age. The TN subgroup had the lowest risk of both positive NSN or ≥4 positive nodes. Several high risk groups with >15% risk for having ≥4 positive nodes were identified. Further data is needed to confirm that ACOSOG Z0011 results are equally applicable to all molecular phenotypes.     

Toxicity in standard melphalan-prednisone therapy among myeloma patients with renal failure--a retrospective analysis and recommendations for dose adjustment

Haematological and infectious toxicity was correlated to renal function in 272 newly diagnosed myeloma patients given standard dose melphalan-prednisone (MP) as initial treatment without dose adjustment for renal impairment. The glomerular filtration rate (GFR) was estimated by calculated creatinine clearance. Haematological toxicity was found to be significantly related to renal dysfunction. Haematological toxicity World Health Organization (WHO) grades 3-4 after the first MP course was seen in 18%, 28% and 36% of patients with a creatinine clearance of >50, 30-50 and <30 ml/min respectively. WHO grades 3-4 infections occurred in 6% and were not significantly related to renal function. We conclude that MP therapy can be used for initial therapy in myeloma patients with renal impairment but suggest that reduction of the melphalan dose should be considered in patients with a GFR of <30 ml/min. As only 2% of our patients had a clearance of < or =10 ml/min no conclusions can be drawn for this subgroup.     

Expression of Phosphofructokinase in Skeletal Muscle Is Influenced by Genetic Variation and Associated With Insulin Sensitivity

Using an integrative approach in which genetic variation, gene expression, and clinical phenotypes are assessed in relevant tissues may help functionally characterize the contribution of genetics to disease susceptibility. We sought to identify genetic variation influencing skeletal muscle gene expression (expression quantitative trait loci [eQTLs]) as well as expression associated with measures of insulin sensitivity. We investigated associations of 3,799,401 genetic variants in expression of >7,000 genes from three cohorts (n = 104). We identified 287 genes with cis-acting eQTLs (false discovery rate [FDR] <5%; P < 1.96 × 10⁻⁵) and 49 expression–insulin sensitivity phenotype associations (i.e., fasting insulin, homeostasis model assessment–insulin resistance, and BMI) (FDR <5%; P = 1.34 × 10⁻⁴). One of these associations, fasting insulin/phosphofructokinase (PFKM), overlaps with an eQTL. Furthermore, the expression of PFKM, a rate-limiting enzyme in glycolysis, was nominally associated with glucose uptake in skeletal muscle (P = 0.026; n = 42) and overexpressed (Bonferroni-corrected P = 0.03) in skeletal muscle of patients with T2D (n = 102) compared with normoglycemic controls (n = 87). The PFKM eQTL (rs4547172; P = 7.69 × 10⁻⁶) was nominally associated with glucose uptake, glucose oxidation rate, intramuscular triglyceride content, and metabolic flexibility (P = 0.016–0.048; n = 178). We explored eQTL results using published data from genome-wide association studies (DIAGRAM and MAGIC), and a proxy for the PFKM eQTL (rs11168327; r² = 0.75) was nominally associated with T2D (DIAGRAM P = 2.7 × 10⁻³). Taken together, our analysis highlights PFKM as a potential regulator of skeletal muscle insulin sensitivity.