Citations

PurposeThe effects of ovarian function suppression (OFS) on survival and patient-reported outcomes were evaluated in a phase III trial in which premenopausal women were randomly assigned to tamoxifen with or without OFS.Patients and MethodsPremenopausal women with axillary node-negative, hormone receptor–positive breast cancer tumors measuring ≤ 3 cm were randomly assigned to tamoxifen alone versus tamoxifen plus OFS; adjuvant chemotherapy was not permitted. Primary end points were disease-free survival (DFS) and overall survival (OS). Secondary end points included toxicity and patient-reported outcomes. Patient-reported outcome data included health-related quality of life, menopausal symptoms, and sexual function. These were evaluated at baseline, 6 months, 12 months, and then annually for up to 5 years after registration.ResultsIn all, 345 premenopausal women were enrolled: 171 on tamoxifen alone and 174 on tamoxifen plus OFS. With a median follow-up of 9.9 years, there was no significant difference between arms for DFS (5-year rate: 87.9% v 89.7%; log-rank P = .62) or OS (5-year rate: 95.2% v 97.6%; log-rank P = .67). Grade 3 or higher toxicity was more common in the tamoxifen plus OFS arm (22.4% v 12.3%; P = .004). Patients treated with tamoxifen plus OFS had more menopausal symptoms, lower sexual activity, and inferior health-related quality of life at 3-year follow-up (P < .01 for all). Differences diminished with further follow-up.ConclusionWhen added to tamoxifen, OFS results in more menopausal symptoms and sexual dysfunction, which contributes to inferior self-reported health-related quality of life. Because of early closure, this study is underpowered for drawing conclusions about the impact on survival when adding OFS to tamoxifen.

ABSTRACT A 65-year-old female with a history of multiple tick bites presented with fever and pancytopenia. Intracytoplasmic rickettsial morulae were detected on peripheral smear and bone marrow biopsy specimens, and PCR amplified Ehrlichia ewingii DNA from both specimens. To our knowledge, this is the first report of E. ewingii infection of human bone marrow.

ABSTRACT The detection of pathogens associated with gastrointestinal disease may be important in certain patient populations, such as immunocompromised hosts, the critically ill, or individuals with prolonged disease that is refractory to treatment. In this study, we evaluated two commercially available multiplex panels (the FilmArray gastrointestinal [GI] panel [BioFire Diagnostics, Salt Lake City, UT] and the Luminex xTag gastrointestinal pathogen panel [GPP] [Luminex Corporation, Toronto, Canada]) using Cary-Blair stool samples ( n = 500) submitted to our laboratory for routine GI testing (e.g., culture, antigen testing, microscopy, and individual real-time PCR). At the time of this study, the prototype (non-FDA-cleared) FilmArray GI panel targeted 23 pathogens (14 bacterial, 5 viral, and 4 parasitic), and testing of 200 μl of Cary-Blair stool was recommended. In contrast, the Luminex GPP assay was FDA cleared for the detection of 11 pathogens (7 bacterial, 2 viral, and 2 parasitic), but had the capacity to identify 4 additional pathogens using a research-use-only protocol. Importantly, the Luminex assay was FDA cleared for 100 μl raw stool; however, 100 μl Cary-Blair stool was tested by the Luminex assay in this study. Among 230 prospectively collected samples, routine testing was positive for one or more GI pathogens in 19 (8.3%) samples, compared to 76 (33.0%) by the FilmArray and 69 (30.3%) by the Luminex assay. Clostridium difficile (12.6 to 13.9% prevalence) and norovirus genogroup I (GI)/GII (5.7 to 13.9% prevalence) were two of the pathogens most commonly detected by both assays among prospective samples. Sapovirus was also commonly detected (5.7% positive rate) by the FilmArray assay. Among 270 additional previously characterized samples, both multiplex panels demonstrated high sensitivity (>90%) for the majority of targets, with the exception of several pathogens, notably Aeromonas sp. (23.8%) by FilmArray and Yersinia enterocolitica (48.1%) by the Luminex assay. Interestingly, the FilmArray and Luminex panels identified mixed infections in 21.1% and 13.0% of positive prospective samples, respectively, compared to only 8.3% by routine methods.

