Fulvestrant, which degrades ER, is used after AI failure in metastatic breast cancer but resistance develops quickly. We hypothesized that using everolimus to inhibit mTOR, a key signaling pathway in endocrine resistance, may delay fulvestrant resistance in patients and thus improve its efficacy. We conducted a phase II trial of combined fulvestrant and everolimus in postmenopausal women with disease progression or relapse after an AI. Primary endpoint was time to progression (TTP) and secondary endpoints included objective response rate, clinical benefit rate (CBR), safety, and biomarker correlates. Tumor blocks were collected and biopsy of accessible tumor was done for future biomarker analysis. Of 33 patients enrolled two were ruled ineligible after enrollment and were excluded from study analysis, for a total of 31 evaluable patients. Median age was 54 years (range 45-85). Prior therapy included tamoxifen (81 %), chemotherapy (71 %), with 26 % of patients having received 3 or more endocrine agents. Median TTP was 7.4 months (95 % CI 1.9-12.1) with an objective response rate of 13 % and CBR of 49 %. Of particular note, 32 % of patients exhibited de novo resistance to study treatment with disease progression as their best response. Most common adverse events (AEs) were elevated AST (87 %) and ALT (77 %), anemia (74 %), hyperglycemia (71 %), and hypercholesterolemia (68 %). Prominent clinical toxicities were mucositis (58 %), weight loss (48 %), and rash (42 %). Most AEs were grade 1 or 2 and largely reversible with infrequent need for everolimus dose reduction. To conclude, everolimus plus fulvestrant is effective after AI failure in heavily pretreated metastatic ER-positive breast cancer and has manageable toxicity. Further study of this combination is warranted in randomized studies. Since not all patients experience benefit, and in view of potential toxicities, biomarker examination is critical to help select patients most likely to benefit from this strategy in future studies.

Despite the 2000 CDC guidelines, wide variation in post-HSCT immunization practices still exists. Updated guidelines have been needed, particularly to address the use of the pneumococcal conjugate vaccine. In conjunction with multiple other groups, the CDC recently released new immunization guidelines in October 2009. Additional data are still needed to adequately address the utility of incorporating immunologic parameters with the timing of vaccination after HSCT.

Objective This report describes findings from a randomized controlled trial of an intervention to increase colorectal cancer (CRC) screening in primary care practices in Appalachian Kentucky. Methods Sixty-six primary care practices were randomized to early or delayed intervention groups. The intervention was provided at practices using academic detailing, a method of education where providers receive information on a specific topic through personal contact. Data were collected in cross-sectional surveys of medical records at baseline and six months post-intervention. Results A total of 3844 medical records were reviewed at baseline and 3751 at the six-month follow-up. At baselines, colonoscopy was recommended more frequently (43.4%) than any other screening modality, followed by fecal occult blood testing (18.0%), flexible sigmoidoscopy (0.4%), and double-contrast barium enema (0.3%). Rates of documented screening results were higher for all practices at the six-month follow-up for colonoscopy (31.8% vs 29.6%) and fecal occult blood testing (12.2% vs 11.2%). For early intervention practices that recommended screening, colonoscopy rates increased by 15.7% at six months compared to an increase of 2.4% in the delayed intervention practices (p=.01). Conclusions Using academic detailing to reach rural primary care providers with a CRC screening intervention was associated with an increase in colonoscopy.

Spatial accessibility is of increasing interest in the health sciences. This paper addresses the statistical use of spatial accessibility and availability indices. These measures are evaluated via an extensive simulation based on cluster models for local food outlet density. We derived Monte Carlo critical values for several statistical tests based on the indices. In particular we are interested in the ability to make inferential comparisons between different study areas where indices of accessibility and availability are to be calculated. We derive tests of mean difference as well as tests for differences in Moran's I for spatial correlation for each of the accessibility and availability indices. We also apply these new statistical tests to a data example based on two counties in South Carolina for various accessibility and availability measures calculated for food outlets, stores, and restaurants.

This article describes a community-based Patient Navigation (PN) project conducted to identify potential barriers to seeking follow-up cervical cancer care in southeastern Kentucky. Patient navigators (PNs) were placed in cervical cancer programs within county public health departments where they interviewed patients about their perceived barriers to seeking follow-up care after receiving a positive Pap test result. Participants identified various potential barriers at three levels: the individual/personal level, the health care system level and the community/environmental level. One identified barrier that was unique to this study was a lack of consistency between follow-up recommendations and follow-up guidelines for patients under age 21. Implications are discussed.

Purpose: To assess the hypothesis that the volume of whole brain that receives a certain dose level is primarily dependent on the treated volume rather than on the number, shape, or location of the lesions. This would help a physician validate the suitability of GammaKnife R based stereotactic radiosurgery (GKSR) prior to treatment. Methods: Simulation studies were performed to establish the hypothesis for both oblong and spherical shaped lesions of various numbers and sizes. Forty patients who underwent GKSR [mean age of 54 years (range 7-80), mean number of lesions of 2.5 (range 1-6), and mean lesion volume of 4.4 cm 3 (range 0.02-22.2 cm 3 )] were also studied retrospectively. Following recommendations of QUANTEC, the volume of brain irradiated by the 12 Gy (VB12) isodose line was measured and a power-law based relation is proposed here for estimating VB12 from the known tumor volume and the prescription dose. Results: In the simulation study on oblong, spherical, and multiple lesions, the volume of brain irradiated by 50%, 10%, and 1% of maximum dose was found to have linear, linear, and exponentially increasing dependence on the volume of the treated region, respectively. In the retrospective study on 40 GKSR patients, a similar relationship was found to predict the brain dose with a Spearman correlation coefficient >0.9. In both the studies, the volume of brain irradiated by a certain dose level does not have a statistically significant relationship (p ≥ 0.05) with the number, shape, or position of the lesions. The measured VB12 agrees with calculation to within 1.7%. Conclusions:The results from the simulation and the retrospective clinical studies indicate that the volume of whole brain that receives a certain percentage of the maximum dose is primarily dependent on the treated volume and less on the number, shape, and location of the lesions.

Multiple reports have shown that low absolute lymphocyte count at day 30 (ALC30) after allogeneic hematopoietic SCT (AHSCT) is associated with higher risk of disease relapse and worse OS. However, these reports included heterogeneous populations with different grafts and GVHD prophylaxis. Therefore, we retrospectively evaluated the association of ALC30 with transplant outcomes in a cohort of 381 consecutive patients who underwent AHSCT between 2005 and 2010 and received T-replete PBSC grafts and Tacrolimus/Mycophenolate combination as GVHD prophylaxis. Median follow-up was 57 months. Lower ALC30 (⩽400 × 10 6 /L) was associated with lower OS and increased nonrelapse mortality (NRM) for the whole cohort as well as for recipients of SD and UD grafts separately. Lower ALC30 was associated with more severe acute GVHD (aGVHD; III-IV) for the entire cohort as well as for the SD and UD groups. No association was found between lower ALC30 and relapse. Pretransplant factors associated with lower ALC30 were: unrelated donors; HLA mismatch; older donors; lower recipient age; and lower CD34+ cell dose. In this large retrospective study, ALC30 ⩽ 400 × 10 6 /L was associated with worse OS, increased NRM and severe aGVHD.

Clinicians should be aware that patients with a history of abnormal results and severe Pap test abnormalities are at risk of misreporting recommendations for follow up.