Toward a better understanding of the comparatively high prostate cancer incidence rates in Utah

BACKGROUND: This study assesses whether comparatively high prostate cancer incidence rates among white men in Utah represent higher rates among members of the Church of Jesus Christ of Latter-day Saints (LDS or Mormons), who comprise about 70% of the state's male population, and considers the potential influence screening has on these rates. METHODS: Analyses are based on 14,693 histologically confirmed invasive prostate cancer cases among men aged 50 years and older identified through the Utah Cancer Registry between 1985 and 1999. Cancer records were linked to LDS Church membership records to determine LDS status. Poisson regression was used to derive rate ratios of LDS to nonLDS prostate cancer incidence, adjusted for age, disease stage, calendar time, and incidental detection. RESULTS: LDS men had a 31% (95% confidence interval, 26% – 36%) higher incidence rate of prostate cancer than nonLDS men during the study period. Rates were consistently higher among LDS men over time (118% in 1985–88, 20% in 1989–92, 15% in 1993–1996, and 13% in 1997–99); age (13% in ages 50–59, 48% in ages 60–69, 28% in ages 70–79, and 16% in ages 80 and older); and stage (36% in local/regional and 17% in unstaged). An age- and stage-shift was observed for both LDS and nonLDS men, although more pronounced among LDS men. CONCLUSIONS: Comparatively high prostate cancer incidence rates among LDS men in Utah are explained, at least in part, by more aggressive screening among these men

Improved human observer performance in digital reconstructed radiograph verification in head and neck cancer radiotherapy.

Purpose: Digitally reconstructed radiographs (DRRs) are routinely used as an a priori reference for setup correction in radiotherapy. The spatial resolution of DRRs may be improved to reduce setup error in fractionated radiotherapy treatment protocols. The influence of finer CT slice thickness reconstruction (STR) and resultant increased resolution DRRs on physician setup accuracy was prospectively evaluated. Methods: Four head and neck patient CT-simulation images were acquired and used to create DRR cohorts by varying STRs at 0.5, 1, 2, 2.5, and 3 mm. DRRs were displaced relative to a fixed isocenter using 0–5 mm random shifts in the three cardinal axes. Physician observers reviewed DRRs of varying STRs and displacements and then aligned reference and test DRRs replicating daily KV imaging workflow. A total of 1,064 images were reviewed by four blinded physicians. Observer errors were analyzed using nonparametric statistics (Friedman’s test) to determine whether STR cohorts had detectably different displacement profiles. Post hoc bootstrap resampling was applied to evaluate potential generalizability. Results: The observer-based trial revealed a statistically significant difference between cohort means for observer displacement vector error (p = 0.02) and for Z-axis (p < 0.01). Bootstrap analysis suggests a 15% gain in isocenter translational setup error with reduction of STR from 3 mm to ≤2 mm, though interobserver variance was a larger feature than STR-associated measurement variance. Conclusions: Higher resolution DRRs generated using finer CT scan STR resulted in improved observer performance at shift detection and could decrease operator-dependent geometric error. Ideally, CT STRs ≤2 mm should be utilized for DRR generation in the head and break neck

American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer

Purpose: To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker. Methods: The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations. Results: Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry (IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy. Recommendations: The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3+ (uniform, intense membrane staining of > 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1+, a FISH result of less than 4.0 HER2 gene copies per nucleus, or FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored with the use of stringent laboratory accreditation standards, proficiency testing, and competency assessment. The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document. Copyright © 2007 by the American Society of Clinical Oncology and College of American Pathologists. All rights reserved