ScopeWe reevaluated previously reported associations between variants in pathways of one‐carbon (1‐C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake.Methods and resultsOdds ratios (OR) for 446 genetic variants were estimated among 13 410 OC cases and 22 635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 × 10−5) and rs828054 (OR = 1.06; p = 1 × 10−4). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10−6) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1‐C transfer, previously reported with OC, suggested lower risk at higher folate (pinteraction = 0.03–0.006).ConclusionVariation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP‐by‐folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.

Purpose A major concern with sublobar resection (SR) for non–small-cell lung cancer (NSCLC) is high local recurrence (LR). Adjuvant brachytherapy may reduce LR This multicenter randomized trial compares SR to SR with brachytherapy (SRB). Patients and Methods High-risk operable patients with NSCLC ≤ 3 cm were randomly assigned to SR or SRB. The primary end point was time to LR, where LR included recurrence at the staple line (local progression), in the primary tumor lobe away from the staple line, and in ipsilateral hilar nodes. The trial was designed to have a 90% power to detect a hazard ratio (HR) of 0.315 in favor of SRB, using a one-sided type I error rate of 0.05 with a sample size of 100 eligible patients in each arm. Results Two hundred twenty-four patients were randomly assigned; 222 patients were evaluable for intent-to-treat analysis. Median age was 71 years (range, 49 to 87 years). No differences were found in baseline characteristics. Median follow-up time was 4.38 years (range, 0.04 to 5.59 years). There was no difference in time to LR (HR, 1.01; 95% CI, 0.51 to 1.98; log-rank P = .98) or in the types of LR. Local progression occurred in only 17 (7.7%) of 222 patients. In patients with potentially compromised margins (margin < 1 cm, margin-to-tumor ratio < 1, positive staple line cytology, wedge resection, nodule size > 2.0 cm), SRB did not reduce LR, although trends favored the SRB arm. This was most marked in 14 patients with positive staple line cytology (HR, 0.22; P = .24). Three-year overall survival rates were similar for patients in the SR (71%) and SRB (71%) arms (P = .97). Conclusion Brachytherapy did not reduce LR after SR. This finding may have been related to closer attention to parenchymal margins by surgeons participating in this study.

ABSTRACT A retrospective analysis of 386,706 specimens representing a variety of matrix types used in qualitative real-time PCR assays determined the overall inhibition rate to be 0.87% when the inhibition control was added preextraction to 5,613 specimens and 0.01% when the inhibition control was added postextraction but preamplification in 381,093 specimens. Inhibition rates of ≤1% were found for all specimen matrix types except urine and formalin-fixed, paraffin-embedded tissue.

BACKGROUNDTo ensure that National Institutes of Health‐funded research is relevant to the population's needs, specific emphasis on proportional representation of minority/sex groups into National Cancer Institute (NCI) cancer centers' clinical research programs is reported to the NCI.METHODSEMPaCT investigators at 5 regionally diverse comprehensive cancer centers compared data reported to the NCI for their most recent Cancer Center Support Grant competitive renewal to assess and compare the centers' catchment area designations, data definitions, data elements, collection processes, reporting, and performance regarding proportional representation of race/ethnicity and sex subsets.RESULTSCancer centers' catchment area definitions differed widely in terms of their cancer patient versus general population specificity, levels of specificity, and geographic coverage. Racial/ethnic categories were similar, yet were defined differently, across institutions. Patients' socioeconomic status and insurance status were inconsistently captured across the 5 centers.CONCLUSIONSCatchment area definitions and the collection of patient‐level demographic factors varied widely across the 5 comprehensive cancer centers. This challenged the assessment of success by cancer centers in accruing representative populations into the cancer research enterprise. Accrual of minorities was less than desired for at least 1 racial/ethnic subcategory at 4 of the 5 centers. Institutions should clearly and consistently declare their primary catchment area and the rationale and should report how race/ethnicity and sex are defined, determined, collected, and reported. More standardized, frequent, consistent collection, reporting, and review of these data are recommended, as is a commitment to collecting socioeconomic data, given that socioeconomic status is a primary driver of cancer disparities in the United States. Cancer 2014;120(7 suppl):1113–21. © 2014 American Cancer Society.