Citations

Abstract BACKGROUND: Mammographic percent dense area, the percent ratio of dense to total breast area in a mammogram, is one of the strongest measures of a woman's risk of breast cancer. However, systematic differences have been observed between readers and mammography technologies (film and digital) that could cause clinically inconsistent associations with risk. The purpose of this study was to evaluate inter- and intra-reproducibility of percent dense area between readers and between film and digital technologies. METHODS: One hundred digitized film mammograms were randomly selected with 25 films in each of quartile of percent density and read by two readers at two different sites (Mayo Clinic and UCSF). The readers had extensive experience and were also jointly trained at university of Toronto using Cumulus software. After training, all films were read twice with at least one year between duplicate readings. The Mayo clinic reading used Cumulus while UCSF used custom semiautomatic software to estimate total and dense tissue area. In addition, digitized films and unprocessed full field digital mammograms of the same women were assessed by one reader. The time between the film and digital acquisitions ranged from nine to twenty-four months. Interclass correlation coefficient (ICC) was calculated for each comparison. RESULTS: The intra- and inter-observer ICCs, consistency for film images, were 0.96 (UCSF) and 0.97 (Mayo), and 0.96 (UCSF vs. Mayo). We found ICC between film and digital mammograms for percent dense area was 0.88. The digital mammogram had 9% significantly higher total breast area and 5% significantly lower percent density area compared to film. CONCLUSIONS: Similarly trained readers had a high reproducibility regardless of the software used. Our results suggest centralized reader training should enable pooling of film breast density results from different clinics. However, pooling film and digital results would need careful calibration due to lower measured percent dense areas than on film. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-08-03.

AbstractGiven the rapidly rising healthcare costs, it is important to understand the economic costs of hematopoietic cell transplantation (HCT), a procedure that is being used more frequently in the treatment of various hematologic disorders. Studies have reported a wide range of costs for HCT, from $36 000 to $88 000 (USD) for a single autologous transplantation for the initial hospitalization, to $200 000 (USD) or more for a myeloablative allogeneic procedure involving an unrelated donor. Common posttransplantation complications, such as infections and GVHD, have been shown to be significant cost drivers. Comparisons across studies are limited by differences in patient populations, cost ascertainment methods, and length of follow-up. This article summarizes the current state of knowledge about costs and cost-effectiveness of HCT, highlighting the challenges in conducting these studies and identifying important areas for future research. We discuss the need for more value-based assessments of HCT using high-quality approaches to measuring costs and outcomes so that potential future efforts to contain costs are well informed and appropriate.

Granulation tissue formation is an example of new tissue development in an adult. Its rich vascular network has been thought to derive via angiogenic sprouting and extension of preexisting vessels from the surrounding tissue. The possibility that circulating cells of hematopoietic origin can differentiate into vascular endothelial cells (ECs) in areas of vascular remodeling has recently gained credibility. However, no quantitative data have placed the magnitude of this contribution into a physiological perspective. We have used hematopoietic chimeras to determine that 0.2% to 1.4% of ECs in vessels in control tissues derived from hematopoietic progenitors during the 4 months after irradiation and hematopoietic recovery. By contrast, 8.3% to 11.2% of ECs in vessels that developed in sponge-induced granulation tissue during 1 month derived from circulating hematopoietic progenitors. This recruitment of circulating progenitors to newly forming vessels would be difficult to observe in standard histological studies, but it is large enough to be encouraging for attempts to manipulate this contribution for therapeutic gain.

Abstract Background: Postmenopausal hormone (PMH) therapy represents a controversial colorectal cancer (CRC) preventive intervention. Because colorectal carcinogenesis is a heterogeneous process, we evaluated associations between PMH therapy and incident CRC in relation to KRAS mutation status in a population-based cohort of older women [Iowa Women's Health Study (IWHS)]. Methods: The IWHS enrolled 41,836 randomly selected women, ages 55 to 69 years, in 1986. PMH therapy and other exposure data were recorded at baseline. Tissue samples from prospectively identified CRC cases (n = 507) were analyzed for somatic KRAS mutations (exon 2, codons 12 and 13). Multivariable Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Results: PMH therapy (ever vs. never) was inversely associated with KRAS mutation–negative (RR = 0.83; 95% CI, 0.66–1.06; P = 0.14) and KRAS mutation–positive (RR = 0.82; 95% CI, 0.58–1.16; P = 0.27) tumors, although the observed risk estimates were not statistically significant. When anatomic subsite was additionally considered, the strongest association was found for KRAS mutation–negative, distal colorectal tumors (RR = 0.64; 95% CI, 0.43–0.96; P = 0.03). Conclusions: To our knowledge, we provide the first report of KRAS-defined CRC risks associated with PMH therapy. These data suggest that PMH therapy may reduce CRC risk through mechanisms beyond KRAS mutation status but might provide greater benefits for KRAS mutation–negative than mutation-positive tumors (at least in the distal colorectum). Impact: Findings from this prospective cohort study provide novel insights about the molecular biology of PMH therapy–related CRC risk reduction. Cancer Epidemiol Biomarkers Prev; 21(4); 681–4. ©2012 AACR.

Purpose Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. In phase I studies, brentuximab vedotin demonstrated significant activity with a favorable safety profile in patients with relapsed or refractory CD30-positive lymphomas. Patients and Methods In this multinational, open-label, phase II study, the efficacy and safety of brentuximab vedotin were evaluated in patients with relapsed or refractory Hodgkin's lymphoma (HL) after autologous stem-cell transplantation (auto-SCT). Patients had histologically documented CD30-positive HL by central pathology review. A total of 102 patients were treated with brentuximab vedotin 1.8 mg/kg by intravenous infusion every 3 weeks. In the absence of disease progression or prohibitive toxicity, patients received a maximum of 16 cycles. The primary end point was the overall objective response rate (ORR) determined by an independent radiology review facility. Results The ORR was 75% with complete remission (CR) in 34% of patients. The median progression-free survival time for all patients was 5.6 months, and the median duration of response for those in CR was 20.5 months. After a median observation time of more than 1.5 years, 31 patients were alive and free of documented progressive disease. The most common treatment-related adverse events were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea. Conclusion The ADC brentuximab vedotin was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed or refractory HL after auto-SCT. Durable CRs approaching 2 years were observed, supporting study in earlier lines of therapy.

Abstract Mechanistic understanding of RP105 has been confounded by the fact that this TLR homolog has appeared to have opposing, cell type-specific effects on TLR4 signaling. Although RP105 inhibits TLR4-driven signaling in cell lines and myeloid cells, impaired LPS-driven proliferation by B cells from RP105−/− mice has suggested that RP105 facilitates TLR4 signaling in B cells. In this article, we show that modulation of B cell proliferation by RP105 is not a function of B cell-intrinsic expression of RP105, and identify a mechanistic role for dysregulated BAFF expression in the proliferative abnormalities of B cells from RP105−/− mice: serum BAFF levels are elevated in RP105−/− mice, and partial BAFF neutralization rescues aberrant B cell proliferative responses in such mice. These data indicate that RP105 does not have dichotomous effects on TLR4 signaling and emphasize the need for caution in interpreting the results of global genetic deletion.