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Qingyan Liu,1 Linda S Weaver,1 David Liewehr,2 David Venzon,2 Maryalice Stetler-Stevenson,1 Constance M Yuan11Flow Cytometry Unit, Laboratory of Pathology, 2Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USAAbstract: Follicular lymphoma (FL) is a relatively common, well-characterized lymphoma with recognizable morphologic and immunophenotypic features. Nevertheless, close examination of its immunophenotypic profile by mean fluorescent intensity (MFI) and potential relationship between antigens, as well as histologic grade, has not been extensively assessed by flow cytometry immunophenotyping (FC). We examined the immunophenotypic profile, including heavy and light chain analysis, of 41 nodal FL cases with FC analysis and tissue diagnosis. Additionally, MFI of CD45, CD19, CD20, CD22, and CD10 were examined. The relationship between the antigen expression on FL cells and normal B cells in the same sample, and any association with each other or with histologic grade, were analyzed statistically. We observed brighter CD45 and CD20 expression in FL than normal B cells (P < 0.0001); dimmer CD19 in FL than normal B cells (P = 0.03); brighter CD20 in grade 2 than grade 1 histology (P = 0.0023). No correlation was observed between CD10 MFI and other antigens. Increased expression of CD20, CD45, and dim expression of CD19 are features of nodal FL. FC assessment of MFI detects subtle changes in antigen expression not entirely apparent by visual examination of dot plots or immunohistochemistry. MFI is a means of uncovering subtle but unique immunophenotypic features in both well-known, and less well-defined neoplastic hematolymphoid entities.Keywords: lymphoma, lymphoproliferative disorder, flow cytometry, mean fluorescent intensity, immunophenotyping, immunoglobulin heavy chain

Abstract Background Hypertension (HT) and hand-foot skin reactions (HFSR) may be related to the activity of bevacizumab and sorafenib. We hypothesized that these toxicities would correspond to favorable outcome in these drugs, that HT and HFSR would coincide, and that VEGFR2 genotypic variation would be related to toxicity and clinical outcomes. Methods Toxicities (≥ grade 2 HT or HFSR), progression-free survival (PFS), and overall survival (OS) following treatment initiation were evaluated. Toxicity incidence and VEGFR2 H472Q and V297I status were compared to clinical outcomes. Results Individuals experiencing HT had longer PFS following bevacizumab therapy than those without this toxicity in trials utilizing bevacizumab in patients with prostate cancer (31.5 vs 14.9 months, n = 60, P = 0.0009), and bevacizumab and sorafenib in patients with solid tumors (11.9 vs. 3.7 months, n = 27, P = 0.052). HT was also linked to a > 5-fold OS benefit after sorafenib and bevacizumab cotherapy (5.7 versus 29.0 months, P = 0.0068). HFSR was a marker for prolonged PFS during sorafenib therapy (6.1 versus 3.7 months respectively, n = 113, P = 0.0003). HT was a risk factor for HFSR in patients treated with bevacizumab and/or sorafenib (OR(95%CI) = 3.2(1.5-6.8), P = 0.0024). Carriers of variant alleles at VEGFR2 H472Q experienced greater risk of developing HT (OR(95%CI) = 2.3(1.2 - 4.6), n = 170, P = 0.0154) and HFSR (OR(95%CI) = 2.7(1.3 - 5.6), n = 170, P = 0.0136). Conclusions This study suggests that HT and HFSR may be markers for favorable clinical outcome, HT development may be a marker for HFSR, and VEGFR2 alleles may be related to the development of toxicities during therapy with bevacizumab and/or sorafenib.

Abstract Background Physical activity is being studied as a breast cancer prevention strategy. Women at risk of breast cancer report interest in lifestyle modification, but recruitment to randomized physical activity intervention studies is challenging. Methods We conducted an analysis of recruitment techniques used for a prospective, randomized pilot study of physical activity in women at risk of breast cancer. We evaluated differences in proportion of eligible patients, enrolled patients, and successful patients identified by each individual recruitment method. The Fisher-Freeman-Halton test (an extension of Fisher's exact test from 2 × 2 tables to general row by column tables) was used to compare the success of different recruitment strategies. Results We received 352 inquiries from women interested in participating, of whom 171 (54%) were eligible. Ninety-nine women completed a baseline activity evaluation, and 58 (34% of eligible; 16% of total inquiries) were randomized. Recruitment methods fell into three broad categories: media techniques, direct contact with potential participants, and contacts with health care providers. Recruitment strategies differed significantly in their ability to identify eligible women (p = 0.01), and women who subsequently enrolled in the study (p = 0.02). Conclusion Recruitment techniques had varying success. Our data illustrate the challenges in recruiting to behavior modification studies, and provide useful information for tailoring future recruitment efforts for lifestyle intervention trials. Trial Registration No(s) CDR0000393790, NCI-04-C-0276, NCI-NAVY-B05-001